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1

Chromosomes of the liver fluke, Clonorchis sinensis  

PubMed Central

A karyological study was carried out in order to compared the chromosome numbers, chromosome morphologies and karyotypes of the oriental liver fluke, Clonorchis sinensis (Trematoda: Opisthorchiidae), collected from Korea and China. Chromosome preparations were made by means of air-drying method. The chromosome number was 2n=56 in both Korean and Chinese flukes, and chromosomes were divided into two groups based on this size; consisting of 8 pairs of large and 20 pairs of small chromosomes. However, the karyotypes showed some differences between Korean and Chinese flukes. The karyotype of liver flukes from Korea consisted of three metacentric pairs, one meta-/submetacentric pair, 16 submetacentric pairs and eight subtelocentric pairs of chromosomes. On the other hand, liver flukes from China consisted of two metacentric pairs, two meta-/submetacentric pairs, 16 submetacentric pairs and eight subtelocentric pairs of chromosomes.

Park, Gab-Man; Im, Kyung-il; Huh, Sun

2000-01-01

2

Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis  

Microsoft Academic Search

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult

Won Gi Yoo; Dae-Won Kim; Jung-Won Ju; Pyo Yun Cho; Tae Im Kim; Shin-Hyeong Cho; Sang-Haeng Choi; Hong-Seog Park; Tong-Soo Kim; Sung-Jong Hong

2011-01-01

3

Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis  

PubMed Central

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens.

Cho, Pyo Yun; Kim, Tae Im; Cho, Shin-Hyeong; Choi, Sang-Haeng; Park, Hong-Seog; Kim, Tong-Soo; Hong, Sung-Jong

2011-01-01

4

The draft genome of the carcinogenic human liver fluke Clonorchis sinensis  

PubMed Central

Background Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome. Results We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines. Conclusions This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control.

2011-01-01

5

Molecular identification of Clonorchis sinensis and discrimination with other opisthorchid liver fluke species using multiple Ligation-depended Probe Amplification (MLPA)  

PubMed Central

Background Infections with the opisthorchid liver flukes Clonorchis sinensis, Opisthorchis viverrini, and O. felineus cause severe health problems globally, particularly in Southeast Asia. Early identification of the infection is essential to provide timely and appropriate chemotherapy to patients. Results In this study we evaluate a PCR-based molecular identification method, Multiplex Ligation-dependent Probe Amplification (MLPA), which allows rapid and specific detection of single nucleotide acid differences between Clonorchis sinensis, Opisthorchis viverrini and O. felineus. Three probe pairs were derived from the Internally Transcribed Spacer 1 (ITS1) of three opisthorchid liver flukes using a systematic phylogenetic analysis. Specific loci were detected in all three species, yielding three amplicons with 198,172 and 152 bp, respectively, while no cross reactions were observed. A panel of 66 C. sinensis isolates was screened using MLPA. All species were positively identified, and no inhibition was observed. The detection limit was 103 copies of the ITS gene for the three liver flukes, or about 60 pg genomic DNA for Clonorchis sinensis. Amplification products can be detected by electrophoresis on agarose gel or in a capillary sequencer. In addition, genomic DNA of Clonorchis sinensis in fecal samples of infected rats was positively amplified by MLPA. Conclusion The flexibility and specificity make MLPA a potential tool for specific identification of infections by opisthorchid liver flukes in endemic areas.

2011-01-01

6

Molecular identification of Clonorchis sinensis and discrimination with other opisthorchid liver fluke species using multiple Ligation-depended Probe Amplification (MLPA)  

Microsoft Academic Search

Background  Infections with the opisthorchid liver flukes Clonorchis sinensis, Opisthorchis viverrini, and O. felineus cause severe health problems globally, particularly in Southeast Asia. Early identification of the infection is essential\\u000a to provide timely and appropriate chemotherapy to patients.\\u000a \\u000a \\u000a \\u000a \\u000a Results  In this study we evaluate a PCR-based molecular identification method, Multiplex Ligation-dependent Probe Amplification (MLPA),\\u000a which allows rapid and specific detection of single

Jiufeng Sun; Jin Xu; Pei Liang; Qiang Mao; Yan Huang; Xiaoli Lv; Chuanhuan Deng; Chi Liang; G S de Hoog; Xinbing Yu

2011-01-01

7

Liver flukes: the malady neglected.  

PubMed

Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected. PMID:21603286

Lim, Jae Hoon

2011-01-01

8

Taxonomy and biology of liver flukes  

Microsoft Academic Search

Opisthorchis viverrini is a human liver fluke endemic in Thailand, Lao PDR and Cambodia. Three subspecies of Bithynia siamensis and 18 species of cyprinoid fish are susceptible first and second intermediate hosts, respectively. The differentiation between the adult worm of O. viverrini and that of the closely related species, Opisthorchis felineus and Clonorchis sinensis, is mainly based on the shape

Sasithorn Kaewkes

2003-01-01

9

The carcinogenic liver fluke, Clonorchis sinensis: new assembly, reannotation and analysis of the genome and characterization of tissue transcriptomes.  

PubMed

Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the ?-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis. PMID:23382950

Huang, Yan; Chen, Wenjun; Wang, Xiaoyun; Liu, Hailiang; Chen, Yangyi; Guo, Lei; Luo, Fang; Sun, Jiufeng; Mao, Qiang; Liang, Pei; Xie, Zhizhi; Zhou, Chenhui; Tian, Yanli; Lv, Xiaoli; Huang, Lisi; Zhou, Juanjuan; Hu, Yue; Li, Ran; Zhang, Fan; Lei, Huali; Li, Wenfang; Hu, Xuchu; Liang, Chi; Xu, Jin; Li, Xuerong; Yu, Xinbing

2013-01-01

10

The Carcinogenic Liver Fluke, Clonorchis sinensis: New Assembly, Reannotation and Analysis of the Genome and Characterization of Tissue Transcriptomes  

PubMed Central

Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the ?-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis.

Wang, Xiaoyun; Liu, Hailiang; Chen, Yangyi; Guo, Lei; Luo, Fang; Sun, Jiufeng; Mao, Qiang; Liang, Pei; Xie, Zhizhi; Zhou, Chenhui; Tian, Yanli; Lv, Xiaoli; Huang, Lisi; Zhou, Juanjuan; Hu, Yue; Li, Ran; Zhang, Fan; Lei, Huali; Li, Wenfang; Hu, Xuchu; Liang, Chi; Xu, Jin; Li, Xuerong; Yu, Xinbing

2013-01-01

11

Taxonomy and biology of liver flukes.  

PubMed

Opisthorchis viverrini is a human liver fluke endemic in Thailand, Lao PDR and Cambodia. Three subspecies of Bithynia siamensis and 18 species of cyprinoid fish are susceptible first and second intermediate hosts, respectively. The differentiation between the adult worm of O. viverrini and that of the closely related species, Opisthorchis felineus and Clonorchis sinensis, is mainly based on the shape and position of the testes and the arrangement of the vitellaria. Eggs of these flukes are morphologically similar and problematic in identification. However, the differentiation between opisthorchid and lecithodendrid eggs is possible. Morphology and biology of each stage are comparatively reviewed. Biological aspects of snail and fish hosts are also included. PMID:14611872

Kaewkes, Sasithorn

2003-11-01

12

Roles of liver fluke infection as risk factor for cholangiocarcinoma.  

PubMed

Several factors are known to be associated with risk of cholangiocarcinoma (CCA) and infection with the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, has often been singled out as the leading risk factor in east and southeast Asia. In this review, current knowledge of their biology, life cycle, and pathogenesis of O.?viverrini, and its role as a carcinogenic parasite are presented. The trends of age-specific incidence of liver cancer in Khon Kaen, northeast Thailand are considered and compared with the prevalence profiles of O.?viverrini. Potential impacts of the liver fluke control program particularly by mass drug administration (MDA) and public health education in the past and a recent drop of incidence of CCA are discussed in relation to primary prevention and control of this fatal bile duct cancer. PMID:24408775

Sithithaworn, Paiboon; Yongvanit, Puangrat; Duenngai, Kunyarat; Kiatsopit, Nadda; Pairojkul, Chawalit

2014-05-01

13

The tumorigenic liver fluke Opisthorchis viverrini -multiple pathways to cancer  

PubMed Central

Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand and adjacent countries. In addition to infection-associated morbidity, infection with O. viverrini and the related Clonorchis sinensis are unarguable risk factors for cholangiocarcinoma, bile duct cancer. Here we review the pathogenesis of opisthorchiasis and the association of O. viverrini infection and bile duct cancer, focusing on the molecular parallels between wound healing, chronic inflammation and cancer development. We review a schema for human disease progression from fluke infection, chronic opisthorchiasis, advanced periductal fibrosis, and cholangiocarcinogenesis, and present a rationale for biomarker discovery to facilitate early intervention. We conclude by addressing post-genomic advances with a view to developing new control strategies to combat this infectious cancer.

Sripa, Banchob; Brindley, Paul J.; Mulvenna, Jason; Laha, Thewarach; Smout, Michael J; Mairiang, Eimorn; Bethony, Jeffrey M.; Loukas, Alex

2012-01-01

14

Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini  

PubMed Central

Background Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum) than to free-living (Schmidtea mediterranea) flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions, drugs and vaccines, to control O. viverrini and related flukes.

Laha, Thewarach; Pinlaor, Porntip; Mulvenna, Jason; Sripa, Banchob; Sripa, Manop; Smout, Michael J; Gasser, Robin B; Brindley, Paul J; Loukas, Alex

2007-01-01

15

Route of Entry of Clonorchis Sinensis to the Mammalian Liver.  

National Technical Information Service (NTIS)

Metacercariae were fed to animals in which the common bile duct had been ligated and severed. No adult flukes were found subsequently in the livers or ducts of any of the animals. In control animals infected in the same way, adult flukes were invariably f...

T. Sun S. T. Chou J. B. Gibson

1967-01-01

16

Opisthorchis viverrini: the carcinogenic human liver fluke.  

PubMed

Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas. PMID:18205254

Kaewpitoon, Natthawut; Kaewpitoon, Soraya-J; Pengsaa, Prasit; Sripa, Banchob

2008-02-01

17

The tumorigenic liver fluke Opisthorchis viverrini--multiple pathways to cancer.  

PubMed

Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand and adjacent countries. In addition to infection-associated morbidity, infection with O. viverrini and the related Clonorchis sinensis are unarguable risk factors for cholangiocarcinoma (CAA, bile-duct cancer). Here we review the pathogenesis of opisthorchiasis and the association between O. viverrini infection and bile-duct cancer, focusing on the molecular parallels between wound healing, chronic inflammation, and cancer development. We review a schema for human disease progression from fluke infection, chronic opisthorchiasis, advanced periductal fibrosis, and cholangiocarcinogenesis, and present a rationale for biomarker discovery to facilitate early intervention. We conclude by addressing post-genomic advances with a view to developing new control strategies to combat this infectious cancer. PMID:22947297

Sripa, Banchob; Brindley, Paul J; Mulvenna, Jason; Laha, Thewarach; Smout, Michael J; Mairiang, Eimorn; Bethony, Jeffrey M; Loukas, Alex

2012-10-01

18

Clonorchis sinensis Associated Cholangiocarcinoma: A Case Report and Review of the Literature  

Microsoft Academic Search

Clonorchis sinensis is a flat, leaf-shaped hermaphroditic trematode endemic throughout Southeast Asia. It belongs to the group of liver flukes, along with Opisthorchis viverrini and Opisthorchis felineus. According to the 1994 report of the World Health Organization and the International Agency for Research on Cancer (IARC), the global number of Clonorchis sinensis infestations is estimated as 7 million, found predominantly

Georgios I. Papachristou; Karen E. Schoedel; Ramesh Ramanathan; Mordechai Rabinovitz

2005-01-01

19

Human Infections with Liver and Minute Intestinal Flukes in Guangxi, China: Analysis by DNA Sequencing, Ultrasonography, and Immunoaffinity Chromatography  

PubMed Central

The prevalence of liver and intestinal fluke infections was determined by surveying inhabitants of Hengxuan, Fusui, and Shanglin villages which were known to be endemic for liver flukes in Guangxi, China in May 2010. A total of 718 people were examined for helminth eggs by the Kato-Katz thick smear technique, ultrasonography, immunoaffinity chromatography, and DNA sequencing. The overall egg positive rate was found to be 59.6% (28.0-70.6%) that included mixed infections with liver and intestinal flukes. Cases showing higher than 20,000 eggs per gram of feces (EPG) were detected between 1.3% and 16.2%. Ultrasonographic findings exhibited overall 28.2% (72 of 255 cases) dilatation rate of the intrahepatic bile duct. Clonorchis sinensis infection was detected serologically in 88.3% (38 of 43 cases) among C. sinensis egg positive subjects by the immunoaffinity chromatography using a specific antigen for C. sinensis. For differential diagnosis of the liver and intestinal flukes, more precise PCR and nucleotide sequencing for copro-DNA were performed for 46 egg positive cases. Mixed infections with C. sinensis and Metagonimus yokogawai were detected in 8 of 46 egg positive cases, whereas 29 specimens were positive for Haplorchis taichui. Ultrasonographic findings and immunoaffinity chromatography results showed usefulness, even in a limited way, in figuring out of the liver fluke endemicity.

Jeon, Hyeong-Kyu; Lee, Dongmin; Park, Hansol; Min, Duk-Young; Rim, Han-Jong; Zhang, Hongman; Yang, Yichao; Li, Xueming

2012-01-01

20

Opisthorchis viverrini: Gene expression profiling of carcinogenic adult liver fluke worms using 5' SAGE.  

PubMed

Opisthorchis viverrini is the only liver fluke that has been proved to be associated with cholangiocarcinoma (CCA). However, the mechanisms by which O. viverrini participates in the carcinogenesis of CCA are still unclear. To understand the biology and host-parasite interaction related to O. viverrini infection, gene expression profiling of this parasite is required. Here, we constructed the first 5' serial analysis of gene expression (5' SAGE) library of the adult O. viverrini and matched the data with the public data of O. viverrini, Clonorchis sinensis and other related Platyhelminthes and Nematodes. We obtained 12,401 unique tag sequences, of which 6515 (53%) could be matched with the 3419 transcript sequences. The two most abundant tag sequences were vitelline B precursor protein and myoglobin. Often several transcription start sites (TSS) were observed for one transcript. This finding may reflect the dynamic nature of transcriptional initiation events of O. viverrini genes in vivo. PMID:18786530

Chutiwitoonchai, Nopporn; Shen, Yan; Zheng, Huajun; Xiong, Hui; Zhao, Guoping; Imtawil, Kanokwan; Intapan, Pewpan M; Wongkham, Sopit; Wongkham, Chaisiri

2008-12-01

21

Infection with the carcinogenic human liver fluke, Opisthorchis viverrini.  

PubMed

Throughout Southeast Asia there is a strikingly high incidence of cholangiocarcinoma (CCA--hepatic cancer of the bile duct epithelium), particularly in people from rural settings in Laos and Northeast Thailand who are infected with the liver fluke, Opisthorchis viverrini, one of only three carcinogenic eukaryotic pathogens. More ubiquitous carcinogenic microbes, such as Helicobacter pylori, induce cancer in less than 1% of infected people, while as many as one-sixth of people with opisthorchiasis will develop CCA. The mechanisms by which O. viverrini causes cancer are multi-factorial, involving mechanical irritation from the activities and movements of the flukes, immunopathology, dietary nitrosamines and the secretion of parasite proteins that promote a tumourigenic environment. Genomic and proteomic studies of the liver fluke secretome have accelerated the discovery of parasite proteins with known/potential roles in pathogenesis and tumourigenesis, establishing a framework towards understanding, and ultimately preventing, the morbidity and mortality attributed to this highly carcinogenic parasite. PMID:21311794

Smout, Michael J; Sripa, Banchob; Laha, Thewarach; Mulvenna, Jason; Gasser, Robin B; Young, Neil D; Bethony, Jeffrey M; Brindley, Paul J; Loukas, Alex

2011-05-01

22

Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini  

Microsoft Academic Search

BACKGROUND: Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. RESULTS: Approximately 5,000 randomly selected cDNAs from the adult stage of O.

Thewarach Laha; Porntip Pinlaor; Jason Mulvenna; Banchob Sripa; Manop Sripa; Michael J Smout; Robin B Gasser; Paul J Brindley; Alex Loukas

2007-01-01

23

Molecular Changes in Opisthorchis viverrini (Southeast Asian Liver Fluke) during the Transition from the Juvenile to the Adult Stage  

PubMed Central

Background The Southeast Asian liver fluke (Opisthorchis viverrini) chronically infects and affects tens of millions of people in regions of Asia, leading to chronic illness and, importantly, inducing malignant cancer (?=?cholangiocarcinoma). In spite of this, little is known, at the molecular level, about the parasite itself, its interplay with its hosts or the mechanisms of disease and/or carcinogenesis. Methodology/Principal Findings Here, we generated extensive RNA-Seq data (Illumina) representing adult and juvenile stages of O. viverrini, and combined these sequences with previously published transcriptomic data (454 technology) for this species, yielding a combined assembly of significantly increased quality and allowing quantitative assessment of transcription in the juvenile and adult stage. Conclusions This enhanced assembly reveals that, despite the substantial biological similarities between the human liver flukes, O. viverinni and Clonorchis sinensis, there are previously unrecognized differences in major aspects of their molecular biology. Most notable are differences among the C13 and cathepsin L-like cysteine peptidases, which play key roles in tissue migration, immune evasion and feeding, and, thus, represent potential drug and/or vaccine targets. Furthermore, these data indicate that major lineages of cysteine peptidases of socioeconomically important trematodes have evolved through a process of gene loss rather than independent radiation, contrasting previous proposals.

Sripa, Jittiyawadee; Hall, Ross S.; Scheerlinck, Jean-Pierre; Laha, Thewarach; Sripa, Banchob; Gasser, Robin B.

2012-01-01

24

Insights into SCP/TAPS Proteins of Liver Flukes Based on Large-Scale Bioinformatic Analyses of Sequence Datasets  

PubMed Central

Background SCP/TAPS proteins of parasitic helminths have been proposed to play key roles in fundamental biological processes linked to the invasion of and establishment in their mammalian host animals, such as the transition from free-living to parasitic stages and the modulation of host immune responses. Despite the evidence that SCP/TAPS proteins of parasitic nematodes are involved in host-parasite interactions, there is a paucity of information on this protein family for parasitic trematodes of socio-economic importance. Methodology/Principal Findings We conducted the first large-scale study of SCP/TAPS proteins of a range of parasitic trematodes of both human and veterinary importance (including the liver flukes Clonorchis sinensis, Opisthorchis viverrini, Fasciola hepatica and F. gigantica as well as the blood flukes Schistosoma mansoni, S. japonicum and S. haematobium). We mined all current transcriptomic and/or genomic sequence datasets from public databases, predicted secondary structures of full-length protein sequences, undertook systematic phylogenetic analyses and investigated the differential transcription of SCP/TAPS genes in O. viverrini and F. hepatica, with an emphasis on those that are up-regulated in the developmental stages infecting the mammalian host. Conclusions This work, which sheds new light on SCP/TAPS proteins, guides future structural and functional explorations of key SCP/TAPS molecules associated with diseases caused by flatworms. Future fundamental investigations of these molecules in parasites and the integration of structural and functional data could lead to new approaches for the control of parasitic diseases.

Cantacessi, Cinzia; Hofmann, Andreas; Young, Neil D.; Broder, Ursula; Hall, Ross S.; Loukas, Alex; Gasser, Robin B.

2012-01-01

25

Retrotransposon OV-RTE-1 from the carcinogenic liver fluke Opisthorchis viverrini: potential target for DNA-based diagnosis.  

PubMed

Infections by the fish-borne liver flukes Opisthorchis viverrini and Clonorchis sinensis can lead to bile duct cancer. These neglected tropical disease pathogens occur in East Asia, with O. viverrini primarily in Thailand and Laos and C. sinensis in Cambodia, Vietnam, and China. Genomic information about these pathogens holds the potential to improve disease treatment and control. Transcriptome analysis indicates that mobile genetic elements are active in O. viverrini, including a novel non-Long Terminal Repeat (LTR) retrotransposon. A consensus sequence of this element, termed OV-RTE-1, was assembled from expressed sequence tags and PCR amplified genomic DNA. OV-RTE-1 was 3330 bp in length, encoded 1101 amino acid residues and exhibited hallmark structures and sequences of non-LTR retrotransposons including a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and reverse transcriptase (RT). Phylogenetic analyses confirmed that OV-RTE-1 was member of the RTE clade of non-LTR retrotransposons. OV-RTE-1 is the first non-LTR retrotransposon characterized from the trematode family Opisthorchiidae. Sequences of OV-RTE-1 were targeted to develop a diagnostic tool for detection of infection by O. viverrini. PCR specific primers for detection of O. viverrini DNA showed 100% specificity and sensitivity for detection of as little as 5 fg of O. viverrini DNA whereas the PCR based approach showed 62% sensitivity and 100% specificity with clinical stool samples. The OV-RTE-1 specific PCR could be developed as a molecular diagnostic for Opisthorchis infection targeting parasite eggs in stool samples, especially in regions of mixed infection of O. viverrini and/or C. sinensis and minute intestinal flukes. PMID:24394447

Thi Phung, Luyen; Loukas, Alex; Brindley, Paul J; Sripa, Banchob; Laha, Thewarach

2014-01-01

26

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini  

PubMed Central

Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labelled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20 ms of 125 volts in the presence of 50 ?g/ml of Cy3-siRNA. The parasites tolerated this manipulation and, at 24 and 48 hours after electroporation, fluorescence from the Cy3-siRNA was evident throughout the parenchyma of the worms, with strong fluorescence evident in the guts and reproductive organs of the adult worms. Second, other worms were treated using the same electroporation settings with double stranded RNA targeting an endogenous papain-like cysteine protease, cathepsin B. This manipulation resulted in a significant reduction in specific mRNA levels encoding cathepsin B, and a significant reduction in cathepsin B activity against the diagnostic peptide, Z-Arg-Arg-AMC. This appears to be the first report of introduction of reporter genes into O. viverrini and the first report of experimental RNA interference (RNAi) in this fluke. The findings indicated the presence of an intact RNAi pathway in these parasites which, in turn, provides an opportunity to probe gene functions in this neglected tropical disease pathogen.

Sripa, Jittiyawadee; Pinlaor, Porntip; Brindley, Paul J.; Sripa, Banchob; Kaewkes, Sasithorn; Robinson, Mark W.; Young, Neil D.; Gasser, Robin B.; Loukas, Alex; Laha, Thewarach

2011-01-01

27

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini.  

PubMed

Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labeled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20 ms of 125V in the presence of 50 ?g/ml of Cy3-siRNA. The parasites tolerated this manipulation and, at 24 and 48 h after electroporation, fluorescence from the Cy3-siRNA was evident throughout the parenchyma of the worms, with strong fluorescence evident in the guts and reproductive organs of the adult worms. Second, other worms were treated using the same electroporation settings with double stranded RNA targeting an endogenous papain-like cysteine protease, cathepsin B. This manipulation resulted in a significant reduction in specific mRNA levels encoding cathepsin B, and a significant reduction in cathepsin B activity against the diagnostic peptide, Z-Arg-Arg-AMC. This appears to be the first report of introduction of reporter genes into O. viverrini and the first report of experimental RNA interference (RNAi) in this fluke. The findings indicated the presence of an intact RNAi pathway in these parasites which, in turn, provides an opportunity to probe gene functions in this neglected tropical disease pathogen. PMID:21565281

Sripa, Jittiyawadee; Pinlaor, Porntip; Brindley, Paul J; Sripa, Banchob; Kaewkes, Sasithorn; Robinson, Mark W; Young, Neil D; Gasser, Robin B; Loukas, Alex; Laha, Thewarach

2011-09-01

28

Genome size estimation of liver fluke Opisthorchis viverrini by real-time polymerase chain reaction based method  

Microsoft Academic Search

The human liver fluke, Opisthorchis viverrini, has been categorized as a class one carcinogenic organism according to its strong association with cholangiocarcinoma, bile duct cancer which has high incidence in the northeast of Thailand. The lack of genome database of this parasite limited the studies aimed to understand the basic molecular biology of this carcinogenic liver fluke. The determination of

Worasak Kaewkong; Kanokwan Imtawil; Wanchai Maleewong; Pewpan M. Intapan; Pusadee Sri-Aroon; Sopit Wongkham; Chaisiri Wongkham

29

Chinese Liver Fluke--Clonorchis Sinensis--Its Occurrence in Hong Kong.  

National Technical Information Service (NTIS)

The life cycle of Clomorchis sinensis is reviewed and related to mechanisms by which man becomes infected. The prevalence of clonorchiasis and changes in incidence since World War II are discussed. The pathologic characteristics of clonorchiasis and its i...

J. B. Gibson M. C. Path T. Sun

1965-01-01

30

The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica  

PubMed Central

Background Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. Methodology/Principal Findings In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. Conclusions/Significance We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity.

LaCourse, E. James; Perally, Samirah; Morphew, Russell M.; Moxon, Joseph V.; Prescott, Mark; Dowling, David J.; O'Neill, Sandra M.; Kipar, Anja; Hetzel, Udo; Hoey, Elizabeth; Zafra, Rafael; Buffoni, Leandro; Perez Arevalo, Jose; Brophy, Peter M.

2012-01-01

31

Resistance of cholangiocarcinoma cells to parthenolide-induced apoptosis by the excretory–secretory products of Clonorchis sinensis  

Microsoft Academic Search

Infection by Clonorchis sinensis, the Chinese or oriental liver fluke, is a significant risk factor for the development of cholangiocarcinoma, a human epithelial\\u000a carcinoma of the intrahepatic bile duct. Parthenolide is a sesquiterpene lactone that has strong anticancer properties and\\u000a is also known to induce apoptosis in cholangiocarcinoma cells. Many investigators have reported that excretory–secretory (ES)\\u000a products of C. sinensis

Young Ju Kim; Min-Ho Choi; Sung-Tae Hong; Young Mee Bae

2009-01-01

32

Evolutionary Origins, Diversification, and Biogeography of Liver Flukes (Digenea, Fasciolidae)  

PubMed Central

Fasciolid flukes are among the largest and best known digenetic trematodes and have considerable historical and veterinary significance. Fasciola hepatica is commonly implicated in causing disease in humans. The origins, patterns of diversification, and biogeography of fasciolids are all poorly known. We have undertaken a molecular phylogenetic study using 28S, internal transcribed spacer 1 and 2 (ITS-1 and ITS-2) of nuclear ribosomal DNA, and mitochondrial nicotinamide dehydrogenase subunit 1 (nad1) that included seven of the nine recognized species in the family. The fasciolids examined comprise a monophyletic group with the most basal species recovered from African elephants. We hypothesize fasciolids migrated from Africa to Eurasia, with secondary colonization of Africa. Fasciolids have been conservative in maintaining relatively large adult body size, but anatomical features of their digestive and reproductive systems are available. These flukes have been opportunistic, with respect to switching to new snail (planorbid to lymnaeid) and mammalian hosts and from intestinal to hepatic habitats within mammals.

Lotfy, Wael M.; Brant, Sara V.; DeJong, Randy J.; Le, Thanh Hoa; Demiaszkiewicz, Aleksander; Rajapakse, R. P. V. Jayanthe; Perera, Vijitha B. V. P.; Laursen, Jeff R.; Loker, Eric S.

2008-01-01

33

Ultrastructural hepatic alterations in hamsters and jirds after experimental infection with the liver fluke Opisthorchis viverrini  

Microsoft Academic Search

Changes in the hepatocytes of male hamsters (Mesocricetus auratus) and jirds (Meriones unguiculatus) at 220 days after experimental infection with the liver flukeOpisthorchis viverrini were studied by light and electron microscopy. The hepatocytes of the control group were characterized by an intracellular compartmentation. A globular nucleus was located centrally. The main features of the perinuclear zone were the cisternae of

R. Adam; E. Hinz; P. Sithithaworn; V. Pipitgool; V. Storch

1993-01-01

34

Morphological Features of the Testes of the Adult Liver Fluke, Opisthorchis viverrini  

Microsoft Academic Search

Background: Infection of Opisthorchis viverrini is widely endemic mainly in Northeast of Thailand including Laos, Cambodia and South Vietnam. Its prevalence and pathogenic effects are associated with several hepatobiliary diseases in human. The liver fluke is monoecious, seft-fertilization can be occurred individually. The male reproductive organ usually consists of two deeply lobed testes, located in the posterior region of the

Siriluk Wannaprapo; Smarn Tesana; Channarong Arunyanat; Pipatpong Kanla

2008-01-01

35

Ionic composition of the liver fluke Fasciola hepatica from different mammalian hosts and comparison with host bile  

Microsoft Academic Search

A qualitative analysis of the cationic profile of bovine and ovine biles and of bovine, ovine and rat liver flukes has been carried out by DC arc emission spectrography. A quantitative assessment of the concentrations of Na+, K+, Ca2+ and Mg2+ ions in bovine, ovine and rat flukes has been determined by atomic absorption spectrophotometry. The levels of these ions

R. H. Caseby; M. Harriott; I. Fairweather

1995-01-01

36

Proteomic analysis of glutathione transferases from the liver fluke parasite, Fasciola hepatica.  

PubMed

The parasite Fasciola hepatica causes major global disease of livestock, with increasing reports of human infection. Vaccine candidates with varying protection rates have been identified by pre-genomic approaches. As many candidates are part of protein superfamilies, sub-proteomics offers new possibilities to systematically reveal the relative importance of individual family proteins to vaccine formulations within populations. The superfamily glutathione transferase (GST) from liver fluke has phase II detoxification and housekeeping roles, and has been shown to contain protective vaccine candidates. GST were purified from cytosolic fractions of adult flukes using glutathione- and S-hexylglutathione-agarose, separated by 2-DE, and identified by MS/MS, with the support of a liver fluke EST database. All previously described F. hepatica GST isoforms were identified in 2-DE. Amongst the isoforms mapped by 2-DE, a new GST, closely related to the Sigma class enzymes is described for the first time in the liver fluke. We also describe cDNA encoding putative Omega class GST in F. hepatica. PMID:17078019

Chemale, Gustavo; Morphew, Russell; Moxon, Joseph V; Morassuti, Alessandra L; Lacourse, E James; Barrett, John; Johnston, David A; Brophy, Peter M

2006-12-01

37

Parasite-associated morbidity: liver fluke infection and bile duct cancer in northeast Thailand.  

PubMed

Infection with the liver fluke, Opisthorchis viverrini, remains a major public health problem in Northeast Thailand, where approximately one-third of the population is infected. The northeast region is largely populated by Laos-descendent Thais who enjoy eating raw fish, which harbour the infective stage of the fluke. The parasite has maintained its presence in the population despite the widespread use of praziquantel and dissemination of health education material throughout the region by vigorous government-sponsored programs in recent years. The most severe consequence of liver fluke infection is cholangiocarcinoma, i.e. cancer of the bile duct epithelium. Although mortality due to the parasites alone appears to be uncommon, cholangiocarcinoma arising as a result of infection is one of the leading causes of death in the region. This paper reviews the pathogenesis of infection and the geographic, hospital-based and community studies which demonstrate the close relationship between infection and cancer. In addition, data from the Cancer Registry of Khon Kaen, Northeast Thailand and population-based studies using ultrasonography to visualize early tumours which illuminate the very high frequency of the cancer among heavily infected individuals and communities are discussed. Finally, the paper will close with a brief commentary on the prospects for control of the parasite and its likely impact on the frequency of cancer given the current epidemiological situation of liver fluke infection. PMID:7982745

Sithithaworn, P; Haswell-Elkins, M R; Mairiang, P; Satarug, S; Mairiang, E; Vatanasapt, V; Elkins, D B

1994-09-01

38

Evolutionary origins, diversification, and biogeography of liver flukes (Digenea, Fasciolidae).  

PubMed

Fasciolid flukes are among the largest and best known digenetic trematodes and have considerable historical and veterinary significance. Fasciola hepatica is commonly implicated in causing disease in humans. The origins, patterns of diversification, and biogeography of fasciolids are all poorly known. We have undertaken a molecular phylogenetic study using 28S, internal transcribed spacer 1 and 2 (ITS-1 and ITS-2) of nuclear ribosomal DNA, and mitochondrial nicotinamide dehydrogenase subunit 1 (nad1) that included seven of the nine recognized species in the family. The fasciolids examined comprise a monophyletic group with the most basal species recovered from African elephants. We hypothesize fasciolids migrated from Africa to Eurasia, with secondary colonization of Africa. Fasciolids have been conservative in maintaining relatively large adult body size, but anatomical features of their digestive and reproductive systems are available. These flukes have been opportunistic, with respect to switching to new snail (planorbid to lymnaeid) and mammalian hosts and from intestinal to hepatic habitats within mammals. PMID:18689632

Lotfy, Wael M; Brant, Sara V; DeJong, Randy J; Le, Thanh Hoa; Demiaszkiewicz, Aleksander; Rajapakse, R P V Jayanthe; Perera, Vijitha B V P; Laursen, Jeff R; Loker, Eric S

2008-08-01

39

Liver fluke-associated and sporadic cholangiocarcinoma: an immunohistochemical study of bile duct, peribiliary gland and tumour cell phenotypes  

Microsoft Academic Search

Aim: To compare cell phenotypes displayed by cholangiocarcinomas and adjacent bile duct lesions in patients from an area endemic in liver-fluke infestation and those with sporadic cholangiocarcinoma.Methods: 65 fluke-associated and 47 sporadic cholangiocarcinomas and 6 normal livers were studied. Serial paraffin-wax sections were stained immunohistochemically with monoclonal antibodies characterising a Brunner or pyloric gland metaplasia cell phenotype (antigens D10 and

N R Hughes; C Pairojkul; S G Royce; A Clouston; P S Bhathal

2006-01-01

40

Molecular Characterization of a Tetraspanin from the Human Liver Fluke, Opisthorchis viverrini  

PubMed Central

Background The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood flukes where they are essential for tegument formation, are directly exposed to the immune system, and are major targets for a schistosomiasis vaccine. We propose that similar molecules in the surface membranes of O. viverrini are integral to tegument biogenesis and will be efficacious vaccine antigens. Methodology/Principal Findings The cDNA sequence encoding O. viverrini tetraspanin-1 (Ov-TSP-1) was identified and cloned. The Ov-tsp-1gene was isolated from a cDNA library. Ov-tsp-1 mRNA was expressed most highly in metacercariae and eggs, and to a lesser extent in juvenile and adult worms. Immunolocalization with adult flukes confirmed that Ov-TSP-1 was expressed in the tegument and eggs in utero. Western blot analysis of rOv-TSP-1 probed with sera from O. viverrini-infected humans and hamsters indicated that both hosts raise antibody responses against the native TSP. Using RNA interference we silenced the expression level of Ov-tsp-1 mRNA in adult flukes by up to 72% by 10 days after delivery of dsRNA. Ultrastructural morphology of adult worms treated with Ov-tsp-1 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Conclusions/Significance This is the first report of a tetraspanin from the tegument of a liver fluke. Our data imply that tetraspanins play important structural roles in the development of the tegument in the adult fluke. Potential uses of O. viverrini tetraspanins as novel interventions are discussed.

Piratae, Supawadee; Tesana, Smarn; Jones, Malcolm K.; Brindley, Paul J.; Loukas, Alex; Lovas, Erica; Eursitthichai, Veerachai; Sripa, Banchob; Thanasuwan, Sirikanda; Laha, Thewarach

2012-01-01

41

Cathepsin F Cysteine Protease of the Human Liver Fluke, Opisthorchis viverrini  

Microsoft Academic Search

Background: The liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct,the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities. Methodology\\/Principal Findings: Here, we describe the cDNA, gene organization,

Porntip Pinlaor; Natthawut Kaewpitoon; Thewarach Laha; Banchob Sripa; Sasithorn Kaewkes; Maria E. Morales; Victoria H. Mann; Sandi K. Parriott; Sutas Suttiprapa; Mark W. Robinson; Joyce To; John P. Dalton; Alex Loukas; Paul J. Brindley

2009-01-01

42

Pesticides, fresh water fish, liver flukes and nitrosamines: A story of cholangiocarcinoma development in Thailand.  

PubMed

Cholangiocarcinoma is a common hepatobiliary carcinoma in Thailand. It is believed that both chronic exposure to liver fluke infestation and nitrosamine exposure are the two main underlying factors leading to the carcinogenesis. Here, the author further extrapolates and proposes a new hypothesis based on the environmental ecological data that the stimulation of fresh water fish by contaminated pesticide in water reservoirs might be a possible background of the high prevalence of cholangiocarcinoma in Thailand. PMID:20162855

Wiwanitkit, Viroj

2009-01-01

43

Cathepsin F Cysteine Protease of the Human Liver Fluke, Opisthorchis viverrini  

Microsoft Academic Search

BackgroundThe liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct, the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities.Methodology\\/Principal FindingsHere, we describe the cDNA, gene organization, phylogenetic relationships,

Porntip Pinlaor; Natthawut Kaewpitoon; Thewarach Laha; Banchob Sripa; Sasithorn Kaewkes; Maria E. Morales; Victoria H. Mann; Sandi K. Parriott; Sutas Suttiprapa; Mark W. Robinson; Joyce To; John P. Dalton; Alex Loukas; Paul J. Brindley

2009-01-01

44

Decreased expression of galectin-3 is associated with metastatic potential of liver fluke-associated cholangiocarcinoma  

Microsoft Academic Search

Galectin-3, a ?-galactoside-binding lectin, is a multifunctional protein implicated in a variety of biological functions, including tumour cell adhesion, proliferation, differentiation, cancer progression and metastasis. The present study was performed to clarify the impact of galectin-3 expression on patients with liver fluke-associated cholangiocarcinoma. Galectin-3 expression was examined immunohistochemically in 53 patients with intrahepatic cholangiocarcinoma, who had undergone surgery without pre-operative

Mutita Junking; Chaisiri Wongkham; Banchob Sripa; Kanlayanee Sawanyawisuth; Norie Araki; Sopit Wongkham

2008-01-01

45

Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis.  

PubMed

Cancers arising during bacterial, viral and parasitic infection provide useful models to investigate the link between inflammation and carcinogenesis. Because the inflammatory agent is known, relationships between immune responses, the production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N-nitroso compounds, and cancer risk can be explored. This paper first describes the close relationship between infection with the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma in humans. Data are then presented which demonstrate an elevation in levels of salivary nitrite and urinary and plasma nitrate among men with moderate and heavy liver fluke infections compared to uninfected controls which was absent 4 months after the parasites were cleared with praziquantel. Because of the strict control over subject selection and dietary intake plus the absence of the increase following treatment, we conclude that the higher levels of nitrate and nitrite reflect endogenous generation of nitric oxide resulting from liver fluke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N-nitroso compounds mediated by activated macrophages. Further work will attempt to demonstrate a link between this increase and both parasite-specific immune responses and the risk of cancer. PMID:7510035

Haswell-Elkins, M R; Satarug, S; Tsuda, M; Mairiang, E; Esumi, H; Sithithaworn, P; Mairiang, P; Saitoh, M; Yongvanit, P; Elkins, D B

1994-03-01

46

The characteristics of the expression of heat shock proteins and COX-2 in the liver of hamsters infected with Clonorchis sinensis, and the change of endocrine hormones and cytokines.  

PubMed

The liver fluke Clonorchis sinensis (Digenea) is a high-risk parasite that causes serious diseases such as cirrhosis, carcinogenic liver damage and clonorchiasis in East Asia. This study was conducted to evaluate the relationship between stress/endocrine hormones and inflammation induced by infection as well as the expression of heat shock proteins (hsp-27, hsp-90), cox-2 and cytokines in the livers of hamsters infected with C. sinensis. The average body weight of infected hamsters decreased up to 25% compared with that of the control group, and bile duct hyperplasia with inflammation, liver fibrosis and hepatic necrosis were observed in C. sinensis-infected livers. The expression of hsp-27, hsp-90, and cox-2 was significantly increased in the livers of C. sinensis-infected hamsters compared with the control group. Moreover, the expression levels of inflammatory cytokines (IL-1beta, IL-2, TGF-beta2 and IFN-alpha1) were markedly increased in the livers of the infected group compared with those of the control group. Consistently, plasma IL-3 and IL-6 levels gradually increased during the infection period, and the concentration levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticosterone, and adrenocorticotropic hormone (ACTH) in C. sinensis-infected hamsters increased over 25%, compared with those of the uninfected normal group. These results demonstrate that C. sinensis infection may increase the expression of hsp27, hsp90 and cox-2 as well as it may cause periductal fibrosis, chronic inflammation and hepatic necrosis in the liver. Furthermore, the results indicate that C. sinensis infection induces not only stress-induced hormone imbalance but also the sustained secretion of inflammatory cytokines through chronic stress/stimuli. PMID:23327006

Choi, WonHyung; Chu, JongPhil

2012-12-01

47

Suppression of aquaporin, a mediator of water channel control in the carcinogenic liver fluke, Opisthorchis viverrini  

PubMed Central

Background Opisthorchiasis and Opisthorchis viverrini-associated bile duct cancer represent major public health threats in Thailand and Laos. The tegument of this food borne fluke plays pivotal roles in parasite metabolism, homeostasis and osmoregulation. Excretory/secretory products also pass from the fluke to the biliary environment, products that likely underlie pathogenesis of liver fluke infection. Aquaporins (AQPs), belong to the major intrinsic protein superfamily of integral plasma membrane channel proteins that selectively transport water across cell membranes. AQPs play key roles as water and ion transport channels through the tegument of helminth parasites. Methods Here, two forms of AQP mRNAs from the adult developmental stage of O. viverrini, termed O. viverrini aquaporin-1 and -2 (Ov-aqp-1 and -2) were investigated. Roles of Ov-aqp-1 and -2 in the movement of water across the tegument of this carcinogenic liver fluke were investigated using RNA interference. Results Ov-AQP-1 and Ov-AQP-2 contain unique characteristic asparagine-proline-alanine (NPA) motifs of AQP transmembrane proteins. Phylogenetic analysis indicated that Ov-AQPs belong to an expanding group of aquaglyceroporin-like water channel proteins characterized from helminth and protozoan parasites, which is pivotal to the specialized requirements of water and solute control during parasitism. Elevated transcription of Ov-aqp-1 was evident in the egg, cercaria, metacercaria and adult stages of O. viverrini, whereas Ov-aqp-2 transcripts were detected at higher level in egg, metacercaria, cercaria and adult stage, respectively. RNA interference using electroporated dsRNA suppressed transcript levels of Ov-aqp-1 and Ov-aqp-2 in adult worms by 58-99% over periods of up to 16 days in vitro. Suppression of Ov-aqp-1 and Ov-aqp-2 in vitro disabled water transport in adult flukes. Conclusion The apparently pivotal roles of Ov-AQP in solute homeostasis at the fluke surface suggest that deeper investigation will be informative for the pathophysiology of O. viverrini, and may uncover intervention targets, particularly in view of the singularly notable predilection of this pathogen for residence within ducts of the biliary tree.

2014-01-01

48

Characterization of the antioxidant enzyme, thioredoxin peroxidase, from the carcinogenic human liver fluke, Opisthorchis viverrini  

PubMed Central

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for many years. The mechanisms by which it avoids oxidative damage are unknown. In this study, thioredoxin peroxidase (TPx), a member of the peroxiredoxin superfamily, was cloned from an O. viverrini cDNA library. O. viverrini TPx cDNA encoded a polypeptide of 212 amino acid residues, of molecular mass 23.57 kDa. The putative amino acid sequence shared 60-70% identity with TPXs from other helminths and from mammals, and phylogenetic analysis revealed a close relationship between TPxs from O. viverrini and other trematodes. Recombinant O. viverrini TPx was expressed as soluble protein in Escherichia coli. The recombinant protein dimerized, and its antioxidant activity was deduced by observing protection of nicking of supercoiled plasmid DNA by hydroxyl radicals. Antiserum raised against O. viverrini TPx recognized native proteins from egg, metacercaria and adult developmental stages of the liver fluke and excretory-secretory products released by adult O. viverrini. Immunolocalization studies revealed ubiquitous expression of TPx in O. viverrini organs and tissues. TPx was also detected in bile fluid and bile duct epithelial cells surrounding the flukes two weeks after infection of hamsters with O. viverrini. In addition, TPx was observed in the secondary (small) bile ducts where flukes cannot reach due to their large size. These results suggested that O. viverrini TPx plays a significant role in protecting the parasite against damage induced by reactive oxygen species from inflammation.

Suttiprapa, Sutas; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Gaze, Soraya; Brindley, Paul J.; Sripa, Banchob

2013-01-01

49

Opisthorchis viverrini (liver fluke) as the lot of baleful parasite of tropical region-A replete synopsis  

PubMed Central

Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts which is highly prominent in the tropical regions. Infection occurs through ingestion of fluke-infested fresh-water raw fish. Opisthorchis viverrini is the biggest causative organism for this disease. Adult flukes get into the body of humans and settle in the small intrahepatic bile ducts, and then they live there for few decades. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts, and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. Major complications of the disease also include pancreatitis, bile duct obstruction etc. The majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the appulse of this food-borne malady on accessible bloom and the astringent accessible analytic consequences, alarmist accident infection should not be abandoned or neglected. This review acts as a complete picture in elucidating the information regarding the parasite and disease condition thereby supporting the researchers worldwide.

Gundamaraju, Rohit; Vemuri, Ravi Chandra

2014-01-01

50

Molecular expression and enzymatic characterization of thioredoxin from the carcinogenic human liver fluke Opisthorchis viverrini  

PubMed Central

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for years. Defense against oxidative damage can be mediated through glutathione and/or thioredoxin utilising systems. Here, we report the molecular expression and biochemical characterization of a thioredoxin (Trx) from O. viverrini. O. viverrini Trx cDNA encoded a polypeptide of 105 amino acid residues, of molecular mass 11.63 kDa. The predicted protein has similarity to previously characterized thioredoxins with 26-51% identity. Recombinant O. viverrini Trx (Ov-Trx-1) was expressed as soluble protein in E. coli. The recombinant protein showed insulin reduction activity and supported the enzymatic function of O. viverrini thioredoxin peroxidase. Expression of Ov-Trx-1at mRNA and protein levels were observed in all obtainable developmental stages of the liver fluke. Ov-Trx-1 was also detected in excretory-secretory products released by adult O. viverrini. Immunohistochemsitry, Ov-Trx-1 was expressed in nearly all parasite tissue excepted ovary and mature sperms. Interestingly, Ov-Trx-1 was observed in the infected biliary epithelium but not normal bile ducts. These results suggest that Ov-Trx-1 is essential for the parasite throughout the life cycle. In the host-parasite interaction aspect, Ov-Trx-1 may support thioredoxin peroxidase in protecting the parasite against damage induced by reactive oxygen species from inflammation.

Suttiprapa, Sutas; Matchimakul, Pitchaya; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Brindley, Paul J.; Sripa, Banchob

2013-01-01

51

Microsatellite alterations in liver fluke related cholangiocarcinoma are associated with poor prognosis.  

PubMed

We have characterized the role of genetic alterations in the development of liver fluke related cholangiocarcinoma. We analyzed the loss of heterozygosity (LOH) and microsatellite instability (MSI) of hMSH2, hMLH1, and p53 genes in 55 patients with intrahepatic cholangiocarcinoma by using polymerase chain reaction based microsatellite markers D2S119, D3S1611, and TP53, respectively and determined the association between microsatellite alterations and patient survival. A total of 27 (49.1%) out of 55 cases exhibited microsatellite alterations in one locus or more. Of 55 samples, 11 (20%) demonstrated MSI at D2S119 and four (7%) showed MSI at D3S1611. LOH was shown in seven out of 36 (19%) informative cases for D3S1611 and 16 out of 50 (32%) for TP53. Microsatellite alterations at loci studied were significantly associated with poor survival (P=0.0098). This study suggests that genetic alterations of DNA mismatch repair genes and tumor suppressor gene p53 may be involved in cholangiocarcinogenesis and these alterations may be of value as prognostic indicators for liver fluke related cholangiocarcinoma. PMID:12175538

Limpaiboon, Temduang; Krissadarak, Kamoltip; Sripa, Banchob; Jearanaikoon, Patcharee; Bhuhisawasdi, Vajarabhongsa; Chau-in, Siri; Romphruk, Amornrat; Pairojkul, Chawalit

2002-07-26

52

Risk biomarkers for assessment and chemoprevention of liver fluke-associated cholangiocarcinoma.  

PubMed

Human liver fluke, Opisthorchis viverrini (Ov), is the major risk factor of cholangiocarcinoma (CCA) in northeastern Thailand. Our approach focuses on genetic progression and molecular changes in the carcinogenic pathway of liver fluke-associated CCA aimed at assessing patients at risk of CCA and using chemoprevention as the secondary cancer prevention to reduce the incidence of CCA. This review summarizes altered gene expressions, biomolecules and their modification, i.e. DNA adducts, oxidized proteins, oxysterols and fibrotic markers in hamster- and human-CCA. Potential risk biomarker(s) and chemopreventive agent(s) criteria and selection were based on results from experimental and epidemiological studies identifying hepatobiliary disease, including CCA. Laboratory results reveal that oxidative stress induced by Ov infection leads to bimolecular damage, tissue remodeling especially periductal fibrosis and alteration of gene expressions, which could be involved in all steps of CCA carcinogenesis. Some of these molecules are reported to change their levels in opisthorchiasis, periductal fibrosis diagnosed by ultrasonography and CCA. Chemoprevention in experimental CCA tumorigenesis is discussed. These multiple risk biomarkers could now be explored for screening including chemopreventive intervention of subjects living in endemic areas where the prevalence of opisthorchiasis remains high. PMID:24408859

Yongvanit, Puangrat; Pinlaor, Somchai; Loilome, Watcharin

2014-05-01

53

Liver fluke disease (fascioliasis): epidemiology, economic impact and public health significance.  

PubMed

Liver fluke disease (fascioliasis) is an important parasitic disease found worldwide affecting sheep, goats, cattle and buffalo, as well as other domestic ruminants. The common causative agents are Fasciola hepatica and F. gigantica which require various species of Lymnaea, fresh water snails, as their intermediate hosts. The epidemiology of the disease and its prevalence in Malaysia is mentioned briefly. The disease causes considerable impact on the economy of the livestock industry. The economic losses consist of costs of anthelmintics, drenches, labor, liver condemnation at meat inspection; and losses in production due to mortality, reduction in meat, milk and wool production; and reduction in growth rate, fertility and draught power. The disease also has public health significance, causing human fascioliasis and "halzoun". PMID:1822928

Saleha, A A

1991-12-01

54

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells  

Microsoft Academic Search

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation

Michael J. Smout; Thewarach Laha; Jason Mulvenna; Banchob Sripa; Sutas Suttiprapa; Alun Jones; Paul J. Brindley; Alex Loukas

2009-01-01

55

Wherefrom and whereabouts of an alien: the American liver fluke Fascioloides magna in Austria: an overview.  

PubMed

The giant liver fluke Fascioloides magna, an invasive species originating from North America, was recorded in Austria in the wild for the first time in 2000. Since then, various data concerning the epidemiology in snail intermediate hosts and cervid final hosts have been reported. Galba truncatula acts as snail intermediate host, and red deer, roe deer and fallow deer act as final hosts. G. truncatula is abundant throughout the region, especially along muddy shores of slow-flowing branches of the river system. Prevalence in deer (20-100?%) is much higher than in snails (0.03-0.2?%). Despite medical treatment of parts of the deer population, the parasite has successfully established itself on both sides of the Danube floodplain environments southeast of Vienna. Genetic analysis revealed that the infection of Austrian deer populations apparently originated from foci in the Czech Republic or from populations of Danube tributaries. Areas adjacent southwards, which will soon be joined through wildlife crossings, have not yet evidenced F. magna. Nonetheless, these environments are inhabited by host snails and deer and therefore constitute suitable habitats for F. magna. Invading alien parasites not only threaten native individual hosts but also influence host populations, thus potentially also modifying parasite communities and interactions. The host range of F. magna includes a variety of potential hosts, notably other Lymnaeidae as potential intermediate hosts and various ungulates, including sheep and cattle, as final hosts. Because eradication after medical treatment was unsuccessful, and due to the risk of further spread of the parasite into unaffected regions, enhanced control strategies need to be developed. We recommend assessment of introduction pathways and dispersal, continuous monitoring of host abundance and distribution and the prevalence of flukes in intermediate and final hosts, as well as coordinated and concerted actions with neighbouring countries. This strategy could help to reduce potential negative impacts of this and other invasive parasites on host populations in Europe. PMID:24535172

Sattmann, Helmut; Hörweg, Christoph; Gaub, Larissa; Feix, Anna Sophia; Haider, Michaela; Walochnik, Julia; Rabitsch, Wolfgang; Prosl, Heinrich

2014-04-01

56

Genome size estimation of liver fluke Opisthorchis viverrini by real-time polymerase chain reaction based method.  

PubMed

The human liver fluke, Opisthorchis viverrini, has been categorized as a class one carcinogenic organism according to its strong association with cholangiocarcinoma, bile duct cancer which has high incidence in the northeast of Thailand. The lack of genome database of this parasite limited the studies aimed to understand the basic molecular biology of this carcinogenic liver fluke. The determination of the genome size is an initial step prior to the full genome sequencing. In this study, we applied an absolute quantitative real-time polymerase chain reaction for this aspect. Our results indicated the genome size of O. viverrini is 75.95 Mb or C value 0.083. The information of O. viverrini genome size is useful for estimation of sequence coverage and the cost of the parasite's whole genome sequencing using next-generation sequencing technologies. PMID:21757028

Kaewkong, Worasak; Imtawil, Kanokwan; Maleewong, Wanchai; Intapan, Pewpan M; Sri-Aroon, Pusadee; Wongkham, Sopit; Wongkham, Chaisiri

2012-03-01

57

Molecular identification of the Indian liver fluke, Fasciola (Trematoda: Fasciolidae) based on the ribosomal internal transcribed spacer regions  

Microsoft Academic Search

The species of liver flukes of the genus Fasciola (Platyhelminthes: Digenea: Fasciolidae) are obligate parasitic trematodes residing in the large biliary ducts of herbivorous\\u000a mammals. While Fasciola hepatica has a cosmopolitan distribution, the other major species, i.e., Fasciola gigantica is reportedly prevalent in the tropical and subtropical regions of Africa and Asia. To determine the phylogenic location\\u000a of Fasciola sp.

P. K. Prasad; V. Tandon; D. K. Biswal; L. M. Goswami; A. Chatterjee

2008-01-01

58

A retrospective survey of liver fluke disease in livestock based on abattoir data in Shiraz, south of Iran  

Microsoft Academic Search

Meat-inspection records in an abattoir located in the Fars province (southern part of Iran) from 20 March 1999 to 19 March 2004 were used to determine the prevalence and long-term trend of liver fluke disease in sheep, cattle and goats in the region. A total of 844,039 animals (cattle 131,716; sheep 577,090; goats 135,233) slaughtered in the 5-year period and

Maryam Ansari-Lari; Mohammad Moazzeni

2006-01-01

59

Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: Functional expression, immunolocalization and subsite specificity  

Microsoft Academic Search

The human liver fluke Opisthorchis viverrini is endemic in Thailand, Laos and Cambodia where long standing infection is associated with cancer of the bile ducts, cholangiocarcinoma. Here we describe a cathepsin D-like aspartic protease from the gut and other tissues in O. viverrini. Phylogenetic analysis indicated that Ov-APR-1 is cathepsin D-like, conforming with Clan AA, Family A1 of the MEROPS

Sutas Suttiprapa; Jason Mulvenna; Ngo Thi Huong; Mark S. Pearson; Paul J. Brindley; Thewarach Laha; Sopit Wongkham; Sasithorn Kaewkes; Banchob Sripa; Alex Loukas

2009-01-01

60

Discovery of Opisthorchis lobatus (Trematoda: Opisthorchiidae): a new record of small liver flukes in the Greater Mekong Sub-region.  

PubMed

Metacercariae, morphologically similar to those of small liver flukes, were found to parasitize red-tailed snakehead fish, Channa limbata, collected from the city of Vientiane, Lao People's Democratic Republic. Adult worms that were recovered from experimentally-infected hamsters showed characteristics distinctly different from Opisthorchis viverrini, but closely similar to Opisthorchis lobatus, which was first reported in poultry (Anas sp.) from Pakistan. The present study aimed to redescribe O. lobatus based on the adult worms recovered from experimentally-infected hamsters. Additionally, it aimed to document the genetic relationships among O. lobatus and other opisthorchiid liver flukes using the mitochondrial cytochrome c oxidase subunit 1 (COI) gene and the internal transcribed spacer 2 (ITS2) region. DNA alignment of the O. lobatus and O. viverrini COI partial sequences (330 bp) showed 3.03% fixed differences (2.72% of amino acids changed) while the ITS2 region (350 bp) indicated a 0.86% difference for nucleotides. Species boundaries between the 2 parasites were determined by neighbor-joining analysis using the molecular sequence data. The phenogram confirmed that O. lobatus was distinctly different from O. viverrini, representing the first reported instance of O. lobatus in the Greater Mekong Sub-region (GMS) and the first record of C. limbata as the second intermediate host of a small liver fluke. Questions regarding human infection and the extent of the geographic distribution of these species should be investigated further. PMID:21682557

Thaenkham, Urusa; Nuamtanong, Supaporn; Vonghachack, Youthanavanh; Yoonuan, Tippayarat; Sanguankiat, Surapol; Dekumyoy, Paron; Prommasack, Bounlay; Kobayashi, Jun; Waikagul, Jitra

2011-12-01

61

Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma  

PubMed Central

Background Cyclophilin A (CypA) expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA) are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines. Methods CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot. Results CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase) activity using cyclosporin A (CsA) decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation. Conclusions CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of CypA activity also reduces CCA cell proliferation. The ERK1/2 pathway may be involved in the CypA-mediated CCA cell proliferation. Thus, CypA may represent an important new therapeutic target for liver fluke-associated CCA.

2011-01-01

62

Stage-specific expression and antigenicity of glycoprotein glycans isolated from the human liver fluke, Opisthorchis viverrini  

PubMed Central

Infection by Opisthorchis viverrini (liver fluke) is a major public health problem in southeastern Asia, resulting in hepatobiliary disease and cholangiocarcinoma. Fluke surface glycoconjugates are prominently presented to the host, thereby constituting a crucial immunological interface that can determine the parasite’s success in establishing infection. Therefore, N- and O-linked glycoprotein glycan profiles of the infective metacercarial stage and of the mature adult were investigated by nanospray ionization-linear ion trap mass spectrometry (NSI-MSn). Glycan immunogenicity was investigated by immunobloting with serum from infected humans. Metacercariae and adult parasites exhibit similar glycan diversity, although the prevalence of individual glycans and glycan classes varies by stage. The N-glycans of the metacercaria are mostly high mannose and monofucosylated, truncated-type oligosaccharides (62.7%), with the remainder processed to complex and hybrid type glycans (37.3%). The N-linked glycan profile of the adult is also dominated by high mannose and monofucosylated, truncated-type oligosaccharides (80.0%), with a smaller contribution from complex and hybrid type glycans (20.0%). At both stages, complex and hybrid type glycans are detected as mono-, bi-, tri-, or tetra-antennary structures. In metacercariae and adults, O-linked glycans are detected as mono- to pentasaccharides. The mucin type core 1 structure, Gal?1-3GalNAc, predominates in both stages but is less prevalent in the adult than in the metacercaria. Immunogenic recognition of liver fluke glycoproteins is reduced after deglycosylation but infected human serum was unable to recognize glycans released from peptides. Therefore, the most potent liver fluke antigenic epitopes are mixed determinants, comprised of glycan and polypeptide elements.

Talabnin, Krajang; Aoki, Kazuhiro; Saichua, Prasert; Wongkham, Sopit; Kaewkes, Sasithorn; Boons, Geert-Jan; Sripa, Banchob; Tiemeyer, Michael

2013-01-01

63

Reduction of periductal fibrosis in liver fluke-infected hamsters after long-term curcumin treatment.  

PubMed

Chronic infection with the liver fluke, Opisthorchis viverrini, induces advanced periductal fibrosis and is a relative risk factor for cholangiocarcinoma in Southeastern Asia. We examined the reducing effect of curcumin on hepatobiliary fibrosis using O. viverrini-infected hamsters supplemented with dietary 1% curcumin (w/w) as an animal model. The expression profile of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), cytokines, and collagens was assessed in relation to liver fibrosis. Histopathological studies revealed that curcumin had no effect on fibrosis at the short-term infection (21 days and 1 month); however, peribiliary fibrosis was significantly reduced after the long-term curcumin treatment for 3 months, compared to the untreated group. Expression of alpha-smooth muscle actin was associated with the reduction of liver fibrosis. A decrease in hepatic hydroxyproline level and mRNA expression of collagen I and III supported the reduction of fibrosis. The expression of TIMP-1, TIMP-2, and tumor necrosis factor-alpha genes was also decreased after curcumin treatment. In contrast, curcumin increased mRNA expression of MMP-13, MMP-7 (at 6 months), interleukin-1 beta, and transforming growth factor beta, implying that increased MMPs activity contributes to extracellular matrix degradation. These results suggest that curcumin reduces periductal fibrosis after long-term treatment by tissue resorption via inhibition of TIMPs expression and enhancement of MMPs expression mediated by cytokines. In conclusion, curcumin may serve as a promising nutraceutical agent exerting antifibrotic effect in O. viverrini-infected patients and contribute to cholangiocarcinoma prevention. PMID:20420820

Pinlaor, Somchai; Prakobwong, Suksanti; Hiraku, Yusuke; Pinlaor, Porntip; Laothong, Umawadee; Yongvanit, Puangrat

2010-07-25

64

Evaluation of liver fluke recombinant cathepsin B-1 protease as a serodiagnostic antigen for human opisthorchiasis  

PubMed Central

A cathepsin B-like cysteine protease belonging to family C1 is abundantly expressed in the transcriptome and proteome of the carcinogenic liver fluke of humans, Opisthorchis viverrini. This enzyme is present in excretory/secretory (ES) products released by parasites cultured in vitro. This study evaluated the performance of recombinant O. viverrini cathepsin B1 (rOv-CB-1) as an antigen for immunodiagnosis of opisthorchiasis. The full length Ov-CB-1 cDNA was cloned and recombinant protein was produced in catalytically active form in Pichia pastoris. The recombinant Ov-CB-1 (rOv-CB-1) was affinity purified via nickel-NTA chromatography and tested in enzyme-linked immunosorbent assays (ELISA) with human sera from an opisthorchiasis endemic area. Sera from egg-positive O. viverrini infections produced a strong IgG antibody response to rOv-CB-1 both in ELISA and immunoblot analysis. The sensitivity and specificity of the ELISA test was 67% and 81%, respectively. These findings support the feasibility of using recombinant Ov-CB-1 in ELISA for the serodiagnosis of human opisthorchiasis.

Sripa, Jittiyawadee; Brindley, Paul J.; Sripa, Banchob; Loukas, Alex; Kaewkes, Sasithorn; Laha, Thewarach

2011-01-01

65

Decreased expression of galectin-3 is associated with metastatic potential of liver fluke-associated cholangiocarcinoma.  

PubMed

Galectin-3, a beta-galactoside-binding lectin, is a multifunctional protein implicated in a variety of biological functions, including tumour cell adhesion, proliferation, differentiation, cancer progression and metastasis. The present study was performed to clarify the impact of galectin-3 expression on patients with liver fluke-associated cholangiocarcinoma. Galectin-3 expression was examined immunohistochemically in 53 patients with intrahepatic cholangiocarcinoma, who had undergone surgery without pre-operative therapy. All bile duct epithelium expressed galectin-3 with different intensities, according to the different histological subtypes. The poorly-differentiated type expressed galectin-3 less intensely than the papillary, well- to moderately-differentiated types (P=0.012). We observed the association of low galectin-3 expression with lymphatic invasion (P=0.002). Suppression of galectin-3 expression in two human cholangiocarcinoma cell lines using siRNA targeted to galectin-3 significantly increased cell migration and invasion without alterations in cell proliferation. Regulation of galectin-3 expression may therefore be an alternative therapeutic approach to control metastasis of cholangiocarcinoma. PMID:18272359

Junking, Mutita; Wongkham, Chaisiri; Sripa, Banchob; Sawanyawisuth, Kanlayanee; Araki, Norie; Wongkham, Sopit

2008-03-01

66

Biochemical characterisation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) from the liver fluke, Fasciola hepatica.  

PubMed

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyses one of the two steps in glycolysis which generate the reduced coenzyme NADH. This reaction precedes the two ATP generating steps. Thus, inhibition of GAPDH will lead to substantially reduced energy generation. Consequently, there has been considerable interest in developing GAPDH inhibitors as anti-cancer and anti-parasitic agents. Here, we describe the biochemical characterisation of GAPDH from the common liver fluke Fasciola hepatica (FhGAPDH). The primary sequence of FhGAPDH is similar to that from other trematodes and the predicted structure shows high similarity to those from other animals including the mammalian hosts. FhGAPDH lacks a binding pocket which has been exploited in the design of novel antitrypanosomal compounds. The protein can be expressed in, and purified from Escherichia coli; the recombinant protein was active and showed no cooperativity towards glyceraldehyde 3-phosphate as a substrate. In the absence of ligands, FhGAPDH was a mixture of homodimers and tetramers, as judged by protein-protein crosslinking and analytical gel filtration. The addition of either NAD? or glyceraldehyde 3-phosphate shifted this equilibrium towards a compact dimer. Thermal scanning fluorimetry demonstrated that this form was considerably more stable than the unliganded one. These responses to ligand binding differ from those seen in mammalian enzymes. These differences could be exploited in the discovery of reagents which selectively disrupt the function of FhGAPDH. PMID:24566472

Zinsser, Veronika L; Hoey, Elizabeth M; Trudgett, Alan; Timson, David J

2014-04-01

67

Development of high-resolution melting (HRM) analysis for population studies of Fascioloides magna (Trematoda: Fasciolidae), the giant liver fluke of ruminants  

Microsoft Academic Search

The high-resolution melting (HRM) technique was successfully optimized as fast and effective method for population study of\\u000a digenetic fluke, Fascioloides magna (Trematoda: Fasciolidae), originally North American liver parasite of free-living and domestic ruminants. Previously selected\\u000a variable region (439 bp) of mitochondrial cytochrome c oxidase subunit I (cox1) of 249 fluke individuals from enzootic European and North American regions were sequenced and

Ján Radvánský; Eva Bazsalovicsová; Ivica Králová-Hromadová; Gabriel Minárik; ?udevít Kádaši

2011-01-01

68

Albendazole enantiomeric metabolism and binding to cytosolic proteins in the liver fluke Fasciola hepatica  

Microsoft Academic Search

Fascioliasis causes important economic losses in ruminant species all over the world. Its control is largely based on the\\u000a use of the flukicidal compound triclabendazole (TCBZ). However, its chemically related benzimidazole anthelmintic albendazole\\u000a (ABZ) is being successfully used to control TCBZ-resistance flukes. This research gains some insights into the comparative\\u000a molecular behaviour of both anthelmintics within the target fluke. The

H. Solana; S. Scarcella; G. Virkel; C. Ceriani; J. Rodríguez; C. Lanusse

2009-01-01

69

Development of Mitochondrial Loop-Mediated Isothermal Amplification for Detection of the Small Liver Fluke Opisthorchis viverrini (Opisthorchiidae; Trematoda; Platyhelminthes)  

PubMed Central

Mitochondrial DNA sequences offer major advantages over the more usual nuclear targets for loop-mediated isothermal amplification approaches (mito-LAMP) because multiple copies occur in every cell. Four LAMP primers [F3, FIP(F1c+F2), BIP(B1c+B2), and B3] were designed based on the mitochondrial nad1 sequence of Opisthorchis viverrini and used for a highly specific assay (mito-OvLAMP) to distinguish DNA of O. viverrini from that of another opisthorchiid (Clonorchis sinensis) and other trematodes (Haplorchis pumilio, Haplorchis taichui, Fasciola hepatica, and Fasciola gigantica). Conventional PCR was applied using F3/B3 primer pairs to verify the specificity of the primers for O. viverrini DNA templates. All LAMP-positive samples could be detected with the naked eye in sunlight, by gel electrophoresis (stained with ethidium bromide), and by addition of SYBR green I to the product in sunlight or under UV light. Only DNA from O. viverrini yielded amplification products by LAMP (and by PCR verification), and the LAMP limit of detection was as little as 100 fg (10?4 ng DNA), indicating that this assay is 10 to 100 times more sensitive than PCR. Field testing was done using representative egg and metacercarial samples collected from localities where the fluke is endemic. With the advantages of simplicity, rapidity, sensitivity, and cost effectiveness, mito-OvLAMP is a good tool for molecular detection and epidemiology studies in regions or countries where O. viverrini is endemic, which can lead to more effective control of opisthorchiasis and trematodiasis.

Nguyen, Nga Thi Bich; Truong, Nam Hai; De, Nguyen Van

2012-01-01

70

A Case of Probable Mixed-Infection with Clonorchis sinensis and Fasciola sp.: CT and Parasitological Findings  

PubMed Central

We report here a human case probably mixed-infected with Clonorchis sinensis and Fasciola sp. who was diagnosed by computed tomography (CT) scan, serological findings, and/or fecal examination. The patient was a 43-year-old Korean female and was admitted to Kyung Hee University Hospital with the complaints of fever and abdominal pain. On admission, marked eosinophilia was noted in her peripheral blood. CT scan showed specific lesions for clonorchiasis and fascioliasis in the liver, along with lesions suggestive of amebic abscess. Micro-ELISA revealed positive results for the 2 helminthic infections. Eggs of C. sinensis and trophozoites of Entamoeba histolytica were observed in the stool. Treatment with praziquantel followed by metronidazole and tinidazole reduced abnormalities in the liver and eosinophilia. This is the first case report of a possible co-infection with 2 kinds of liver flukes in the Republic of Korea.

Kim, Tae Yun; Lee, Yun-Sik; Yun, Ji Hye; Kim, Jeong Ju; Choi, Won Hyung; Oh, In Hwan; Song, Hyun Ouk

2010-01-01

71

Efficacy of two formulations of albendazole against liver flukes in cattle.  

PubMed

Albendazole (10 mg/kg of body weight) was administered as a drench suspension or as a feed additive to 24 cattle with naturally acquired infections of Fasciola hepatica and Fascioloides magna. Cattle were euthanatized 16 to 30 days after treatment, and the number of viable flukes was counted. Viable F hepatica and F magna were decreased by 91.4% and 70.6% for drench administration and by 82.9% and 71.9% for the feed additive treatment, respectively. There was no significant difference between the efficacy of the 2 formulations in decreasing viable fluke numbers, compared with untreated controls. PMID:1497187

Craig, T M; Qureshi, T; Miller, D K; Wade, C G; Rogers, J A

1992-07-01

72

Inflammatory response to liver fluke Opisthorchis viverrini depends on host master coregulator, MTA1, a marker for parasite induced cholangiocarcinoma  

PubMed Central

Based on the recently established role for the master coregulator MTA1 and MTA1-containing nuclear remodeling complexes, in oncogenesis and inflammation, we explored the links between parasitism by the carcinogenic liver fluke Opisthorchis viverrini and this coregulator using both an Mta1?/? mouse model of infection and a tissue microarray of liver fluke induced human cholangiocarcinomas. Intense foci of inflammation and periductal fibrosis in the liver and kidney of wild type, Mta1+/+ mice were evident at 23 days post-infection with O. viverrini. In contrast, little inflammatory response was observed in the same organs of infected Mta1?/? mice. Livers of infected Mta1+/+ mice revealed strong upregulation of fibrosis-associated markers such as cytokeratins 18, 19, and annexin-2, as determined by both by immunostaining and by reverse transcription PCR compared to infected Mta1?/? mice. CD4 expression was upregulated by infection in the liver of both experimental groups; however, its levels were several folds higher in the Mta1+/+ mice than in infected Mta1?/? mice. Mta1?/? infected mice also exhibited significantly higher systemic and hepatic levels of host cytokines such as IL-12p70, IL-10 and IFN-? compared to the levels of these cytokines in the Mta1+/+ mice, suggesting an essential role of MTA1 in the cross-regulation of the Th1 and Th2 responses, presumably due to chromatin remodeling of the target chromatin genes. Immunohistochemical analysis of ~300 liver tissue cores from confirmed cases of O. viverrini induced cholangiocarcinoma showed that MTA1 expression was elevated in more than 80% of the specimens. These findings suggest that MTA1 status plays an important role in conferring an optimal cytokine response in mice following infection with O. viverrini and is a major player in parasite-induced cholangiocarcinoma in humans.

Nair, Sujit S.; Bommana, Anitha; Pakala, Suresh B; Ohshiro, Kazufumi; Lyon, Amanda J.; Suttiprapa, Sutas; Periago, Maria V; Laha, Thewarach; Hotez, Peter J.; Bethony, Jeffrey M; Sripa, Banchob; Brindley, Paul J; Kumar, Rakesh

2011-01-01

73

Low genetic diversity in wide-spread Eurasian liver fluke Opisthorchis felineus suggests special demographic history of this trematode species.  

PubMed

Opisthorchis felineus or Siberian liver fluke is a trematode parasite (Opisthorchiidae) that infects the hepato-biliary system of humans and other mammals. Despite its public health significance, this wide-spread Eurasian species is one of the most poorly studied human liver flukes and nothing is known about its population genetic structure and demographic history. In this paper, we attempt to fill this gap for the first time and to explore the genetic diversity in O. felineus populations from Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Analysis of marker DNA fragments from O. felineus mitochondrial cytochrome c oxidase subunit 1 and 3 (cox1, cox3) and nuclear rDNA internal transcribed spacer 1 (ITS1) sequences revealed that genetic diversity is very low across the large geographic range of this species. Microevolutionary processes in populations of trematodes may well be influenced by their peculiar biology. Nevertheless, we suggest that lack of population genetics structure observed in O. felineus can be primarily explained by the Pleistocene glacial events and subsequent sudden population growth from a very limited group of founders. Rapid range expansion of O. felineus through Asian and European territories after severe bottleneck points to a high dispersal potential of this trematode species. PMID:23634228

Brusentsov, Ilja I; Katokhin, Alexey V; Brusentsova, Irina V; Shekhovtsov, Sergei V; Borovikov, Sergei N; Goncharenko, Grigoriy G; Lider, Lyudmila A; Romashov, Boris V; Rusinek, Olga T; Shibitov, Samat K; Suleymanov, Marat M; Yevtushenko, Andrey V; Mordvinov, Viatcheslav A

2013-01-01

74

Low Genetic Diversity in Wide-Spread Eurasian Liver Fluke Opisthorchis felineus Suggests Special Demographic History of This Trematode Species  

PubMed Central

Opisthorchis felineus or Siberian liver fluke is a trematode parasite (Opisthorchiidae) that infects the hepato-biliary system of humans and other mammals. Despite its public health significance, this wide-spread Eurasian species is one of the most poorly studied human liver flukes and nothing is known about its population genetic structure and demographic history. In this paper, we attempt to fill this gap for the first time and to explore the genetic diversity in O. felineus populations from Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Analysis of marker DNA fragments from O. felineus mitochondrial cytochrome c oxidase subunit 1 and 3 (cox1, cox3) and nuclear rDNA internal transcribed spacer 1 (ITS1) sequences revealed that genetic diversity is very low across the large geographic range of this species. Microevolutionary processes in populations of trematodes may well be influenced by their peculiar biology. Nevertheless, we suggest that lack of population genetics structure observed in O. felineus can be primarily explained by the Pleistocene glacial events and subsequent sudden population growth from a very limited group of founders. Rapid range expansion of O. felineus through Asian and European territories after severe bottleneck points to a high dispersal potential of this trematode species.

Brusentsov, Ilja I.; Katokhin, Alexey V.; Brusentsova, Irina V.; Shekhovtsov, Sergei V.; Borovikov, Sergei N.; Goncharenko, Grigoriy G.; Lider, Lyudmila A.; Romashov, Boris V.; Rusinek, Olga T.; Shibitov, Samat K.; Suleymanov, Marat M.; Yevtushenko, Andrey V.; Mordvinov, Viatcheslav A.

2013-01-01

75

Survey of transcripts expressed by the invasive juvenile stage of the liver fluke Fasciola hepatica  

PubMed Central

Background The common liver fluke Fasciola hepatica is the agent of a zoonosis with significant economic consequences in livestock production worldwide, and increasing relevance to human health in developing countries. Although flukicidal drugs are available, re-infection and emerging resistance are demanding new efficient and inexpensive control strategies. Understanding the molecular mechanisms underlying the host-parasite interaction provide relevant clues in this search, while enlightening the physiological adaptations to parasitism. Genomics and transcriptomics are still in their infancy in F. hepatica, with very scarce information available from the invasive newly excysted juveniles (NEJ). Here we provide an initial glimpse to the transcriptomics of the NEJ, the first stage to interact with the mammalian host. Results We catalogued more than 500 clusters generated from the analysis of F. hepatica juvenile expressed sequence tags (EST), several of them not detected in the adult stage. A set of putative F. hepatica specific transcripts, and a group of sequences conserved exclusively in flatworms were identified. These novel sequences along with a set of parasite transcripts absent in the host genomes are putative new targets for future anti-parasitic drugs or vaccine development. Comparisons of the F. hepatica sequences with other metazoans genomes or EST databases were consistent with the basal positioning of flatworms in the bilaterian phylogeny. Notably, GC content, codon usage and amino acid frequencies are remarkably different in Schistosomes to F. hepatica and other trematodes. Functional annotation of predicted proteins showed a general representation of diverse biological functions. Besides proteases and antioxidant enzymes expected to participate in the early interaction with the host, various proteins involved in gene expression, protein synthesis, cell signaling and mitochondrial enzymes were identified. Differential expression of secreted protease gene family members between juvenile and adult stages may respond to different needs during host colonization. Conclusion The knowledge of the genes expressed by the invasive stage of Fasciola hepatica is a starting point to unravel key aspects of this parasite's biology. The integration of the emerging transcriptomics, and proteomics data and the advent of functional genomics tools in this organism are positioning F. hepatica as an interesting model for trematode biology.

2010-01-01

76

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells  

PubMed Central

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma.

Smout, Michael J.; Laha, Thewarach; Mulvenna, Jason; Sripa, Banchob; Suttiprapa, Sutas; Jones, Alun; Brindley, Paul J.; Loukas, Alex

2009-01-01

77

A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells.  

PubMed

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma. PMID:19816559

Smout, Michael J; Laha, Thewarach; Mulvenna, Jason; Sripa, Banchob; Suttiprapa, Sutas; Jones, Alun; Brindley, Paul J; Loukas, Alex

2009-10-01

78

Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: functional expression, immunolocalization and subsite specificity.  

PubMed

The human liver fluke Opisthorchis viverrini is endemic in Thailand, Laos and Cambodia where long standing infection is associated with cancer of the bile ducts, cholangiocarcinoma. Here we describe a cathepsin D-like aspartic protease from the gut and other tissues in O. viverrini. Phylogenetic analysis indicated that Ov-APR-1 is cathepsin D-like, conforming with Clan AA, Family A1 of the MEROPS classification. Ov-APR-1 is expressed in the gut of the mature hermaphroditic parasite, in the reproductive tissues including the testis and immature spermatids, and the developing miracidium within the eggshell. The enzyme was also detected in the excretory/secretory products of cultured adult flukes, indicating a role in host-parasite relationships. A recombinant form of the enzyme expressed in Escherichia coli and refolded from denatured inclusion bodies underwent autocatalytic activation and demonstrated hydrolytic activity against the peptide substrate 7-methoxycoumarin-4-acetyl-GKPILFFRLK(DNP)-D-Arg-amide with a k(cat)/K(m)=1.7 x 10(4)M(-1)s(-1) and a pH optimum around pH 2.5-3.0. The recombinant enzyme digested hemoglobin and bovine serum albumin. Forty-six serum albumin peptides were detected after digestion with recombinant Ov-APR-1 and sequenced. Like many other aspartic proteases, Ov-APR-1 displayed promiscuous preferences for residues accommodated at the key subsites of the binding pocket although hydrophobic (Leu, Ala, Ile), positively charged (Lys) and bulky aromatic (Phe) residues, in that order, were preferred at P1. Similar residues were accommodated at P1' although even less selectivity was exerted at this position. PMID:18996218

Suttiprapa, Sutas; Mulvenna, Jason; Huong, Ngo Thi; Pearson, Mark S; Brindley, Paul J; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Sripa, Banchob; Loukas, Alex

2009-05-01

79

Liver fluke (Fasciola hepatica)-derived peptides activate rat peritoneal mast cells.  

PubMed

Short peptides with sequences derived from those found in the tegumental antigen of Fasciola hepatica have been synthesised. Incubation of some of these peptides with rat peritoneal mast cells resulted in the degranulation of the cells as measured by a histamine release assay. This activity was shown to be associated with the proline-lysine-proline motif, which is responsible for the induction of mast cell degranulation by the mammalian bioactive peptide substance P. Studies on the mode of action of the fluke-derived peptide indicated that it was operating through the same biochemical pathways as substance P. The implications of these findings for the development of immune responses during parasite infections are discussed. PMID:12757746

Trudgett, A; Watt, A P; Harriott, P; Ennis, M

2003-05-01

80

Expression, refolding and purification of Ov-GRN-1, a granulin-like growth factor from the carcinogenic liver fluke, that causes proliferation of mammalian host cells  

Microsoft Academic Search

Granulins (GRNs) are potent growth factors that are upregulated in many aggressive cancers from a wide range of organs. GRNs form tight, disulphide bonded, beta hairpin stacks, making them difficult to express in recombinant form. We recently described Ov-GRN-1, a GRN family member secreted by the carcinogenic liver fluke of humans, Opisthorchis viverrini, and showed that recombinant Ov-GRN-1 expressed and

Michael J. Smout; Jason P. Mulvenna; Malcolm K. Jones; Alex Loukas

2011-01-01

81

Resistance of cholangiocarcinoma cells to parthenolide-induced apoptosis by the excretory-secretory products of Clonorchis sinensis.  

PubMed

Infection by Clonorchis sinensis, the Chinese or oriental liver fluke, is a significant risk factor for the development of cholangiocarcinoma, a human epithelial carcinoma of the intrahepatic bile duct. Parthenolide is a sesquiterpene lactone that has strong anticancer properties and is also known to induce apoptosis in cholangiocarcinoma cells. Many investigators have reported that excretory-secretory (ES) products of C. sinensis as well as Opisthorchis viverrini promote the development of cholangiocarcinomas. However, the intrinsic mechanism is not clearly understood. Therefore, we investigated the biological roles of the ES products in a cholangiocarcinoma cell line, HuCCT1. The ES products of C. sinensis increased proliferation of HuCCT1 cells and augmented the expression of cyclooxygenase (COX)-2. To determine whether cells treated with ES products would respond differently to parthenolide, HuCCT1 cells were treated with parthenolide alone or parthenolide after pretreatment with ES products. Cells pretreated with ES products were resistant to parthenolide-induced apoptosis. Because parthenolide has been reported to be a COX-2 inhibitor, we hypothesize that COX-2 might be a key factor that promotes resistance of cholangiocarcinoma cancer cells to parthenolide-induced apoptosis. These results suggest that chemotherapy treatment regimens in cholangiocarcinoma patients with C. sinensis infection should be modulated to account for ES products excreted by the liver fluke. PMID:19066964

Kim, Young Ju; Choi, Min-Ho; Hong, Sung-Tae; Bae, Young Mee

2009-04-01

82

Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica.  

PubMed

Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member. PMID:23167294

Morphew, Russell M; Eccleston, Neil; Wilkinson, Toby J; McGarry, John; Perally, Samirah; Prescott, Mark; Ward, Deborah; Williams, Diana; Paterson, Steve; Raman, M; Ravikumar, G; Khalid Saifullah, M; Abbas Abidi, S M; McVeigh, Paul; Maule, Aaron G; Brophy, Peter M; LaCourse, E James

2012-12-01

83

Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers.  

PubMed

The impact of different carcinogenic exposures on the specific patterns of somatic mutation in human tumors remains unclear. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by infection with the liver fluke Opisthorchis viverrini and 101 cases caused by non-O. viverrini-related etiologies. Whole-exome sequencing (n = 15) and prevalence screening (n = 194) identified recurrent somatic mutations in BAP1 and ARID1A, neither of which, to our knowledge, has previously been reported to be mutated in CCA. Comparisons between intrahepatic O. viverrini-related and non-O. viverrini-related CCAs demonstrated statistically significant differences in mutation patterns: BAP1, IDH1 and IDH2 were more frequently mutated in non-O. viverrini CCAs, whereas TP53 mutations showed the reciprocal pattern. Functional studies demonstrated tumor suppressive functions for BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations, even within the same tumor type. PMID:24185513

Chan-On, Waraporn; Nairismägi, Maarja-Liisa; Ong, Choon Kiat; Lim, Weng Khong; Dima, Simona; Pairojkul, Chawalit; Lim, Kiat Hon; McPherson, John R; Cutcutache, Ioana; Heng, Hong Lee; Ooi, London; Chung, Alexander; Chow, Pierce; Cheow, Peng Chung; Lee, Ser Yee; Choo, Su Pin; Tan, Iain Bee Huat; Duda, Dan; Nastase, Anca; Myint, Swe Swe; Wong, Bernice Huimin; Gan, Anna; Rajasegaran, Vikneswari; Ng, Cedric Chuan Young; Nagarajan, Sanjanaa; Jusakul, Apinya; Zhang, Shenli; Vohra, Priya; Yu, Willie; Huang, DaChuan; Sithithaworn, Paiboon; Yongvanit, Puangrat; Wongkham, Sopit; Khuntikeo, Narong; Bhudhisawasdi, Vajaraphongsa; Popescu, Irinel; Rozen, Steven G; Tan, Patrick; Teh, Bin Tean

2013-12-01

84

Opisthorchis viverrini-like liver fluke in birds from Vietnam: morphological variability and rDNA/mtDNA sequence confirmation.  

PubMed

Flukes were found in the bile ducts of domestic ducks (Anas platyrhynchos), necropsied in the Binh Dinh province of Central Vietnam. Following staining, morphological characteristics of the bird flukes were compatible with Opisthorchis viverrini, although some characteristics differed from those described in specimens collected from mammal hosts. Computation of the phylogenetic trees on the partial sequences of the second internal ribosomal spacer (ITS2) of the ribosomal DNA and cytochrome c oxidase subunit I (COI) markers of the mitochondrial DNA showed close similarity of the 'bird' Opisthorchis sp. with O. viverrini. We speculate that these bird flukes are O. viverrini that show intraspecies morphological and molecular variability compared to isolates from mammals. This demonstrates the complex epidemiological situation of opisthorchiasis in Vietnam and urges investigations on the potential of birds as a reservoir host of this zoonotic fluke. PMID:23721954

Dao, T H; Nguyen, T G; Victor, B; Gabriël, S; Dorny, P

2013-05-31

85

ClonorESTdb: a comprehensive database for Clonorchis sinensis EST sequences  

PubMed Central

Background Clonorchiasis, which is primarily caused by liver fluke (Platyhelminthes), is a fatal infectious disease that is mainly associated with bile duct malignancy and the subsequent development of cholangiocarcinoma. Thus, a genomic approach now represents an important step to further our knowledge of biology and the pathology of these parasites. The results of expressed sequence tags (ESTs) sequencing need to be well organized into databases to provide an integrated set of tools and functional information. Findings Here, the ClonorESTdb database represents a collection of Clonorchis sinensis ESTs that is intended as a resource for parasite functional genomics. A total of 55,736 successful EST sequences, which are cleaned and clustered into non-redundant 13,305 C. sinensis assembled EST sequences (6,497 clusters and 6,808 singletons), were obtained from three in-house prepared cDNA libraries of C. sinensis at different developmental stages. The assembled consensus sequences were annotated using the BLAST algorithm or/and hmm against NCBI NR, UniProt, KEGG and InterProScan. The ClonorESTdb database provides functional annotation, their expression profiles, tandem repeats and putative single nucleotide polymorphisms with utility tools such as local BLAST search and text retrieval. Conclusions This resource enables the researcher to identify and compare expression signatures under different biological stages and promotes ongoing parasite drug and vaccine development and biological research. Database URL: http://pathod.cdc.go.kr/clonorestdb/

2014-01-01

86

Unlocking the Transcriptomes of Two Carcinogenic Parasites, Clonorchis sinensis and Opisthorchis viverrini  

PubMed Central

The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer (?=?cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next-generation (high throughput) sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies.

Young, Neil D.; Campbell, Bronwyn E.; Hall, Ross S.; Jex, Aaron R.; Cantacessi, Cinzia; Laha, Thewarach; Sohn, Woon-Mok; Sripa, Banchob; Loukas, Alex; Brindley, Paul J.; Gasser, Robin B.

2010-01-01

87

Liver Fluke Induces Cholangiocarcinoma  

Microsoft Academic Search

The authors discuss the molecular pathogenesis of opisthorchiasis and associated cholangiocarcinogenesis, particularly nitrative and oxidative DNA damage and the clinical manifestations of cholangiocarcinoma.

Banchob Sripa; Sasithorn Kaewkes; Paiboon Sithithaworn; Eimorn Mairiang; Thewarach Laha; Michael Smout; Chawalit Pairojkul; Vajaraphongsa Bhudhisawasdi; Smarn Tesana; Bandit Thinkamrop; Jeffrey M Bethony; Alex Loukas; Paul J Brindley

2007-01-01

88

Cloning and Expression of the Major Secreted Cathepsin B-Like Protein from Juvenile Fasciola hepatica and Analysis of Immunogenicity following Liver Fluke Infection  

PubMed Central

The functions of the cathepsin B-like proteases in liver flukes are unknown and analysis has been hindered by a lack of protein for study, since the protein is produced in small amounts by juvenile flukes. To circumvent this, we isolated and characterized a cDNA encoding the major secreted cathepsin B from Fasciola hepatica. The predicted preproprotein is 339 amino acids in length, with the mature protease predicted to be 254 amino acids long, and shows significant similarity to parasite and mammalian cathepsin B. Only one of the two conserved histidine residues required for cathepsin B exopeptidase activity is predicted to be present. Recombinant preproprotein was produced in yeast, and it was shown that the recombinant proprotein can undergo a degree of self-processing in vitro to the mature form, which is active against gelatin and synthetic peptide substrates. The recombinant protein is antigenic in vaccinated rats, and antibodies to the protein are detected early after infection of rats and sheep with F. hepatica. The kinetics of the response to cathepsin B and cathepsin L after infection of sheep and rats confirm the temporal expression of these proteins during the life cycle of the parasite.

Law, Ruby H. P.; Smooker, Peter M.; Irving, James A.; Piedrafita, David; Ponting, Rebecca; Kennedy, Nicholas J.; Whisstock, James C.; Pike, Robert N.; Spithill, Terry W.

2003-01-01

89

Cytokine/chemokine secretion and proteomic identification of upregulated annexin A1 from peripheral blood mononuclear cells cocultured with the liver fluke Opisthorchis viverrini.  

PubMed

We investigated the cytokine/chemokine secretions and alteration of protein expression from peripheral blood mononuclear cells (PBMCs) cocultured with adult liver flukes (Opisthorchis viverrini) for 6 to 24 h. PBMC-derived proteins were identified by two-dimensional electrophoresis and mass spectrometry, and the cytokines/chemokines in the supernatant were assessed using a cytokine array. Exposure to O. viverrini induced increases in secretion of proinflammatory cytokines, costimulating protein, adhesion molecules, and chemotactic chemokines relative to untreated controls. In contrast, secretion of the CD40 ligand, interleukin 16, and macrophage inflammatory protein 1? decreased. Proteomic analysis revealed that expression of 48 proteins was significantly altered in PBMCs stimulated with O. viverrini. Annexin A1 (ANXA1) was selected for further study, and immunoblotting showed upregulation of ANXA1 expression in PBMCs after 12 and 24 h coculture with liver flukes. In an in vivo study, transcription and translation of ANXA1 significantly increased in livers of hamsters infected with O. viverrini at 21 days and from 3 months onwards compared to normal controls. Interestingly, immunohistochemistry revealed that ANXA1 was present not only in the cytoplasm of inflammatory cells but also in the cytoplasm of cholangiocytes, which are in close contact with the parasite and its excretory/secretory products in the biliary system. Expression of ANXA1 increased with time concomitant with bile duct enlargement, bile duct formation, and epithelial cell proliferation. In conclusion, several cytokines/chemokines secreted by PBMCs and upregulation of ANXA1 in PBMCs and biliary epithelial cells might have a role in host defense against O. viverrini infection and tissue resolution of inflammation. PMID:24614660

Hongsrichan, Nuttanan; Intuyod, Kitti; Pinlaor, Porntip; Khoontawad, Jarinya; Yongvanit, Puangrat; Wongkham, Chaisiri; Roytrakul, Sittiruk; Pinlaor, Somchai

2014-05-01

90

Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B.  

PubMed

Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that autocatalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot autocatalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma. PMID:20070308

Sripa, Jittiyawadee; Laha, Thewarach; To, Joyce; Brindley, Paul J; Sripa, Banchob; Kaewkes, Sasithorn; Dalton, John P; Robinson, Mark W

2010-06-01

91

Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B  

PubMed Central

Summary Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that auto-catalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot auto-catalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma.

Sripa, Jittiyawadee; Laha, Thewarach; To, Joyce; Brindley, Paul J.; Sripa, Banchob; Kaewkes, Sasithorn; Dalton, John P.; Robinson, Mark W.

2010-01-01

92

Liver enzyme activity and histological changes in the liver of silver foxes ( Vulpes vulpes fulva ) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis  

Microsoft Academic Search

Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units\\/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose,

Rolf Schuster; Kerstin Dell; Karsten Nöckler; Jens Vöster; Dorothea Schwartz-Porsche; Wolfram Haider

2003-01-01

93

Molecular Differentiation of Opisthorchis viverrini and Clonorchis sinensis Eggs by Multiplex Real-Time PCR with High Resolution Melting Analysis  

PubMed Central

Opisthorchis viverrini and Clonorchis sinensis are parasites known to be carcinogenic and causative agents of cholangiocarcinoma in Asia. The standard method for diagnosis for those parasite infections is stool examination to detect parasite eggs. However, the method has low sensitivity, and eggs of O. viverrini and C. sinensis are difficult to distinguish from each other and from those of some other trematodes. Here, we report a multiplex real-time PCR coupled with high resolution melting (HRM) analysis for the differentiation of O. viverrini and C. sinensis eggs in fecal samples. Using 2 pairs of species-specific primers, DNA sequences from a portion of the mitochondrial NADH dehydrogenase subunit 2 (nad 2) gene, were amplified to generate 209 and 165 bp products for O. viverrini and C. sinensis, respectively. The distinct characteristics of HRM patterns were analyzed, and the melting temperatures peaked at 82.4±0.09? and 85.9±0.08? for O. viverrini and C. sinensis, respectively. This technique was able to detect as few as 1 egg of O. viverrini and 2 eggs of C. sinensis in a 150 mg fecal sample, which is equivalent to 7 and 14 eggs per gram of feces, respectively. The method is species-specific, rapid, simple, and does not require fluorescent probes or post-PCR processing for discrimination of eggs of the 2 species. It offers a new tool for differentiation and detection of Asian liver fluke infections in stool specimens.

Kaewkong, Worasak; Intapan, Pewpan M.; Sanpool, Oranuch; Janwan, Penchom; Thanchomnang, Tongjit; Laummaunwai, Porntip; Lulitanond, Viraphong; Doanh, Pham Ngoc

2013-01-01

94

The identification of antigenic proteins: 14-3-3 protein and propionyl-CoA carboxylase in Clonorchis sinensis.  

PubMed

Clonorchis sinensis, the causative agent of clonorchiasis, is widespread in East and Southeast Asia, including China, Vietnam and the Republic of Korea. We identified antigenic proteins from adult C. sinensis liver flukes using immunoproteomic analysis. In this study, we found 23 candidate antigenic proteins with a pI in the range of 5.4-6.2 in total lysates of C. sinensis. The antigenic protein spots reacted against sera from clonorchiasis patients and were identified as cysteine proteases, glutathione transferases, gelsolin, propionyl-CoA carboxylase (PCC), prohibitin and 14-3-3 protein (14-3-3) using LC-coupled ESI-MS/MS and an EST database for C. sinensis. PCC and 14-3-3 were identified for the first time as serological antigens for the diagnosis of C. sinensis. To validate the antigenicity of PCC and 14-3-3, recombinant proteins were immunoblotted with sera from clonorchiasis patients. The structural, functional and immunological characteristics of the putative amino acid sequence were predicted by bioinformatics analysis. Our novel finding will contribute to the development of diagnostics for clonorchiasis. These results suggest that immunoproteomic approaches are valuable tools to identify antigens that could be used as targets for effective parasitic infection control strategies. PMID:22119288

Lee, Myoung-Ro; Kim, Yu-Jung; Kim, Dae-Won; Yoo, Won Gi; Cho, Shin-Hyeong; Hwang, Kwang Yeon; Ju, Jung-Won; Lee, Won-Ja

2012-01-01

95

Molecular differentiation of Opisthorchis viverrini and Clonorchis sinensis eggs by multiplex real-time PCR with high resolution melting analysis.  

PubMed

Opisthorchis viverrini and Clonorchis sinensis are parasites known to be carcinogenic and causative agents of cholangiocarcinoma in Asia. The standard method for diagnosis for those parasite infections is stool examination to detect parasite eggs. However, the method has low sensitivity, and eggs of O. viverrini and C. sinensis are difficult to distinguish from each other and from those of some other trematodes. Here, we report a multiplex real-time PCR coupled with high resolution melting (HRM) analysis for the differentiation of O. viverrini and C. sinensis eggs in fecal samples. Using 2 pairs of species-specific primers, DNA sequences from a portion of the mitochondrial NADH dehydrogenase subunit 2 (nad 2) gene, were amplified to generate 209 and 165 bp products for O. viverrini and C. sinensis, respectively. The distinct characteristics of HRM patterns were analyzed, and the melting temperatures peaked at 82.4±0.09? and 85.9±0.08? for O. viverrini and C. sinensis, respectively. This technique was able to detect as few as 1 egg of O. viverrini and 2 eggs of C. sinensis in a 150 mg fecal sample, which is equivalent to 7 and 14 eggs per gram of feces, respectively. The method is species-specific, rapid, simple, and does not require fluorescent probes or post-PCR processing for discrimination of eggs of the 2 species. It offers a new tool for differentiation and detection of Asian liver fluke infections in stool specimens. PMID:24516275

Kaewkong, Worasak; Intapan, Pewpan M; Sanpool, Oranuch; Janwan, Penchom; Thanchomnang, Tongjit; Laummaunwai, Porntip; Lulitanond, Viraphong; Doanh, Pham Ngoc; Maleewong, Wanchai

2013-12-01

96

Expression, refolding and purification of Ov-GRN-1, a granulin-like growth factor from the carcinogenic liver fluke, that causes proliferation of mammalian host cells.  

PubMed

Granulins (GRNs) are potent growth factors that are upregulated in many aggressive cancers from a wide range of organs. GRNs form tight, disulphide bonded, beta hairpin stacks, making them difficult to express in recombinant form. We recently described Ov-GRN-1, a GRN family member secreted by the carcinogenic liver fluke of humans, Opisthorchis viverrini, and showed that recombinant Ov-GRN-1 expressed and refolded from Escherichia coli caused proliferation of mammalian cell lines at nanomolar concentrations. We now report on an optimized method to express and purify monomeric Ov-GRN-1 in E. coli using a straightforward and scalable purification and refolding process. Purified monomeric protein caused proliferation at nanomolar concentrations of cancerous and non-cancerous cell lines derived from human bile duct tissue. The expression and purification method we describe herein will serve as a backbone upon which to develop expression and purification processes for recombinant GRNs from other organisms, accelerating research on this intriguing family of proteins. PMID:21757010

Smout, Michael J; Mulvenna, Jason P; Jones, Malcolm K; Loukas, Alex

2011-10-01

97

A proteomic approach to investigate the distribution and abundance of surface and internal Fasciola hepatica proteins during the chronic stage of natural liver fluke infection in cattle.  

PubMed

Fasciola hepatica, a trematode helminth, causes an economically important disease (fasciolosis) in ruminants worldwide. Proteomic analysis of the parasite provides valuable information to understand the relationship between the parasite and its host. Previous studies have identified various parasite proteins, some of which are considered as vaccine candidates or important drug targets. However, the approximate distribution and abundance of the proteins on the surface and within internal parts of the liver fluke are unknown. In this study, two fractions including surface protein fraction (representing surface part of the parasite, near subplasma membrane of the tegument and above the basal membrane of the tegument) and internal protein fraction (representing internal part of the parasite, mainly deeper sides of the tegument including subbasal membrane and other further internal elements of the parasite) were obtained. Components of these two fractions were investigated by an advanced proteomics approach using a high-definition mass spectrometer with nano electrospray ionization source coupled to a high-performance liquid chromatography system (nanoUPLC-ESI-qTOF-MS). FABP1 was found highly abundant in the SPF fraction. Potentially novel F. hepatica proteins showing homology with AKT interacting protein (Xenopus tropicalis), sterol O-acyltransferase 2 (Homo sapiens), and integrin beta 7 (Mus musculus) were identified with high quantities in only the surface fraction of the parasite and may be possible candidates for future control strategies. PMID:22642211

Haçar?z, Orçun; Sayers, Gearóid; Baykal, Ahmet Tar?k

2012-07-01

98

Overexpression of microRNA-21 regulating PDCD4 during tumorigenesis of liver fluke-associated cholangiocarcinoma contributes to tumor growth and metastasis.  

PubMed

MicroRNA, an endogenous noncoding RNA modulating gene expression, is a key molecule that by its dysregulation plays roles in inflammatory-driven carcinogenesis. This study aimed to investigate the role of oncomiR miR-21 and its target, the programmed cell death 4 (PDCD4) in tumor growth and metastasis of the liver fluke Opisthorchis viverrini-associated cholangiocarcinoma (CCA). The expression levels of miR-21 and PDCD4 were analyzed using the TaqMan miRNA expression assay and immunohistochemistry in liver tissues of both O. viverrini plus N-nitrosodimethylamine (NDMA)-treated hamsters and human CCA samples (n=23 cases). The functional assay for miR-21 was performed in CCA cell lines by the anti-miR-21 and pre-miR-21 transfection procedures. The peak of miR-21 levels were reached at 2 (hyperplastic lesions) and 6 (CCA)?months of the O. viverrini plus NDMA-induced group and had a reverse response with its target PDCD4 proteins. In human CCA, miR-21 was overexpressed in tumor tissues when compared with nontumor tissues (P=0.0034) and had a negative correlation with PDCD4 protein (P=0.026). It was also found that high expression of miR-21 was significantly correlated with shorter survival (P<0.05) and lymph node metastasis (P=0.037) of CCA patients. Transient transfection of pre-miR-21 reduced the PDCD4 level and resulted in an increase of M213 CCA cell growth and wound-induced migration ability. These results indicated that miR-21 plays a role in the carcinogenesis and metastasis of O. viverrini-associated CCA by suppressing the function of PDCD4. Modulation of aberrantly expressed miR-21 may be a useful strategy to inhibit tumor cell phenotypes or improve response to chemotherapy. PMID:23417858

Chusorn, P; Namwat, N; Loilome, W; Techasen, A; Pairojkul, C; Khuntikeo, N; Dechakhamphu, A; Talabnin, C; Chan-On, W; Ong, C K; Teh, B T; Yongvanit, P

2013-06-01

99

Lipid peroxidation and etheno DNA adducts in white blood cells of liver fluke-infected patients: protection by plasma alpha-tocopherol and praziquantel.  

PubMed

Chronic infection by the liver fluke Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. To clarify the involvement of oxidative stress and lipid peroxidation-derived DNA damage, etheno (epsilon)-DNA adducts (epsilondA, epsilondC) in WBC and plasma alpha-tocopherol were measured in samples collected from O. viverrini-infected Thai patients (n = 50) and healthy noninfected volunteers (n = 20). epsilondA and epsilondC levels were three to five times higher (P < 0.001) in infected patients than in controls; O. viverrini infection also increased two to three times in the plasma inflammatory indicators, 8-isoprostane, malondialdehyde, and nitrate/nitrite. Mean plasma alpha-tocopherol levels were two times lower in patients than in healthy controls (P < 0.001). Two months after a single dose to infected patients of the antiparasitic drug praziquantel, epsilondA and epsilondC levels in WBC were decreased to control level (P < 0.03); plasma 8-isoprostane, malondialdehyde, nitrate/nitrite, and alkaline phosphatase (ALP) were concomitantly lowered. epsilondA and epsilondC levels in WBC were positively correlated with plasma 8-isoprostane, malondialdehyde, and nitrate/nitrite levels and ALP activity, whereas plasma alpha-tocopherol levels showed inverse correlations. We conclude that chronic O.viverrini infection induces an accumulation of lipid peroxidation-derived DNA damage through oxidative/nitrative stress, which is lowered by the plasma alpha-tocopherol and by antiparasitic drug therapy. Etheno adducts in WBC and urine should be explored as a risk marker for opisthorchiasis-related cholangiocarcinoma, and to assess the efficacy of preventive and therapeutic interventions. PMID:20056652

Dechakhamphu, Somkid; Pinlaor, Somchai; Sitthithaworn, Paiboon; Nair, Jagadeesan; Bartsch, Helmut; Yongvanit, Puangrat

2010-01-01

100

Accumulation of miscoding etheno-DNA adducts and highly expressed DNA repair during liver fluke-induced cholangiocarcinogenesis in hamsters.  

PubMed

Infection by Opisthorchis viverrini, a risk factor for cholangiocarcinoma (CCA) may act through chronic inflammation, oxidative stress and lipid peroxidation (LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine (epsilondA), and 3,N4-etheno-2'-deoxycytidine (epsilondC), markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients. In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model, in O. viverrini-infected hamsters that had received N-nitrosodimethylamine (NDMA, 12.5 ppm in dw) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method, from 21 up to 180 days post-O. viverrini-infection. In inflamed areas of the liver, etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct. Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters, treated with or w/o NDMA when compared with untreated controls. Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters. Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development. Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase (ALP) activity, bile duct hyperplasia, dysplasia, precancerous lesions, and CCA appearance. Also elevated expression of alkyladenine DNA glycosylase (AAG), which excises 1,N6-ethenoadenine (epsilonA) was linked to higher adduct formation, suggesting imbalanced repair. Our results implicate accumulation of inflammation-related, promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis. PMID:20541562

Dechakhamphu, Somkid; Pinlaor, Somchai; Sitthithaworn, Paiboon; Bartsch, Helmut; Yongvanit, Puangrat

2010-09-10

101

Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian hamsters with liver fluke infection and administration of N-nitrosodimethylamine.  

PubMed

Chronic infection with Opisthorchis viverrini for many years has been associated with the development of hepatobiliary diseases including cholangiocarcinoma. It is well known that inflammation is a key component of the tumor microenvironment, and that chronic inflammation plays an important role in tumorigenesis. Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters in order to observe the cancer-related inflammation. The Syrian hamsters were divided into 5 groups: uninfected controls; normal Syrian hamsters infected with O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were later observed for gross pathology and histopathological changes; COX2 was analyzed by immunohistochemical staining. We found a decreased number of inflammatory cells surrounding the hepatic bile duct in the OVis group, but not in the OV and CCAis groups. However, in the CCAis group (with suppressed immunity) early appearance and greater severity of cholangiocarcinoma were observed; gross pathological examination revealed many cancer nodularities on the liver surface, and histopathological studies showed the presence of cancer cells, findings which correlated with the predominant expression of COX2. The present study suggests that host immune responses are intended to ameliorate pathology, and they are also crucially associated with pathogenesis in O. viverrini infection; the unbalancing of host immunity may enhance cancer-related inflammation. PMID:22851165

Juasook, Amornrat; Boonmars, Thidarut; Wu, Zhiliang; Loilome, Watcharin; Veteewuthacharn, Kulathida; Namwat, Nissana; Sudsarn, Pakkayanee; Wonkchalee, Orasa; Sriraj, Pranee; Aukkanimart, Ratchadawan

2013-01-01

102

Cholecystolithiasis Is Associated with Clonorchis sinensis Infection  

PubMed Central

Background The objective of this study was to analyze gallbladder stones for direct evidence of a relationship between Clonorchis sinensis infection and gallbladder stones formation. Methodology We investigated one hundred eighty-three gallbladder stones for the presence of Clonorchis sinensis eggs using microscopy, and analyzed their composition using Fourier transform infrared spectroscopy. We confirmed the presence of Clonorchis sinensis eggs in the gallbladder stones using real-time fluorescent PCR and scanning electron microscopy. Principal Findings Clonorchis sinensis eggs were detected in 122 of 183 gallbladder stones based on morphologic characteristics and results from real-time fluorescent PCR. The proportion of pigment stones, cholesterol stones and mixed gallstones in the egg-positive stones was 79.5% (97/122), 3.3% (4/122) and 17.2% (21/122), respectively, while 29.5% (18/61), 31.1% (19/61) and 39.3% (24/61) in the egg-negative stones. The proportion of pigment stone in the Clonorchis sinensis egg-positive stones was higher than in egg-negative stones (P<0.0001). In the 30 egg-positive stones examined by scanning electron microscopy, dozens or even hundreds of Clonorchis sinensis eggs were visible (×400) showing a distinct morphology. Many eggs were wrapped with surrounding particles, and in some, muskmelon wrinkles was seen on the surface of the eggs. Also visible were pieces of texture shed from some of the eggs. Some eggs were depressed or without operculum while most eggs were adhered to or wrapped with amorphous particles or mucoid matter (×3000). Conclusion Clonorchis sinensis eggs were detected in the gallbladder stones which suggests an association between Clonorchis sinensis infection and gallbladder stones formation, especially pigment stones.

Qiao, Tie; Ma, Rui-hong; Luo, Xiao-bing; Luo, Zhen-liang; Zheng, Pei-ming

2012-01-01

103

DNA copy-number loss on 1p36.1 harboring RUNX3 with promoter hypermethylation and associated loss of RUNX3 expression in liver fluke-associated intrahepatic cholangiocarcinoma.  

PubMed

Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene, localized on 1p36, involved in TGF-beta-Smads signaling. To assess its role in liver fluke-associated intrahepatic cholangiocarcinoma (ICC), the promoter methylation status was investigated in 53 ICCs by methylation-specific PCR, with determination of loss of 1p36.1 by microarray comparative genomic hybridization and RUNX3 protein expression by immunohistochemistry. Loss at 1p36.1 was found 41.5% of ICCs (22/53). In addition, DNA hypermethylation of the RUNX3 promoter was found in 49.1% (26/53) of cancers and 57.1% (4/7) of ICC cell lines. The protein was highly expressed in normal bile ducts but mostly decreased in ICCs, 67.9% (n= 36) being negative for immunohistochemical staining. Promoter hypermethylation of RUNX3 was associated with reversible decrease or absence of RUNX3 protein expression (p<0.001), but this was not found to differ with the ICC subtype. In contrast, loss of 1p36.1 demonstrated a significant link (p= 0.020). In conclusion, RUNX3 promoter hypermethylation and loss of 1p36.1 are causal mechanisms for loss of RUNX3 function in liver fluke-associated ICC carcinogenesis. PMID:19827872

Dachrut, Somkid; Banthaisong, S; Sripa, M; Paeyao, A; Ho, C; Lee, S A; Kosinski, C; Patil, M A; Zhang, J; Chen, X; Sripa, Banchob; Pairojkul, Chawalit

2009-01-01

104

Proteomic identification of potential Clonorchis sinensis excretory/secretory products capable of binding and activating human hepatic stellate cells.  

PubMed

Epidemiological and experimental evidence demonstrated that Clonorchis sinensis is an important risk factor of hepatic fibrosis and cholangiocarcinoma. C. sinensis excretory/secretory products (CsESPs) are protein complex including proteases, antioxidant enzymes, and metabolic enzymes, which may contribute to pathogenesis of liver fluke-associated hepatobiliary diseases. However, potential CsESP candidates involved into hepatic fibrosis and cholangiocarcinoma still remain to be elucidated. In the present study, we performed proteomic identification of CsESP candidates capable of binding and activating human hepatic stellate cell line LX-2. Immunofluorescence analysis confirmed the interaction of CsESPs with LX-2 cell membrane. LX-2 cells could be stimulated by CsESPs from 24 h post incubation (p?

Wang, Xiaoyun; Hu, Fengyu; Hu, Xuchu; Chen, Wenjun; Huang, Yan; Yu, Xinbing

2014-08-01

105

Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions  

SciTech Connect

Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection.

Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)] [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)] [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)] [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of)] [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

2011-04-22

106

Epidemiological Survey on the Infection of Intestinal Flukes in Residents of Muan-gun, Jeollanam-do, the Republic of Korea  

PubMed Central

Infection status of intestinal flukes was investigated in residents of Muan-gun, Jeollanam-do, the Republic of Korea. Total 1,257 fecal samples of residents were examined by formalin-ether sedimentation technique and Kato-Katz thick smear method. Helminth eggs were detected from 95 (7.6%) residents, and eggs of heterophyid flukes and Clonorchis sinensis were found from 62 (4.9%) and 40 (3.2%) cases, respectively. The larger heterophyid eggs, somewhat dark-brown in color and 37.7 × 21.5 µm in average size, and found in 32 (2.6%) out of 62 egg positive cases of heterophyid flukes. To confirm the adult flukes, we performed worm recovery from 12 cases after praziquantel treatment and purgation with MgSO4. A total of 1,281 adult flukes, assigned to 7 species, were recovered from 9 cooperative cases. Heterophyes nocens (total 981 specimens) was collected from 9 cases, Stictodora fuscata (80) from 7, Gymnophalloides seoi (75) from 5, Pygidiopsis summa (140) from 3, Stellantchasmus falcatus (3) from 2, and Stictodora lari and Acanthotrema felis (each 1 worm) from 1 case each. The intrauterine eggs of S. fuscata collected from the recovered worm were identical with the larger heterophyid eggs detected in the stool examination. By the present study, it was confirmed that A. felis is a new intestinal fluke infecting humans, and residents in Muan-gun, Jeollanam-do are infected with variable species of intestinal trematodes.

Cho, Shin-Hyeong; Cho, Pyo-Yun; Lee, Dong-Min; Kim, Tong-Soo; Kim, In-Sang; Hwang, Eun-Jung; Na, Byoung-Kuk

2010-01-01

107

Unchanged triclabendazole kinetics after co-administration with ivermectin and methimazole: failure of its therapeutic activity against triclabendazole-resistant liver flukes  

PubMed Central

Background The reduced drug accumulation based on enhanced drug efflux and metabolic capacity, identified in triclabendazole (TCBZ)-resistant Fasciola hepatica may contribute to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics and clinical efficacy of TCBZ administered alone or co-administered with ivermectin (IVM, efflux modulator) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica-parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica (Sligo isolate) were divided into three groups (n = 4): untreated control, TCBZ-treated (i.r. at 10 mg/kg) and TCBZ+IVM+MTZ treated sheep (10 i.r., 0.2 s.c. and 1.5 i.m. mg/kg, respectively). Plasma samples were collected and analysed by HPLC. In the clinical efficacy study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. Results The presence of IVM and MTZ did not affect the plasma disposition kinetics of TCBZ metabolites after the i.r. administration of TCBZ. The AUC value of TCBZ.SO obtained after TCBZ administration (653.9 ± 140.6 ?g.h/ml) was similar to that obtained after TCBZ co-administered with IVM and MTZ (650.7 ± 122.8 ?g.h/ml). Efficacy values of 56 and 38% were observed for TCBZ alone and for the combined treatment, respectively. No statistical differences (P > 0.05) were observed in fluke counts between treated groups and untreated control, which confirm the resistant status of the Sligo isolate. Conclusions The presence of IVM and MTZ did not affect the disposition kinetics of TCBZ and its metabolites. Thus, the combined drug treatment did not reverse the poor efficacy of TCBZ against TCBZ-resistant F. hepatica.

2010-01-01

108

PRKAR1A overexpression is associated with increased ECPKA autoantibody in liver fluke-associated cholangiocarcinoma: application for assessment of the risk group.  

PubMed

Cholangiocarcinoma (CCA) associated with Opisthorchis viverrini (Ov) chronic infection is the most frequent primary liver cancer in Thailand, and current approaches to early diagnosis and curative treatments are largely disappointing. We hypothesize a role for protein kinase A (PKA) in Ov-induced CCA. First, we studied the PKA isozyme switching in the liver from the hamster CCA model using quantitative (q) PCR, in situ hybridization, and immunohistochemical and western blot analysis. Second, the presence of extracellular PKA (ECPKA) in CCA cell lines and their conditioned media was demonstrated by western blot and PKA activity assay. Third, we determined the association between PRKAR1A expression and serum ECPKA autoantibody in patients with CCA by ELISA. We demonstrated that an increased PRKAR1A expression is restricted to the biliary cells starting from week 1, with remarkable up-regulation when CCA has completely developed by week 24. The switching of the PKA regulatory subunit isoforms from PRKAR2B/PKAII to PRKAR1A/PKAI is significantly associated with cholangiocyte proliferation. Further, we observed that human CCA cell lines express PRKAR1A but not PRKAR2B and excrete ECPKA. Finally, ECPKA autoantibodies are detected in serum of patients with CCA, adenocarcinoma, and Ov infection with periductal fibrosis, but not from Ov-infected subjects without periductal fibrosis lesion and healthy controls. We conclude that PKA isozyme switching and the PRKAR1A/PKAI pathway might contribute to the induction of cholangiocyte transformation and proliferation in Ov-induced CCA. Overexpression of PRKAR1A leads to secretion of ECPKA which is associated with serum autoantibody that may constitute a biomarker for human CCA genesis. PMID:22922884

Loilome, Watcharin; Yooyuen, Sasithorn; Namwat, Nisana; Sithithaworn, Paiboon; Puapairoj, Anucha; Kano, Junko; Noguchi, Masayuki; Miwa, Masanao; Yongvanit, Puangrat

2012-12-01

109

Opisthorchis viverrini : The carcinogenic human liver fluke  

Microsoft Academic Search

Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological

Soraya J Kaewpitoon; Prasit Pengsaa; Banchob Sripa

2008-01-01

110

Microscopic Examination of Gallbladder Stones Improves Rate of Detection of Clonorchis sinensis Infection  

PubMed Central

To improve the rate of detection of Clonorchis sinensis infection, we compared different specimens from patients with cholecystolithiasis. Feces, gallbladder bile, and gallbladder stones collected from 179 consecutive patients with cholecystolithiasis underwent microscopic examination, and according to the results, 30 egg-positive and 30 egg-negative fecal, gallbladder bile, and gallbladder stone specimens, respectively, underwent real-time fluorescent PCR. The detection rates of eggs in feces, bile, and gallbladder stones were 30.7%, 44.7%, and 69.8%, respectively, and the differences were statistically significant (P < 0.01). The PCR results confirmed that the eggs in the specimens were C. sinensis eggs. Eggs in the feces were “fresh” and in the gallbladder stones were “old.” Microscopic examination of gallbladder stones may improve the detection rates of C. sinensis infection, which is important for developing individualized treatments to prevent the recurrence of gallbladder stones and to prevent the occurrence of severe liver damage and cholangiocarcinoma.

Ma, Rui-hong; Luo, Xiao-bing; Zheng, Pei-ming; Luo, Zhen-liang; Yang, Liu-qing

2013-01-01

111

Cytokine responses in mice infected with Clonorchis sinensis  

Microsoft Academic Search

FVB and BALB\\/c mice show different morbidity, development of Clonorchis sinensis, and pathological changes following C. sinensis infection. FVB mice are susceptible and BALB\\/c mice are relatively more resistant to C. sinensis infection. To investigate the relationship between cytokine reaction and susceptibility to C. sinensis infection in FVB and BALB\\/c mice, we described both the patterns and kinetics of Th1

Yang Kyu Choi; Byung Il Yoon; Young Suk Won; Chul Ho Lee; Byung Hwa Hyun; Hyoung Chin Kim; Goo Taeg Oh; Dae Yong Kim

2003-01-01

112

Cloning and expression of mitochondrial malate dehydrogenase of Clonorchis sinensis  

Microsoft Academic Search

The NAD-dependent mitochondrial malate dehydrogenase (mMDH, EC1.1.1.37) plays pivotal roles in tricarboxylic acid and is crucial\\u000a for the survival and pathogenecity of parasites. A cDNA, which was identified by high throughput sequencing from the cDNA\\u000a library constructed from adult Clonorchis sinensis, encoded a putative peptide of 341 amino acids with more than 50% identity with mMDHs from other organisms. The

Nancai Zheng; Baoming Huang; Jin Xu; Shansheng Huang; Jinzhong Chen; Xuchu Hu; Chaoneng Ji; Kang Ying; Xinbing Yu

2008-01-01

113

Two endemic foci of heterophyids and other intestinal fluke infections in southern and western coastal areas in Korea  

PubMed Central

Two endemic foci of heterophyid infections were discovered in coastal villages of Puan-gun, Chollabuk-do, and Sachon-gun. Kyongsangnam-do, Korea. Fecal examinations were performed on 153 inhabitants of Puan-gun and 138 of Sachon-gun, using cellophane thick smear and formalin-ether sedimentation technique. The helminth egg and/or protozoan cyst positive rate was 21.5% (33/153) in Puan-gun and 39.1% (54/138) in Sachon-gun. In Puan-gun, the egg positive rate of heterophyids was the highest, 17.6%, and that of other parasites was 0.7-2.6% by parasite species. In Sachon-gun, that of heterophyids was 18.8%, followed by Clonorchis sinensis (12.3%), and other parasites (0.7-5.0%). Twenth-two (Puan-gun) and six (Sachon-gun) heterophyid egg positive cases were treated with praziquantel, and adult flukes were collected from their diarrheic stools. A total of 3,284 adult flukes of Heterophyes nocens was collected from all of the 22 patients treated in Puan-gun (3-778 individually), and other trematodes were also collected from 2-15 patients: Pygidiopsis summa, Stellantchasmus falcalus, Metagonimus yokogawai, M. miyatai, Stictodora fuscata, Heterophyopsis continua, Acanthoparyphium kurogamo, and Gymnophalloides seoi. In Sachon-gun, M. yokogawai (3,007 specimens), H. nocens (120), and S. falcatus (46) were collected from 5 of 6 treated patients, and H. continua and S. lari each from one patient. The present study revealed that heterophyid flukes, especially H. nocens and M. yokogawai, are prevalent in the southern and western coastal areas of Korea where fresh and/or brackish water fishes are popularly eaten raw.

Song, Tae-Eui; Han, Eun-Taek; Guk, Sang-Mee; Park, Yun-Kyu; Choi, Min-Ho; Lee, Soon-Hyung

1998-01-01

114

Prevalence, distribution and pathological significance of the bile fluke Pseudamphistomum truncatum in Eurasian otters (Lutra lutra) in Great Britain.  

PubMed

Postmortem examinations on 160 otters found dead in Great Britain from 2005 to 2007 showed a high prevalence of infection with the bile fluke Pseudamphistomum truncatum in otters from Somerset and Dorset but no infection in otters from other areas, including Cornwall, the western half of Devon, north-east England and Scotland. Cases were also recorded for the first time in Gloucestershire and East Anglia. Eighteen of the 28 infected otters were male and no cubs were infected, but there was no significant correlation between infection status and sex or age. There was a strong positive correlation between bile fluke infection and gall bladder pathology. Thirty otters had thickened gall bladders resulting from hyperplasia of the epithelial and smooth muscle layers, fibrosis and infiltration by inflammatory cells and 19 of these were infected. No flukes were detected in the other 11 otters with abnormal gall bladders, possibly as a result of a successful immune response. The majority of otters with thickened gall bladders were in good physical condition but a positive association was not confirmed statistically. Fluke infection was also detected in nine of the 130 otters with apparently normal gall bladders. Liver pathology ranged from mild bile duct hyperplasia and periportal fibrosis to severe sclerosing cholangitis, hepatocyte necrosis and bile stasis. No otters were found to have died as a result of fluke infection, but there was a negative association, approaching significance, between infection and body condition. PMID:19329809

Simpson, V R; Tomlinson, A J; Molenaar, F M

2009-03-28

115

Discovery of Opisthorchis viverrini metacercariae in freshwater fish in southern Cambodia  

Microsoft Academic Search

Small liver flukes, Clonorchis sinensis and Opisthorchis viverini, are fish-borne trematodes (FBTs) causing significant public health problems in Asia. While C. sinensis is distributing mainly in far east Asia, O. viverini is distributing in Indochina peninsula. Recently, however, the geographical distributions of those small liver flukes were proven to be far wider than expected. Nevertheless, little is known about the

Sarun Touch; Chalit Komalamisra; Prayong Radomyos; Jitra Waikagul

2009-01-01

116

Paragonimus kellicotti flukes in Missouri, USA.  

PubMed

Paragonimiasis is an infection caused by lung flukes of the genus Paragonimus. In Asia, P. westermani infections are relatively common because of dietary practices. However, in North America, cases of paragonimiasis, which are caused by P. kellicotti flukes, are rare. Only 7 autochthonous cases of paragonimiasis were reported during 1968-2008. In 2009, we reported 3 new case-patients with paragonimiasis who had been seen at our medical center over an 18-month period. Six additional case-patients were identified in St. Louis, Missouri, USA, and treated at Washington University-affiliated health centers in 2009-2010. We report detailed descriptions of these case-patients, which includes unusual clinical manifestations. We also describe public health interventions that were undertaken to inform the general public and physicians about the disease and its mode of transmission. PMID:22840191

Lane, Michael A; Marcos, Luis A; Onen, Nur F; Demertzis, Lee M; Hayes, Ericka V; Davila, Samuel Z; Nurutdinova, Diana R; Bailey, Thomas C; Weil, Gary J

2012-08-01

117

Foodborne intestinal flukes in Southeast Asia.  

PubMed

In Southeast Asia, a total of 59 species of foodborne intestinal flukes have been known to occur in humans. The largest group is the family Heterophyidae, which constitutes 22 species belonging to 9 genera (Centrocestus, Haplorchis, Heterophyes, Heterophyopsis, Metagonimus, Procerovum, Pygidiopsis, Stellantchasmus, and Stictodora). The next is the family Echinostomatidae, which includes 20 species in 8 genera (Artyfechinostomum, Acanthoparyphium, Echinochasmus, Echinoparyphium, Echinostoma, Episthmium, Euparyphium, and Hypoderaeum). The family Plagiorchiidae follows the next containing 5 species in 1 genus (Plagiorchis). The family Lecithodendriidae includes 3 species in 2 genera (Phaneropsolus and Prosthodendrium). In 9 other families, 1 species in 1 genus each is involved; Cathaemaciidae (Cathaemacia), Fasciolidae (Fasciolopsis), Gastrodiscidae (Gastrodiscoides), Gymnophallidae (Gymnophalloides), Microphallidae (Spelotrema), Neodiplostomidae (Neodiplostomum), Paramphistomatidae (Fischoederius), Psilostomidae (Psilorchis), and Strigeidae (Cotylurus). Various types of foods are sources of human infections. They include freshwater fish, brackish water fish, fresh water snails, brackish water snails (including the oyster), amphibians, terrestrial snakes, aquatic insects, and aquatic plants. The reservoir hosts include various species of mammals or birds.The host-parasite relationships have been studied in Metagonimus yokogawai, Echinostoma hortense, Fasciolopsis buski, Neodiplostomum seoulense, and Gymnophalloides seoi; however, the pathogenicity of each parasite species and host mucosal defense mechanisms are yet poorly understood. Clinical aspects of each parasite infection need more clarification. Differential diagnosis by fecal examination is difficult because of morphological similarity of eggs. Praziquantel is effective for most intestinal fluke infections. Continued efforts to understand epidemiological significance of intestinal fluke infections, with detection of further human cases, are required. PMID:19885337

Chai, Jong-Yil; Shin, Eun-Hee; Lee, Soon-Hyung; Rim, Han-Jong

2009-10-01

118

Foodborne Intestinal Flukes in Southeast Asia  

PubMed Central

In Southeast Asia, a total of 59 species of foodborne intestinal flukes have been known to occur in humans. The largest group is the family Heterophyidae, which constitutes 22 species belonging to 9 genera (Centrocestus, Haplorchis, Heterophyes, Heterophyopsis, Metagonimus, Procerovum, Pygidiopsis, Stellantchasmus, and Stictodora). The next is the family Echinostomatidae, which includes 20 species in 8 genera (Artyfechinostomum, Acanthoparyphium, Echinochasmus, Echinoparyphium, Echinostoma, Episthmium, Euparyphium, and Hypoderaeum). The family Plagiorchiidae follows the next containing 5 species in 1 genus (Plagiorchis). The family Lecithodendriidae includes 3 species in 2 genera (Phaneropsolus and Prosthodendrium). In 9 other families, 1 species in 1 genus each is involved; Cathaemaciidae (Cathaemacia), Fasciolidae (Fasciolopsis), Gastrodiscidae (Gastrodiscoides), Gymnophallidae (Gymnophalloides), Microphallidae (Spelotrema), Neodiplostomidae (Neodiplostomum), Paramphistomatidae (Fischoederius), Psilostomidae (Psilorchis), and Strigeidae (Cotylurus). Various types of foods are sources of human infections. They include freshwater fish, brackish water fish, fresh water snails, brackish water snails (including the oyster), amphibians, terrestrial snakes, aquatic insects, and aquatic plants. The reservoir hosts include various species of mammals or birds.The host-parasite relationships have been studied in Metagonimus yokogawai, Echinostoma hortense, Fasciolopsis buski, Neodiplostomum seoulense, and Gymnophalloides seoi; however, the pathogenicity of each parasite species and host mucosal defense mechanisms are yet poorly understood. Clinical aspects of each parasite infection need more clarification. Differential diagnosis by fecal examination is difficult because of morphological similarity of eggs. Praziquantel is effective for most intestinal fluke infections. Continued efforts to understand epidemiological significance of intestinal fluke infections, with detection of further human cases, are required.

Shin, Eun-Hee; Lee, Soon-Hyung; Rim, Han-Jong

2009-01-01

119

Promoting role of Clonorchis sinensis infection on induction of cholangiocarcinoma during two-step carcinogenesis.  

PubMed

Chronic Clonorchis sinensis (CS) infection is etiologically related to cholangiocarcinoma (CHCA) in human and animals. This study was carried out to clarify the role of CS infection on dimethylnitrosamine (DMN)-induced cholangiocarcinogenesis. Fifteen hamsters were administered with 15 ppm DMN for 4 weeks and one week later, the hamsters were infected with 15 metacercariae of CS (DMN-->CS group). The other 15 hamsters were infected with CS and after 5 weeks they were treated with the drug, praziquantel. Again one week later, the hamsters were administered with DMN (CS-->DMN group). The other 15 hamsters were administered with DMN and CS simultaneously (CS+DMN group). Histopathological examination of the livers showed CHCA with papillary or adenomatous hyperplasia of bile ductules in 3 of 15 hamsters of DMN-->CS group and in 11 of 15 hamsters of DMN+CS group. These results suggest that CS infection to hamsters may have a promoting effect on the development of CHCA. PMID:8167103

Lee, J H; Yang, H M; Bak, U B; Rim, H J

1994-03-01

120

Comparative Morphology of Minute Intestinal Fluke Eggs That Can Occur in Human Stools in the Republic of Korea  

PubMed Central

The egg morphology of minute intestinal flukes (MIF) that can occur as human infections in the Republic of Korea, i.e., Metagonimus yokogawai, M. miyatai, M. takahashii, Heterophyes nocens, Heterophyopsis continua, Stellantchasmus falcatus, Stictodora fuscata, Pygidiopsis summa, and Gymnophalloides seoi, was studied in comparison with Clonorchis sinensis. The adult worms were obtained from residents of endemic areas, and their intrauterine eggs were studied and measured using light microscopy; the length, width, length-width ratio (LWR), and Faust-Meleney index (FMI). Several specimens were processed for scanning electron microscopy (SEM), and before gold-coating, the uterine portion of each fluke was etched with a sharp pin in order to expose the eggs. The MIF eggs were ovoid, pyriform, or elliptical with a size range of 21-35×12-21 µm. S. fuscata eggs revealed the highest FMI (largest in the area) and lowest LWR, whereas P. summa eggs showed the lowest FMI and medium LWR. SEM revealed that G. seoi and S. fuscata had remarkably clean shell surface lacking the muskmelon-like structure which is prominent in C. sinensis eggs. In Metagonimus spp., H. continua, H. nocens, and S. falcatus eggs, minute surface ridges were recognizable though less prominent compared with C. sinensis. On the surface of P. summa eggs, thread-like curly structures were characteristically seen. The results revealed that important differential keys for MIF eggs include the length, width, area (FMI), shape of the eggs, and the extent of the muskmelon-like structure or ridges on their shell surface and operculum.

Lee, Jin-Joo; Jung, Bong-Kwang; Lim, Hyemi; Lee, Mi Youn; Choi, Sung-Yil; Shin, Eun-Hee

2012-01-01

121

Drag anchor fluke?soil interaction in clays  

Microsoft Academic Search

Finite element analysis of the fluke-soil interaction behaviour of drag anchors in undrained soil has allowed calculation of plastic yield loci for characterisation of fluke failure states. The yield loci produced are examined in terms of soil deformation mechanisms and kinematics and are incorporated into a novel method for drag anchor design.

M. F. Bransby; M. P. O'Neill; M. F. Randolph

2003-01-01

122

Cyst formation, increased anti-inflammatory cytokines and expression of chemokines support for Clonorchis sinensis infection in FVB mice.  

PubMed

To verify the hypothesis that different pathology of Clonorchis sinensis infection by mouse strains is determined by different responses of cytokines and chemokines, we compared those responses of FVB with those of BALB/c mice. All of FVB mice infected with 30 metacercariae of C. sinensis showed cystic dilatation in the liver, whereas infected BALB/c mice did not. Mature worms were recovered from 19 of 20 liver sections of FVB mice while only one of 20 sections of BALB/c mice revealed a mature worm. In both strains the proportion of CD4(+) T cells was lower in C. sinensis-infected than in the uninfected group. However, the proportion of CD8(+) T cells was elevated in C. sinensis-infected from both strains compared to uninfected mice. The Th2-associated anti-inflammatory cytokines such as IL-4, IL-5 and IL-13, IL-10 and TGF-?, were significantly more produced by the lymphocytes of FVB than by those of BALB/c mice. Especially, the 2 anti-inflammatory cytokines, IL-10 and TGF-?, were presumably related with susceptibility and the development of worms in the liver. C. sinensis infected FVB mice also produced more chemokines such as RANTES and MIP-1? in the liver lymphocytes than BALB/c mice. In conclusion, the FVB mice provide the favorable niche for C. sinensis by cyst formation in the bile duct, increased production of Th2-associated anti-inflammatory cytokines and upregulation of chemokines. PMID:21820080

Kim, Eun-Min; Bae, Young Mee; Choi, Min-Ho; Hong, Sung-Tae

2012-03-01

123

Opisthorchiasis and intestinal fluke infections in northern Thailand.  

PubMed

Four hundred and thirty-one residents from 16 provinces in northern Thailand who had previously been found positive for Opisthorchis viverrini or Opisthorchis viverrini-like eggs were given praziquantel 40 mg/kg. The stool was collected for 4 to 6 times and examined for adult worms. The prevalence of Opisthorchis viverrini in this group was 11.6%. Intestinal flukes, Haplorchis taichui and Haplorchis yokogawai, were predominantly found in 63.11% and 10.44% respectively. Other intestinal flukes (Centrocestus caninus, Echinostoma malayanum, Haplorchis pumilio, Phaneropsolus bonnei, Plagiorchid flukes, Prosthodendrium molenkampi and Stellantchasmus falcatus) were also found in small numbers. PMID:9740284

Radomyos, B; Wongsaroj, T; Wilairatana, P; Radomyos, P; Praevanich, R; Meesomboon, V; Jongsuksuntikul, P

1998-03-01

124

Diagnostic Methods in Intestinal Fluke Infections: A Review.  

National Technical Information Service (NTIS)

In this report emphasis will be placed upon the diagnosis of the more important intestinal flukes of Asia with additional information on some of the unusual, yet interesting, intestinal trematodes that have been reported from man. The various species will...

J. H. Cross

1974-01-01

125

Efficacy and Safety of Tribendimidine Against Clonorchis sinensis  

PubMed Central

Background.?Clonorchiasis is of considerable public health importance, particularly in the People's Republic of China (PR China), where most of the 15 million individuals infected with Clonorchis sinensis are currently concentrated. Praziquantel is the drug of choice, but tribendimidine might be an alternative. Methods.?We performed a randomized open-label trial in Guangxi, PR China, to assess the efficacy and safety of 400 mg tribendimidine once, 400 mg tribendimidine daily for 3 days, and 75 mg/kg praziquantel in 1 day divided in 3 doses against parasitological-confirmed C. sinensis infections. Cure and egg reduction rates were determined 3 weeks posttreatment using available case analysis. Clinical symptoms were documented at baseline, and adverse events were recorded and graded 3 and 24 hours after each dose. Results.?A total of 74 patients were included in the final analysis. Single-dose tribendimidine achieved a cure rate of 44%, whereas cure rates of 58% and 56% were obtained for tribendimidine administered for 3 days and praziquantel, respectively. High egg reduction rates (97.6%–98.8%) were observed for all treatment regimens. Single-dose tribendimidine was the best-tolerated treatment scheme. Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05). Conclusions.?Tribendimidine has an efficacy comparable to praziquantel in the treatment of C. sinensis infection and resulted in fewer adverse events compared to praziquantel. Larger clinical trials are warranted among C. sinensis–infected patients to determine the potential of tribendimidine against clonorchiasis and other helminthiases. Clinical Trials Registration.?Controlled-Trials.com, ISRCTN80829842.

Qian, Men-Bao; Yap, Peiling; Yang, Yi-Chao; Liang, Hai; Jiang, Zhi-Hua; Li, Wei; Tan, Yu-Guang; Zhou, Hui; Utzinger, Jurg; Zhou, Xiao-Nong; Keiser, Jennifer

2013-01-01

126

Unlocking the Transcriptomes of Two Carcinogenic Parasites, Clonorchis sinensis and Opisthorchis viverrini  

Microsoft Academic Search

The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as

Neil D. Young; Bronwyn E. Campbell; Ross S. Hall; Aaron R. Jex; Cinzia Cantacessi; Thewarach Laha; Woon-Mok Sohn; Banchob Sripa; Alex Loukas; Paul J. Brindley; Robin B. Gasser

2010-01-01

127

Exome sequencing of liver fluke-associated cholangiocarcinoma.  

PubMed

Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA. PMID:22561520

Ong, Choon Kiat; Subimerb, Chutima; Pairojkul, Chawalit; Wongkham, Sopit; Cutcutache, Ioana; Yu, Willie; McPherson, John R; Allen, George E; Ng, Cedric Chuan Young; Wong, Bernice Huimin; Myint, Swe Swe; Rajasegaran, Vikneswari; Heng, Hong Lee; Gan, Anna; Zang, Zhi Jiang; Wu, Yingting; Wu, Jeanie; Lee, Ming Hui; Huang, DaChuan; Ong, Pauline; Chan-on, Waraporn; Cao, Yun; Qian, Chao-Nan; Lim, Kiat Hon; Ooi, Aikseng; Dykema, Karl; Furge, Kyle; Kukongviriyapan, Veerapol; Sripa, Banchob; Wongkham, Chaisiri; Yongvanit, Puangrat; Futreal, P Andrew; Bhudhisawasdi, Vajarabhongsa; Rozen, Steve; Tan, Patrick; Teh, Bin Tean

2012-06-01

128

Proteomic analysis of differentially expressed proteins in human cholangiocarcinoma cells treated with Clonorchis sinensis excretory-secretory products.  

PubMed

Severe Clonorchis sinensis infection is a significant risk factor for malignant changes in bile ducts and surrounding liver tissues occurring as a result of direct contact with C. sinensis worms and their excretory-secretory products (ESP). However, the intrinsic molecular mechanisms involved in these processes remain obscure. To determine the effects of C. sinensis infection on protein expression in host bile duct epithelium, we examined proteomic profile changes in the human cholangiocarcinoma cell line (HuCCT1) treated with ESP at 24 h. Using a combination of 2-DE, quantitative image and MALDI-TOF MS analysis, we identified 83 proteins that were translationally modulated in response to ESP, among which 49 were up-regulated and 34 down-regulated. These proteins were classified under various biological categories, including metabolism, cell structure and architecture, proteolysis, protein modification, transport, signal transduction, and reactive oxygen species (ROS) detoxification. In particular, ESP induced the expression of redox-regulating proteins, including peroxiredoxins (Prdx 2, 3, and 6) and thioredoxin 1 (Trx 1), possibly via intracellular ROS generation. Application of the proteomic approach to identify ESP response proteins should be a prerequisite before further investigation to clarify the molecular pathways and mechanisms involved in C. sinensis infection of host cells. PMID:19798681

Pak, Jhang Ho; Moon, Ju Hyun; Hwang, Seung-Jun; Cho, Shin-Hyeong; Seo, Sang-Beom; Kim, Tong-Soo

2009-12-15

129

Differential gene expression profiling in human cholangiocarcinoma cells treated with Clonorchis sinensis excretory-secretory products  

Microsoft Academic Search

Clonorchiasis is associated with bile duct malignancy and the subsequent development of cholangiocarcinoma. Although this\\u000a is likely caused by adult Clonorchis sinensis and its excretory–secretory products (ESP), the precise molecular mechanisms remain obscure. To evaluate the effect of C. sinensis infection on differential gene expression in host hepatocytes, we examined the kinetics of changes in gene expression in\\u000a the human

Jhang Ho Pak; Dong-Wook Kim; Ju Hyun Moon; Joo-Hyun Nam; Jong-Hyeok Kim; Jung Won Ju; Tong-Soo Kim; Sang-Beom Seo

2009-01-01

130

Correlation of egg counts of Clonorchis sinensis by three methods of fecal examination  

Microsoft Academic Search

The Kato-Katz (KK) method is a well-known method of fecal examination for helminthiases. Its diagnostic sensitivity was found very high for clonorchiasis. The present study evaluated the correlation of Clonorchis sinensis egg counts by the KK method with those by direct smear and formalin-ether (FE) technique. The egg counts obtained by the KK method (Y) were correlated with the counts

Min-Ho Choi; Tao Ge; Shang Yuan; Sung-Tae Hong

2005-01-01

131

Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment  

Microsoft Academic Search

A cohort was established for evaluation of cancer risk factors in Sancheong-gun, Gyeongsangnam-do, Korea. As one of the cohort studies, stools of 947 residents (403 males and 544 females, age range: 29-86 years) were screened for Clonorchis sinensis eggs using both Kato-Katz method and formalin-ether sedimentation tech- nique. The overall egg positive rate of C. sinensis was 37.7% and individual

Chenghua Shen; Jae-hwan Kim; Jeong-Keun Lee; Young Mee Bae; Min-Ho Choi; Jin-Kyoung Oh; Min Kyung Lim; Hai-Rim Shin; Sung-Tae Hong

2007-01-01

132

Tracing of the Bile-Chemotactic Migration of Juvenile Clonorchis sinensis in Rabbits by PET-CT  

PubMed Central

Background Adult Clonorchis sinensis live in the bile duct and cause clonorchiasis. It is known that the C. sinensis metacercariae excyst in the duodenum and migrate up to the bile duct through the common bile duct. However, no direct evidence is available on the in vivo migration of newly excysted C. sinensis juveniles (CsNEJs). Advanced imaging technologies now allow the in vivo migration and localization to be visualized. In the present study, we sought to determine how sensitively CsNEJs respond to bile and how fast they migrate to the intrahepatic bile duct using PET-CT. Methodology/Principal Findings CsNEJs were radiolabeled with 18F-fluorodeoxyglucose (18F-FDG). Rabbits with a gallbladder contraction response to cholecystokinin-8 (CCK-8) injection were pre-screened using cholescintigraphy. In these rabbits, gallbladders contracted by 50% in volume at an average of 11.5 min post-injection. The four rabbits examined were kept anesthetized and a catheter inserted into the mid duodenum. Gallbladder contraction was stimulated by injecting CCK-8 (20 ng/kg every minute) over the experiment. Anatomical images were acquired by CT initially and dynamic PET was then carried out for 90 min with a 3-min acquisition per frame. Twelve minutes after CCK-8 injection, about 3,000 18F-FDG-labeled CsNEJs were inoculated into the mid duodenum through the catheter. Photon signals were detected in the liver 7–9 min after CsNEJs inoculation, and these then increased in the whole liver with stronger intensity in the central area, presenting that the CsNEJs were arriving at the intrahepatic bile ducts. Conclusion In the duodenum, CsNEJs immediately sense bile and migrate quickly with bile-chemotaxis to reach the intrahepatic bile ducts by way of the ampulla of Vater.

Kim, Tae Im; Yoo, Won Gi; Kwak, Byung Kook; Seok, Ju-Won; Hong, Sung-Jong

2011-01-01

133

[A case of clonorchiasis complicated with the expansion of liver cyst].  

PubMed

A 61-year-old man was admitted to our hospital for examination of the cause of rapid growth of a liver cyst. We found a slight dilatation of bile duct in the vicinity of the liver cyst. Then, we underwent ERCP and found a communication between the bile duct and liver cyst. Bile cytodiagnosis revealed a large quantity of clonorchis eggs. The patient like to do eat raw freshwater fish and we suspected that the acute expansion of the cyst was due to clonorchiasis. Following administration of 40mg/kg praziquantel, the blood clonorchis antibody disappeared and the liver cyst also disappeared after 6 months. We encountered a case of clonorchiasis complicated with growth of a liver cyst. Medical interviews should be conducted carefully along with meticulous examinations. PMID:23459541

Kominami, Yoko; Aikata, Hiroshi; Hiramatsu, Ken; Tanaka, Mio; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yoji; Nagaoki, Yuko; Murakami, Eisuke; Miyaki, Daisuke; Miki, Daiki; Kawaoka, Tomokazu; Takaki, Shintaro; Hiraga, Nobuhiko; Tsuge, Masaki; Serikawa, Masahiro; Imamura, Michio; Hyogo, Hideyuki; Kawakami, Yoshiiku; Takahashi, Shoichi; Sasaki, Tamito; Chayama, Kazuaki

2013-03-01

134

The inability of tapeworm Hymenolepis diminuta and fluke Dicrocoelium dendriticum to metabolize praziquantel.  

PubMed

Biotransformation enzymes can, to a certain extent, protect parasitic worms against the toxic effects of anthelmintics and can contribute to drug-resistance development. The objective of our work was (1) to find and identify phase I and II metabolites of the anthelmintic praziquantel (PZQ) formed by the lancet fluke (Dicrocoelium dendriticum) and the rat tapeworm (Hymenolepis diminuta) and (2) to compare PZQ metabolites in helminths with PZQ biotransformation in rat as host species. Ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) was used for this purpose. During in vitro incubations, mitochondria-like and microsomes-like fractions (prepared from homogenates of adult worms or from rat liver homogenate) were incubated with 10 and 100 ?M PZQ. Liquid/liquid extraction was used for samples during in vitro experiments. In the ex vivo study, living D. dendriticum and H. diminuta adults were incubated in RPMI-1640 medium in the presence of 50 nM or 100 nM PZQ for 24h. After incubation, the worms were removed from the medium and homogenized. Homogenates of worms, medium from the incubation of worms or rat hepatocytes and rat urine (collected during 24h after oral PZQ administration) were separately extracted using solid-phase extraction. The results showed that both D. dendriticum and H. diminuta enzymatic systems are not able to metabolize PZQ. On the other hand, thirty one different phase I and four phase II PZQ metabolites were detected in rat samples using UHPLC/MS/MS analyses. These results show that our experimental helminths, as the members of tapeworm and fluke groups of parasites, are not able to deactivate PZQ, and that the biotransformation enzymes of the studied helminths do not contribute to PZQ-resistance. PMID:21996005

Vok?ál, Ivan; Jirásko, Robert; Jedli?ková, Veronika; Bártíková, Hana; Skálová, Lenka; Lamka, Ji?í; Hol?apek, Michal; Szotáková, Barbora

2012-04-30

135

[Detection of Clonorchis sinensis eggs in the ground gallbladder stones by microscopy].  

PubMed

Sera, feces, bile and gallbladder stones were collected from 179 patients who accepted gallbladder-preserving cholelithotomy during the period of January to June 2010 at the general surgery department in the Second People's Hospital of Panyu District in Guangzhou. Rapid colloidal gold immunochromatography was used to detect IgG against Clonorchis sinensis. C. sinensis eggs were examined by fecal direct smear, and in bile sediments and ground gallbladder stones. The results showed that the positive rate of rapid colloidal gold immunochromatographic assay for IgG was 51.4%, and the egg positive rate in feces, bile sediments and gallbladder stones was 30.7%, 44.7% and 69.8%, respectively. The detection rate of fecal direct smear was the lowest, while that of the gallbladder stone examination was the highest (P < 0.05). Those patients with egg-positive feces and/or bile sediments were all with egg-positive gallbladder stones. PMID:23072161

Ma, Rui-Hong; Qiao, Tie; Luo, Xiao-Bing

2012-08-30

136

In vitro effects of various neuropharmacological agents on the motility of adult Clonorchis sinensis.  

PubMed

Stimulatory effects were observed in vitro when 5-HT was applied to whole worm preparations of Clonorchis sinensis. The stimulatory action of 5-HT was antagonized by tryptophol, clomipramine and imipramine. Strychnine remarkably stimulated motility. The action of strychnine was enhanced by 5-HT but inhibited by tryptophol. GABA, Phenylephrine, isoproterenol, dibenamine and phentolamine showed little influence on motility. Inhibitory effects were caused by eserine, arecoline, carbachol, DMPP and hemicholinium-3, but not by ACh, pilocarpine and McN-A-343. The inhibitory actions of eserine or carbachol were not antagonized by d-tubocurarine, hexamethonium or atropine. These results suggest that in regulating the motility of C. sinensis ACh may function as an inhibitory neurotransmitter and 5-HT as an excitatory transmitter in a manner similar to that already established for other trematodes such as Fasciola hepatica and Schistosoma mansoni. PMID:9780596

Shyu, L Y; Terada, M; Lee, H H

1998-08-01

137

Echinostome flukes receovered from humans in Khammouane Province, Lao PDR.  

PubMed

Echinostome eggs were detected in 22 (1.1%) of 2,074 people residing in riparian villages along the Mekong River in Khammouane Province, Lao PDR. In order to recover the adult flukes, 9 persons were treated with praziquantel and purged with magnesium salts. A total of 55 echinostome specimens (4 species) were recovered from the 9 persons. Echinostoma revolutum (8 specimens) was recovered from 3 persons, Artyfechinostomum malayanum (8 specimens) was from 2 persons, Echinochasmus japonicus (33 specimens) was from 7 persons, and Euparyphium sp. (6 specimens) was from 1 person. In Lao PDR, only human infections with E. japonicus were previously known. Therefore, the present study describes human infections with E. revolutum, A. malayanum, and Euparyphium sp. for the first time in Lao PDR. These results indicate that the surveyed villages of Khammouane Province, Lao PDR are low-grade endemic foci of echinostomiasis. PMID:22949759

Chai, Jong-Yil; Sohn, Woon-Mok; Yong, Tai-Soon; Eom, Keeseon S; Min, Duk-Young; Hoang, Eui-Hyug; Phammasack, Bounlay; Insisiengmay, Bounnaloth; Rim, Han-Jong

2012-09-01

138

Taxonomic and Ecological Studies on the Lung Fluke, 'Paragonimus' in Central and South America.  

National Technical Information Service (NTIS)

In Tingo Maria, Peru, 25 crabs, Pseudothelphusa chilensis were examined for Paragonimus metacercariae with negative results. Five lung flukes were obtained from two kinds of mammals; two worms from one of two four-eyed opossums, Philander opossum, and thr...

I. Miyazaki

1973-01-01

139

The genome of the blood fluke Schistosoma mansoni  

PubMed Central

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. We report here analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and novel families of micro-exon genes that undergo frequent alternate splicing. As the first sequenced flatworm, and a representative of the lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, while the identification of membrane receptors, ion channels and more than 300 proteases, provide new insights into the biology of the life cycle and novel targets. Bioinformatics approaches have identified metabolic chokepoints while a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

Berriman, Matthew; Haas, Brian J.; LoVerde, Philip T.; Wilson, R. Alan; Dillon, Gary P.; Cerqueira, Gustavo C.; Mashiyama, Susan T.; Al-Lazikani, Bissan; Andrade, Luiza F.; Ashton, Peter D.; Aslett, Martin A.; Bartholomeu, Daniella C.; Blandin, Gaelle; Caffrey, Conor R.; Coghlan, Avril; Coulson, Richard; Day, Tim A.; Delcher, Art; DeMarco, Ricardo; Djikeng, Appoliniare; Eyre, Tina; Gamble, John A.; Ghedin, Elodie; Gu, Yong; Hertz-Fowler, Christiane; Hirai, Hirohisha; Hirai, Yuriko; Houston, Robin; Ivens, Alasdair; Johnston, David A.; Lacerda, Daniela; Macedo, Camila D.; McVeigh, Paul; Ning, Zemin; Oliveira, Guilherme; Overington, John P.; Parkhill, Julian; Pertea, Mihaela; Pierce, Raymond J.; Protasio, Anna V.; Quail, Michael A.; Rajandream, Marie-Adele; Rogers, Jane; Sajid, Mohammed; Salzberg, Steven L.; Stanke, Mario; Tivey, Adrian R.; White, Owen; Williams, David L.; Wortman, Jennifer; Wu, Wenjie; Zamanian, Mostafa; Zerlotini, Adhemar; Fraser-Liggett, Claire M.; Barrell, Barclay G.; El-Sayed, Najib M.

2009-01-01

140

Coinfection with Clonorchis sinensis modulates murine host response against Trichinella spiralis infection.  

PubMed

Concomitant infections of different species of parasites are common in the field. Infection with one parasite species likely triggers host responses that may influence the subsequent infection of another species and alter disease outcomes. So far, the majority of studies have focused on single species parasite infection, and the mechanisms of protection induced by the first parasite infection against the secondary infection remain poorly defined. In this study, we assess the impact of trematode Clonorchis sinensis infection on the course of another tissue nematode Trichinella spiralis challenge. We observed that mice with preexisting C. sinensis infection had lower worm burden of intestinal T. spiralis than those infected with T. spiralis alone; mice with preexisting C. sinensis also had severe enteric histopathological changes and higher counts of intestinal Paneth cells in responses to T. spiralis challenge. The mRNA levels of interleukin (IL)-4, IL-10, IL-13, and tumor necrosis factor (TNF)-? from the small intestine and spleen of the different groups were analyzed using quantitative real-time polymerase chain reaction. Compared with that in mice infected with T. spiralis alone, the mRNA expression of IL-13 was significantly increased in the small intestine tissues and IL-4, IL-13, and TNF-? were significantly increased in the spleen tissues in the dually infected mice. Our findings suggest that a "preexisting" trematode infection of C. sinensis is a factor which contributes to reducing the establishment of T. spiralis adult worms in the small intestine. PMID:23846239

Chen, Ying; Huang, Bo; Huang, Shiguang; Yu, Xinbing; Li, Yonglong; Song, Wenjian; Li, Yongxiang; Lu, Fangli

2013-09-01

141

Clonorchis sinensis: molecular cloning and functional expression of a novel cytosolic glutathione transferase.  

PubMed

Glutathione transferases (GSTs) represent a large family of enzymes. In the high throughput sequencing of the cDNA library constructed from the adult stage of Clonorchis sinensis (Cs), we isolate another cDNA clone encoding a novel cytosolic GST enzyme. To discriminate with our former reported CsGST, we designated this GST as CsGST1. This new cDNA contains 744 bp with a putative open reading frame of 213 amino acids. The deduced amino acid sequence exhibits 88% identity to Opisthorchis viverrini 28GST (Ov28GST), 60 and 52% identity to C. sinensis cytosolic 28-kDa GST (Cs28GST) and CsGST, respectively. The CsGST1 was expressed in Escherichia coli BL21(DE3) as a His-tag fusion protein and was purified by Ni-NTA agarose. The recombinant CsGST1 showed moderate GST activity of 0.79 U mg(-1). The average K (m) of the CsGST1 for 1-chloro-2, 4-dinitrobenzene is 150 microM. Cibacron blue F3GA and albendazole inhibited the CsGST1 activity with average IC(50) values of 9.1 and 265.4 muM, respectively. The nucleotide sequence reported in this paper was submitted to the GenBank Database with accession number DQ342327. PMID:17048005

Wu, Zhongluan; Hu, Xuchu; Wu, De; Xu, Jin; Chen, Shouyi; Wu, Zhongdao; Yu, Xinbing

2007-01-01

142

Prevalence of Clonorchis sinensis Infections Along the Five Major Rivers in Republic of Korea, 2007  

PubMed Central

Objectives The prevalence of Clonorchis sinensis infection was investigated among residents of the five major river basins, that is, Hangang, Nakdonggang, Seomjingang, Yeongsangang, and Geumgang River basins in Korea. Methods From January to December 2007, a total of 31,268 stool samples were collected from 29 localities and examined by the formalin-ether sedimentation technique. Results Intestinal parasite eggs and/or protozoan cysts were detected from 2957 (9.5%) inhabitants. Number of residents harbouring helminth eggs in the faeces was 2542 (8.1%) for C. sinensis, 255 (0.8%) for Heterophyes spp., 36 (0.1%) for Echinostoma spp., 30 (0.1%) for Trichuris trichiura, 8 (0.03%) for Ascaris lumbricoides, 7 (0.02%) for Gymnophalloide seoi, and 50 (0.02%) for Trichostrongylus orientalis. Number of residents harbouring protozoan cysts in the faeces was 133 (1.3%) for Entamoeba spp. and 50 (0.2%) for Giardia lamblia. The positive rates of C. sinensis in Nakdonggang, Seomjingang, Yeongsangang, Geumgang, and Hangang River basins were 12.2%, 9.5%, 3.3%, 3.0%, and 1.0%, respectively. The egg positive rate of C. sinensis was higher in male (10.6%) than in female (6.1%), and the age group of 50s had the highest positive rate (10.4%). Conclusion The result of this study revealed little decrease in positive rate of C. sinensis compared with the result of southern endemic areas of Korea in 2006.

Kim, Hyun-Kyung; Cheun, Hyeng-Il; Cheun, Byung-Suk; Lee, Ki-Yeon; Kim, Tong-Soo; Lee, Sang-Eun; Lee, Won-ja; Cho, Shin-Hyeong

2010-01-01

143

Molecular cloning and characterization of a mu-class glutathione S-transferase from Clonorchis sinensis.  

PubMed

In biliary passages, Clonorchis sinensis causes epithelial hyperplasia and is assumed to promote carcinogenesis. Glutathione S-transferase (GST) is an antioxidant enzyme involved in phase II defense in trematodes. A clone (pcsGSTM1) encoding a GST was identified by screening a C. sinensis cDNA library with a PCR-synthesized cDNA probe. The predicted amino acid sequence encoded by pcsGSTM1 cDNA had a high degree of sequence identity and folding topology similar to the mu-class GSTs. The estimated molecular mass of the protein, 26 kDa, was consistent with an expression by pcsGSTM1 cDNA. The bacterially expressed recombinant csGSTM1 protein possessed an enzymatic GST activity and conjugated GSH to reactive carbonyls of lipid peroxidation. The recombinant csGSTM1 protein did not share antigenic epitope(s) with GSTs of Fasciola hepatica, Paragonimus westermani and Schistosoma japonicum. The csGSTM1 was identified to a mu-class GST in C. sinensis. PMID:11377741

Hong, S J; Lee, J Y; Lee, D H; Sohn, W M; Cho, S Y

2001-06-01

144

Intraductal papillary neoplasm of the bile duct associated with Clonorchis sinensis infection.  

PubMed

Intraductal papillary neoplasm of bile duct (IPNB) is one of the precursor lesions of cholangiocarcinoma. Although hepatolithiasis has been extensively studied in its association with IPNBs, there had been no comprehensive study of IPNBs with Clonorchis sinensis infection. Twelve IPNBs were selected from 20 surgically resected cholangiocarcinomas, positive for C. sinensis tests (60%) and compared with eight IPNBs, selected from 51 resected cholangiocarcinomas, negative for C. sinensis tests (16%), by histologic and immunohistochemical studies of mucin core proteins and cytokeratin panels. The predominant immuno-phenotype of IPNB cases with Clonorchiasis was pancreatobiliary type (MUC1+/MUC2-/CDX2-; 9/12 cases), while that of IPNB cases with negative for C. sinensis was intestinal type (MUC1-/MUC2+/CDX2+; 6/8; p = 0.04). The prevalence of IPNBs was higher when patients with cholangiocarcinoma had Clonorchiasis. IPNBs with Clonorchiasis tended to have a more pancreatobiliary phenotype, which suggests IPNBs with Clonorchiasis may have a different tumorigenesis pathway from IPNBs with other etiologies. PMID:18855009

Jang, Kee-Taek; Hong, Seung-Mo; Lee, Kyu Taek; Lee, Jong Gyun; Choi, Seoung Ho; Heo, Jin Seok; Choi, Dong Wook; Choi, Dongil; Lim, Jae Hoon

2008-12-01

145

Fasciola hepatica: Histology of the testis in egg-producing adults of several laboratory-maintained isolates of flukes grown to maturity in cattle and sheep and in flukes from naturally infected hosts.  

PubMed

A total of 8 calves approximately 6 months old and 22 lambs of similar age were infected with metacercariae of Fasciola hepatica of various laboratory-maintained isolates including: Cullompton (sensitive to triclabendazole) and Sligo, Oberon and Leon (reported as resistant to triclabendazole). Ten to 16 weeks after infection, flukes were harvested from these experimental animals and the histology of the testis tissue was examined in a representative sample of flukes from each population. Adult wild-type flukes were also collected from 5 chronically infected cattle and 7 chronically infected sheep identified at post-mortem inspection. The testis tissue of these flukes was compared with that of the various laboratory-maintained isolates. Whilst the testes of the wild-type, Oberon and Leon flukes displayed all the usual cell types associated with spermatogenesis in Fasciola hepatica (spermatogonia, spermatocytes, spermatids and mature sperm), the Cullompton flukes from both cattle and sheep showed arrested spermatogenesis, with no stages later than primary spermatocytes represented in the testis profiles. The presence of numerous eosinophilic apoptotic bodies and nuclear fragments suggested that meiotic division was anomalous and incomplete. In contrast to the wild-type flukes, no mature spermatozoa were present in the testes or amongst the shelled eggs in the uterus. A high proportion of the eggs collected from these flukes hatched to release normal-appearing miracidia after an appropriate incubation period, as indeed was the case with all isolates examined and the wild-type flukes. It is concluded that the eggs of Cullompton flukes are capable of development without fertilization, i.e. are parthenogenetic. The implications of this for rapid evolution of resistant clones following an anthelmintic selection event are discussed. Amongst the Sligo flukes examined, two subtypes were recognised, namely, those flukes with all stages of spermatogenesis and mature spermatozoa present in the testes (type 1), and those flukes with all stages of spermatogenesis up to spermatids present, but no maturing spermatozoa in the testes (type 2). Each sheep infected with the Sligo isolate had both type 1 (approximately 60%) and type 2 (approximately 40%) flukes present in the population. Spermatozoa were found amongst the eggs in the uterus in 64% of flukes and this did not necessarily reflect the occurrence of spermatozoa in the testis profiles of particular flukes, suggesting that cross-fertilization had occurred. The apparent disruption of meiosis in the spermatocytes of the Cullompton flukes is consistent with reports that Cullompton flukes are triploid (3n=30), whereas the Sligo and wild-type flukes are diploid (2n=20). In the Sligo flukes the populations are apparently genetically heterogenous, with a proportion of the flukes unable to produce fully formed spermatozoa perhaps because of a failure in spermiogenesis involving elongation of the nucleus during morphogenesis. PMID:18774647

Hanna, R E B; Edgar, H; Moffett, D; McConnell, S; Fairweather, I; Brennan, G P; Trudgett, A; Hoey, E M; Cromie, L; Taylor, S M; Daniel, R

2008-11-01

146

Hyperparasitism of trichodinid ciliates on monogenean gill flukes of two marine fish.  

PubMed

Two unusual cases of hyperparasitism of trichodinid ciliates on monogenean gill flukes are described from southern Israel (Red Sea). The first case occurred in cultured European sea bass Dicentrarchus labrax infected by Diplectanum aequans, while the second was observed in a feral devil firefish Pterois miles infected by Haliotrema sp. In both cases, the trichodinids heavily co-infested the host fish gills. The flukes were completely coated by the ciliates, which gave them a cobblestone appearance, but no damage to their tegument was apparent. Both cases are most likely a result of accidental hyperparasitism, brought about by perturbed environmental conditions. PMID:16060271

Colorni, A; Diamant, A

2005-06-01

147

Chronic diarrhea in returing travelers: intestinal parasitic infection with the fluke Metagonimus yokogawai.  

PubMed

An unusual intestinal infection with the parasite Metagonimus yokogawai was acquired by an American traveling in the Orient. Diarrhea began abroad, and recurred at intervals until she was seen 1 1/2 years later. Stool examinations resulted in the recovery of small operculated ova characteristic of intestinal or biliary fluke infection. Treatment with hexylresorcinol failed to eradicate the infection, but subsequent use of tetrachloroethylene was successful and facilitated recovery of adult parasites, leading to the specific diagnosis of metagonimiasis. Metagonimiasis and related intestinal fluke infections should be considered as a possible cause of persistent diarrhea in travelers returning from endemic areas abroad. PMID:725630

Goldsmith, R S

1978-12-01

148

Biochemical and immunological characterization of annexin B30 from Clonorchis sinensis excretory/secretory products.  

PubMed

Clonorchis sinensis has been classified as group I biological carcinogen for cholangiocarcinoma by the World Health Organization. Biological studies on excretory/secretory products (ESPs) enabled us to understand the pathogenesis mechanism of C. sinensis and develop new strategies for the prevention of clonorchiasis. In this study, sequence analysis showed that annexin B30 from C. sinensis (CsANXB30) is composed of four annexin repeats which were characterized by type II and III Ca(2+)-binding sites or KGD motif with the capability of Ca(2+)-binding. In addition, immunoblot assay revealed that recombinant CsANXB30 (rCsANXB30) could be recognized by the sera from rats infected with C. sinensis and the sera from rats immunized by CsESPs. Real-time PCR showed that its transcriptional level was the highest at the stage of metacercaria. Immunofluorescence assay was employed to confirm that CsANXB30 was distributed in the tegument, intestine, and egg of adult worms, as well as the tegument and vitellarium of metacercaria. rCsANXB30 was able to bind phospholipid in a Ca(2+)-dependent manner and human plasminogen in a dose-dependent manner. Moreover, cytokine and antibody measurements indicated that rats subcutaneously immunized with rCsANXB30 developed a strong IL-10 production in spleen cells and a high level of IgG1 isotype, indicating that rCsANXB30 could trigger specific humoral and cellular immune response in rats. The present results implied that CsANXB30 might be involved in a host-parasite interaction and affected the immune response of the host during C. sinensis infection. PMID:24861011

He, Lei; Ren, Mengyu; Chen, Xueqing; Wang, Xiaoyun; Li, Shan; Lin, Jinsi; Liang, Chi; Liang, Pei; Hu, Yue; Lei, Huali; Bian, Meng; Huang, Yan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

2014-07-01

149

Prevalence of Clonorchis sinensis Metacercariae in Freshwater Fish from Three Latitudinal Regions of the Korean Peninsula  

PubMed Central

A large-scale survey was conducted to investigate the infection status of fresh water fishes with Clonorchis sinensis metacercariae (CsMc) in 3 wide regions, which were tentatively divided by latitudinal levels of the Korean peninsula. A total of 4,071 freshwater fishes were collected from 3 regions, i.e., northern (Gangwon-do: 1,543 fish), middle (Chungcheongbuk-do and Gyeongsangbuk-do: 1,167 fish), and southern areas (Jeollanam-do, Ulsan-si, and Gyeongsangnam-do: 1,361 fish). Each fish was examined by the artificial digestion method from 2003 to 2010. In northern areas, only 11 (0.7%) fish of 2 species, Pungtungia herzi and Squalidus japonicus coreanus from Hantan-gang, Cheolwon-gun, Gangwon-do were infected with av. 2.6 CsMc. In middle areas, 149 (12.8%) fish were infected with av. 164 CsMc. In southern areas, 538 (39.5%) fish were infected with av. 159 CsMc. In the analysis of endemicity in 3 regions with an index fish, P. herzi, 9 (6.2%) of 146 P. herzi from northern areas were infected with av. 2.8 CsMc. In middle areas, 34 (31.8%) of 107 P. herzi were infected with av. 215 CsMc, and in southern areas, 158 (92.9%) of 170 P. herzi were infected with av. 409 CsMc. From these results, it has been confirmed that the infection status of fish with CsMc is obviously different among the 3 latitudinal regions of the Korean peninsula with higher prevalence and burden in southern regions.

Cho, Shin-Hyeong; Na, Byoung-Kuk; Kim, Tong-Soo; Kong, Yoon; Eom, Keeseon; Seok, Won-Seok; Lee, Taejoon

2011-01-01

150

Molecular characterization and immune modulation properties of Clonorchis sinensis-derived RNASET2  

PubMed Central

Background Clonorchis sinensis (C. sinensis, Cs) is a trematode parasite that often causes chronic cumulative infections in the hepatobiliary ducts of the host and can lead to pathological changes by continuously released excretory/secretory proteins (ESPs). A T2 ribonuclease in trematode ESPs, has been identified as a potent regulator of dendritic cell (DCs) modulation. We wondered whether there was a counterpart present in CsESPs with similar activity. To gain a better understanding of CsESPs associated immune responses, we identified and characterized RNASET2 of C. sinensis (CsRNASET2) in this paper. Methods We expressed CsRNASET2 in Pichia pastoris and identified its molecular characteristics using bioinformatic analysis and experimental approaches. The immune modulation activities of CsRNASET2 were confirmed by evaluating cytokine production and surface markers of recombinant CsRNASET2 (rCsRNASET2) co-cultured DCs, and monitoring levels of IgG isotypes from rCsRNASET2 administered BALB/c mice. Results CsRNASET2 appeared to be a glycoprotein of T2 ribonuclease family harboring conserved CAS motifs and rich in B-cell epitopes. Furthermore, CsRNASET2 was present in CsESPs and was able to modulate cytokine production of DCs. In addition, rCsRNASET2 could significantly suppress the expression of lipopolysaccharide-induced DCs maturation markers. In addition, when subcutaneously administered with rCsRNASET2 there was a marked effect on IgG isotypes in mouse sera. Conclusion Collectively, we revealed that CsRNASET2, a T2 ribonuclease present in CsESPs, could modulate DCs maturation and might play an important role in C. sinensis associated immune regulation in the host.

2013-01-01

151

Identification, sequence analysis, and characterization of serine/threonine protein kinase 17A from Clonorchis sinensis.  

PubMed

This is the first report of a novel protein from Clonorchis sinensis (C. sinensis), serine/threonine protein kinase 17A (CsSTK17A), which belongs to a member of the death-associated protein kinase (DAPK) family known to regulate diverse biological processes. The full-length sequence encoding CsSTK17A was isolated from C. sinensis adult cDNA plasmid library. Two transcribed isoforms of the gene were identified from the genome of C. sinensis. CsSTK17A contains a kinase domain at the N-terminus that shares a degree of conservation with the DAPK families. Besides, the catalytic domain contains 11 subdomains conserved among STKs and shares the highest identity with STK from Schistosoma mansoni (55.9%). Three-dimensional structure of CsSTK17A displays the canonical STK fold, including the helix C, P-loop, and the activation loop. We obtained recombinant CsSTK17A (rCsSTK17A) and anti-rCsSTK17A IgG. The rCsSTK17A could be probed by anti-rCsSTK17A rat serum, C. sinensis-infected rat serum and the sera from rats immunized with C. sinensis excretory-secretory products, indicating that it is a circulating antigen possessing a strong immunocompetence. Moreover, quantitative RT-PCR and western blotting analyses revealed that CsSTK17A exhibited the highest mRNA and protein expression level in eggs, followed by metacercariae and adult worms. Intriguingly, in the immunolocalization assay, CsSTK17A was intensively localized to the operculum region of eggs in uterus, as well as the vitelline gland of both adult worm and metacercaria, implying that the protein was associated with the reproduction and development of C. sinensis. Overall, these fundamental studies might contribute to further researches on signaling systems of the parasite. PMID:24578258

Huang, Lisi; Lv, Xiaoli; Huang, Yan; Hu, Yue; Yan, Haiyan; Zheng, Minghui; Zeng, Hua; Li, Xuerong; Liang, Chi; Wu, Zhongdao; Yu, Xinbing

2014-05-01

152

Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.  

PubMed

Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (P<0.001), intraperitoneally (P<0.01) and intramuscularly (P<0.001) with worm reduction rate of 56.29%, 15.38% and 37.42%, respectively. More importantly, Csenolase could be successfully expressed as a fusion protein (55kDa) on B. subtilis spore indicated by immunoblot and immunofluorescence assays. Killed spores triggered reactive Th1/Th2 immune response and exhibited protective efficacy against C. sinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (P<0.001) and 80.67% (P<0.001), respectively. The shuttle genetic engineering system facilitated the development of oral vaccine with B. subtilis stably overexpressing target protein. Comparably vaccinal trails with Csenolase in different immunization routes potentialize Csenolase an oral vaccine candidate in C. sinensis prevention. PMID:24486347

Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

2014-03-10

153

Disability Weight of Clonorchis sinensis Infection: Captured from Community Study and Model Simulation  

PubMed Central

Background Clonorchiasis is among the most neglected tropical diseases. It is caused by ingesting raw or undercooked fish or shrimp containing the larval of Clonorchis sinensis and mainly endemic in Southeast Asia including China, Korea and Vietnam. The global estimations for population at risk and infected are 601 million and 35 million, respectively. However, it is still not listed among the Global Burden of Disease (GBD) and no disability weight is available for it. Disability weight reflects the average degree of loss of life value due to certain chronic disease condition and ranges between 0 (complete health) and 1 (death). It is crucial parameter for calculating the morbidity part of any disease burden in terms of disability-adjusted life years (DALYs). Methodology/Principal Findings According to the probability and disability weight of single sequelae caused by C. sinensis infection, the overall disability weight could be captured through Monte Carlo simulation. The probability of single sequelae was gained from one community investigation, while the corresponding disability weight was searched from the literatures in evidence-based approach. The overall disability weights of the male and female were 0.101 and 0.050, respectively. The overall disability weights of the age group of 5–14, 15–29, 30–44, 45–59 and 60+ were 0.022, 0.052, 0.072, 0.094 and 0.118, respectively. There was some evidence showing that the disability weight and geometric mean of eggs per gram of feces (GMEPG) fitted a logarithmic equation. Conclusion/Significance The overall disability weights of C. sinensis infection are differential in different sex and age groups. The disability weight captured here may be referred for estimating the disease burden of C. sinensis infection.

Qian, Men-Bao; Chen, Ying-Dan; Fang, Yue-Yi; Xu, Long-Qi; Zhu, Ting-Jun; Tan, Tan; Zhou, Chang-Hai; Wang, Guo-Fei; Jia, Tie-Wu; Yang, Guo-Jing; Zhou, Xiao-Nong

2011-01-01

154

Molecular Cloning and Characterization of Growth Factor Receptor Bound-Protein in Clonorchis sinensis  

PubMed Central

Background Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2) is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2) from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. Methodology/Principal Findings A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. Conclusion Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths.

Bai, Xuelian; Lee, Ji-Yun; Kim, Tae Im; Dai, Fuhong; Lee, Tae-Jin; Hong, Sung-Jong

2014-01-01

155

Epidemiological profile of Clonorchis sinensis infection in one community, Guangdong, People's Republic of China  

PubMed Central

Background Clonorchiasis caused by ingesting improperly prepared fish ranks among the most important but still neglected food-borne parasitic diseases, especially in the People’s Republic of China (P.R. China). To promote the implementation of interventions efficiently, the demonstration of an epidemiological profile of Clonorchis sinensis infection is essential in hyper-epidemic areas. Methods In one community with higher levels of economic development in Guangdong province, P.R. China, villagers were motivated to provide stool samples for examining helminth eggs. Then, those infected with C. sinensis completed the structured questionnaire including demographical characteristics, knowledge and behavior. Results A total of 293 villagers infected with C. sinensis participated in questionnaire investigation. Among them, 94.54% were adult and 93.17% were indigenous. The geometric mean of C. sinensis eggs per gram of feces in the children, adult females and adult males was 58, 291 and 443, respectively. The divergence between knowledge and behavior in the adults, especially the adult males, was shown. Out of 228 persons eating raw fish, 160 did it more frequently at restaurants, the proportion of which varied in different populations, showing 25.00%, 54.88% and 80.28% in the children, adult females and adult males, respectively. Conclusions Different interventions need to be adopted in different populations. Chemotherapy should be prioritized in the adults, especially the adult males. In addition, health education targeting the children, is essential and may play a crucial role in controlling clonorchiasis in the long term. In order to successfully control clonorchiasis, intervention in the restaurant should not be overlooked in some endemic areas.

2013-01-01

156

Discovery of Opisthorchis viverrini metacercariae in freshwater fish in southern Cambodia.  

PubMed

Small liver flukes, Clonorchis sinensis and Opisthorchis viverini, are fish-borne trematodes (FBTs) causing significant public health problems in Asia. While C. sinensis is distributing mainly in far east Asia, O. viverini is distributing in Indochina peninsula. Recently, however, the geographical distributions of those small liver flukes were proven to be far wider than expected. Nevertheless, little is known about the epidemiology of small liver flukes in Cambodia. The present study is, therefore, aimed at clarifying the status of small liver fluke infections in various species of freshwater fish in southern Cambodia. A total of 1479 freshwater fish, 1316 (89%) comprised of 20 different species of the cyprinoid family and 163 (11%) belonging to 8 families of non-cyprinoids, were collected during May 2007 and February 2008, and the presence of small liver fluke metacercariae was examined by the compression method. Small liver fluke metacercariae were found in 10 species of cyprinoids with the infection rate ranging 2.1-66.7% and the mean intensity of infection of 1.0-15.0 (range: 1-65). For the speciation, adult worms were obtained by experimental infection in hamsters. The small liver fluke found in this study were identified as Opisthorchis viverrini by the morphological features of adult worms, and this identification was confirmed by partial COI sequencing of the metacercariae. PMID:19524077

Touch, Sarun; Komalamisra, Chalit; Radomyos, Prayong; Waikagul, Jitra

2009-08-01

157

Mixed infections with Opisthorchis viverrini and intestinal flukes in residents of Vientiane Municipality and Saravane Province in Laos.  

PubMed

Faecal examinations for helminth eggs were performed on 1869 people from two riverside localities, Vientiane Municipality and Saravane Province, along the Mekong River, Laos. To obtain adult flukes, 42 people positive for small trematode eggs (Opisthorchis viverrini, heterophyid, or lecithodendriid eggs) were treated with a 20-30 mg kg(-1) single dose of praziquantel and purged. Diarrhoeic stools were then collected from 36 people (18 in each area) and searched for helminth parasites using stereomicroscopes. Faecal examinations revealed positive rates for small trematode eggs of 53.3% and 70.8% (average 65.2%) in Vientiane and Saravane Province, respectively. Infections with O. viverrini and six species of intestinal flukes were found, namely, Haplorchis taichui, H. pumilio, H. yokogawai, Centrocestus caninus, Prosthodendrium molenkampi, and Phaneropsolus bonnei. The total number of flukes collected and the proportion of fluke species recovered were markedly different in the two localities; in Vientiane, 1041 O. viverrini (57.8 per person) and 615 others (34.2 per person), whereas in Saravane, 395 O. viverrini (21.9 per person) and 155207 others (8622.6 per person). Five people from Saravane harboured no O. viverrini but numerous heterophyid and/or lecithodendriid flukes. The results indicate that O. viverrini and several species of heterophyid and lecithodendriid flukes are endemic in these two riverside localities, and suggest that the intensity of infection and the relative proportion of fluke species vary by locality along the Mekong River basin. PMID:16153322

Chai, J-Y; Park, J-H; Han, E-T; Guk, S-M; Shin, E-H; Lin, A; Kim, J-L; Sohn, W-M; Yong, T-S; Eom, K S; Min, D-Y; Hwang, E-H; Phommmasack, B; Insisiengmay, B; Rim, H-J

2005-09-01

158

First Demonstration of the Lung Fluke, Paragonimus from Man in Peru.  

National Technical Information Service (NTIS)

Two adult lung flukes, Paragonimus sp. were demonstrated from man for the first time in Peru. They were surgically obtained from the right lung of a 36-yera-old Peruvian male, who was suspected to have been infected in the district of Aguaytia, Department...

I. Miyazaki O. Grados B R. C. Arellano Z

1973-01-01

159

New Lung Fluke Found in Peru, Paragonimus amazonicus sp. n. (Trematoda: Troglotrematidae).  

National Technical Information Service (NTIS)

A peculiar lung fluke, Paragonimus amazonicus was described from the lungs of two of four mammals, a four-eyed opossum Philander opossum and a water opossum, Chironectes mimimus in Tingo Maria, Department of Huanuco. For identification of the new species ...

I. Miyazaki N. Uyema O. Grados

1973-01-01

160

Eye-Flukes in Fish, Living in Cooling Water from Nuclear Power Plants.  

National Technical Information Service (NTIS)

We report here on the effects of raised water temperature on the prevalence, mean infrapopulation density and consequences of eye-flukes in fish. The study was mainly performed in the Biotest basin situated 120 km north of Stockholm, Sweden. This 1 km/sup...

J. Hoeglund J. Thulin

1988-01-01

161

Fluke (Spirorchiidae) infections in sea turtles stranded on Taiwan: prevalence and pathology.  

PubMed

The prevalence of spirorchiid fluke infections of marine turtles is high and may cause the death of the hosts throughout their ranges. Virtually nothing has been reported regarding the infective status of sea turtles stranded on Taiwan. Between 2007 and 2010, 30 green turtles (Chelonia mydas) and 2 loggerhead turtles ( Caretta caretta ), stranded and dead, were examined for spirorchiid flukes and their eggs. Twenty-four of the green turtles were juveniles, and the stranded loggerhead turtles were subadults. Adult spirorchiid flukes were found in 13 green turtles but not in the loggerheads. Four species of flukes were identified, namely, Leardius learedi , Hapalotrema postorchis , H. mehrai , and Carettacola hawaiiensis . The main infection sites were the major arteries and heart. Seventy percent of the green turtles harbored spirorchiid eggs, but no eggs were found in loggerheads. The largest eggs with bipolar spines, type I eggs, were found in every case. Although more than half of the stranded turtles were infected, parasite infections were not the main cause of death in the green turtles. Fishery by-catch is probably responsible for the mortality of these stranded turtles. PMID:22032290

Chen, Hochang; Kuo, R-J; Chang, T-C; Hus, C-K; Bray, R A; Cheng, I-J

2012-04-01

162

Identification of the Boudicca and Sinbad retrotransposons in the genome of the human blood fluke Schistosoma haematobium.  

PubMed

Schistosomes have a comparatively large genome, estimated for Schistosoma mansoni to be about 270 megabase pairs (haploid genome). Recent findings have shown that mobile genetic elements constitute significant proportions of the genomes of S. mansoni and S. japonicum. Much less information is available on the genome of the third major human schistosome, S. haematobium. In order to investigate the possible evolutionary origins of the S. mansoni long terminal repeat retrotransposons Boudicca and Sinbad, several genomes were searched by Southern blot for the presence of these retrotransposons. These included three species of schistosomes, S. mansoni, S. japonicum, and S. haematobium, and three related platyhelminth genomes, the liver flukes Fasciola hepatica and Fascioloides magna and the planarian, Dugesia dorotocephala. In addition, Homo sapiens and three snail host genomes, Biomphalaria glabrata, Oncomelania hupensis, and Bulinus truncatus, were examined for possible indications of a horizontal origin for these retrotransposons. Southern hybridization analysis indicated that both Boudicca and Sinbad were present in the genome of S. haematobium. Furthermore, low stringency Southern hybridization analyses suggested that a Boudicca-like retrotransposon was present in the genome of B. truncatus, the snail host of S. haematobium. PMID:17072464

Copeland, Claudia S; Lewis, Fred A; Brindley, Paul J

2006-08-01

163

Identification and biochemical characterization of adenylate kinase 1 from Clonorchis sinensis.  

PubMed

Adenylate kinase 1 is responsible for the conversion of AMP into ADP involved in purine metabolism. In the present study, adenylate kinase 1 gene (CsADK1) was isolated from an adult cDNA library of Clonorchis sinensis, and the recombinant protein was expressed in Escherichia coli. Bioinformatics analysis implied that the putative protein contained 197 amino acids, and some residues in conservative binding sites of CsADK1 were substituted. The structure modeling analysis showed that CsADK1 was composed of a core domain, an NMP-binding domain, and a LID domain, which was just a small loop. It demonstrated that CsADK1 was a short isoform of ADKs. Moreover, CsADK1 was identified as an excretory/secretory product by western blot analysis. Real-time quantitative PCR showed that expression level of CsADK1 at the stage of excysted metacercaria was higher than those of adult worm (18.8-folds, P<0.01), metacercariae (1.5-folds, P<0.01), and eggs (5.6-folds, P<0.01). In addition, histochemistry analysis showed that CsADK1 was extensively distributed in metacercariae and in the vitellaria and eggs of adult worms. The Km and Vmax value for substrate ADP were 2.2 mM and 0.9 mM/min, respectively. The optimal temperature and pH value were 37 °C and from 7.5 to 8.0, respectively. The enzyme activity was highly dependent on Mg2+, and the optimal concentration of Mg2+ was 2 mM. However, the enzyme activity was slightly activated by Ca2+, and Mn2+ has no effect on activity. For monovalent ions, activity was highly activated by K+ and NH4+, but slightly by Li+. Taken together, CsADK1 was a metal ion-dependent enzyme involved in purine metabolism, which was important for development and reproduction, and might be a potential candidate for drug target for clonorchiasis. PMID:23455935

Liang, Pei; Zhang, Fan; Chen, Wenjun; Hu, Xuchu; Huang, Yan; Li, Shan; Ren, Mengyu; He, Lei; Li, Ran; Li, Xuerong; Xu, Jin; Wu, Zhongdao; Lu, Gang; Yu, Xinbing

2013-04-01

164

Molecular characterization of Clonorchis sinensis secretory myoglobin: Delineating its role in anti-oxidative survival  

PubMed Central

Background Clonorchiasis is a globally important, neglected food-borne disease caused by Clonorchis sinensis (C. sinensis), and it is highly related to cholangiocarcinoma and hepatocellular carcinoma. Increased molecular evidence has strongly suggested that the adult worm of C. sinensis continuously releases excretory-secretory proteins (ESPs), which play important roles in the parasite-host interactions, to establish successful infection and ensure its own survival. Myoglobin, a hemoprotein, is present in high concentrations in trematodes and ESPs. To further understand the biological function of CsMb and its putative roles in the interactions of C. sinensis with its host, we explored the molecular characterization of CsMb in this paper. Methods We expressed CsMb and its mutants in E. coli BL21 and identified its molecular characteristics using bioinformatics analysis and experimental approaches. Reverse transcription PCR analysis was used to measure myoglobin transcripts of C. sinensis with different culture conditions. The peroxidase activity of CsMb was confirmed by spectrophotometry. We co-cultured RAW264.7 cells with recombinant CsMb (rCsMb), and we then measured the production of hydrogen peroxide (H2O2) and nitric oxide (NO) in addition to the mRNA levels of inducible nitric oxide synthase (iNOS), Cu-Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in activated RAW264.7 cells. Results In the in vitro culture of adult worms, the transcripts of CsMb increased with the increase of oxygen content. Oxidative stress conditions induced by H2O2 increased the levels of CsMb transcripts in a dose-dependent manner. Furthermore, CsMb catalyzed oxidation reactions in the presence of H2O2, and amino acid 34 of CsMb played an essential role in its reaction with H2O2. In addition, CsMb significantly reduced H2O2 and NO levels in LPS-activated macrophages, and CsMb downregulated iNOS and SOD expression in activated macrophages. Conclusion The present study is the first to investigate the peroxidase activity of CsMb. This investigation suggested that C. sinensis may decrease the redox activation of macrophages by CsMb expression to evade host immune responses. These studies contribute to a better understanding of the role of CsMb in the molecular mechanisms involved in ROS detoxification by C. sinensis.

2014-01-01

165

Comparative Characterization of MicroRNAs from the Liver Flukes Fasciola gigantica and F. hepatica  

PubMed Central

MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcription level. The present study specifically explored and compared the miRNA expression profiles of F. gigantica and F. hepatica using an integrated sequencing and bioinformatics platform and quantitative real-time PCR. Nineteen and 16 miRNA candidates were identified from F. gigantica and F. hepatica, respectively. The two parasites shared 11 miRNAs, with 8 also showing similarity to miRNAs of Schistosoma japonicum. Another 8 miRNAs were identified as F. gigantica-specific and 5 as F. hepatica-specific, most of which were novel. Predicted target analysis with 11465 mRNA and EST sequences of F. hepatica and F. gigantica revealed that all of the miRNAs had more than one target, ranging from 2 to 398 with an average of 51 targets. Some functions of the predicted targets were only found in F. gigantica, such as “transcription regulator”, while some others were only found in F. hepatica, such as “reproduction” and “response to stimulus”, indicating the different metabolism and gene regulation patterns of the two parasites. The present study represents the first global comparative characterization of miRNA expression profiles of F. gigantica and F. hepatica, which has provided novel valuable resources for a better understanding of the two zoonotic trematodes.

Fu, Jing-Hua; Nisbet, Alasdair J.; Liu, Qing-You; Chen, Mu-Xin; Zhou, Dong-Hui; Zhu, Xing-Quan

2012-01-01

166

Microsatellite loci in the carcinogenic liver fluke, Opisthorchis viverrini and their application as population genetic markers.  

PubMed

Opisthorchis viverrini is a carcinogenic foodborne trematode endemic in Southeast Asia especially in Thailand and the Lao People's Democratic Republic. Opisthorchiasis causes hepatobiliary diseases and cholangiocarcinoma (bile duct cancer). Currently there is substantial evidence on genetic variation of O. viverrini but the information on population genetic structure is lacking. Because microsatellite DNA of this parasite is not available, we for the first time isolated and utilized microsatellite DNA as genetic markers to examine genetic diversity and the population structure of O. viverrini. Partial genomic DNA libraries were constructed by conventional and enrichment methods which yielded microsatellite-containing clones of 0.18-0.25% and 16.84%, respectively. Within 41 microsatellite loci isolated 36.59% were perfect, 60.98% were interrupted and 2.44% were compound microsatellites. The CA repetitions were the most frequent, followed by GT and CAT. Primers specific to the flanking regions of 12 microsatellite loci were developed to genotype 150 O. viverrini individuals from geographical localities in Thailand and Lao PDR. Allele numbers per locus ranged from 2 to 15, with the mean expected heterozygosity of 0.03-0.66. Analyses of O. viverrini from 5 localities revealed a high level of genetic diversity and had significant deviation from Hardy-Weinberg equilibrium. Significant heterozygote deficiency as well as heterozygote excess was detected across all localities indicating the possibility of selfing (inbreeding) as a predominant reproductive mode. Significant genetic differentiation (F(ST)) was also detected between worms from different localities with varying levels of genetic heterogeneity. We discuss our results in terms of what these novel microsatellite markers reveal about the epidemiology and transmission dynamics of this medically important parasite, both in terms of the current study and their potential for future comprehensive population genetic studies O. viverrini sensu lato in Southeast Asia. PMID:19900579

Laoprom, Nonglak; Sithithaworn, Paiboon; Ando, Katsuhiko; Sithithaworn, Jiraporn; Wongkham, Sopit; Laha, Thewarach; Klinbunga, Sirawut; Webster, Joanne P; Andrews, Ross H

2010-01-01

167

Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini  

Microsoft Academic Search

Protease activities in extracts of Opisthorchis viverrini were investigated using gelatin zymography and fluorogenic peptide substrates. Using gelatin-impregnated X-ray film, 2 ?g\\u000a of O. viverrini excretory–secretory products (Ov-ES) and adult somatic extract (Ov-SE) showed proteolytic activity. Zymography of both O. viverrini extracts revealed bands at ~30 kDa. Using fluorogenic peptide substrates, the majority of O. viverrini activity was determined to be cathepsin

Natthawut Kaewpitoon; Thewarach Laha; Sasithorn Kaewkes; Puangrat Yongvanit; Paul J. Brindley; Alex Loukas; Banchob Sripa

2008-01-01

168

Suppression of galectin-3 expression enhances apoptosis and chemosensitivity in liver fluke-associated cholangiocarcinoma.  

PubMed

Cholangiocarcinoma (CCA) is a fatal disease with high resistance to anticancer drugs. This is probably in part due to enhanced resistance to apoptosis. We have previously shown that galectin-3 (Gal-3), a beta-galactoside-binding lectin, is highly expressed in CCA tissues. In this study, we demonstrated further that Gal-3 plays a direct role in anti-apoptosis regardless of the apoptotic insults. The anti-apoptotic activity and chemoresistance of CCA cells were related to Gal-3 expression level. Suppression of Gal-3 expression with siRNA stimulated apoptosis. siGal-3-K626 transiently depleted Gal-3 expression to the baseline and dramatically induced apoptosis, while siGal-3-K402 suppressed Gal-3 expression by 50% and provoked cell apoptosis, but only under apoptotic insults (hypoxic conditions or short UV radiation). These actions were reversed in Gal-3 overexpressing CCA cells. The correlation between the degree of anti-apoptotic activity and the level of endogenous Gal-3 was demonstrated. Suppression of Gal-3 expression in CCA cells with siGal-3-K402 significantly enhanced apoptosis induced by cisplatin or 5-fluorouracil by approximately 10 times, whereas overexpression of Gal-3 led to an increased resistance to drugs. In summary, the present study showed that the cellular level of Gal-3 might contribute to the anti-apoptotic activity and chemoresistance of CCA cells. Hence, Gal-3 expression level in cancer cells or tissues may be a marker for predicting chemotherapeutic response, and Gal-3 may be a specific gene-targeting therapy option for treating CCA. PMID:19723119

Wongkham, Sopit; Junking, Mutita; Wongkham, Chaisiri; Sripa, Banchob; Chur-In, Siri; Araki, Norie

2009-11-01

169

Microsatellite loci in the carcinogenic liver fluke, Opisthorchis viverrini and their application as population genetic markers  

Microsoft Academic Search

Opisthorchis viverrini is a carcinogenic foodborne trematode endemic in Southeast Asia especially in Thailand and the Lao People's Democratic Republic. Opisthorchiasis causes hepatobiliary diseases and cholangiocarcinoma (bile duct cancer). Currently there is substantial evidence on genetic variation of O. viverrini but the information on population genetic structure is lacking. Because microsatellite DNA of this parasite is not available, we for

Nonglak Laoprom; Paiboon Sithithaworn; Katsuhiko Ando; Jiraporn Sithithaworn; Sopit Wongkham; Thewarach Laha; Sirawut Klinbunga; Joanne P. Webster; Ross H. Andrews

2010-01-01

170

Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus  

Microsoft Academic Search

SummaryBackground We investigated an outbreak of acute clinical illness among 19 people who ate raw fish (sashimi) prepared from the white sucker, Catostomus commersoni, caught in a river north of Montreal, Canada.Methods We collected epidemiological, clinical, laboratory, and serological data on 19 individuals who ate the sashimi and six who did not. Because of the suggestive clinical picture, we set

J. D MacLean; B. J Ward; E Kokoskin; J. R Arthur; T. W Gyorkos; M. A Curtis

1996-01-01

171

A review of the cat liver fluke Platynosomum fastosum Kossack, 1910 (Trematoda: Dicrocoeliidae).  

PubMed

Platynosomum fastosum is a small hepatic trematode found in the biliary ducts and gall bladder of cats and other mammals. It is commonly found in tropical and subtropical regions. Some aspect of the life cycle of this parasite is not fully understood, however terrestrial snails, lizards and isopods are implicated as intermediate/paratenic hosts. The disease caused by P. fastosum is platynosomiais (named after the parasite) or 'lizard poisoning' since it is assumed that affected cats acquire the parasite by eating infected lizards. The clinical signs due to infection with P. fastosum may range from asymptomatic to progressive disease and at times death due to biliary tract obstruction and hepatic failure. Infection with this parasite should, therefore, be included in the differential diagnosis of cats with signs of hepatic diseases. PMID:24412358

Basu, A K; Charles, R A

2014-02-24

172

Bovine fasciolosis: coprological, abattoir survey and its economic impact due to liver condemnation at Soddo municipal abattoir, Southern Ethiopia  

Microsoft Academic Search

A study was carried out to determine the prevalence and the species of liver flukes in indigenous adult cattle, to compare\\u000a the diagnostic efficiency of fecal and post mortem examination and to assess the economic significance of bovine fasciolosis\\u000a due to liver condemnation in the abattoir. Of the 406 livers and fecal samples examined, 57 (14.0%) and 20 (4.9%) were

Fufa Abunna; Loma Asfaw; Bekele Megersa; Alemayehu Regassa

2010-01-01

173

Food-borne trematode infections of humans in the United States of America  

Microsoft Academic Search

This review examines the literature on imported (allochthonous) and local (autochthonous) cases of food-borne trematode (FBT)\\u000a infections in the United States of America (USA) from 1890 to 2009. Most of the literature is concerned with imported cases\\u000a of the opisthorchiids Clonorchis sinensis and Opisthorchis viverrini. These flukes cause serious pathology in the liver and biliary system of humans. Chronic cases

Bernard Fried; Amy Abruzzi

2010-01-01

174

PCR diagnosis of infections with different species of Opisthorchiidae using a rapid clean-up procedure for stool samples and specific primers  

Microsoft Academic Search

Infections with the opisthorchiid liver flukes Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus cause serious health problems in endemic areas of Southeast Asia and countries of the former Soviet Union. Chronic infections—even\\u000a with low worm burdens—may lead to the development of fatal cholangiocarcinoma and related symptoms. A more sensitive diagnosis\\u000a is needed since the tiny eggs of the worms are

Boris Müller; Jürgen Schmidt; Heinz Mehlhorn

2007-01-01

175

Cholecystitis in otters (Lutra lutra) and mink (Mustela vison) caused by the fluke Pseudamphistomum truncatum.  

PubMed

Between 1988 and 2004, postmortem examinations were carried out on 445 otters found dead, mostly as a result of road traffic accidents, in southern and south-west England. Thickened, shrunken gall bladders were observed in 10 cases, the first in 2000 and the others between February 2002 and August 2004. A digenean fluke, Pseudamphistomum truncatum, was found in the gall bladders of three cases and also in three of seven American mink examined. Nine of the 10 otters and all the mink came from a localised area of Somerset, indicating that the fluke has become established in the local fish population. P. truncatum has not been recorded previously in Britain, and the results suggest that it has been introduced recently, possibly in imported fish. PMID:16006641

Simpson, V R; Gibbons, L M; Khalil, L F; Williams, J L R

2005-07-01

176

Rapid and simple identification of human pathogenic heterophyid intestinal fluke metacercariae by PCR-RFLP  

Microsoft Academic Search

Six species of heterophyid intestinal flukes (HIFs) constitute the major endemic zoonotic fish-borne pathogens in Asia: Haplorchis taichui, H. pumilio, H. yokogawai, Procerovum varium, Stellantchasmus falcatus, and Centrocestus formosanus. Several different species of these parasites are often found co-infecting the same second intermediate fish host. Because of their morphological similarities, differentiating between species of HIF metacercariae is difficult, time-consuming, and

Urusa Thaenkham; Orawan Phuphisut; Wallop Pakdee; Nirundorn Homsuwan; Surapol Sa-nguankiat; Jitra Waikagul; Yukifumi Nawa; Do Trung Dung

177

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni  

Microsoft Academic Search

BackgroundBlood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins.Methodology\\/Principal FindingsWe identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence

Jan Dvo?ák; Susan T. Mashiyama; Mohammed Sajid; Simon Braschi; Melaine Delcroix; Eric L. Schneider; Wilson H. McKerrow; Mahmoud Bahgat; Elizabeth Hansell; Patricia C. Babbitt; Charles S. Craik; James H. McKerrow; Conor R. Caffrey

2009-01-01

178

Epidemiology of cholangiocarcinoma: an update focusing on risk factors.  

PubMed

Cholangiocarcinoma is relatively rare, but high incidence rates have been reported in Eastern Asia, especially in Thailand. The etiology of this cancer of the bile ducts appears to be mostly due to specific infectious agents. In 2009, infections with the liver flukes, Clonorchis sinensis or Opistorchis viverrini, were both classified as carcinogenic to humans by the International Agency for Research on Cancer for cholangiocarcinoma. In addition, a possible association between chronic infection with hepatitis B and C viruses and cholangiocarcinoma was also noted. The meta-analysis of published literature revealed the summary relative risks of infection with liver fluke (both Opistorchis viverrini and Clonorchis sinensis), hepatitis B virus, and hepatitis C virus to be 4.8 (95% confidence interval [95% CI]: 2.8-8.4), 2.6 (95% CI: 1.5-4.6), and 1.8 (95% CI: 1.4-2.4), respectively - liver fluke infection being the strongest risk factor for cholangiocarcinoma. Countries where human liver fluke infection is endemic include China, Korea, Vietnam, Laos, and Cambodia. The number of infected persons with Clonorchis sinensis in China has been estimated at 12.5 million with considerable variations among different regions. A significant regional variation in Opistorchis viverrini prevalence was also noted in Thailand (average 9.6% or 6 million people). The implementation of a more intensive preventive and therapeutic program for liver fluke infection may reduce incidence rates of cholangiocarcinoma in endemic areas. Recently, advances have been made in the diagnosis and management of cholangiocarcinoma. Although progress on cholangiocarcinoma prevention and treatment has been steady, more studies related to classification and risk factors will be helpful to develop an advanced strategy to cure and prevent cholangiocarcinoma. PMID:20085587

Shin, Hai-Rim; Oh, Jin-Kyoung; Masuyer, Eric; Curado, Maria-Paula; Bouvard, Veronique; Fang, Yue-Yi; Wiangnon, Surapon; Sripa, Banchob; Hong, Sung-Tae

2010-03-01

179

Development of a polymerase chain reaction applicable to rapid and sensitive detection of Clonorchis sinensis eggs in human stool samples  

PubMed Central

Microscopic examination of eggs of parasitic helminths in stool samples has been the most widely used classical diagnostic method for infections, but tiny and low numbers of eggs in stool samples often hamper diagnosis of helminthic infections with classical microscopic examination. Moreover, it is also difficult to differentiate parasite eggs by the classical method, if they have similar morphological characteristics. In this study, we developed a rapid and sensitive polymerase chain reaction (PCR)-based molecular diagnostic method for detection of Clonorchis sinensis eggs in stool samples. Nine primers were designed based on the long-terminal repeat (LTR) of C. sinensis retrotransposon1 (CsRn1) gene, and seven PCR primer sets were paired. Polymerase chain reaction with each primer pair produced specific amplicons for C. sinensis, but not for other trematodes including Metagonimus yokogawai and Paragonimus westermani. Particularly, three primer sets were able to detect 10 C. sinensis eggs and were applicable to amplify specific amplicons from DNA samples purified from stool of C. sinensis-infected patients. This PCR method could be useful for diagnosis of C. sinensis infections in human stool samples with a high level of specificity and sensitivity.

Cho, Pyo Yun; Na, Byoung-Kuk; Mi Choi, Kyung; Kim, Jin Su; Cho, Shin-Hyeong; Lee, Won-Ja; Lim, Sung-Bin; Cha, Seok Ho; Park, Yun-Kyu; Pak, Jhang Ho; Lee, Hyeong-Woo; Hong, Sung-Jong; Kim, Tong-Soo

2013-01-01

180

Liver Transplant  

MedlinePLUS

... Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

181

Gene/protein expression level, immunolocalization and binding characteristics of fatty acid binding protein from Clonorchis sinensis (CsFABP).  

PubMed

Clonorchis sinensis fatty acid-binding protein (CsFABP) belongs to a multigene family of lipid-binding proteins and is considered to be a promising vaccine candidate for human clonorchiasis. In this study, binding characteristics of CsFABP have been examined for the first time. The recombinant CsFABP (rCsFABP) was found to bind 11-(dansylamino) undecanoic acid (DAUDA), causing a blue shift in the fluorescence emission from 543 to 531 nm with an excitation wavelength of 345 nm and a substantial increase in fluorescence intensity. Fluorimetric titration of rCsFABP with DAUDA exhibited an apparent dissociation constant (K (d)) of 1.58 ± 0.14 ?M. In the competitive experiment, the rCsFABP efficiently bound saturated C(10)-C(18) fatty acids and unsaturated fatty acids (oleic acid and linoleic acid), and the latter presented the higher affinity. Furthermore, quantitative RT-PCR and western blotting analysis revealed that CsFABP mRNA and protein were differentially expressed throughout the developmental cycle stages of the parasite, which occur in the definitive host (metacercariae, adult worms, and eggs). In addition, immunolocalization assay showed that CsFABP was localized on the vitelline gland, tegument, intestine, seminal vesicle, eggs in uterus, ovary, and testicle of C. sinensis adult worm, as well as on the vitelline gland of metacercaria. Intriguingly, the surface tissue of the bile duct where C. sinensis resided in the infected Sprague-Dawley rat was also strongly labeled, implying that CsFABP may possibly mediate direct interactions with host cells as a component of excretory/secretory products. PMID:22189506

Huang, Lisi; Hu, Yue; Huang, Yan; Fang, Hang; Li, Ran; Hu, Dong; Li, Wenfang; Li, Xuerong; Liang, Chi; Yu, Xinbing

2012-04-01

182

A Bile Based Study of Clonorchis sinensis Infections in Patients with Biliary Tract Diseases in Ulsan, Korea  

PubMed Central

Stool examination is believed to be the most reliable method for detecting Clonorchis sinensis (CS) eggs. However, it has limited value for diagnosing clonorchiasis when the biliary tract is obstructed or when there is a light infection. We evaluated the infection states of CS in patients with biliary tract diseases using a bile sample. From January 2001 to August 2003, 238 patients who had undergone endoscopic biliary drainage were prospectively included in the study. The patients' bile samples were obtained directly from the nasobiliary drainage tube and then analyzed to detect CS eggs. The overall CS egg positive rate was 28.2% (35.4% in males, 19.4% in females). The egg positive rate was similar in all age groups examined: 26.7% in 30-39 years, 25.0% in 40-49 years, 24.4% in 50-59 years, 30.2% in 60-69 years, 35.3% in 70-79 years, and 25.0% in 80 years of age and over. There were no significant differences in the egg positive rate between the disease groups: 32.6% in bile duct cancer, 38.5% in gallbladder cancer, and 26.4% in gallstone diseases. Our results show that the CS infection rate was very high, regardless of the age, gender, and type of diseases of the patients. Although the study population was limited to patients with biliary tract diseases, it is assumed that clonorchiasis is still an endemic disease in Ulsan, Korea.

Bang, Sung-Jo

2005-01-01

183

Characteristics and molecular phylogeny of Fasciola flukes from Bangladesh, determined based on spermatogenesis and nuclear and mitochondrial DNA analyses.  

PubMed

This study aimed to precisely discriminate Fasciola spp. based on DNA sequences of nuclear internal transcribed spacer 1 (ITS1) and mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (nad1) gene. We collected 150 adult flukes from the bile ducts of cattle, buffaloes, sheep, and goats from six different regions of Bangladesh. Spermatogenic status was determined by analyzing stained seminal vesicles. The ITS1 types were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The nad1 haplotypes were identified based on PCR and direct sequencing and analyzed phylogenetically by comparing with nad1 haplotypes of Fasciola spp. from other Asian countries. Of the 127 aspermic flukes, 98 were identified as Fg type in ITS1, whereas 29 were identified as Fh/Fg type, indicating a combination of ITS1 sequences of Fasciola hepatica and Fasciola gigantica. All the 127 aspermic flukes showed Fsp-NDI-Bd11 in nad1 haplotype with nucleotide sequences identical to aspermic Fasciola sp. from Asian countries. Further, 20 spermic flukes were identified as F. gigantica based on their spermatogenic status and Fg type in ITS1. F. gigantica population was thought to be introduced into Bangladesh considerably earlier than the aspermic Fasciola sp. because 11 haplotypes with high haplotype diversity were detected from the F. gigantica population. However, three flukes from Bangladesh could not be precisely identified, because their spermatogenic status, ITS1 types, and nad1 haplotypes were ambiguous. Therefore, developing a robust method to distinguish aspermic Fasciola sp. from other Fasciola species is necessary in the future. PMID:24781019

Mohanta, Uday Kumar; Ichikawa-Seki, Madoka; Shoriki, Takuya; Katakura, Ken; Itagaki, Tadashi

2014-07-01

184

Efficacy of benzimidazole carbamate on an intestinal fluke co-infected with nematodes.  

PubMed

The efficacy of a single dose of benzimidazole, drugs commonly used for the treatment of Ascaris and hookworm, was evaluated against one of the tiny-sized intestinal flukes, Haplorchis sp in the endemic area where mixed infections of roundworms and flatworms existed. At day 7 after treatment, albendazole (400 mg) induced 42.5% cure rate, mebendazole (500 mg) a cure rate of 32.4%, on the other hand, praziquantel (40 mg/kg) gave 94.6% cure rate and the placebo at 15.9%. At the single dose, benzimidazole could not completely expelled the haplorchid; but could reduce one third to two fifth of the infection, similar to the drugs efficacy against Trichuris infection. PMID:15962676

Waikagul, Jitra; Watthanakulpanich, Dorn; Muennoo, Chatree; Maipanich, Wanna; Sa-nguankiat, Surapol; Phubampen, Somchit

2005-02-01

185

Air sac fluke Circumvitellatrema momota in a captive blue-crowned motmot (Momotus momota) in France.  

PubMed

Postmortem examination of a 4-mo-old captive-born blue-crowned motmot (Momotus momota) at the Montpellier Zoo in France revealed the presence of air sac flukes. Circumvitellatrema momota (Digenea: Cyclocoelidae) was suspected and confirmed by molecular genetic analysis. Digenean metacercariae were extracted from an invasive species of terrestrial snail, the conical periwinkle, Subulina striatella. Molecular genetic analysis determined that these metacercariae were also C. momota, confirming that all the stages of this parasite's life cycle were present and that birds were likely becoming infected by eating these infected snails. It is likely that this trematode was imported into the greenhouse with a wild-caught motmot. The conical periwinkle snail appears to have been imported into the zoo with the plants in 2007 when the greenhouse was built. Treatments, which have been disappointing, are discussed, as well as preventive measures to avoid dissemination of the parasite into other bird collections in Europe. PMID:23082545

Libert, Cédric; Jouet, Damien; Ferté, Hubert; Lemberger, Karin; Keck, Nicolas

2012-09-01

186

Global status of fish-borne zoonotic trematodiasis in humans.  

PubMed

Fishborne zoonotic trematodes (FZT), infecting humans and mammals worldwide, are reviewed and options for control discussed. Fifty nine species belonging to 4 families, i.e. Opisthorchiidae (12 species), Echinostomatidae (10 species), Heterophyidae (36 species) and Nanophyetidae (1 species) are listed. Some trematodes, which are highly pathogenic for humans such as Clonorchis sinensis, Opisthorchis viverrini, O. felineus are discussed in detail, i.e. infection status in humans in endemic areas, clinical aspects, symptoms and pathology of disease caused by these flukes. Other liver fluke species of the Opisthorchiidae are briefly mentioned with information about their infection rate and geographical distribution. Intestinal flukes are reviewed at the family level. We also present information on the first and second intermediate hosts as well as on reservoir hosts and on habits of human eating raw or undercooked fish. PMID:23990419

Hung, Nguyen Manh; Madsen, Henry; Fried, Bernard

2013-09-01

187

Current status of lung fluke metacercarial infection in freshwater crabs in the Kawane area of Shizuoka Prefecture, Japan.  

PubMed

Feline cases of lung fluke infection were recently reported in the upper basin of the Oi River in Shizuoka Prefecture. The causative species of these cases were not identified, although a field survey conducted about 40 years ago in this area demonstrated the prevalence of Paragonimus miyazakii metacercariae in intermediate host crabs. To clarify the current status of lung fluke metacercarial infection in host crabs, we collected the Japanese freshwater crab or Sawagani, Geothelphusa dehaani, at 14 sampling sites in the Kawane area, which is located in the upper basin of the Oi River. Sawagani harboring Paragonimus metacercariae were collected at all sampling sites in this study with a total prevalence of 42% (281 of 677 crabs examined) and a range of 16% to 92%. The number of metacercariae per infected crab ranged from 1 to 19 with a mean of 2.2. Based on the morphological features of the metacercariae and adult worms recovered from rats that were experimentally infected with the metacercariae, the lung flukes examined were identified as P. miyazakii Kamo, Nishida, Hatsushika and Tomimura, 1961; ITS2 sequence data corroborate this conclusion. P. miyazakii is still widely prevalent in this area, implying that the recently reported feline paragonimiasis cases were likely caused by P. miyazakii infection. PMID:23076034

Sugiyama, Hiromu; Shibata, Katsumasa; Morishima, Yasuyuki; Muto, Maki; Yamasaki, Hiroshi; Kawakami, Yasushi

2013-01-01

188

Liver Cancer  

MedlinePLUS

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189

Liver metastases  

MedlinePLUS

Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that may spread to the liver include: Breast cancer Colorectal cancer Esophageal ...

190

Cellular and humoral responses in liver of cattle and buffaloes infected with a single dose of Fasciola gigantica.  

PubMed

The cellular components of the hepatic inflammatory infiltrate in cattle and buffaloes infected with a single dose of 1000 Fasciola gigantica were analysed by immunohistochemistry and histology. T and B lymphocytes, plasma cells, eosinophils and mast cells were present in the hepatic lesions. It is proposed that both cellular and humoral immune responses were induced in the liver of cattle and buffaloes during infection with F. gigantica probably by antigens released by the developing flukes and by damage caused by the flukes during their migration in the liver. The local T cell response differed between these animals, with the response decreasing after 3 weeks post-infection in cattle in contrast to a gradually increasing response in buffaloes. Difference in the T cell response between cattle and buffaloes may be related to their differences in resistance and resilience to infection with F. gigantica. PMID:15936148

Molina, Elizabeth C; Skerratt, Lee F

2005-07-15

191

Differential Activation of Diverse Glutathione Transferases of Clonorchis sinensis in Response to the Host Bile and Oxidative Stressors  

PubMed Central

Background Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma. Approximately 35 million people are infected and 600 million people are at risk of infections worldwide. C. sinensis excretory-secretory products (ESP) constitute the first-line effector system affecting the host-parasite interrelationship by interacting with bile fluids and ductal epithelium. However, the secretory behavior of C. sinensis in an environment close to natural host conditions is unclear. C. sinensis differs from Fasciola hepatica in migration to, and maturation in, the hepatic bile duct, implying that protein profile of the ESP of these two trematodes might be different from each other. Methodology/Principal Findings We conducted systemic approaches to analyze the C. sinensis ESP proteome and the biological reactivity of C. sinensis glutathione transferases (GSTs), such as global expression patterns and induction profiles under oxidative stress and host bile. When we observed ex host excretion behavior of C. sinensis in the presence of 10% host bile, the global proteome pattern was not significantly altered, but the amount of secretory proteins was increased by approximately 3.5-fold. Bioactive molecules secreted by C. sinensis revealed universal/unique features in relation to its intraluminal hydrophobic residing niche. A total of 38 protein spots identified abundantly included enzymes involved in glucose metabolism (11 spots, 28.9%) and diverse-classes of glutathione transferases (GSTs; 10 spots, 26.3%). Cathepsin L/F (four spots, 10.5%) and transporter molecules (three spots, 7.9%) were also recognized. The universal secretory proteins found in other parasites, such as several enzymes involved in glucose metabolism and oxygen transporters, were commonly detected. C. sinensis secreted less cysteine proteases and fatty acid binding proteins compared to other tissue-invading or intravascular trematodes. Interestingly, secretion of a 28 kDa ?-class GST (Cs28?GST3) was significantly affected by the host bile, involving reduced secretion of the 28 kDa species and augmented secretion of Cs28?GST3-related high-molecular-weight 85 kDa protein. Oxidative stressors induced upregulated secretion of 28 kDa Cs28?GST3, but not an 85 kDa species. A secretory 26 kDa ?-class GST (Cs26?GST2) was increased upon treatment with oxidative stressors and bile juice, while another 28 kDa ?-class GST (Cs28?GST1) showed negligible responses. Conclusions/Significance Our results represent the first analysis of the genuine nature of the C. sinensis ESP proteome in the presence of host bile mimicking the natural host environments. The behavioral patterns of migration and maturation of C. sinensis in the bile ducts might contribute to the secretion of copious amounts of diverse GSTs, but a smaller quantity and fewer kinds of cysteine proteases. The Cs28?GST1 and its paralog(s) detoxify endogenous oxidative molecules, while Cs28?GST3 and Cs26?GST2 conjugate xenobiotics/hydrophobic substances in the extracellular environments, which imply that diverse C. sinensis GSTs might have evolved for each of the multiple specialized functions.

Bae, Young-An; Ahn, Do-Whan; Lee, Eung-Goo; Kim, Seon-Hee; Cai, Guo-Bin; Kang, Insug; Sohn, Woon-Mok; Kong, Yoon

2013-01-01

192

The current status of opisthorchiasis and clonorchiasis in the Mekong Basin  

PubMed Central

This review highlights the current status and control of liver fluke infections in the Mekong Basin countries where Opisthorchis and Clonorchis are highly endemic. Updated data on prevalence and distribution have been summarized from presentations in the “96 Years of Opisthorchiasis. International Congress of Liver Flukes”. It is disturbing that despite treatment and control programs have been in place for decades, all countries of the Lower Mekong Basin are still highly endemic with O. viverrini and/or C. sinensis as well as alarmingly high levels of CCA incidence. A common pattern that is emerging in each country is the difference in transmission of O. viverrini between lowlands which have high prevalence versus highlands which have low prevalence. This seems to be associated with wetlands, flooding patterns and human movement and settlement. A more concerted effort from all community, educational, public health and government sectors is necessary to successfully combat this fatal liver disease of the poor.

Sithithaworn, Paiboon; Andrews, Ross H.; Van De, Nguyen; Wongsaroj, Thitima; Sinuon, Muth; Odermatt, Peter; Nawa, Yukifumi; Liang, Song; Brindley, Paul J.; Sripa, Banchob

2013-01-01

193

The current status of opisthorchiasis and clonorchiasis in the Mekong Basin.  

PubMed

This review highlights the current status and control of liver fluke infections in the Mekong Basin countries where Opisthorchis and Clonorchis are highly endemic. Updated data on prevalence and distribution have been summarized from presentations in the "96 Years of Opisthorchiasis. International Congress of Liver Flukes". It is disturbing that despite treatment and control programs have been in place for decades, all countries of the Lower Mekong Basin are still highly endemic with O. viverrini and/or C. sinensis as well as alarmingly high levels of CCA incidence. A common pattern that is emerging in each country is the difference in transmission of O. viverrini between lowlands which have high prevalence versus highlands which have low prevalence. This seems to be associated with wetlands, flooding patterns and human movement and settlement. A more concerted effort from all community, educational, public health and government sectors is necessary to successfully combat this fatal liver disease of the poor. PMID:21893213

Sithithaworn, Paiboon; Andrews, Ross H; Nguyen, Van De; Wongsaroj, Thitima; Sinuon, Muth; Odermatt, Peter; Nawa, Yukifumi; Liang, Song; Brindley, Paul J; Sripa, Banchob

2012-03-01

194

Eosinophilic proliferative pylephlebitis in the liver of Japanese beef cattle with fascioliasis.  

PubMed

Intrahepatic pylephlebitis was detected in 17 Japanese beef cattle. Grossly, the intrahepatic vessels in the caudate lobe and/or in the periphery of the other hepatic lobes were thickened and protruded above the lobar surface. The vessel lumina were packed with white to red, waste thread-like contents. A few immature flukes were found in the bile ducts in 3 of the 7 cases with biliary thickening. Foci of hepatic necrosis and hemorrhage were scattered around the thickened vessels in 8 cases. Histologically, the interlobular veins were thickened due to severe intimal hyperplasia with endothelial proliferation and eosinophilic accumulation and medial hypertrophy, accompanied by fibrosis and eosinophilic infiltration in the portal areas. Hepatic tissues with necrosis and hemorrhage were surrounded by eosinophils and histiocytes including a granulomatous reaction. One immature fluke was detected in one of these regions of necrosis. Immunoperoxidase staining revealed that the small fluke, Kupffer cells, and histiocytes in the liver of all cases were positively stained with anti-Japanese Fasciola sp. antiserum. Enzyme-linked immunosorbent assay of the sera of 15 cases revealed that all were positive for the anti-Fasciola antibody. On the basis of these findings, the present cases were regarded as an atypical form of fascioliasis, characterized by eosinophilic proliferative pylephlebitis of the liver. PMID:9819759

Tanimoto, T; Shirota, K; Ohtsuki, Y; Araki, K

1998-10-01

195

Heterophysiasis, an intestinal fluke infection of man and vertebrates transmitted by euryhaline gastropods and fish  

NASA Astrophysics Data System (ADS)

Heterophyes heterophyes, agent of human heterophyiasis in the Near East, is transmitted in marine lagoons and saline inland waters, where the euryhaline intermediate hosts are abundant. In Egypt, mullets, the predominant second intermediate hosts, are customarily consumed raw; thus man becomes infected easily. Symptoms of human infections are usually considered mild. Mullets do not seem to be affected by the metacercariae encysted in the muscles, whereas the growth of the snail host Pirenella conica was found to be enhanced due to the infestation by the trematodes. In laboratory experiments, the flukes were found to be well developed in dogs, foxes and cats, but failed to reach sexual maturity in several other potentially piscivorous mammals and birds. In nature, dogs probably serve as the major reservoir hosts. Heterophyiasis is most prevalent in the Nile Delta, a huge brackish water area which is densely populated by humans and, consequently, also by dogs and cats. In the Far East, besides Heterophyes nocens, several other heterophysids with marine or fresh-water life-cycles are known to infect humans.

Taraschewski, H.

1984-03-01

196

Cystic liver disease related to high Platynosomum fastosum infection in a domestic cat.  

PubMed

Platynosomum fastosum is a small fluke found in the biliary ducts and gallbladder of cats. Its lifecycle includes the snail Sublima octona as intermediate host, and lizards, toads and geckos as paratenic hosts. Affected cats are usually adult and acquire the parasite by feeding on infected lizards. This parasite occurs across the world but is more frequent in tropical areas. The clinical signs range from none to obstruction of the biliary tract, with hepatic failure and death, reinforcing the necessity of including the liver fluke Platynosomum fastosum in the differential diagnosis of hepatic diseases in cats. This report describes an unusual case of a cat with a polycystic hepatic disease and a severe infestation by Platynosomum fastosum and presents a review of the literature. PMID:17241806

Xavier, Fabiana G; Morato, Geraldo S; Righi, Dario A; Maiorka, Paulo C; Spinosa, Helenice S

2007-02-01

197

Identification of Fasciola flukes in Thailand based on their spermatogenesis and nuclear ribosomal DNA, and their intraspecific relationships based on mitochondrial DNA.  

PubMed

We analyzed 147 Fasciola flukes obtained from cattle in Thailand based on their spermatogenetic ability, and nuclear ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial nicotiamide adenine dinucleotide dehydrogenase subunit 1 (ND1) genes as molecular markers. One hundred twenty-eight flukes, which had abundant sperm in their seminal vesicles (spermic) and showed the PCR-RFLP pattern of F. gigantica in the ITS1, were accurately identified as F. gigantica. The other 19 flukes that had no sperm in their seminal vesicles were aspermic Fasciola sp. with the RFLP patterns identical to that of F. gigantica. Twenty-nine ND1 haplotypes (Fg-ND1-Thai 2-30) were distinguished in the 128 F. gigantica flukes and were divided into haplotypes unique to Thailand and those common to other countries, suggesting the possibility that ancestral haplotypes were introduced into Thailand. Three haplotypes (Fg-ND1-Thai 7, 9 and 27) appeared to be the major haplotypes found in F. gigantica from Thailand. Only one haplotype (Fg-ND1-Thai 1) was found in the 19 aspermic Fasciola sp. flukes obtained from geographical regions, and the nucleotide sequence of Fg-ND1-Thai 1 was identical to that of the aspermic Fasciola sp. from Japan, Korea, China, Vietnam and Myanmar, suggesting that they were descendants with a common provenance and expanded to these countries in the relatively recent past. PMID:22575172

Chaichanasak, Pannigan; Ichikawa, Madoka; Sobhon, Prasert; Itagaki, Tadashi

2012-12-01

198

Carcinogenic liver fluke Opisthorchis viverrini oxysterols detected by LC-MS/MS survey of soluble fraction parasite extract.  

PubMed

Liquid chromatography in tandem mass spectrometry (LC-MS/MS) has emerged as an informative tool to investigate oxysterols (oxidized derivatives of cholesterol) in helminth parasite associated cancers. Here, we used LC-MS/MS to investigate in soluble extracts of the adult developmental stage of Opisthorchis viverrini from experimentally infected hamsters. Using comparisons with known bile acids and the metabolites of estrogens, the LC-MS data indicated the existence of novel oxysterol derivatives in O. viverrini. Most of these derivatives were ramified at C-17, in similar fashion to bile acids and their conjugated salts. Several were compatible with the presence of an estrogen core, and/or hydroxylation of the steroid aromatic ring A, hydroxylation of both C-2 and C-3 of the steroid ring and further oxidation into an estradiol-2,3-quinone. PMID:23973383

Vale, Nuno; Gouveia, Maria João; Botelho, Mónica; Sripa, Banchob; Suttiprapa, Sutas; Rinaldi, Gabriel; Gomes, Paula; Brindley, Paul J; Correia da Costa, José Manuel

2013-12-01

199

Accumulation of miscoding etheno-DNA adducts and highly expressed DNA repair during liver fluke-induced cholangiocarcinogenesis in hamsters  

Microsoft Academic Search

Infection by Opisthorchis viverrini, a risk factor for cholangiocarcinoma (CCA) may act through chronic inflammation, oxidative stress and lipid peroxidation (LPO)-related damage and growth stimuli. 1,N6-Etheno-2?-deoxyadenosine (?dA), and 3,N4-etheno-2?-deoxycytidine (?dC), markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients. In order to investigate tissue specificity etheno adducts were measured in

Somkid Dechakhamphu; Somchai Pinlaor; Paiboon Sitthithaworn; Helmut Bartsch; Puangrat Yongvanit

2010-01-01

200

Proteomic Identification of Plasma Protein Tyrosine Phosphatase Alpha and Fibronectin Associated with Liver Fluke, Opisthorchis viverrini, Infection  

PubMed Central

Opisthorchiasis caused by Opisthorchis viverrini induces periductal fibrosis via host immune/inflammatory responses. Plasma protein alteration during host-parasite interaction-mediated inflammation may provide potential diagnostic and/or prognostic biomarkers. To search for target protein changes in O. viverrini-infected hamsters, a 1-D PAGE gel band was trypsin-digested and analyzed by a LC-MS/MS-based proteomics approach in the plasma profile of infected hamsters, and applied to humans. Sixty seven proteins were selected for further analysis based on at least two unique tryptic peptides with protein ID score >10 and increased expression at least two times across time points. These proteins have not been previously identified in O. viverrini-associated infection. Among those, proteins involved in structural (19%), immune response (13%), cell cycle (10%) and transcription (10%) were highly expressed. Western blots revealed an expression level of protein tyrosine phosphatase alpha (PTP?) which reached a peak at 1 month and subsequently tended to decrease. Fibronectin significantly increased at 1 month and tended to increase with time, supporting proteomic analysis. PTP? was expressed in the cytoplasm of inflammatory cells, while fibronectin was observed mainly in the cytoplasm of fibroblasts and the extracellular matrix at periductal fibrosis areas. In addition, these protein levels significantly increased in the plasma of O. viverrini-infected patients compared to healthy individuals, and significantly decreased at 2-months post-treatment, indicating their potential as disease markers. In conclusion, our results suggest that plasma PTP? and fibronectin may be associated with opisthorchiasis and the hamster model provides the basis for development of novel diagnostic markers in the future.

Khoontawad, Jarinya; Laothong, Umawadee; Roytrakul, Sittiruk; Pinlaor, Porntip; Mulvenna, Jason; Wongkham, Chaisiri; Yongvanit, Puangrat; Pairojkul, Chawalit; Mairiang, Eimorn; Sithithaworn, Paiboon; Pinlaor, Somchai

2012-01-01

201

High excretion of etheno adducts in liver fluke-infected patients: protection by praziquantel against DNA damage.  

PubMed

Chronic infection by Opisthorchis viverrini (OV) is a strong risk factor for developing cholangiocarcinoma (CCA). To clarify the involvement of oxidative stress and lipid peroxidation (LPO)-derived DNA damage, the excretion of LPO-derived etheno DNA adducts was measured in urine samples collected from healthy volunteers and OV-infected Thai subjects. 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) and 3,N(4)-etheno-2'-deoxycytidine (epsilondC) levels were quantified by immunoprecipitation/high-performance liquid chromatography/fluorescence detection and (32)P-postlabeling TLC. Excreted etheno adduct levels were related to indicators of inflammatory conditions [malondialdehyde (MDA) and nitrate/nitrite levels in urine and plasma alkaline phosphatase (ALP) activity]. Mean epsilondA and epsilondC levels were 3 to 4 times higher in urine of OV-infected patients; MDA, nitrate/nitrite, and ALP were also increased up to 2-fold. MDA and ALP were positively related to epsilondA excretion. Two months after a single dose of the antiparasitic drug Praziquantel, epsilondA and epsilondC concentrations in urine of OV-infected subjects were decreased; MDA, nitrate/nitrite, and ALP were concomitantly lowered. We conclude that chronic OV infection through oxidative/nitrative stress leads to increased urinary excretion of the etheno-bridged deoxyribonucleosides, reflecting high LPO-derived DNA damage in vivo. These promutagenic DNA etheno adducts in bile duct epithelial cells may increase the risk of OV-infected patients to later develop CCA. Urinary epsilondA and epsilondC levels should be explored (a) as noninvasive risk markers for developing opisthorchiasis-related CCA and (b) as promising biomarkers to assess the efficacy of preventive and therapeutic interventions. PMID:18628417

Dechakhamphu, Somkid; Yongvanit, Puangrat; Nair, Jagadeesan; Pinlaor, Somchai; Sitthithaworn, Paiboon; Bartsch, Helmut

2008-07-01

202

The hispid cotton rat ( Sigmodon hispidus) as an experimental host for the bovine liver fluke ( Fasciola hepatica)  

Microsoft Academic Search

The results of a study testing the susceptibility of the hispid cotton rat, Sigmodon hispidus, to infection with Fasciola hepatica are described. Ten cotton rats were placed into one of four test groups, one uninfected control or three animals each receiving two, five, or 10 F. hepatica metacercariae. Three of nine (33%) became infected, and two of these animals carried

Richard D McKown; Robert K Ridley; George A Kennedy

2000-01-01

203

Liver Facts  

MedlinePLUS

... Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ... Camps for kids Contacting my donor family Data Facts about living donation Financing a transplant Matching organs ...

204

Rhaphidotrema kiatkiongi, a new genus and species of blood fluke (Digenea: Aporocotylidae) from Arothron hispidus (Osteichthyes: Tetraodontidae) from the Great Barrier Reef, Australia.  

PubMed

A new genus of fish blood flukes (Aporocotylidae Odhner, 1912) is proposed for a species found on reefs surrounding Lizard Island on the northern Great Barrier Reef. Rhaphidotrema kiatkiongi gen. et sp. n. was recovered from the heart of the stars-and-stripes pufferfish, Arothron hispidus (L.) (Tetraodontidae). Rhaphidotrema kiatkiongi is notable as the first digenean reported to possess a penis stylet. It also differs from all other aporocotylid flukes in having a combination of 18-19 testes in a group at the ends of the intestinal caeca, a broad lanceolate body shape with a dextrally-directed posterior bend at the level of the male genital pore, and separate genital pores, with the female genital pore distinctly sinistral and the male genital pore slightly dextral to midline. This is the second species of aporocotylid fluke reported from this pufferfish. PMID:22263308

Yong, Russell Q Y; Cribb, Thomas H

2011-11-01

205

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni  

PubMed Central

Background Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins. Methodology/Principal Findings We identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence data. An ortholog is present in Schistosoma japonicum. SmCL3 was heterologously expressed as an active enzyme in the yeast, Pichia pastoris. Recombinant SmCL3 has a broad pH activity range against peptidyl substrates and is inhibited by Clan CA protease inhibitors. Consistent with a function in degrading host proteins, SmCL3 hydrolyzes serum albumin and hemoglobin, is localized to the adult gastrodermis, and is expressed mainly in those life stages infecting the mammalian host. The predominant form of SmCL3 in the parasite exists as a zymogen, which is unusual for proteases. This zymogen includes an unusually long prodomain with alpha helical secondary structure motifs. The striking specificity of SmCL3 for amino acids with large aromatic side chains (Trp and Tyr) at the P2 substrate position, as determined with positional scanning-synthetic combinatorial library, is consistent with a molecular model that shows a large and deep S2 pocket. A sequence similarity network (SSN) view clusters SmCL3 and other cathepsins L in accordance with previous large-scale phylogenetic analyses that identify six super kingdoms. Conclusions/Significance SmCL3 is a gut-associated cathepsin L that may contribute to the network of proteases involved in degrading host blood proteins as nutrients. Furthermore, this enzyme exhibits some unusual sequence and biophysical features that may result in additional functions. The visualization of network inter-relationships among cathepsins L suggests that these enzymes are suitable ‘marker sequences’ for inclusion in future phylogenetic analyses.

Dvorak, Jan; Mashiyama, Susan T.; Sajid, Mohammed; Braschi, Simon; Delcroix, Melaine; Schneider, Eric L.; McKerrow, Wilson H.; Bahgat, Mahmoud; Hansell, Elizabeth; Babbitt, Patricia C.; Craik, Charles S.; McKerrow, James H.; Caffrey, Conor R.

2009-01-01

206

Tracking the fate of iron in early development of human blood flukes  

PubMed Central

Iron (Fe) is an important trace element found in nearly all organisms, and is used as a cofactor in many biological reactions. One role for Fe in some invertebrates is in stabilization of extracellular matrices. The human blood fluke, Schistosoma japonicum, is responsible for significant human disease in developing and tropical nations. Disease in humans arises from host immunological reaction to parasite eggs that lodge in tissues. Schistosomes require Fe for development in their hosts, and store abundant Fe in vitelline (eggshell-forming) cells of the female system. The understanding of Fe metabolism and functionality are aspects of its biology that may be exploited in future therapeutics. The biology of Fe stores in vitelline cells of S. japonicum was investigated to illuminate possible functions of this element in early development of these parasites. Vitelline Fe is stored in yolk ferritin that is upregulated in females and is also expressed at low levels in egg-stages and adult males. Laser microdissection microscopy, coupled with reverse transcriptase- and real time-PCR amplification of schistosome ferritin sequences, confirmed that the vitelline cells are the likely progenitor cells of yolk ferritin. Assessment of Fe concentrations in whole male and whole female adult worms, eggs and purified eggshells by colorimetric assays and mass spectroscopy demonstrated higher levels of Fe in the female parasite, but also high levels of the element in whole parasite eggs and purified eggshell. Qualitative energy dispersive spectroscopy of purified eggshells, revealed that Fe is abundant in the eggshell, the matrix of which is composed of heavily cross-linked eggshell precursor proteins. Thus, vitelline stores of Fe are implicated in eggshell cross-linking in platyhelminths. These observations emphasise the importance of Fe in schistosome metabolism and egg formation and suggest new avenues for disruption of egg formation in these pathogenic parasites.

Jones, Malcolm K.; McManus, Donald P.; Sivadorai, Padma; Glanfield, Amber; Moertel, Luke; Belli, Sabina I.; Gobert, Geoffrey N.

2007-01-01

207

Helminths in human carcinogenesis.  

PubMed

This review examines the salient literature on selected helminths involved in carcinogenicity in humans and updates information in an earlier review on cancer and helminths by Mayer and Fried (2007, Advances in Parasitology 65, 239-296). The earlier review was concerned with various helminths, i.e., trematodes, cestodes, and nematodes, that are definitely implicated as being carcinogenic. This review examines only those helminths, all of which turn out to be trematodes, that are definitely implicated as being carcinogenic. These trematodes are the blood flukes Schistosoma haematobium, associated with inducing human carcinoma of the urinary bladder and the liver flukes Opisthorchis viverrini and Clonorchis sinensis, associated with inducing cancer of the bile duct (cholangiocarcinoma) and cancer of the liver (hepatocarcinoma) in humans. The review examines mainly the epidemiology and pathology of these helminthic infections in humans and considers what we know about the mechanisms associated with the carcinogenicity of these three trematodes in humans. PMID:20667649

Fried, Bernard; Reddy, Aditya; Mayer, David

2011-06-28

208

Bovine fasciolosis: coprological, abattoir survey and its economic impact due to liver condemnation at Soddo municipal abattoir, Southern Ethiopia.  

PubMed

A study was carried out to determine the prevalence and the species of liver flukes in indigenous adult cattle, to compare the diagnostic efficiency of fecal and post mortem examination and to assess the economic significance of bovine fasciolosis due to liver condemnation in the abattoir. Of the 406 livers and fecal samples examined, 57 (14.0%) and 20 (4.9%) were positive for fasciolosis. The most common liver fluke species affecting the cattle was Fasciola gigantica, 9.1% of cattle were infected with F. gigantica while, Fasciola. hepatica, mixed infections and unidentified or immature forms of Fasciola spp. were present in 3.2 %, 0.7% and 1 % of cattle, respectively. A retrospective abattoir survey revealed that the prevalence of fasciolosis was 12.7%. The prevalence of fasciolosis recorded in this study was lower than that reported by other researchers in this country. There was a strong relationship between fecal examination and postmortem findings of liver lesions, (K = 0.23) but under local conditions, postmortem examination was considered a better diagnostic tool for fasciolosis. Fasciolosis is of significant economic importance as the resultant liver condemnations caused an average loss of 4000 USD per annum. Hence, this disease deserves serious attention by the various stakeholders in order to promote the beef industry in the study area in particular and in the country in general. PMID:19680772

Abunna, Fufa; Asfaw, Loma; Megersa, Bekele; Regassa, Alemayehu

2010-02-01

209

Transcriptional induction of minichromosome maintenance protein 7 (Mcm7) in human cholangiocarcinoma cells treated with Clonorchis sinensis excretory-secretory products.  

PubMed

Clonorchiasis is an infection associated with bile duct malignancy and subsequent development of cholangiocarcinoma. This disease is mainly caused by Clonorchis sinensis worms and their excretory-secretory products (ESP). However, the precise molecular mechanisms of carcinogenesis remain to be determined. Previously, we established differential gene expression profiles from microarrays containing 23,920 human genes of known function in a human cholangiocarcinoma cell line, HuCCT1, treated with ESP. Among the upregulated genes, we focused on minichromosome maintenance protein 7 (Mcm7), which is implicated in various cancer types, and analyzed transcriptional regulation mediated by ESP to further elucidate its role in cholangiocarcinoma development. Global histone acetylation levels were increased in ESP-treated cells, along with histone acetyltransferase (HAT) protein expression. Detailed promoter analysis using reporter and chromatin immunoprecipitation assays revealed that transcriptional activation of Mcm7 is mediated by HAT recruitment to the promoter region upon C. sinensis ESP treatment. These findings contribute to clarification of the intrinsic mechanism underlying the cellular carcinogenesis process stimulated by Mcm7 in C. sinensis-treated host cells. PMID:20236609

Kim, Dong-Wook; Kim, Ji-Young; Moon, Ju Hyun; Kim, Kee-Beom; Kim, Tong-Soo; Hong, Sung-Jong; Cheon, Young Pil; Pak, Jhang Ho; Seo, Sang-Beom

2010-09-01

210

The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements  

Microsoft Academic Search

BACKGROUND: Of the major families of long terminal repeat (LTR) retrotransposons, the Pao\\/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. RESULTS: A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of

Claudia S Copeland; Victoria H Mann; Maria E Morales; Bernd H Kalinna; Paul J Brindley

2005-01-01

211

Taxonomical and Ecological Studies on the Lung Fluke, Paragonimus in the Pacific Area, with Special Reference to South-East Asia.  

National Technical Information Service (NTIS)

In Japan, the cat was added to the list of natural host for Paragonimus sadoensis, and it was experimentally revealed that the Japanese vole, Microtus montebelli and the woods mouse, Apodemus speciosus can be the final host of the same lung fluke. In Mala...

I. Miyazaki

1968-01-01

212

Liver biopsy  

MedlinePLUS

Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. The skin will be cleansed, and a small ... chance of puncturing the lung or tearing the liver. The needle is removed quickly. Pressure will be ...

213

Liver Panel  

MedlinePLUS

... Hepatitis , Hemochromatosis , Wilson Disease , Cirrhosis Elsewhere On The Web American Liver Foundation MayoClinic.com: Liver function tests KidsHealth from Nemours: Hepatic [Liver] Function Panel National ...

214

Liver Wellness  

MedlinePLUS

... chemicals, and additives in cigarettes • Do not smoke Common Liver Diseases and Prevention One out of every 10 Americans ... liver diseases. Below are some of the most common liver diseases, and ways you can help prevent them and ...

215

Liver enzymes and blood metabolites in a population of free-ranging red deer (Cervus elaphus) naturally infected with Fascioloides magna.  

PubMed

We investigated the effects of Fascioloides magna infection on the serum biochemistry values of the naturally infected red deer population in eastern Croatia. The investigation was performed on 47 red deer with F. magna infection confirmed patho-anatomically in 27 animals (57.4%). Fibrous capsules and migratory lesions were found in 14 deer while only fibrous capsules without migratory lesions were found in 13 deer. In 13 deer both immature and mature flukes were found, in 5 deer only immature flukes were found and in 9 deer only mature flukes were found. Fascioloides magna infected deer with fibrous capsules and migratory lesions had significantly higher values for lactate dehydrogenase (LDH), glutamate dehydrogenase (GLDH) and globulin, and lower values for albumin/globulin ratio and glucose compared to uninfected deer. Fascioloides magna infected deer with fibrous capsules without the presence of migratory lesions had higher values for alanine aminotransferase (ALT) and globulin, and lower values for albumin/globulin ratio and glucose, than the uninfected deer. The number of immature flukes was positively correlated with values of aspartate aminotransferase (AST), ?-glutamyltransferase (GGT), LDH, GLDH, urea and triglycerides. The number of migratory lesions was positively correlated with GGT, GLDH, globulin and urea values. The creatinine value was positively correlated with the number of mature flukes. The trial showed that F. magna infection causes significant changes in serum biochemistry. Moreover, these changes do not completely resemble changes following F. hepatica infection. Further investigation of changes in liver enzymes and other serum metabolites in controlled, experimentally induced fascioloidosis in red deer is needed to better understand the pathogenesis of F. magna. PMID:21729388

Severin, K; Mašek, T; Janicki, Z; Konjevi?, D; Slavica, A; Marinculi?, A; Martinkovi?, F; Vengušt, G; Džaja, P

2012-06-01

216

Austropeplea ollula (Pulmonata: Lymnaeidae): A new molluscan intermediate host of a human intestinal fluke, Echinostoma cinetorchis (Trematoda: Echinostomatidae) in Korea  

PubMed Central

Three freshwater snail species of the family Lymnaeidae have been reported from Korea, Radix auricularia coreana, Austropeplea ollula and Fossaria truncatula. Out of 3 lymnaeid snail species, A. ollula was naturally infected with the Echinostoma cinetorchis cercariae (infection rate = 0.7%). In the experiments with the laboratory-bred snails, F. truncatula as well as A. ollula was also susceptible to the E. cinetorchis miracidia with infection rates of 25% and 40%, respectively. All of three lymnaeid snail species exposed to the E. cinetorchis cercariae were infected with the E. cinetorchis metacercariae. It is evident that A. ollula acts as the first molluscan intermediate host of E. cinetorchis in Korea, and F. truncatula may be a possible candidate for the first intermediate host of this intestinal fluke. Also, three lymnaeid snail species targeted were experimentally infected with E. cinetorchis metacercariae.

Jung, Younghun; Park, Yun-Kyu; Hwang, Myung-Ki

2001-01-01

217

Molecular characterization of the North American lung fluke Paragonimus kellicotti in Missouri and its development in Mongolian gerbils.  

PubMed

Human paragonimiasis is an emerging disease in Missouri. To characterize local parasites, we examined crayfish from three rivers. Metacercaeriae consistent with Paragonimus kellicotti were detected in 69%, 67%, and 37% of crayfish from the Big Piney, Huzzah, and Black Rivers, respectively. Sequencing of the second internal transcribed spacer and other DNA markers confirmed the species identification and the presence of identical parasite sequences in clinical specimens from two human cases. Mongolian gerbils were infected by intraperitoneal injection with 3-8 metacercariae. Most gerbils died 15-49 days post-infection. Necropsies showed pulmonary hemorrhage with necrosis, and flukes as long as 8 mm were recovered from intrathoracic tissues. Western blot analysis using P. kellicotti antigen showed a strong antibody response in gerbils 39 days post-infection. These results demonstrate that P. kellicotti is common in Missouri crayfish. The gerbil model may be useful for research on the pathogenesis, immunology, and treatment of paragonimiasis. PMID:21633042

Fischer, Peter U; Curtis, Kurt C; Marcos, Luis A; Weil, Gary J

2011-06-01

218

Molecular Characterization of the North American Lung Fluke Paragonimus kellicotti in Missouri and its Development in Mongolian Gerbils  

PubMed Central

Human paragonimiasis is an emerging disease in Missouri. To characterize local parasites, we examined crayfish from three rivers. Metacercaeriae consistent with Paragonimus kellicotti were detected in 69%, 67%, and 37% of crayfish from the Big Piney, Huzzah, and Black Rivers, respectively. Sequencing of the second internal transcribed spacer and other DNA markers confirmed the species identification and the presence of identical parasite sequences in clinical specimens from two human cases. Mongolian gerbils were infected by intraperitoneal injection with 3–8 metacercariae. Most gerbils died 15–49 days post-infection. Necropsies showed pulmonary hemorrhage with necrosis, and flukes as long as 8 mm were recovered from intrathoracic tissues. Western blot analysis using P. kellicotti antigen showed a strong antibody response in gerbils 39 days post-infection. These results demonstrate that P. kellicotti is common in Missouri crayfish. The gerbil model may be useful for research on the pathogenesis, immunology, and treatment of paragonimiasis.

Fischer, Peter U.; Curtis, Kurt C.; Marcos, Luis A.; Weil, Gary J.

2011-01-01

219

High annealing temperature-random amplified polymorphic DNA (HAT-RAPD) analysis of three paramphistome flukes from Thailand.  

PubMed

The rumen flukes of 37 cows (Bos indicus) from Chiang Mai and Lamphun provinces were investigated, and the overall prevalence of infection was 78.38% (29/37). Three species were found: Paramphistomum epiclitum, Orthocoelium streptocoelium, and Fischoederius elongatus with prevalences of infection of 75.68%, 48.65%, and 40.54%, respectively. Genomic DNA was amplified by polymerase chain reaction based on the high annealing temperature-random amplification of polymorphic DNA (HAT-RAPD) technique. Five random 10-mer oligonucleotide primers (OPA2, OPA4, OPB18, OPC9, and OPH11) produced distinct banding patterns in three species. No genetic variations in these three species were identified using 10 arbitary primers. PMID:16889772

Sripalwit, Pralongyut; Wongsawad, Chalobol; Wongsawad, Pheravut; Anuntalabhochai, Somboon

2007-01-01

220

Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells  

PubMed Central

Background Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. Methodology/Principal Findings There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. Conclusions/Significance Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC patients combined with C. sinensis infection.

He, Lei; Wang, Xiaoyun; Liang, Pei; Chen, Wenjun; Bian, Meng; Ren, Mengyu; Lin, Jinsi; Liang, Chi; Xu, Jin; Wu, Zhongdao; Li, Xuerong; Huang, Yan; Yu, Xinbing

2013-01-01

221

Expression, immunolocalization, and serological reactivity of a novel sphingomyelin phosphodiesterase-like protein, an excretory/secretory antigen from Clonorchis sinensis.  

PubMed

Clonorchiasis, caused by Clonorchis sinensis infection, is a zoonotic parasitic disease of hepatobiliary system in which the proteins released by adult are major pathogenetic factors. In this study, we first characterized a putative sphingomyelin phosphodiesterase (CsSMPase) A-like secretory protein, which was highly expressed in the adult worm. The full-length gene was cloned. The putative protein is of relatively low homology comparing with SMPase from other species, and of rich T cell and B cell epitopes, suggesting that it is an antigen of strong antigenicity. The complete coding sequence of the gene was expressed in the Escherichia coli. The recombinant CsSMPase (rCsSMPase) can be recognized by C. sinensis-infected serum, and the protein immunoserum can recognize a specific band in excretory/secretory products (ESPs) of C. sinensis adult by western blotting. Immunolocalization revealed that CsSMPase was not only localized on tegument, ventral sucker of metacercaria, and the intestine of adult but also on the nearby epithelium of bile duct of the infected Sprague-Dawley rats, implying that CsSMPase was mainly secreted and excreted through adult intestine and directly interacted with bile duct epithelium. Although immunized rats evoked high level antibody response, the antigen level was low in clonorchiasis patients. And the sensitivity and specificity of rCsSMPase were 50.0 % (12/24) and 88.4 % (61/69), in sera IgG-ELISA, respectively. It is likely due to the fact that CsSMPase binding to the plasma membrane of biliary epithelium decreases the antigen immune stimulation. PMID:23568580

Huang, Yanwei; Zheng, Youwei; Li, Yuzhe; Yang, Mei; Li, Ting; Zeng, Suxiang; Yu, Xinbing; Huang, Huaiqiu; Hu, Xuchu

2013-06-01

222

Bilirubin binding with liver cystatin induced structural and functional changes.  

PubMed

Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279?×?10(4) M(-1). The cystatin binding with bilirubin has a significant biophysical and pathophysiological significance, hence our effort to study the same. PMID:24711081

Mustafa, Mir Faisal; Bano, Bilqees

2014-05-01

223

Blood flukes (Digenea: Aporocotylidae) of walking catfishes (Siluriformes: Clariidae): new genus and species from the Mekong River (Vietnam) with comments on related catfish aporocotylids.  

PubMed

Nomasanguinicola canthoensis gen. et sp. n. infects the branchial vessels of bighead catfish, Clarias macrocephalus Günther (Siluriformes: Clariidae), in the Mekong River near Can Tho, southern Vietnam. Nomasanguinicola differs from all other genera of fish blood flukes (Digenea: Aporocotylidae) by the combination of lacking body spines and by having an anterior sucker with two flanking columns of large denticles, an intestine comprising several short papilla-like caeca, an inverse U-shaped uterus, and an ootype located near the separate genital pores. The new species has an ootype that is posterior to the level of the female genital pore. That feature most easily differentiates it from the only other putative aporocotylid species having an anterior sucker with two flanking columns of large denticles, Plehniella dentata Paperna, 1964 and Sanguinicola clarias Imam, Marzouk, Hassan et Itman, 1984, which have an ootype that is lateral (P. dentata) or anterior (S. clarias) to the level of the female genital pore. These two species apparently lack extant type materials, infect North African catfish, Clarias gariepinus (Burchell), and herein are considered incertae sedis, but likely comprise species of Nomasanguinicola. An updated list of hosts, sites of infection and geographic localities for the six species and three genera of blood flukes that mature in catfishes is provided. The new species is the first fish blood fluke recorded from Vietnam and only the third reported from a walking catfish (Clariidae). PMID:23951931

Truong, Triet Nhat; Bullard, Stephen A

2013-07-01

224

Liver Transplantation  

PubMed Central

Liver transplantation has become a lifesaving procedure for patients who have chronic end-stage liver disease and acute liver failure. The satisfactory outcome of liver transplantation has led to insufficient supplies of deceased donor organs, particularly in East Asia. Hence, East Asian surgeons are concentrating on developing and performing living-donor liver transplantation (LDLT). This review article describes an update on the present status of liver transplantation, mainly in adults, and highlights some recent developments on indications for transplantation, patient selection, donor and recipient operation between LDLT and deceased-donor liver transplantation (DDLT), immunosuppression, and long-term management of liver transplant recipients. Currently, the same indication criteria that exist for DDLT are applied to LDLT, with technical refinements for LDLT. In highly experienced centers, LDLT for high-scoring (>30 points) Model of End-Stage Liver Disease (MELD) patients and acute-on-chronic liver-failure patients yields comparably good outcomes to DDLT, because timely liver transplantation with good-quality grafting is possible. With increasing numbers of liver transplantations and long-term survivors, specialized attention should be paid to complications that develop in the long term, such as chronic renal failure, hypertension, diabetes mellitus, dyslipidemia, obesity, bone or neurological complications, and development of de novo tumors, which are highly related to the immunosuppressive treatment.

Moon, Deok-Bog

2009-01-01

225

Liver regeneration  

Microsoft Academic Search

The liver can precisely regulate its growth and mass. Surgical resection of hepatic lobes or hepatocyte loss caused by viral or chemical injury triggers hepatocyte replication while enlarged liver mass is corrected by apoptosis. Hepatocytes have a great replicative capacity and are capable of repopulating the liver. However, “stem-like” cells proliferate when hepatocyte replication is blocked or delayed. Detailed studies

Nelson Fausto

2000-01-01

226

Population dynamics and host reactions in young foxes following experimental infection with the minute intestinal fluke, Haplorchis pumilio  

PubMed Central

Background Infections with fish-borne zoonotic trematodes (FZT) including the minute intestinal fluke, Haplorchis pumilio, are highly prevalent in Southeast Asia. However, little is known about the infection dynamics and clinical symptoms in the final hosts which include a range of animal species and man. We aimed to generate such information using an experimental model with H. pumilio in foxes. Method Eight commercially bred foxes were each orally infected with 2000 H. pumilio metacercariae. Another three foxes served as uninfected controls. Faecal examination for eggs was performed twice weekly. The body weight was measured, standard haematological and biochemical analysis were performed regularly. All foxes were euthanized at day 56 post infection (p.i.). Adult worms were quantified and location in the small intestine noted. Results Anorexia was observed in all infected foxes starting day 12 p.i. and lasting for approximately a week. A weight loss was noticed in the infected group in weeks 3–6 p.i. Five of eight infected foxes excreted H. pumilio eggs day 9 p.i. onwards, the remaining three started on day 13 p.i. Mean (± SD) faecal egg counts showed an initial peak at day 16–20 with a maximum of 1443?±?1176 eggs per gram of faeces (epg), where after a stable egg output around 4–500 epg was seen. Worm burdens ranged between 116–2070 adult flukes with a mean (± SD) worm recovery of 948?±?666. The majority of worms were found in the lower part of the jejunum. Total white blood cell and lymphocyte counts were significant lower in the infected group from first week p.i. onwards and throughout the study period. A significantly lower level of eosinophils was found in week 2 p.i. and transient anaemia was seen in week 2 and 4 p.i. Conclusion This study showed a short prepatency period, an initial peak in egg excretion, establishment of infection in all animals with predilection site in the lower jejunum and a marked but transient clinical effect of the infection. The findings on egg output and prepatency should be taken into consideration when control programs targeting dogs and other reservoir hosts are to be established.

2013-01-01

227

Liver Biopsy  

MedlinePLUS

... the liver and quickly withdrawn. This removes a core of liver tissue. After the procedure, the child is observed and monitored regularly until it’s safe to go home. The time of discharge differs according to the age of the child and the reason for the biopsy. It can vary from 6 to 24 hours. ...

228

Fishborne Zoonotic Intestinal Trematodes, Vietnam  

PubMed Central

Although fishborne zoonotic trematodes that infect the liver are well documented in Vietnam, intestinal fishborne zoonotic trematodes are unreported. Recent discoveries of the metacercarial stage of these flukes in wild and farmed fish prompted an assessment of their risk to a community that eats raw fish. A fecal survey of 615 persons showed a trematode egg prevalence of 64.9%. Infected persons were treated to expel liver and intestinal parasites for specific identification. The liver trematode Clonorchis sinensis was recovered from 51.5%, but >1 of 4 intestinal species of the family Heterophyidae was recovered from 100%. The most numerous were Haplorchis spp. (90.4% of all worms recovered). These results demonstrate that fishborne intestinal parasites are an unrecognized food safety risk in a country whose people have a strong tradition of eating raw fish.

Dung, Do Trung; Van De, Nguyen; Waikagul, Jitra; Dalsgaard, Anders; Chai, Jong-Yil; Sohn, Woon-Mok

2007-01-01

229

Fluke egg characteristics for the diagnosis of human and animal fascioliasis by Fasciola hepatica and F. gigantica.  

PubMed

In trematodiases, shape and size of the fluke eggs shed with faeces are crucial diagnostic features because of their typically reduced intraspecific variability. In fascioliasis, the usual diagnosis during the biliary stage of infection is based on the classification of eggs found in stools, duodenal contents or bile. The aim of the present study is to validate the identification of Fasciola species based on the shape and size of eggs shed by humans, characterizing their morphometric traits using a computer image analysis system (CIAS). The influence of both the geographical location and of the host (human and livestock) has been analysed. Coprological studies were carried out in fascioliasis human endemic areas, where only F. hepatica is present (the northern Bolivian Altiplano and the Cajamarca valley in Peru), and where F. hepatica and F. gigantica coexist (the Kutaisi region of Georgia, the Nile Delta in Egypt, and the Quy Nhon province in Vietnam). Classically, it is considered that at the abopercular end of the shell of Fasciola eggs there is often a roughened or irregular area. Nevertheless, results show that the frequency of the presence of this feature in F. hepatica is population-dependent, and therefore is not a pathognomonic criterion in diagnosis. The study reveals that eggs shed by humans show morphological traits different from eggs shed by animals. In humans, F. hepatica eggs are bigger and F. gigantica eggs are smaller than reported to date from livestock, and their measurements overlap when compared. The material analysed in this study shows that the size of eggs shed by humans from Georgia and Egypt corresponds to the F. hepatica morph, while the size of eggs shed by humans from Vietnam corresponds to the F. gigantica morph. Measurements of F. hepatica and F. gigantica eggs originating from humans and animals from sympatric areas overlap, and, therefore, they do not allow differential diagnosis when within this overlapping range. In this sense, the new results should aid clinicians since the application of the classic egg size range in human samples may lead to erroneous conclusions. Fasciolid egg size in human stool samples ought to be corrected in books and monographs related to medical parasitology and/or tropical medicine as well as in guides for clinicians and parasitic disease diagnosis analysts. PMID:19375410

Valero, M Adela; Perez-Crespo, Ignacio; Periago, M Victoria; Khoubbane, Messaoud; Mas-Coma, Santiago

2009-08-01

230

Expression of ATP-binding cassette multidrug transporters in the giant liver fluke Fasciola gigantica and their possible involvement in the transport of bile salts and anthelmintics  

Microsoft Academic Search

ATP-binding cassette (ABC) transporters belong to one of the largest protein families that either import or export a wide\\u000a spectrum of different substrates. Certain members of this superfamily have been implicated in multidrug resistance in various\\u000a types of cancer as well as in pathogenic microorganisms. The role of ABC proteins in parasitic multidrug resistance becomes\\u000a increasingly evident. However, studies on

Supeecha Kumkate; Supatra Chunchob; Tavan Janvilisri

2008-01-01

231

Liver disease - resources  

MedlinePLUS

Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation - www.liverfoundation.org Children's Liver Association for Support Services - www.classkids.org Hepatitis ...

232

Diet and Your Liver  

MedlinePLUS

... how much protein to have in your diet Fatty Liver Disease Fatty liver disease is the build up of fat in ... shellfish and mushrooms • Do not use copper pots Liver Diseases and Diet Some liver diseases have specific diet ...

233

AN APPROACH TO REVEALING BLOOD FLUKE LIFE CYCLES, TAXONOMY, AND DIVERSITY: PROVISION OF KEY REFERENCE DATA INCLUDING DNA SEQUENCE FROM SINGLE LIFE CYCLE STAGES  

PubMed Central

Revealing diversity among extant blood flukes, and the patterns of relationships among them, has been hindered by the difficulty of determining if specimens described from different life cycle stages, hosts, geographic localities, and times represent the same or different species. Persistent collection of all available life cycle stages and provision of exact collection localities, host identification, reference DNA sequences for the parasite, and voucher specimens eventually will provide the framework needed to piece together individual life cycles and facilitate reconciliation with classical taxonomic descriptions, including those based on single life cycle stages. It also provides a means to document unique or rare species that might only ever be recovered from a single life cycle stage. With an emphasis on the value of new information from field collections of any available life cycle stages, here we provide data for several blood fluke cercariae from freshwater snails from Kenya, Uganda, and Australia. Similar data are provided for adult worms of Macrobilharzia macrobilharzia and miracidia of Bivitellobilharzia nairi. Some schistosome and sanguinicolid cercariae that we recovered have peculiar morphological features, and our phylogenetic analyses (18S and 28S rDNA and mtDNA CO1) suggest that 2 of the new schistosome specimens likely represent previously unknown lineages. Our results also provide new insights into 2 of the 4 remaining schistosome genera yet to be extensively characterized with respect to their position in molecular phylogenies, Macrobilharzia and Bivitellobilharzia. The accessibility of each life cycle stage is likely to vary dramatically from one parasite species to the next, and our examples validate the potential usefulness of information gleaned from even one such stage, whatever it might be.

Brant, Sara V.; Morgan, Jess A. T.; Mkoji, Gerald M.; Snyder, Scott D.; Rajapakse, R. P. V. Jayanthe; Loker, Eric S.

2008-01-01

234

An approach to revealing blood fluke life cycles, taxonomy, and diversity: provision of key reference data including DNA sequence from single life cycle stages.  

PubMed

Revealing diversity among extant blood flukes, and the patterns of relationships among them, has been hindered by the difficulty of determining if specimens described from different life cycle stages, hosts, geographic localities, and times represent the same or different species. Persistent collection of all available life cycle stages and provision of exact collection localities, host identification, reference DNA sequences for the parasite, and voucher specimens eventually will provide the framework needed to piece together individual life cycles and facilitate reconciliation with classical taxonomic descriptions, including those based on single life cycle stages. It also provides a means to document unique or rare species that might only ever be recovered from a single life cycle stage. With an emphasis on the value of new information from field collections of any available life cycle stages, here we provide data for several blood fluke cercariae from freshwater snails from Kenya, Uganda, and Australia. Similar data are provided for adult worms of Macrobilharzia macrobilharzia and miracidia of Bivitellobilharzia nairi. Some schistosome and sanguinicolid cercariae that we recovered have peculiar morphological features, and our phylogenetic analyses (18S and 28S rDNA and mtDNA CO1) suggest that 2 of the new schistosome specimens likely represent previously unknown lineages. Our results also provide new insights into 2 of the 4 remaining schistosome genera yet to be extensively characterized with respect to their position in molecular phylogenies, Macrobilharzia and Bivitellobilharzia. The accessibility of each life cycle stage is likely to vary dramatically from one parasite species to the next, and our examples validate the potential usefulness of information gleaned from even one such stage, whatever it might be. PMID:16629320

Brant, Sara V; Morgan, Jess A T; Mkoji, Gerald M; Snyder, Scott D; Rajapakse, R P V Jayanthe; Loker, Eric S

2006-02-01

235

Towards improved diagnosis of zoonotic trematode infections in Southeast Asia.  

PubMed

Humans in Southeast Asia are at risk for at least 70 species of food-borne and water-borne trematodes, including blood flukes, intestinal flukes, liver flukes and lung flukes, which are shared with a great variety of animals. Co-infection with several other zoonotic trematodes is pervasive, and hence differential diagnosis represents a major challenge. Many zoonotic trematodes are commonly overlooked, leading to unreliable prevalence data, underappreciation of their veterinary and public health burden and impact, and general neglect with respect to treatment and control. Additionally, many eggs are indistinguishable by microscopy. For example, failure to address this diagnostic dilemma has resulted in overestimation of Clonorchis sinensis prevalence and underestimation of minute intestinal flukes. Test insensitivity is becoming a problem of prime interest as surveillance is gaining in importance and various control programmes now regularly register progress. Hence, the likelihood of underestimating the true burden of disease is growing in well-controlled areas when the faecal egg excretion among infected individuals approaches zero. While antibody testing has ultimate sensitivity, its use as a test of cure remains contentious. On the other hand, employing faecal egg detection as the diagnostic 'gold' standard makes many positive antibody test results (incorrectly) appear false. Polymerase chain reaction (PCR)-based diagnostics could solve this dilemma, but more experience is needed and costs must be brought down to permit large-scale use of this approach. The future development of virtual microscopy to be used for diagnosis of parasitic infections in the field could make ordinary microscopy obsolete by electronically capturing specimens at point-of-contact in remote areas. PMID:20627143

Johansen, Maria Vang; Sithithaworn, Paiboon; Bergquist, Robert; Utzinger, Jürg

2010-01-01

236

Liver cirrhosis.  

PubMed

Cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14th most common cause of death worldwide but fourth in central Europe. Increasingly, cirrhosis has been seen to be not a single disease entity, but one that can be subclassified into distinct clinical prognostic stages, with 1-year mortality ranging from 1% to 57% depending on the stage. We review the current understanding of cirrhosis as a dynamic process and outline current therapeutic options for prevention and treatment of complications of cirrhosis, on the basis of the subclassification in clinical stages. The new concept in management of patients with cirrhosis should be prevention and early intervention to stabilise disease progression and to avoid or delay clinical decompensation and the need for liver transplantation. The challenge in the 21st century is to prevent the need for liver transplantation in as many patients with cirrhosis as possible. PMID:24480518

Tsochatzis, Emmanuel A; Bosch, Jaime; Burroughs, Andrew K

2014-05-17

237

Partial liver transplantation.  

PubMed

Partial liver transplantation, including reducedsize liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud's anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situ to ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations-including anatomical, liver volume, and liver function evaluations-is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society. PMID:21681668

Gong, Nianqiao; Chen, Xiaoping

2011-03-01

238

Liver in systemic disease  

PubMed Central

Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

Shimizu, Yukihiro

2008-01-01

239

Pyogenic liver abscess  

MedlinePLUS

Liver abscess; Bacterial liver abscess ... There are many potential causes of liver abscesses, including: Abdominal infection such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

240

American Liver Foundation  

MedlinePLUS

... the American Liver Foundation! Read our statement on Hepatitis B screening and visit our media center by clicking below: Additional Resources Liver Disease ... @liverUSA Online Hepatitis C Resource Please Visit Our New Online Hepatic ...

241

Liver transplantation in acute liver failure.  

PubMed

Acetaminophen and idiosyncratic drug induced hepatotoxicity are the most commonly identified etiologies of acute liver failure in Western countries. Infectious complications and cerebral edema remain the leading causes of death. Moderate hypothermia and other medical interventions may improve cerebral edema in selected patients with acute liver failure. In addition, pilot studies suggest that recombinant factor VIIa infusions may allow for the safe placement of intracranial pressure monitoring devices in patients with cerebral edema and severe coagulopathy. Auxiliary liver transplantation and bioartificial liver devices offer the hope of temporary liver support for selected patients with a high likelihood of native liver regeneration. Prognostic survival models that include arterial lactate levels may improve our ability to identify acetaminophen overdose patients in urgent need of liver transplantation. The lower 1-year patient survival following liver transplantation for acute liver failure compared to chronic liver failure (60 vs 80%) is in part due to the emergent nature of surgery, concomitant vital organ failure, and the higher incidence of immunologically mediated graft dysfunction. Vaccination against hepatotrophic viruses and other public health measures designed to minimize the incidence of both intentional and non-intentional acetaminophen overdose may help reduce the future incidence of acute liver failure. In the meanwhile, it is recommended that acute liver failure patients be managed in experienced centers with ready access to liver transplantation to optimize outcomes in this rare but frequently fatal illness. PMID:12855932

Higgins, P D R; Fontana, R J

2003-06-01

242

Differences in susceptibility and immune responses of three-spined sticklebacks (Gasterosteus aculeatus) from lake and river ecotypes to sequential infections with the eye fluke Diplostomum pseudospathaceum  

PubMed Central

Background The eye fluke Diplostomum pseudospathaceum is a frequent parasite of many fresh-water fish species, among those three-spined sticklebacks, particularly in lakes with lymnaeid snails, its first intermediate hosts. Cercariae released from host-snails, penetrate the skin of their fish hosts and within 24 h migrate to the immunologically inert eye lenses. Thus, individual D. pseudospathaceum are exposed to the fish immune system only for a short time, suggesting that only innate immunity can be active against the parasite. However, in nature sticklebacks are exposed to D. pseudospathaceum repeatedly since snails are shedding cercariae from late spring to autumn. Therefore, acquired immunity after initial infection would be advantageous against subsequent parasite encounters. Methods We investigated if sticklebacks originating from a lake with high and from a river with low prevalence of D. pseudospathaceum differ in susceptibility to repeated exposure to the parasite. We compared infection success and immune functions in laboratory-bred sticklebacks from both habitats in naïve fish with fish that had been pre-exposed to eye flukes. Head kidney leukocytes (HKL) from experimental sticklebacks were investigated for respiratory burst activity and the proliferation of lymphocytes and monocytes 1.5, 5 and 15 days after infection. Results Lake sticklebacks were less susceptible than river sticklebacks, however, in both populations pre-exposure led to a similar relative reduction in infection success. The respiratory burst activity was higher with HKL from lake sticklebacks and was up-regulated in pre-exposed fish but dropped 1.5d after an additional exposure, suggesting that activation of phagocytic cells is crucial for the defense against D. pseudospathaceum. Changes in lymphocyte proliferation were only detectable 1.5d after the last exposure in lake sticklebacks, but not 5 and 15d post exposure, indicating that a lymphocyte mediated acquired immune response was not induced. Proliferation of monocytes was significantly increased 1.5d after the last exposure with HKL from both stickleback populations. Conclusions Increased resistance to D. pseudospathaceum in sticklebacks from both populations upon pre-exposure cannot be explained by a prominent adaptive immune response. Monocytic leukocytes were more responsive, suggesting that rather cells of the innate than the adaptive immune system are active in the defense of D. pseudospathaceum.

2014-01-01

243

Metabolic liver disease.  

PubMed

Diagnosis of metabolic liver disease requires a high level of diagnostic suspicion. Diet is usually the primary treatment for metabolic liver disease. Where indicated, liver transplantation provides lifelong functional correction of liver-based metabolic defects. Liver cell therapy warrants further study for the future treatment of metabolic liver disease. All families should receive genetic advice and pre-emptive management of future affected siblings. PMID:22521124

McKiernan, Pat

2012-06-01

244

Amebic Liver Abscess  

MedlinePLUS

Hepatic amebiasis; Extraintestinal amebiasis; Abscess - amebic liver ... Amebic liver abscess is caused by Entamoeba histolytica. This is the same parasite that causes amebiasis , an intestinal infection ...

245

Liver cell adenoma and liver cell adenomatosis  

PubMed Central

During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection.

Barthelmes, Ludger

2005-01-01

246

Molecular and functional characterization of a tandem-repeat galectin from the freshwater snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni  

PubMed Central

In the present study, a tandem-repeat type galectin was characterized from an embryonic cell line (Bge) and circulating hemocytes of the snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni. The predicted B. glabrata galectin (BgGal) protein of 32 kDa possessed 2 carbohydrate recognition domains, each displaying 6 of 8 conserved amino acids involved in galactoside-binding activity. A recombinant BgGal (rBgGal) demonstrated hemagglutinating activity against rabbit erythrocytes, which was specifically inhibited by galactose-containing sugars (lacNAc/lac > galNAc/gal). Although native galectin was immunolocalized in the cytoplasm of Bge cells and the plasma membrane of a subset of snail hemocytes (60%), it was not detected in cell-free plasma by Western blot analysis. The findings that rBgGal selectively recognizes the schistosome-related sugar, lacNAc, and strongly binds to hemocytes and the tegument of S. mansoni sporocysts in a sugar-inhibitable fashion suggest that hemocyte-bound galectin may be serving as pattern recognition receptor for this, or other pathogens possessing appropriate sugar ligands. Based on molecular and functional features, BgGal represents an authentic galectin, the first to be fully characterized in the medically-important molluscan Class Gastropoda.

Yoshino, Timothy P.; Dinguirard, Nathalie; Kunert, John; Hokke, Cornelius H.

2008-01-01

247

Living with Your Liver  

NSDL National Science Digital Library

Students learn the function of the liver and how biomedical engineers can use liver regeneration to help people. Students test the effects of toxic chemicals on a beef liver by adding hydrogen peroxide to various liver and salt solutions. They observe, record and graph their results.

Integrated Teaching And Learning Program

248

Genetic diversity of nuclear ITS1-5.8S-ITS2 rDNA sequence in Clonorchis sinensis Cobbold, 1875 (Trematoda: Opisthorchidae) from the Russian Far East.  

PubMed

The present study examined the molecular organisation and sequence variation in the nuclear ribosomal DNA (rDNA) region, including the two internal transcribed spacers (ITS1 and ITS2) and the 5.8S gene of the Clonorchis sinensis from the Russian Far East. The relevant sequences from other parts of this species' area were downloaded from GenBank. The results showed 100% identity for all investigated 5.8S-ITS2 rDNA sequences. In contrast, two levels of intraspecific variations were revealed in the complete ITS1 sequences. The intra-genomic variation resulted from a C/T polymorphism in a single position. The inter-individual differences between the ITS1 sequences were both due to nucleotide and size polymorphisms resulting from a varying number of five-nucleotide repeats and followed by two ITS1 length variants. These variant frequencies correlate with the clonorchiasis level in some geographical localities. ITS1 differences, both in the mutation profile and mutation localisation, were revealed between northern and southern geographical samples. The presence of GC boxes that are identical to known regulatory motifs in eukaryotes was detected within the ITS1 sub-repeats. The predicted secondary structures for ITS1 consist of two large branches, one of which was invariable, while another depended on ITS1 length. The predicted secondary structure for ITS2 includes four helices around the core. The main differences between C. sinensis and other opisthorchids were localised on the tops of helices 2, 3, and 4. A phylogenetic MST reconstruction subdivided all ITS1 sequences into two well differentiated clusters, each with the major widespread ribotype, and showed that ribotype diversity in both Russia and Korea is much lower than in China. The results obtained demonstrate the feasibility of complete ITS1 sequences in C. sinensis population genetics and can be considered as a basis for further studies of the parasite infection because they may help to elucidate the molecular mechanisms of pathogen evolution and adaptation. PMID:22824337

Tatonova, Yulia V; Chelomina, Galina N; Besprosvannykh, Vladimir V

2012-12-01

249

Liver fibrosis markers in alcoholic liver disease  

PubMed Central

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), ?-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

Chrostek, Lech; Panasiuk, Anatol

2014-01-01

250

SR2 elements, non-long terminal repeat retrotransposons of the RTE-1 lineage from the human blood fluke Schistosoma mansoni.  

PubMed

As in other eukaryotes, a substantial portion of the genome of the human blood flukes belonging to the genus Schistosoma appears to be composed of mobile genetic elements and other repetitive sequences. The constitutent elements and their relative organization are not well understood, although retroposons (the SM alpha elements) and a family of non-long terminal repeat (LTR) retrotransposons (the SR1 elements) have been reported from the genome of Schistosoma mansoni. Here, we report the presence of a second family of non-LTR retrotransposons from S. mansoni which we have termed the SR2 elements. SR2 elements are members of a recently described lineage of non-LTR retrotransposons typified by the RTE-1 non-LTR retrotransposon of Caenorhabditis elegans. We determined the sequence for approximately 3.9 kb of a consensus full-length SR2 element, which included a long 5' untranslated region (UTR), potential first and second open reading frames (ORFs) of 78 and 1,018 amino acid residues, respectively, a short 3' UTR, and an A-rich 3' terminus. SR2 elements were bound by target site duplications. The putative first and second ORFs did not overlap. The second ORF was homologous to retroviral pol and encoded an apurinic/apyrimidinic endonuclease and a reverse transcriptase. A number of extremely short SR2 elements of less than 0.5 kb, reminiscent of SINEs, were also characterized. These consisted solely of the 5' and 3' UTRs of full-length SR2 elements, having both ORFs deleted. Analysis indicated that these SINE-like SR2 elements were produced by replication of a SINE-like SR2 element, rather than by repeated deletions within larger SR2 elements. PMID:10486981

Drew, A C; Minchella, D J; King, L T; Rollinson, D; Brindley, P J

1999-09-01

251

Chronic Liver Diseases as Liver Tumor Precursors  

Microsoft Academic Search

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence

Jan Lata

2010-01-01

252

Living Donor Liver Transplantation  

MedlinePLUS

... go through certain medical tests like blood work, radiology studies, and a liver biopsy A person should ... for me to donate my liver? The recipient’s health insurance pays for the donor’s health care costs. This ...

253

Isolated polycystic liver disease.  

PubMed

Isolated polycystic liver disease (PCLD) is an autosomal dominant disease with genetic and clinical heterogeneity. Apart from liver cysts, it exhibits few extrahepatic manifestations, and the majority of patients with this condition are asymptomatic or subclinical. However, a small fraction of these patients develop acute liver cyst-related complications and/or massive cystic liver enlargement, causing morbidity and mortality. Currently, the management for symptomatic PCLD is centered on palliating symptoms and treating complications. PMID:20219621

Qian, Qi

2010-03-01

254

ISOLATED POLYCYSTIC LIVER DISEASE  

PubMed Central

Isolated polycystic liver disease (PCLD) is an autosomal dominant disease with genetic and clinical heterogeneity. Apart from liver cysts, it exhibits few extra-hepatic manifestations and the majority of patients with this condition are asymptomatic or subclinical. However, a small fraction of these patients develop acute liver-cyst-related complications and/or massive cystic liver enlargement, causing morbidity and mortality. Currently, the management for symptomatic PCLD is centered on palliating symptoms and treating complications.

Qian, Qi

2010-01-01

255

Cell Therapies for Liver Diseases  

PubMed Central

Cell therapies, which include bioartificial liver support and hepatocyte transplantation, have emerged as potential treatments for a variety of liver diseases. Acute liver failure (ALF), acute-on-chronic liver failure, and inherited metabolic liver diseases are examples of liver diseases that have been successfully treated with cell therapies at centers around the world. Cell therapies also have the potential for wide application in other liver diseases, including non-inherited liver diseases and liver cancer, and in improving the success of liver transplantation. Here we briefly summarize current concepts of cell therapy for liver diseases.

Yu, Yue; Fisher, James E.; Lillegard, Joseph B.; Rodysill, Brian; Amiot, Bruce; Nyberg, Scott L.

2011-01-01

256

Liver abnormalities in pregnancy.  

PubMed

Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication. PMID:24090943

Than, Nwe Ni; Neuberger, James

2013-08-01

257

Ultrasound elastography in liver.  

PubMed

Conventional imaging techniques cannot provide information about tissue mechanical properties. Many injuries can cause changes in tissue stiffness, especially tumors and fibrosis. In recent years, various non-invasive ultrasound methods have been developed to study tissue elasticity for a large number of applications (breast, thyroid, prostate, kidneys, blood vessels, liver…). For non-invasive assessment of liver diseases, several ultrasound elastography techniques have been investigated: Transient elastography (the most extensively used), Real Time Elastography (RTE), Acoustic Radiation Force Impulse Imaging (ARFI) and more recently Shear Wave Elastography (SWE). Even if evaluation of liver fibrosis in chronic liver disease remains the principal application, there are many others applications for liver: predicting cirrhosis-related complications; monitoring antiviral treatments in chronic viral liver disease; characterizing liver tumors; monitoring local treatments, etc. The aim of this article is to report on the different hepatic ultrasound elastography techniques, their advantages and disadvantages, their diagnostic accuracy, their applications in clinical practice. PMID:23623211

Frulio, N; Trillaud, H

2013-05-01

258

The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements  

PubMed Central

Background Of the major families of long terminal repeat (LTR) retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. Results A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT), RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs representing transcripts of Sinbad in numerous developmental stages of S. mansoni along with the identical 5'- and 3'-LTR sequences suggests that Sinbad is an active retrotransposon. Conclusion Sinbad is a Pao/BEL type retrotransposon from the genome of S. mansoni. The Pao/BEL group appears to be comprised of at least five discrete subfamilies, which tend to cluster with host species phylogeny. Pao/BEL type elements appear to have colonized only the genomes of the Animalia. The distribution of these elements in the Ecdysozoa, Deuterostomia, and Lophotrochozoa is discontinuous, suggesting horizontal transmission and/or efficient elimination of Pao-like mobile genetic elements from some genomes.

Copeland, Claudia S; Mann, Victoria H; Morales, Maria E; Kalinna, Bernd H; Brindley, Paul J

2005-01-01

259

pido, a non-long terminal repeat retrotransposon of the chicken repeat 1 family from the genome of the Oriental blood fluke, Schistosoma japonicum.  

PubMed

A newly described non-long terminal repeat (non-LTR) retrotransposon element was isolated from the genome of the Oriental schistosome, Schistosoma japonicum. At least 1000 partial copies of the element, which was named pido, were dispersed throughout the genome of S. japonicum. As is usual with non-LTR retrotransposons, it is expected that many pido elements will be 5'-truncated. A consensus sequence of 3564 bp of the truncated pido element was assembled from several genomic fragments that contained pido-hybridizing sequences. The sequence encoded part of the first open reading frame (ORF), the entire second ORF and, at its 3'-terminus, a tandemly repetitive, A-rich (TA(6)TA(5)TA(8)) tail. The ORF1 of pido encoded a nucleic acid binding protein and ORF2 encoded a retroviral-like polyprotein that included apurinic/apyrimidinic endonuclease (EN) and reverse transcriptase (RT) domains, in that order. Based on its sequence and structure, and phylogenetic analyses of both the RT and EN domains, pido belongs to the chicken repeat 1 (CR1)-like lineage of elements known from the chicken, turtle, puffer fish, mosquitoes and other taxa. pido shared equal similarity with CR1 from chicken, an uncharacterized retrotransposon from Caenorhabditis elegans and SR1 (a non-LTR retrotransposon) from the related blood fluke Schistosoma mansoni; the level of similarity between pido and SR1 indicated that these two schistosome retrotransposons were related but not orthologous. The findings indicate that schistosomes have been colonized by at least two discrete CR1-like elements. Whereas pido did not appear to have a tight target site specificity, at least one copy of pido has inserted into the 3'-untranslated region of a protein-encoding gene (GenBank AW736757) of as yet unknown identity. mRNA encoding the RT of pido was detected by reverse transcription-polymerase chain reaction in the egg, miracidium and adult developmental stages of S. japonicum, indicating that the RT domain was transcribed and suggesting that pido was replicating actively and mobile within the S. japonicum genome. PMID:11891056

Laha, Thewarach; Brindley, Paul J; Verity, Christiana K; McManus, Donald P; Loukas, Alex

2002-02-01

260

Elucidating the transcriptome of Fasciola hepatica - a key to fundamental and biotechnological discoveries for a neglected parasite.  

PubMed

Liver flukes of animals are parasitic flatworms (Platyhelminthes: Digenea) of major socioeconomic importance in many countries. Key representatives, such as Fasciola hepatica and F. gigantica, cause "liver fluke disease" (= fascioliasis), which is of major animal health significance worldwide. In particular, F. hepatica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. This parasite is also a major food-borne pathogen of humans throughout parts of the Middle East, Asia and South America. Currently, there is a significant focus on the development of new approaches for the prevention and control of fascioliasis in livestock. Recent technological advances in genomics and bioinformatics provide unique opportunities for the identification and prevalidation of drug targets and vaccines through a better understanding of the biology of F. hepatica and related species as well as their relationship with their hosts at the molecular level. Surprisingly, despite the widespread socioeconomic impact of fascioliasis, genomic datasets for F. hepatica are scant, limiting the molecular biological research of this parasite. The present article explores specifically the transcriptome of the adult stage of F. hepatica using an integrated genomic-bioinformatic platform. The analysis of the current data reveals numerous molecules of biological relevance, some of which are inferred to be involved in key biological processes or pathways that could serve as targets for new trematocidal drugs or vaccines. Improved insights into the transcriptome of F. hepatica should pave the way for future, comparative analysis of the transcriptomes of other developmental stages of this and related parasites, such as F. gigantica, cancer-causing flatworms (Clonorchis sinensis and Opisthorchis viverrini) and blood flukes (Schistosoma mansoni and S. japonicum). Prediction of the essentiality of genes and their products, molecular network connectivity of trematode genes as well as experimental exploration of function should also add value to the genomic discovery efforts in the future, focused on biotechnological outcomes. PMID:20006979

Young, Neil D; Hall, Ross S; Jex, Aaron R; Cantacessi, Cinzia; Gasser, Robin B

2010-01-01

261

Farm-Level Risk Factors for Fish-Borne Zoonotic Trematode Infection in Integrated Small-Scale Fish Farms in Northern Vietnam  

PubMed Central

Background Northern Vietnam is an endemic region for fish-borne zoonotic trematodes (FZT), including liver and intestinal flukes. Humans acquire the FZT infection by eating raw or inadequately cooked fish. The production of FZT-free fish in aquaculture is a key component in establishing a sustainable program to prevent and control the FZT transmission to humans. Interventions in aquaculture should be based on knowledge of the main risk factors associated with FZT transmission. Methodology/Principal Findings A longitudinal study was carried out from June 2006 to May 2007 in Nam Dinh province, Red River Delta to investigate the development and risk factors of FZT infections in freshwater cultured fish. A total of 3820 fish were sampled six times at two-month intervals from 96 fish farms. Logistic analysis with repeated measurements was used to evaluate potential risk factors based on information collected through questionnaire interviews with 61 fish farm owners. The results showed that the FZT infections significantly increased from first sampling in June to July 2006 (65%) to sixth sampling in April to May, 2007 (76%). The liver fluke, Clonorchis sinensis and different zoonotic intestinal flukes including Haplochis pumilio, H. taichui, H. yokogawai, Centrocestus formosanus and Procerovum varium were found in sampled fish. Duration of fish cultured (sampling times), mebendazole drug self-medication of household members, presence of snails in the pond, and feeding fish with green vegetation collected outside fish farms all had a significant effect on the development of FZT prevalence in the fish. Conclusions/Significance The FZT prevalence in fish increased by 11 percentage points during a one-year culture period and the risk factors for the development of infection were identified. Results also highlight that the young fish are already highly infected when stocked into the grow-out systems. This knowledge should be incorporated into control programs of FZT transmission in integrated small-scale aquaculture nursery and grow-out systems in Vietnam.

Phan, Van Thi; Ersb?ll, Annette Kjaer; Nguyen, Khue Viet; Madsen, Henry; Dalsgaard, Anders

2010-01-01

262

Transplantable liver production plan  

PubMed Central

Organ grafts developed in the xenogeneic pig scaffold are expected to resolve most issues of donor safety and ethical concerns about living-donor liver transplantation in Japan. We have been working on so-called “Yamaton” projects to develop transplantable organs using genetically engineered pigs. Our goal is to produce chimeric livers with human parenchyma in such pigs. The Yamaton-Liver project demonstrated the proof of concept by showing that rat–mouse chimeric livers could develop in mice and be successfully transplanted into syngeneic or allogeneic rats. Under conventional immunosuppression, the transplanted livers showed long-term function and protection against rejection. Because chimeric liver grafts have xenogeneic components, additional strategies, such as humanization of pig genes, induction of hematopoietic chimeras in donors, and replacement of pig endothelial cells with human ones, might be required in clinical use. Our projects still need to overcome various hurdles but can bring huge benefits to patients in the future.

Hata, Toshiyuki; Uemoto, Shinji; Kobayashi, Eiji

2013-01-01

263

Ductopenia related liver sarcoidosis  

PubMed Central

Sarcoidosis is a systemic granulomatous disease which may involve many organs. In approximately 95% of patients there is liver involvement, with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis. Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry. The occurrence of jaundice in sarcoidosis is rare; extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic. Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver- related death. We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded. The patient follow up was 8 years. Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis. A review of the literature of reported cases of ductopenia related to sarcoidosis is provided.

Farouj, Nourr-Eddine; Cadranel, Jean-Francois D; Mofredj, Ali; Jouannaud, Vincent; Lahmiri, Maria; Lann, Pierre Le; Cazier, Alain

2011-01-01

264

Immunology of liver transplantation.  

PubMed

In comparison with other solid-organ transplants, liver allografts are immunologically privileged. Allografts are rejected by immune reactions of the host, and clinical therapy for liver allografts includes immunosuppression to prevent rejection. Orthotopic liver transplant causes systemic donor-specific T-cell tolerance. In addition, antigens introduced into hepatocytes or the portal vein cause tolerance. The basic mechanism in liver tolerance may include continuous exposure of diverse liver cell types to endotoxin derived from intestinal bacteria. This exposure promotes the expression of cytokines, antigen-presenting molecules, and costimulatory signals that inactivate T cells, partly by effects on liver antigen-presenting cells. A simple, reliable, noninvasive assay to evaluate antidonor alloreactivity may be important in implementing these approaches in the laboratory and clinic. PMID:24635783

?nal, Ali

2014-03-01

265

Autoimmune paediatric liver disease  

Microsoft Academic Search

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and\\/or antinuclear antibody (SMA\\/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients

Giorgina Mieli-Vergani; Diego Vergani

2008-01-01

266

Autotaxin in liver fibrosis.  

PubMed

Autotaxin (ATX) hydrolyzes lysophosphatidylcholine to produce lysophosphatidic acid (LPA), a multi-functional bioactive lipid mediator. ATX is a major determinant of LPA levels in the blood, and the pathophysiological functions of ATX are thought to be largely attributed to its ability to produce LPA. Liver fibrosis is one of the rare disorders exhibiting the increased ATX and LPA levels in the blood. This review summarizes the recent findings on the relation between ATX or LPA and liver fibrosis, the usefulness of serum ATX levels to predict the stages of liver fibrosis, and speculated roles of increased serum ATX and plasma LPA levels in liver fibrosis. PMID:22820036

Ikeda, Hitoshi; Yatomi, Yutaka

2012-11-20

267

Fatty liver and nonalcoholic steatohepatitis  

Microsoft Academic Search

Fatty liver is a relatively common incidental finding on imaging studies. Although generally a benign condition, fat in the liver can be troubling for clinicians because it can cause persistently elevated liver enzyme levels. The finding of fatty liver may also indicate the presence of nonalcoholic steatohepatitis (NASH). NASH is a histologic diagnosis applied to a constellation of liver biopsy

Brent A. Neuschwander-Tetri

2001-01-01

268

About the Operation: Liver Transplant  

MedlinePLUS

... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both of ...

269

Arterioportal Fistula Following Liver Biopsy  

PubMed Central

Liver biopsy is a diagnostic procedure which is utilized frequently in liver transplant recipients. Here we report the experience of the University of Pittsburgh with an unusual complication of this procedure occurring in liver transplant recipients.

JABBOUR, NICOLAS; REYES, JORGE; ZAJKO, ALBERT; NOUR, BAKR; TZAKIS, ANDREAS G.; STARZL, THOMAS E.; VAN THIEL, DAVID H.

2010-01-01

270

Acute liver failure  

Microsoft Academic Search

Acute liver failure is a complex multisystemic illness that evolves quickly after a catastrophic insult to the liver leading to the development of encephalopathy. The underlying aetiology and the pace of progression strongly influence the clinical course. The commonest causes are paracetamol, idiosyncratic drug reactions, hepatitis B, and seronegative hepatitis. The optimal care is multidisciplinary and up to half of

J G O’Grady

2005-01-01

271

Reversal of Liver Fibrosis  

PubMed Central

Hepatic fibrosis is a scarring process associated with an increased and altered deposition of extracellular matrix in the liver. It is caused by a variety of stimuli and if fibrosis continues unopposed, it would progress to cirrhosis which poses a significant health problem worldwide. At the cellular and molecular level, this progressive process is characterized by cellular activation of hepatic stellate cells and aberrant activity of transforming growth factor-? with its downstream cellular mediators. Liver biopsy has been the reference test for assessment of hepatic fibrosis, but because of its limitations, noninvasive markers of liver fibrosis were developed. Liver fibrosis or cirrhosis was considered irreversible in the past but progress of research on the molecular pathogenesis of liver fibrosis has shown that hepatic cellular recovery is possible. Currently, no acceptable therapeutic strategies exist, other than removal of the fibrogenic stimulus, to treat this potentially devastating disease.

Ismail, Mona H.; Pinzani, Massimo

2009-01-01

272

Schistosomiasis of the liver.  

PubMed

Schistosomiasis is an infection of trematodes, Schistosoma, causing periportal fibrosis and liver cirrhosis due to deposition of eggs in the small portal venules. In schistosomiasis caused by S. mansoni, sonography shows echogenic thickening or fibrotic band along the portal veins. CT shows low-attenuation bands or rings around the large portal vein branches in the central part of the liver with marked enhancement. Hepatoplenomegaly, liver cirrhosis, portal hypertension and gastroesophageal varies are commonly associated. In schistosomiasis caused by S. japonicum, sonography shows echogenic septae in the liver, utlining the polygonal liver lobules, mimicking "fish-scale" network appearance, reflecting fibrosis. CT shows periportal septae in the peripheral part of the liver parenchyma, producing "turtle-back" appearance, representing calcified eggs along the portal tracts. The portal tracts and hepatic capsule are enhanced on contrast-enhanced CT images. The size and shape of the liver are relatively preserved. MR images show fibrous septae as low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and these fibrous septae are enhanced. CT images of the lungs show multiple scattered nodules with halo of ground-glass opacities. Exudative granulomatous inflammation of the colonic wall may produce inflammatory polyps, fibrous thickening or stenosis of the colonic wall. PMID:17912583

Manzella, Adonis; Ohtomo, Kuni; Monzawa, Shuichi; Lim, Jae Hoon

2008-01-01

273

Pathogenesis of liver cirrhosis  

PubMed Central

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.

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

2014-01-01

274

Anesthesia for liver transplantation.  

PubMed

Orthotopic liver transplantation is the only definitive treatment for end-stage liver disease. More than 6000 procedures are performed in the United States annually with excellent survival rates. The shortage of donor organs leads to continued interest in techniques to enlarge the potential donor pool. Patients presenting for liver transplant suffer from important cardiovascular, respiratory, renal, neurological, and gastroenterological comorbidity. In the Western world, liver failure is increasingly caused by steatohepatitis, and transplant candidates are thus becoming older and more comorbid. The role of the transplant anesthesiologist is highly important in the preoperative assessment, intraoperative management, and postoperative care of these complex and sick patients. Appropriate investigation and management of comorbidities such as coronary artery disease and portopulmonary hypertension is controversial and differs between programs. The transplant procedure is a major surgery, and although massive transfusion is no longer commonplace, there is potential for significant hemodynamic instability, coagulopathy, and metabolic disturbance. Liver transplant surgery can be divided into the preanhepatic phase, the anhepatic phase, and the reperfusion phase, with important anesthetic considerations at each point. ?An understanding of the surgical techniques used for vascular exclusion of the liver and the role of venovenous bypass is crucial for the anesthesiologist. Recent trends in perioperative care include the use of antifibrinolytic drugs and point-of-care coagulation tests, intraoperative renal replacement therapy, and "fast-track" extubation and postoperative care. Care of patients with fulminant hepatic failure or those receiving split-liver grafts requires special consideration. PMID:23482506

Hall, Timothy H; Dhir, Achal

2013-09-01

275

Alcoholic liver disease  

PubMed Central

Alcohol use disorders affect millions of individuals worldwide. Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs. Alcoholic liver disease (ALD) may take the form of acute involvement (alcoholic hepatitis) or chronic liver disease (steatosis, steatohepatitis, fibrosis and cirrhosis). The severity and prognosis of alcohol-induced liver disease depends on the amount, pattern and duration of alcohol consumption, as well as on the presence of liver inflammation, diet, nutritional status and genetic predisposition of an individual. While steatosis is an almost completely benign disease, liver cirrhosis is associated with marked morbidity, mortality and life expectancy shortening. The median survival of patients with advanced cirrhosis is 1-2 years. Severe acute alcoholic hepatitis (AH) is associated with mortality as high as 50%. It has been managed with corticoids, pentoxifylline and enteral nutrition, although evidence based data are still conflicting. Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH. Absolute abstinence is a basic condition for any treatment of acute or chronic ALD, the other therapeutical procedure being of a supportive nature and questionable significance. Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alcohol dependent patients. Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation, which leads to a markedly prolonged life expectancy. The crucial step in ALD prevention is in the prevention of alcohol abuse, whereas the prevention of liver injury in active alcohol abusers is not clinically applicable.

Bruha, Radan; Dvorak, Karel; Petrtyl, Jaromir

2012-01-01

276

Evidence for liver cell proliferation during fatal acute liver failure  

Microsoft Academic Search

Liver cell regeneration was assessed by determining the mitotic index and the frequency of liver cells with interploid DNA values in livers from patients dying from fulminant hepatitis. For comparison, the same parameters were determined in patients with uncomplicated hepatitis. We found comparable levels of regeneration in the two groups, indicating that the rate of liver cell destruction is a

M Milandri; J Gaub; L Ranek

1980-01-01

277

Probiotics and Liver Disease  

PubMed Central

Intestinal microbiota play an important role in health and disease. The gut-liver axis provides for an interaction between bacterial components like lipopolysaccharide and hepatic receptors (Toll-like receptors). Dysbiosis and altered intestinal permeability may modulate this interaction and therefore result in hepatic disorders or worsening of hepatic disorders. Administration of health-promoting microbial strains may help ameliorate these harmful interactions and hepatic disorders. This review focuses on changes in gut microbiota in the context of liver disease and possible roles of probiotics, prebiotics, and synbiotics in liver disease.

Sharma, Vishal; Garg, Shashank; Aggarwal, Sourabh

2013-01-01

278

Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant  

ClinicalTrials.gov

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

2014-05-05

279

Infections in liver transplant recipients.  

PubMed

Liver transplant is a life-saving procedure for many end-stage liver diseases. Despite measures such as the use of protective barriers, antimicrobial prophylaxis, and vaccination, infections still represent a major cause of morbidity and mortality after liver transplant. This article reviews major infectious concerns after liver transplant. PMID:24635787

Arslan, Hande

2014-03-01

280

Pediatric liver transplantation  

PubMed Central

In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation.

Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

2009-01-01

281

Modular extracorporeal liver support.  

PubMed

Modular extracorporeal liver support (MELS) is an integrative concept for the treatment of hepatic failure with appropriate extracorporeal therapy units tailored to suit the actual clinical needs of each patient. The CellModule is a specific bioreactor charged with primary human liver cells harvested from human donor livers found to be unsuitable for transplantation due to steatosis, cirrhosis, or traumatic injury. The DetoxModule enables albumin dialysis for the removal of albumin-bound toxins, reducing the biochemical burden of the liver cells and replacing the bile excretion of hepatocytes in the bioreactor. A DialysisModule for continuous venovenous hemofiltration can be added to the system if required in hepatorenal syndrome. PMID:12139497

Sauer, Igor M; Gerlach, Joerg C

2002-08-01

282

Fatty Liver Disease.  

National Technical Information Service (NTIS)

The relationship between liver disease and prior exposure to hepatotoxic agents was investigated in four separate studies. The first was a cross sectional study of hazardous waste workers who were well protected. The study examined the relationship betwee...

M. J. Hodgson D. H. Van Thiel

1991-01-01

283

Fusobacterium liver abscess.  

PubMed

Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome); its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation. PMID:24348321

Buelow, Ben D; Lambert, Joelle M; Gill, Ryan M

2013-01-01

284

Autoimmune liver disease panel  

MedlinePLUS

... liver/kidney microsomal antibodies Anti-mitochondrial antibodies Anti-nuclear antibodies Anti-smooth muscle antibodies Sometimes the panel may also include other tests. Often immune protein levels in the blood are ...

285

Fusobacterium Liver Abscess  

PubMed Central

Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome); its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation.

Buelow, Ben D.; Lambert, Joelle M.; Gill, Ryan M.

2013-01-01

286

Nonalcoholic Fatty Liver Disease  

Microsoft Academic Search

\\u000a Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in North America, affecting approximately\\u000a 30% of the population [1]. It is the hepatic manifestation of the metabolic syndrome, and is directly linked to the escalating\\u000a prevalence of obesity and the associated insulin resistance. Histologically, NAFLD is characterized by a spectrum that ranges\\u000a from nonalcoholic fatty

Onpan Cheung; Arun J. Sanyal

287

Acute liver failure  

Microsoft Academic Search

Opinion statement  Acute liver failure (ALF) is an uncommon medical emergency whose rapid progression and high mortality demand early diagnosis\\u000a and expert management, including immediate transfer of any potential case to facilities for intensive care and orthotopic\\u000a liver transplantation (OLT). All patients with ALF must be screened aggressively for acetaminophen toxicity (history, serum\\u000a levels, “hyperacute” presentation with renal failure), for other

J. Eileen Hay

2004-01-01

288

Liver resection in octogenarians  

PubMed Central

Background. Liver resections are increasingly being perfomed safely in elderly patients. There are no present reports of thje operative safety of liver resection in octogenarians who represents a rapidly increasing segment of the population. The purpose of this study was to analyse the results of liver resection in octogenarians over a 5 year period within a tertiary referral liver surgery unit. Methods. Prospective data collection and analysis of octogenarians having liver resection between 1999 and 2004. Retrospective detailed case note analysis was performed to determine peri-operative mortality and morbidity. Comparison were made to other large series of liver resection in younger patient cohorts. The primary outcome measure was 30 day mortality and secondarily a detailed analysis of post-operative complications was performed. Results. A total 15 octogenarians (median age 82) were identified from the database. Ther was 1 peri-operative mortality. The remaining patients were all alive at 1, 3 and 6 month follow-ups with a median follow-up of 18 months. The commonest indication for liver resection was metastatic colorectal cancer (n=1). The median operating time was 142.5 minutes and 67% of patients (n=10) had portal clamping for a median of 21.5 minutes. The median length of hospitalization was 12 days with an ICU stay of 1 day, 27% (n=4) had major surgical complications. A further 20% (n=3) had exacerbations of pre-existing comorbities. Conclusion. Liver resection can be performed safely in octogenarians within a tertiary referral unit. It has a low mortality and an acceptable level of morbidity in carefully selected octogenarians.

Riffat, F.; Chu, F.

2006-01-01

289

Fortuitously discovered liver lesions  

PubMed Central

The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible.

Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

2013-01-01

290

Fortuitously discovered liver lesions.  

PubMed

The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible. PMID:23745019

Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

2013-06-01

291

Epidemiology of cancer of the liver and intrahepatic bile ducts in an Australian population.  

PubMed

The incidence of liver and intrahepatic bile duct cancer in Australia is low at about one third the world average but increases are evident. South Australian registry data have been used to describe: age-standardized incidence and mortality trends; and disease-specific survivals, using Kaplan-Meier estimates and Cox proportional hazards regression. The study included 1,220 incident cancers (901 hepatocellular carcinomas; 201 cholangiocarcinomas; 118 other types) and 983 deaths. Incidence and mortality rates increased by 2-3 fold during 1977-2007. Incidence increases affected males, females and all ages. There was a strong: male predominance (3 to 1); and age gradient (70+ year old incidence >30 times under 50 year old incidence). Compared with hepatocellular carcinomas, cholangiocarcinomas and other histology types more often affected females and older ages and less often the Asian born. All histology types showed similar incidence increases. Apart from recognized risk factors (e.g., hepatitis B/C infection and aflatoxins for hepatocellular carcinoma; liver-fluke infection for cholangiocarcinomas, etc.), common risk factors may include excess alcohol consumption and possibly obesity and diabetes mellitus. Five-year disease-specific survival in 1998-2007 was 16%, with higher fatalities applying for earlier periods, older patients, males, lower socio-economic groups, and cholangiocarcinomas. Aboriginal patients tended to have higher case fatalities (p=0.054). Survival increases may be due to earlier diagnosis from alpha feta protein testing and diagnostic imaging, plus more aggressive treatment of localized disease. Mortality increases require a preventive response, including hepatitis B vaccination, prevention of viral infection though contaminated blood and other body fluids, early detection initiatives for high-risk patients, aggressive surgery for localized disease, and experimentation with new systemic therapies. PMID:21338184

Luke, Colin; Price, Timothy; Roder, David

2010-01-01

292

Stereoscopic liver surface reconstruction  

PubMed Central

The paper presents a practical approach to measuring liver motion, both respiratory and laparoscopic, with a tool guided in the operating room. The presented method is based on standard operating room equipment, i.e. rigid laparoscopic cameras and a single incision laparoscopic surgery trocar. The triangulation algorithm is used and stereo correspondence points are marked manually by two independent experts. To calibrate the cameras two perpendicular chessboards, a pinhole camera model and a Tsai algorithm are used. The data set consists of twelve real liver surgery video sequences: ten open surgery and two laparoscopic, gathered from different patients. The setup equipment and methodology are presented. The proposed evaluation method based on both calibration points of the chessboard reconstruction and measurements made by the Polaris Vicra tracking system are used as a reference system. In the analysis stage we focused on two specific goals, measuring respiration and laparoscopic tool guided liver motions. We have presented separate examples for left and right liver lobes. It is possible to reconstruct liver motion using the SILS trocar. Our approach was made without additional position or movement sensors. Diffusion of cameras and laser for distance measurement seems to be less practical for in vivo laparoscopic data, but we do not exclude exploring such sensors in further research.

Karwan, Adam; Rudnicki, Jerzy; Wroblewski, Tadeusz

2012-01-01

293

Thiazolidinediones and liver toxicity.  

PubMed

Thiazolidinediones or glitazones specifically target insulin resistance. They have proven efficacy for reducing plasma glucose levels of type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. In addition, they may be associated to some improvement of cardiovascular risk profile. However, troglitazone, the first compound approved by the FDA in the US, proved to be hepatotoxic and was withdrawn from the market after the report of several dozens of deaths or cases of severe hepatic failure requiring liver transplantation. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. Rosiglitazone and pioglitazone, two other glitazones, appear to have similar efficacy on blood glucose control of type 2 diabetic patients as compared to troglitazone. In controlled clinical trials, the incidence of significant increases in liver enzyme levels (ALT) was similar with rosiglitazone or pioglitazone as compared to placebo, whereas troglitazone was associated with a threefold greater incidence. In contrast to the numerous case reports of acute liver failure in patients receiving troglitzone, only two cases of severe reversible liver failure have been reported in patients treated with rosiglitazone, with a causal relationship remaining uncertain. Furthermore, no single case of severe hepatotoxicity has been reported yet with pioglitazone. While regular monitoring of liver enzymes is still recommended and more long-term data are desirable, current clinical evidence supports the conclusion that rosiglitazone and pioglitazone do not share the hepatotoxic profile of troglitazone. PMID:11431595

Scheen, A J

2001-06-01

294

Stereoscopic liver surface reconstruction.  

PubMed

The paper presents a practical approach to measuring liver motion, both respiratory and laparoscopic, with a tool guided in the operating room. The presented method is based on standard operating room equipment, i.e. rigid laparoscopic cameras and a single incision laparoscopic surgery trocar. The triangulation algorithm is used and stereo correspondence points are marked manually by two independent experts. To calibrate the cameras two perpendicular chessboards, a pinhole camera model and a Tsai algorithm are used. The data set consists of twelve real liver surgery video sequences: ten open surgery and two laparoscopic, gathered from different patients. The setup equipment and methodology are presented. The proposed evaluation method based on both calibration points of the chessboard reconstruction and measurements made by the Polaris Vicra tracking system are used as a reference system. In the analysis stage we focused on two specific goals, measuring respiration and laparoscopic tool guided liver motions. We have presented separate examples for left and right liver lobes. It is possible to reconstruct liver motion using the SILS trocar. Our approach was made without additional position or movement sensors. Diffusion of cameras and laser for distance measurement seems to be less practical for in vivo laparoscopic data, but we do not exclude exploring such sensors in further research. PMID:23256023

Spinczyk, Dominik; Karwan, Adam; Rudnicki, Jerzy; Wróblewski, Tadeusz

2012-08-01

295

[Chronic liver diseases and diabetes].  

PubMed

The presence of chronic liver diseases may drastically limit the use of anti-diabetic drugs. Chronic liver diseases increase insulin resistance, and in some risk groups promote the development of diabetes. Therefore, antidiabetic treatment should be adapted to the severity of liver disease. However, diabetes, notably when associated with obesity and dyslipidemia, participates in the development of nonalcoholic fatty liver disease and to steato-hepatitis that may progress to cirrhosis and hepatocellular carcinoma. Other relations between diabetes and chronic liver disease will be discussed in this article. Finally, the indications and limits of each anti-diabetic therapy group will be discussed according to the degree of liver damage. PMID:25004772

Jaafar, Jaafar; de Kalbermatten, Bénédicte; Philippe, Jacques; Scheen, André; Jornayvaz, François R

2014-06-01

296

[Liver diseases and pregnancy].  

PubMed

The pregnancy determines a deep variation in the human physiology mediated through sexual hormones. These changes can entail the appearance of diseases that affect the liver such as hyperemesis gravidarum, HELLP syndrome, intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy. The knowledge of the specific features of these diseases is crucial for their prompt recognition, since they are uncommon diseases in the clinical daily setting of the hepatologist. In addition, several preexisting chronic hepatopathies, including the liver post-transplant status, can affect the course of pregnancy and the maternal-fetal health. Understanding the distinct hepatic diseases which develop during pregnancy must be based on the knowledge of the perceptible physiological changes both on physical examination and laboratory tests which occur during the uneventful gestation. PMID:11766287

Nicolás Pérez, D; Ortiz Bellver, V; Pastor Plasencia, M A; Berenguer Haym, M; Ponce García, J

2001-10-01

297

Liver physiology and liver diseases in the elderly  

PubMed Central

The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Moreover, elderly patients have significantly decreased reserve functions of various organs, reducing their tolerability to treatments for liver diseases. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients.

Tajiri, Kazuto; Shimizu, Yukihiro

2013-01-01

298

[Alcoholic liver disease and liver transplantation].  

PubMed

Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed. PMID:23439536

Testino, Gianni; Patussi, Valentino; Scafato, Emanuele

2013-01-01

299

Protective effect of melatonin against Opisthorchis viverrini-induced oxidative and nitrosative DNA damage and liver injury in hamsters.  

PubMed

The liver fluke, Opisthorchis viverrini, is the risk factor of cholangiocarcinoma, which is a major health problem in northeastern Thailand. Production of reactive oxygen and nitrogen species during the host's response leads to oxidative and nitrosative stress contributing to carcinogenesis. We investigated the protective effect of melatonin against O. viverrini-induced oxidative and nitrosative stress and liver injury. Hamsters were infected with O. viverrini followed by oral administration of various doses of melatonin (5, 10, and 20 mg/kg body weight) for 30 days. Uninfected hamsters served as controls. Compared to the levels in O. viverrini-infected hamsters without melatonin treatment, the indoleamine decreased the formation of oxidative and nitrosative DNA lesions, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-nitroguanine, in the nucleus of bile duct epithelium and inflammatory cells, in parallel with a reduction in 3-nitrotyrosine. Melatonin also reduced the expression of heme oxygenase-1 and cytokeratin 19, nitrate/nitrite levels, and bile duct proliferation in the liver. Alanine transaminase activity and the levels of 8-isoprostane and vitamin E were also dose dependently decreased in the plasma of melatonin-treated hamsters. Melatonin reduced the mRNA expression of oxidant-generating genes [inducible nitric oxide synthase, nuclear factor-kappa B (NF-?B), and cyclooxygenase-2] and proinflammatory cytokines (TNF-? and IL-1?), accompanied by an increase in the expression of antioxidant genes [nuclear erythroid 2-related factor 2 (Nrf2) and manganese superoxide dismutase]. Thus, melatonin may be an effective chemopreventive agent against O. viverrini-induced cholangiocarcinoma by reducing oxidative and nitrosative DNA damage via induction of Nrf2 and inhibition of NF-?B-mediated pathways. PMID:20626588

Laothong, Umawadee; Pinlaor, Porntip; Hiraku, Yusuke; Boonsiri, Patcharee; Prakobwong, Suksanti; Khoontawad, Jarinya; Pinlaor, Somchai

2010-10-01

300

Neoplasms of the liver  

SciTech Connect

Primary Liver Cancer is perhaps the most prevalent malignancy in the world, particularly in South East Asia and Africa. After the discovery of hepatitis B virus as a cause of chronic liver disease often terminating cirrhosis and hepatocellular carcinoma, and, more recently, the integration of viral DNA into host chromosomal DNA, the progress made in this field has been remarkable. This book contains 35 chapters and covers all topical aspects, such as oncogenes, epidemiology, carcinogenic role of hepatitis viruses, histopathology, new imaging techniques and new treatment modalities that include ultrasound-guided intratumor injections of ethanol and targeting chemotherapy.

Okuda, K.; Ishak, K.G.

1987-01-01

301

Aging Liver. A review.  

PubMed

Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver. Endogenous free radicals are generated within mitochondria and suspected to cause severe injury to mitochondrial DNA. This damaged DNA accumulates with aging. In addition, polyunsaturated fatty acids, highly sensitive to ROS, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity. Diet is considered the main environmental factor having effect on lifespan. It has a major impact on aging liver, the central metabolic organ of the body. The ubiquitin proteolytic pathway in the liver serves to destroy many proteins, among them p21 which is encoded by abundant mRNA in senescent cells, can inhibit cell proliferation and favors DNA repair. Drug therapy in the elderly may be complicated by several factors such as decline in body weight, renal function, liver mass and hepatic blood flow, making adverse drug reactions more frequent. Hepatic drug metabolism is mainly mediated by the cytochrome P(450 )system and drug interactions in the elderly are likely related to the progressive decline of this system after the fifth decade of life and another decrease in individuals aged >70. Antihypertensive therapy in the elderly depends upon either hepatic or renal function and should be adjusted accordingly. Finally, telomerases are the biological clocks of replicative lifespan. Shortening of telomeric ends of chromosomes correlates with aging and decline in the replicative potential of the cell: replicative senescence. Telomere DNA of human somatic cells shortens during each cell division thus leading to a finite proliferation. Transfection of the telomerase reverse transcriptase gene results in elongation of telomeres and extension of lifespan. This also applies to humans. Replicative senescence in human cells evolved as a mechanism to protect them from continuous divisions leading to multiple mutations. Longer-lived species such as humans had to develop replicative senescence to ensure that they would have the increased protection that their longevity necessitates. PMID:12393949

Anantharaju, Abhinandana; Feller, Axel; Chedid, Antonio

2002-01-01

302

Auxiliary partial orthotopic liver transplantation for acute liver failure  

Microsoft Academic Search

Background\\/Aims: Auxiliary partial orthotopic liver transplantation holds potential advantages over conventional orthotopic liver transplantation, but experience with the technique in acute liver failure is limited.Methods: We describe our initial experience in seven patients (4 men, 3 women; mean age 28, range 14–35 years) with acute liver failure (paracetamol 3, non A-E 2, autoimmune 1, Ecstasy 1) who fulfilled criteria for

Stephen P. Pereira; Michelle McCarthy; Antony J. Ellis; Julia Wendon; Bernard Portmann; Mohammed Rela; Nigel Heaton; Roger Williams

1997-01-01

303

Auxiliary versus orthotopic liver transplantation for acute liver failure  

Microsoft Academic Search

Background\\/Aims\\/Methods: We report 1-year results after auxiliary liver transplantation for acute liver failure in a cohort of 47 patients transplanted in 12 European centers as compared with those of 384 consecutive patients undergoing orthotopic liver transplantation for acute liver failure in the Eurotransplant area.Results: One-year patient survival resp. retransplant-free patient survival did not differ between orthotopic (61%, 232\\/384 resp. 52%,

Bart van Hoek; Jan de Boer; Karim Boudjema; Roger Williams; Oscar Corsmit; Onno T Terpstra

1999-01-01

304

Liver biopsy and prognosis in acute liver failure  

Microsoft Academic Search

Liver biopsy was performed in 38 patients with fulminant hepatitis and coma and repeated in 22. Stereological estimation of hepatocyte volume was correlated with levels of clotting factors.Early liver biopsy allowed prognosis in 55% of the cases. All patients with a hepatocyte volume of 10% recovered consciousness (n = 9) or at least showed evidence of marked liver regeneration (n

J. Scotto; P. Opolon; J. Étévé; D. Vergoz; M. Thomas; J. Caroli

1973-01-01

305

Medical Aspects of Liver Transplantation  

PubMed Central

The methods used to screen prospective candidates for orthotopic liver transplantation are described. Both the indication and the contraindications for the procedure are discussed. The timing of the procedure during the course of an individual candidate’s liver disease is also discussed. Additionally, the institutional requirements of a liver transplant center are identified. Finally, the problems experienced by a liver transplant patient and his physician during the postoperative period are identified and discussed.

Van Thiel, David H.; Schade, Robert R.; Gavaler, Judith S.; Shaw, Byers W.; Iwatsuki, Shunzaburo; Starzl, Thomas E.

2010-01-01

306

Oxidative Stress and Liver Injury  

Microsoft Academic Search

\\u000a Oxidative stress and liver injury are strongly associated. Oxidative stress in the liver can be triggered during different\\u000a conditions and by specific etiologies, including hepatotoxins (acetaminophen [1]), viruses (e.g., hepatitis C virus [2]),\\u000a nonalcoholic steatohepatitis (NASH) [3], hepatocellular carcinoma [4], alcoholic liver disease (ALD) [5], ischemia-­reperfusion,\\u000a and liver fibrosis [6]. Oxidative stress is a state of imbalance between the production

Francisco Javier Cubero; Christian Trautwein

307

Liver transplantation for neonatal haemochromatosis.  

PubMed Central

Two cases of neonatal haemochromatosis, a rare and often fatal metabolic disorder, presenting with acute liver failure, are reported. Both presented in the first week of life with hypoglycaemia, jaundice, and coagulopathy, with rapid deterioration of liver function. Both received a transplantation using reduced liver grafts. One child was well 18 months later. Few survivors have been reported and despite the difficult perioperative management, liver transplantation is the best treatment for neonatal haemochromatosis. Images pF179-a

Muiesan, P.; Rela, M.; Kane, P.; Dawan, A.; Baker, A.; Ball, C.; Mowat, A. P.; Williams, R.; Heaton, N. D.

1995-01-01

308

Liver (Hepatocellular) Cancer Screening  

MedlinePLUS

... the disease is found and treated at an early stage . Clinical trials that study cancer screening methods are taking place in many parts ... levels. Specific tumor markers that may lead to early detection of liver cancer are ... about ongoing clinical trials is available from the NCI Web site . ...

309

Alcoholic Liver Disease  

Microsoft Academic Search

These recommendations provide a data-supported approach. They are based on the following: (i) a formal review and analysis of the recently published world literature on the topic (Medline search); (ii) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines (1); (iii) guideline policies, including the American Association for the Study of Liver Diseases (AASLD) Policy on

Robert S O’Shea; Srinivasan Dasarathy; Arthur J. McCullough

2010-01-01

310

Ton That Tung's Livers.  

PubMed

Born in the early 20th century, the Vietnamese surgeon Ton That Tung received his medical education in French colonial Indochina at the fledgling l'Ecole de Médecine de Hanoi, the first indigenous medical school in Southeast Asia. The benefactor of a postgraduate position at the medical school, Ton That Tung subsequently obtained his surgical training at the Phù Doãn Hospital in Hanoi and concurrently developed a passion for the study of liver anatomy, pathology, and surgery. His contributions to an understanding of liver anatomy based on meticulous dissection of autopsy specimens antedated and rivaled later work by the famous Western anatomists Couinaud, Healey, Schroy, and others. Ton That Tung's contributions, however, were overshadowed by the intense national struggles of the Vietnamese to establish independent rule and self-governance from the French and by eventual alignment with eastern bloc Communist countries, thus isolating much of his work behind the "Iron Curtain" until well after the end of the Cold War. Nevertheless, Ton That Tung remains a pioneer in liver anatomy and liver surgery. His commitment to surgical science and, more importantly, to the Vietnamese people stands as a tribute to the tireless pursuit of his ideals. PMID:24335785

Helling, Thomas S; Azoulay, Daniel

2014-06-01

311

Sirolimus in liver transplantation  

Microsoft Academic Search

Since its introduction in renal transplantation in 1999, sirolimus is being used by an increasing number of liver transplant centers. Compared to the calcineurin inhibitors, sirolimus acts through a separate signal transduction pathway and has a myriad of important biologic effects including: inhibition of lymphocyte proliferation, inhibition of fibrosis and fibroblast proliferation, and antineoplastic effects. The clinical side-effect profile of

J. F Trotter

2003-01-01

312

Blood Flukes (Digenea: Aporocotylidae) of Elopomorphs: Emendation of Paracardicoloides, Supplemental Observations of Paracardicoloides yamagutii, and a New Genus and Species from Ladyfish, Elops saurus, (Elopiformes: Elopidae) in the Gulf of Mexico.  

PubMed

Abstract : Monotypic Paracardicoloides Martin, 1974 is emended based on supplemental observations of 2 voucher specimens of Paracardicoloides yamagutii Martin, 1974 . Features of the anterior sucker, esophagus, and intestine as well as the male and female genitalia previously attributed to, or omitted from the diagnosis and description of, this fluke are resolved and further detailed herein. The holotype of P. yamagutii, originally deposited in the Allan Hancock Parasitology Collection, apparently has been lost, and Queensland Museum voucher G222650 is designated as the neotype. Elopicola nolancribbi n. gen., n. sp. infects the ladyfish, Elops saurus , (Elopiformes: Elopidae) in the north-central Gulf of Mexico. The new genus resembles Paracardicoloides by having the combination of a bowl-shaped anterior sucker, inverse U-shaped intestine, short posterior ceca, post-cecal ovary, pre-ovarian ootype, compact uterus, and prominent excretory arms and vesicle. It differs from Paracardicoloides by lacking robust tegumental body spines and by having a single testis, post-testicular ovary, and primarily post-testicular uterus. The present study is the first confirmed report of an aporocotylid infecting a member of Elopiformes as well as the first report of an infection in an elopomorph outside of Australia and New Zealand or in marine waters. PMID:24467621

Bullard, Stephen A

2014-06-01

313

Liver abnormalities in celiac disease  

Microsoft Academic Search

Celiac disease is an intolerance of the small bowel to gluten. Although most symptomatic patients have symptoms related to the gastrointestinal tract, many extra-intestinal manifestations have been described. A wide spectrum of hepatobiliary diseases have been described, including asymptomatic elevations of liver enzyme levels, nonspecific hepatitis, nonalcoholic fatty liver disease, and autoimmune and cholestatic liver disease. In addition, celiac disease

Ayman Abdo; Jonathan Meddings; Mark Swain

2004-01-01

314

Augmenter of liver regeneration  

PubMed Central

‘Augmenter of liver regeneration’ (ALR) (also known as hepatic stimulatory substance or hepatopoietin) was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability) protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa), but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa) found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-?, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa) of human recombinant ALR was reported to be equipotent as or even stronger than TGF-? or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule.

2012-01-01

315

Liver function impairment in liver transplantation and after extended hepatectomy  

PubMed Central

Extended hepatectomy, or liver transplantation of reduced-size graft, can lead to a pattern of clinical manifestations, namely “post-hepatectomy liver failure” and “small-for-size syndrome” respectively, that can range from mild cholestasis to irreversible organ non-function and death of the patient. Many mechanisms are involved in their occurrence but in the recent past, high portal blood flow through a relatively small liver vascular bed has taken a central role. Therefore, several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation, such as portocaval shunt, mesocaval shunt, splenorenal shunt, splenectomy or ligation of the splenic artery. However, high portal flow is not the only factor responsible, and before major liver resections, preoperative assessment of the residual liver function is necessary. Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume, preventing post-hepatectomy liver failure. More recently, a new surgical procedure, that combines in situ splitting of the liver and portal vein ligation, has gradually come to light, inducing remarkable hypertrophy of the healthy liver in just a few days. Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.

Serenari, Matteo; Cescon, Matteo; Cucchetti, Alessandro; Pinna, Antonio Daniele

2013-01-01

316

Evidence for liver cell proliferation during fatal acute liver failure.  

PubMed

Liver cell regeneration was assessed by determining the mitotic index and the frequency of liver cells with interploid DNA values in livers from patients dying from fulminant hepatitis. For comparison, the same parameters were determined in patients with uncomplicated hepatitis. We found comparable levels of regeneration in the two groups, indicating that the rate of liver cell destruction is a major determinant in the prognosis of acute liver failure. Accordingly, measures to prevent liver cell necrosis seem at least as important as stimulation of regeneration. Judged from available experimental evidence, substances with documented hepatotrophic effect in animals, such as insulin and glucagon, may therefore not be effective in acute liver failure unless the patient has impaired secretion of these substances. PMID:7429306

Milandri, M; Gaub, J; Ranek, L

1980-05-01

317

Hedgehog Signaling in the Liver  

PubMed Central

Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regeneration, but also hepatic accumulation of inflammatory cells, liver fibrogenesis, and vascular remodeling. All of these latter responses are known to be involved in the pathogenesis of cirrhosis. In addition, Hh signaling may play a role in primary liver cancers, such as cholangiocarcinoma and hepatocellular carcinoma. Study of Hedgehog signaling in liver cells is in its infancy. Additional research in this area is justified given growing experimental and clinical data supporting a role for the pathway in regulating outcomes of liver injury.

Omenetti, Alessia; Choi, Steve; Michelotti, Gregory; Diehl, Anna Mae

2010-01-01

318

Liver transplantation for hepatocellular carcinoma  

PubMed Central

Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early, unresectable HCC particularly in the setting of chronic liver disease. Following on from disappointing initial results, the seminal study by Mazzaferro et al in 1996 established OLT as a viable treatment for HCC. In this study, the “Milan criteria” were applied achieving a 4-year survival rate similar to OLT for benign disease. Since then various groups have attempted to expand these criteria whilst maintaining long term survival rates. The technique of living donor liver transplantation has evolved over the past decade, particularly in Asia, and published outcome data is comparable to that of OLT. This article will review the evidence, indications, and the future direction of liver transplantation for liver cancer.

Tanwar, Sudeep; Khan, Shahid A; Grover, Vijay Paul Bob; Gwilt, Catherine; Smith, Belinda; Brown, Ashley

2009-01-01

319

Lipids changes in liver cancer*  

PubMed Central

Liver is one of the most important organs in energy metabolism. Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver. It depends on the integrity of liver cellular function, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs, these processes are impaired and the plasma lipid and lipoprotein patterns may be changed. Liver cancer is the fifth common malignant tumor worldwide, and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV). HBV and HCV infections are quite common in China and other Southeast Asian countries. In addition, liver cancer is often followed by a procession of chronic hepatitis or cirrhosis, so that hepatic function is damaged obviously on these bases, which may significantly influence lipid and lipoprotein metabolism in vivo. In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

Jiang, Jing-ting; Xu, Ning; Zhang, Xiao-ying; Wu, Chang-ping

2007-01-01

320

Alcohol-related liver disease.  

PubMed

Alcohol is one of the three leading causes of liver disease in the developed world. Patients with alcohol-related liver disease are often cared for in general wards and hospitals, rather than specialist centres. This may be a result of the number of patients being admitted or a lack of referral to specialist services by healthcare professionals. The financial cost of caring for patients with alcohol-related injuries is continuing to rise. This article explores the mechanisms of liver injury caused by alcohol; the risk factors associated with alcohol-related liver disease; assessment tools used to identify patients with alcohol use disorders; withdrawal from alcohol; chronic liver disease; and issues surrounding transplantation. The importance of the nursing role in assessing and monitoring patients undergoing withdrawal from alcohol, information giving and advice on the prevention of alcohol-related liver injury, and supporting patients with alcohol-related liver injury is highlighted. PMID:25027923

Fullwood, Danielle

2014-07-16

321

Drug-induced Liver Injury  

PubMed Central

Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms.

David, Stefan; Hamilton, James P

2011-01-01

322

Liver regeneration is impaired in lipodystrophic fatty liver dystrophy mice.  

PubMed

We previously reported that mice subjected to partial hepatectomy exhibit rapid development of hypoglycemia followed by transient accumulation of fat in the early regenerating liver. We also showed that disrupting these metabolic alterations results in impaired liver regeneration. The studies reported here were undertaken to further characterize and investigate the functional importance of changes in systemic adipose metabolism during normal liver regeneration. The results showed that a systemic catabolic response is induced in each of two distinct, commonly used experimental models of liver regeneration (partial hepatectomy and carbon tetrachloride treatment), and that this response occurs in proportion to the degree of induced hepatic insufficiency. Together, these observations suggest that catabolism of systemic adipose stores may be essential for normal liver regeneration. To test this possibility, we investigated the hepatic regenerative response in fatty liver dystrophy (fld) mice, which exhibit partial lipodystrophy and have diminished peripheral adipose stores. The results showed that the development of hypoglycemia and hepatic accumulation of fat was attenuated and liver regeneration was impaired following partial hepatectomy in these animals. The fld mice also exhibited increased hepatic p21 expression and diminished plasma levels of the adipose-derived hormones adiponectin and leptin, which have each been implicated as regulators of liver regeneration. Conclusion: These data suggest that the hypoglycemia that develops after partial hepatectomy induces systemic lipolysis followed by accumulation of fat derived from peripheral stores in the early regenerating liver, and that these events may be essential for initiation of normal liver regeneration. PMID:20967828

Gazit, Vered; Weymann, Alexander; Hartman, Eric; Finck, Brian N; Hruz, Paul W; Tzekov, Anatoly; Rudnick, David A

2010-12-01

323

[Antioxidants in liver protection].  

PubMed

Great importance has been attributed to antioxidants in the prevention and treatment of conditions associated with oxidative stress for many years. At the same time the antioxidants are free radicals themselves, and they can exert prooxidant activity depending on the concentration. They influence the cell redox homeostasis by their prooxidant and antioxidant activity as well. Drugs of chronic liver diseases should be considered, because free radicals are generated during the activity of the monooxygenase system, which affect the tissue oxidised status. Combined antioxidant treatment is more favourable compared with monotherapy, because antioxidants have scavenger-, compartment- and tissue-specificity and they regenerate each other directly, too. Beside their antioxidant property they may also directly regulate many important processes, e.g. cell cycle. We have some favourable results with regard combined antioxidant therapy of liver disease of different etiology. PMID:15320484

Hagymási, Krisztina; Blázovics, Anna

2004-07-01

324

Foods and liver health.  

PubMed

Chronic liver damage is a worldwide common pathology, characterised by an inflammatory and fibrotic process that leads to a progressive evolution from chronic hepatitis to cirrhosis and hepatocellular carcinoma (HCC). A major role for fats and oxidative stress has been recently demonstrated in the pathogenesis of liver diseases. In the clinical practice, dietary recommendations in the management of chronic diseases often rely on denying patients certain foods, which results in a severe reduction of quality of life. In this paper a new perspective based on the development of Food intended for Specific Medical Purposes (FSMP) containing highly bioavailable antioxidant compounds or polyunsaturated-fatty acids, has been highlighted as a tool for preventive and curative medicine, to be associated to pharmacological treatments. PMID:18061253

Morisco, Filomena; Vitaglione, Paola; Amoruso, Daniela; Russo, Barbara; Fogliano, Vincenzo; Caporaso, Nicola

2008-01-01

325

Experimental liver diseases.  

PubMed

The use of animal models in the experimental production of liver diseases similar to those of man is still in its infancy. There is a need to discover new models more closely related to counterpart syndromes in man in the fields of hepatorenal syndrome, neonatal jaundice, Wilson's disease, cholelithiasis, viral hepatitis, biliary atresia, and cirrhosis, to mention only a few. With the continued indiscriminate inbreeding of companion animals as well as the planned inbreeding of laboratory animals, there is little doubt that many more will soon be available. The current availability of mutant rats and sheep with bilirubin transport defects has allowed for a better understanding of how organic anions are transported by the liver. Many other currently available experimental animal models herein briefly reviewed have been only superficially studied. It is the intent of this chapter to provide for post-doctoral students an appreciation for the many animal model systems available for experimental hepatic research. PMID:1105063

Cornelius, C E; Himes, J A; Gronwall, R R

1975-01-01

326

Fatty liver in childhood  

PubMed Central

Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

Ozturk, Yesim; Soylu, Ozlem Bekem

2014-01-01

327

Descriptive epidemiology of cholangiocarcinoma and clonorchiasis in Korea.  

PubMed

In 2009, infection with the liver fluke Clonorchis sinensis (C. sinensis) was classified as "carcinogenic to humans" (Group 1) based on its involvement in the etiology of cholangiocarcinoma by the International Agency for Research on Cancer. However, little is known about the descriptive epidemiology of cholangiocarcinoma in Korea. We examined incidence trends of intrahepatic and extrahepatic cholangiocarcinomas, using data from the Korea National Cancer Incidence database for 1999-2005. The prevalence of C. sinensis infection was estimated from a recent population-based survey in rural endemic areas. Cholangiocarcinoma incidence rates are currently rising, even while primary liver cancer incidence rates are decreasing. Annual percent changes in cholangiocarcinoma incidence rates were 8% for males and 11% in females. Known areas of C. sinensis endemicity showed high incidence rates of cholangiocarcinoma. The positivity of C. sinensis eggs in stool samples from endemic areas was more than 25% of adults tested during 2005-2008. From a meta-analysis, the summary odds ratio for cholangiocarcinoma due to C. sinensis infection was 4.7 (95% confidence interval: 2.2-9.8). Approximately 10% of cholangiocarcinomas in Korea were caused by chronic C. sinensis infections. More specific policies, including health education and an extensive effort for early detection in endemic areas, are needed. PMID:20592891

Shin, Hai-Rim; Oh, Jin-Kyoung; Lim, Min Kyung; Shin, Aesun; Kong, Hyun-Joo; Jung, Kyu-Won; Won, Young-Joo; Park, Sohee; Park, Sang-Jae; Hong, Sung-Tae

2010-07-01

328

The liver and lovastatin.  

PubMed

The cholesterol-lowering agents, known as statins, have been in use for 15 years and are among the most commonly prescribed drugs. Animal studies and premarketing clinical trials have given signals of hepatotoxicity, primarily minor elevations in serum alanine aminotransferase enzyme (ALT) levels. For that reason, all of the cholesterol-lowering drugs have labeling that requires monitoring of liver enzymes. Postmarketing experience, however, suggests that hepatotoxicity is rare and thus it is timely to revisit the issue. The first of the statins, lovastatin, was approved in 1986 and has acquired 24 million patient-years of clinical experience. Minor elevations in liver enzymes, i.e., ALT 3 x the upper limit of normal (ULN) occur in 2.6% and 5.0% of patients on lovastatin doses of 20 and 80 mg/day, respectively. These elevations are reversible with continuing therapy, are dose related, and are probably related to cholesterol lowering per se. Rare cases of acute liver failure (ALF) have been reported with all of the cholesterol-lowering drugs. With lovastatin, the rate is approximately 1/1.14 million patient-treatment years, which is 9% of the background rate of all causes of ALF and approximately equal to the background rate of idiopathic ALF. Monitoring for hepatotoxicity has not been effective in preventing serious liver disease, largely because of its rarity and the poor predictive value of minor ALT elevations. In fact, it may increase patient risk because of needless discontinuation of cholesterol-lowering therapy for false-positive results in patients who are benefiting from treatment. PMID:12062731

Tolman, Keith G

2002-06-15

329

Vascular liver diseases  

Microsoft Academic Search

This article reviews the primary circulatory liver diseases, which include Budd-Chiari syndrome, obstruction of the hepatic\\u000a portion of the inferior vena cava, portal vein thrombosis, sinusoidal obstruction syndrome (veno-occlusive disease), nodular\\u000a regenerative hyperplasia, and peliosis hepatis. In addition, two systemic cardiovascular diseases that impair hepatic circulation,\\u000a ischemic hepatitis and congestive hepatopathy, are briefly discussed. A characteristic of the primary circulatory

Laurie D. DeLeve

2003-01-01

330

Cholestatic liver disease.  

PubMed

Cholestasis develops as a consequence of impaired bile formation and/or bile flow and can be classified as intra- or extrahepatic. Chronic cholestatic diseases are mostly intrahepatic with the exception of primary and secondary sclerosing cholangitis affecting intra- and extrahepatic bile ducts. Recent genome-wide association studies have confirmed major histocompatibility complex associations and discovered multiple susceptibility loci in primary biliary cirrhosis and primary sclerosing cholangitis, providing new insights into disease pathogenesis, which may translate into more precise therapeutic prevention and intervention in the future. Diagnostic steps in cholestatic conditions comprise a thorough patient history, abdominal imaging and distinct serological studies including antimitochondrial antibodies and IgG4 levels; if the diagnosis remains unclear, liver biopsy is warranted. Genetic testing should also be considered, as mutations in the hepatobiliary transporters ATP8B1, ABCB11 and ABCB4 are causative for three different forms of familial intrahepatic cholestasis. Disease severity is dependent on the genotypic variants of these transporters, ranging from mildly elevated liver enzymes in adults to cirrhosis in early childhood. Ligands of nuclear receptors, which represent important regulators of hepatobiliary transporters, and modified bile salts are new promising therapeutic options in cholestatic liver disease and are currently being investigated in clinical trials. PMID:23797137

Jüngst, Christoph; Lammert, Frank

2013-01-01

331

Living donor liver transplantation in polycystic liver disease.  

PubMed

In the current Model for End-Stage Liver Disease system, patients with polycystic liver disease (PCLD) who have a poor quality of life secondary to their massive hepatomegaly are no longer competitive for a deceased donor liver transplant if their liver function is well preserved. Traditionally, a caval resection has been advocated in these patients because of the difficulty of the hepatectomy with hepatomegaly, which makes living donation impossible. This series looks at 3 patients who underwent a caval sparing hepatectomy and subsequent living donor liver transplantation (LDLT) for PCLD. Graft and patient survival was 100%, and there were few complications in either donors or recipients. LDLT is an ideal option for patients with PCLD and preserved liver function but poor quality of life. PMID:18433036

Mekeel, Kristin L; Moss, Adyr A; Reddy, Kunam S; Douglas, David D; Vargas, Hugo E; Carey, Elizabeth J; Byrne, Thomas J; Harrison, M E; Rakela, Jorge; Mulligan, David C

2008-05-01

332

Chronic liver disease: relaxometry in the brain after liver transplantation  

Microsoft Academic Search

Relaxometry revealed changes in the basal ganglia in T1 and T2 relaxation times due to liver disease. Manganese is probably responsible for T1 and T2 shortening (as the concentration is known to be higher in both the liver and blood due to hepatic cirrhosis). The aim of\\u000a this study was to follow possible recovery after liver transplantation by MR relaxometry.

V??t Herynek; Milan Babiš; Pavel Trune?ka; Karel Filip; Josef Vymazal; Monika Dezortová; Milan Hájek

2001-01-01

333

[Current trends in liver biopsy indications in chronic liver diseases].  

PubMed

Liver biopsy (LB) remains a major tool in chronic liver disease evaluation. Main current indications of LB in chronic liver disease are reviewed in this manuscript. Major development of non-invasive tools for evaluation of liver fibrosis led to decrease of LB indications in patients with chronic hepatitis C. LB is the only tool for exploration of necroinflammatory and fibrosis lesions in chronic hepatitis B as well as in autoimmune hepatitis. LB is the sole exam that can differentiate between bland steatosis and steatohepatitis in the setting of metabolic syndrome and to confirm the diagnosis of alcoholic hepatitis when corticosteroids are indicated. PMID:22425478

Cadranel, Jean-François; Nousbaum, Jean-Baptiste

2012-11-01

334

Role of liver progenitors in acute liver injury.  

PubMed

Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte function and frequently exhibits a fulminant course, characterized by high mortality in the absence of immediate state-of-the-art intensive care and/or emergency liver transplantation (ELT). The role of hepatocyte-mediated liver regeneration during acute and chronic liver injury has been extensively investigated, and recent studies suggest that hepatocytes are not exclusively responsible for the regeneration of the injured liver during fulminant liver injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. This review aims to provide an overview of the role of the LPC population during ALF, and the role of putative cytokines, growth factors, mitogens, and hormones in the LPC response. We will highlight the potential interaction among cellular compartments during ALF, and discuss the possible prognostic value of the LPC response on ALF outcomes. PMID:24133449

Best, Jan; Dollé, Laurent; Manka, Paul; Coombes, Jason; van Grunsven, Leo A; Syn, Wing-Kin

2013-01-01

335

Liver-Spleen Scintigrams, Epigastric Sonograms and Liver Function Scintigram for Comparative Studies of Various Cases of Liver Cirrhosis.  

National Technical Information Service (NTIS)

23 patients where liver cirrhosis was established were subjected to an epigastric sonogram, a liver-spleen scintigram, a liver-function scintigram, and to various relevant laboratory tests. The liver-spleen scintigram was evaluated for size of the liver, ...

R. Geiger

1983-01-01

336

Biliary complications following liver transplantation  

PubMed Central

Biliary tract complications are the most common complications after liver transplantation. These complications are encountered more commonly as a result of increased number of liver transplantations and the prolonged survival of transplant patients. Biliary complications remain a major source of morbidity in liver transplant patients, with an incidence of 5%-32%. Post liver transplantation biliary complications include strictures (anastomotic and non-anastomotic), leaks, stones, sphincter of Oddi dysfunction, and recurrence of primary biliary disease such as primary sclerosing cholangitis and primary biliary cirrhosis. The risk of occurrence of a specific biliary complication is related to the type of biliary reconstruction performed at the time of liver transplantation. In this article we seek to review the major biliary complications and their relation to the type of biliary reconstruction performed at the time of liver tranplantation.

Kochhar, Gursimran; Parungao, Jose Mari; Hanouneh, Ibrahim A; Parsi, Mansour A

2013-01-01

337

Liver transplantation for Wilson's disease.  

PubMed

Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ?5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors. PMID:24820352

Schilsky, Michael L

2014-05-01

338

[Liver transplantation and living donors].  

PubMed

LIVER SPLITTING: Classically, cadaver livers are split ex situ to provide two grafts for transplantation. This procedure could be performed in situ, limiting the duration of the operation and improving recovery of liver function. LIVING RELATED DONORS: Living donor liver transplantation is a well established technique in children. Donor mortality is nil and morbidity very acceptable. For adults, the results have been less satisfactory with increasing risk for the recipient, with biliary and venous problems due to the "small-for-size" implant. ORGAN HARVESTING: The left lobe, classically used for children, can also be grafted into adults, but under certain restrictive conditions. If the donor's residual liver volume is below 0.8% of the total body mass, the biological alterations remain limited and transient. EMERGENCY TRANSPLANTATIONS: Liver transplantations using a living donor can save critically ill patients with a life expectancy of less than 3 months. Remarkable survival rates have been achieved. PMID:11577581

Campan, P

2001-09-01

339

Biliary complications following liver transplantation.  

PubMed

Biliary tract complications are the most common complications after liver transplantation. These complications are encountered more commonly as a result of increased number of liver transplantations and the prolonged survival of transplant patients. Biliary complications remain a major source of morbidity in liver transplant patients, with an incidence of 5%-32%. Post liver transplantation biliary complications include strictures (anastomotic and non-anastomotic), leaks, stones, sphincter of Oddi dysfunction, and recurrence of primary biliary disease such as primary sclerosing cholangitis and primary biliary cirrhosis. The risk of occurrence of a specific biliary complication is related to the type of biliary reconstruction performed at the time of liver transplantation. In this article we seek to review the major biliary complications and their relation to the type of biliary reconstruction performed at the time of liver tranplantation. PMID:23704818

Kochhar, Gursimran; Parungao, Jose Mari; Hanouneh, Ibrahim A; Parsi, Mansour A

2013-05-21

340

Autoimmune Diseases in Transplanted Livers  

Microsoft Academic Search

Liver transplantation (LT) is a standard therapeutic approach for the treatment of end-stage acute and chronic liver disease\\u000a of various etiologies including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis\\u000a (PSC). Results of LT for these autoimmune liver diseases are good, with a patient survival of 80 to 85% at 5 yr after LT.\\u000a Transplant recipients, however,

Hiromi Ishibashi; Shinji Shimoda; Minoru Nakamura; M. Eric Gershwin

341

Drug-Induced Liver Injury  

Microsoft Academic Search

Many drugs and environmental chemicals are capable of evoking some degree of liver injury. The liver represents a primary\\u000a target for adverse drug reactions due to its central role in biotransformation and excretion of foreign compounds, its portal\\u000a location within the circulation exposing it to a wide variety of substances, and its anatomic and physiologic structure. Drug-induced\\u000a liver injury (DILI)

Michael Holt; Cynthia Ju

342

Mesenchymal tumors of the liver.  

PubMed

Primary angiosarcoma of the liver accounts for up to 2% of all primary liver tumors and is the second most common primary malignant neoplasm of the liver. Approximately 10 to 20 new cases are diagnosed every year in the United States and the prevalence varies from 0.14 to 0.25 per million. In an autopsy series from Chicago, one hepatic angiosarcoma was noted for every 30 cases of hepatocellular carcinoma. PMID:11218917

Mani, H; Van Thiel, D H

2001-02-01

343

Radiation-Associated Liver Injury  

SciTech Connect

The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

Pan, Charlie C., E-mail: cpan@umich.ed [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, CO (United States); Dawson, Laura A. [Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Das, Shiva K. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Miften, Moyed [Department of Radiation Oncology, University of Colorado, Aurora, CO (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States)

2010-03-01

344

Liver Transplantation and Vascular Disorders  

Microsoft Academic Search

\\u000a One of the main advantages of liver transplantation (LT) has been to ­concentrate particular and rare liver diseases in a\\u000a restricted number of ­centers. This policy has led to a much better understanding, diagnosis, and treatment of these, many\\u000a times, difficult conditions. This chapter gives a comprehensive and updated review in relation to vascular liver diseases.\\u000a It is without any

Jan P. Lerut; Eliano Bonaccorsi-Riani; Pierre Goffette

345

Hepatitis B and Liver Transplantation  

Microsoft Academic Search

Over 300 million people are infected with the hepatitis B virus (HBV); of these, approximately 20% will develop cirrhosis\\u000a and complications of end-stage liver disease including hepatocellular carcinoma. Thus, liver transplantation has emerged as\\u000a an important therapy for selected patients with HBV infection. The authors review the management of HBV before and after liver\\u000a transplantation, which has become more complex

Geoffrey McCaughan; Jade D. Jamias; Qingchun Fu; Nicholas Shackel; Simone Strasser

346

Dermatologic disorders and the liver.  

PubMed

Chronic liver disease is associated with several cutaneous manifestations. Although many of these changes are nonspecific, some are associated with distinct liver diseases and correlate with the severity of hepatic pathology. Often the first clue to a liver disease is manifested through skin. Although cirrhosis is associated with spider nevi and palmar erythema, disorders can result in noncirrhotic cutaneous manifestations. It is important for physicians to be familiar with the spectrum of these manifestations, to recognize, help detect, and treat the underlying hepatic disease. This article reviews the medical literature and discusses the spectrum of dermatologic manifestations of liver disorders and their pathogenesis, significance, and treatment. PMID:21111999

Satapathy, Sanjaya K; Bernstein, David

2011-02-01

347

Future of bioartificial liver support  

PubMed Central

Many different artificial liver support systems (biological and non-biological) have been developed, tested pre-clinically and some have been applied in clinical trials. Based on theoretical considerations a biological artificial liver (BAL) should be preferred above the non-biological ones. However, clinical application of the BAL is still experimental. Here we try to analyze which hurdles have to be taken before the BAL will become standard equipment in the intensive care unit for patients with acute liver failure or acute deterioration of chronic liver disease.

Chamuleau, Robert AFM

2009-01-01

348

Iron homeostasis in the liver  

PubMed Central

Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma.

Anderson, Erik R; Shah, Yatrik M

2014-01-01

349

Protothecosis after liver transplantation.  

PubMed

Prototheca species are unicellular algae of low virulence that are rarely associated with human infections. We report a liver transplant recipient with disseminated protothecosis and review the literature on this unusual opportunistic infection in transplant recipients. Of 9 cases, including ours, 5 had a localized infection, and 4 had disseminated protothecosis. Seven cases were due to Prototheca wickerhamii, and 2 were due to Prototheca zopfii. Overall mortality in transplant recipients with Prototheca infections was 88% (7/8). All 4 cases of disseminated protothecosis died despite therapy with amphotericin B. Posttransplant protothecosis is a rare but significant infection that is associated with a grave prognosis. PMID:18668655

Narita, Masashi; Muder, Robert R; Cacciarelli, Thomas V; Singh, Nina

2008-08-01

350

Chronic liver inflammation: clinical implications beyond alcoholic liver disease.  

PubMed

Chronic alcohol exposure can lead to alcoholic liver disease, including hepatitis, cirrhosis and hepatocellular carcinoma, and chronic inflammation can simultaneously cause systemic medical illness. Recent evidence suggests that alcoholic liver disease is a predictor for liver-related diseases, cardiovascular disease, immunologic disease, and bone disease. Chronic inflammation in alcoholic liver disease is mediated by a direct inflammatory cascade from the alcohol detoxification process and an indirect inflammatory cascade in response to gut microflora-derived lipopolysaccharides (LPS). The pathophysiology of alcoholic liver disease and its related systemic illness is characterized by oxidative stress, activation of the immune cascade, and gut-liver interactions. Integrative therapeutic strategies for alcoholic liver disease include abstaining from alcohol consumption; general anti-inflammatories such as glucocorticoid, pentoxifylline, and tumour necrosis factor-? antagonist; antioxidants such as N- acetylcysteine; gut microflora and LPS modulators such as rifaximin and/or probiotics. This review focuses on the impact of chronic liver inflammation on systemic health problems and several potential therapeutic targets. PMID:24605015

Park, Byoung-Jin; Lee, Yong-Jae; Lee, Hye-Ree

2014-03-01

351

Liver disease in India.  

PubMed Central

One hundred and twenty-five children with chronic liver disease were seen in Pune in 13 months. Fifty-nine of them, aged 8-39 months, had Indian childhood cirrhosis histologically diagnosed. Their characteristics included an insidious onset of symptoms, a geographical clustering of cases in rural areas north-east of Pune, a high rate of parental consanguinity and affected siblings, and a very high hepatic copper concentration (790-6654 micrograms/g dry weight). Only 8 survived for 6 months, adverse prognostic features being jaundice, ascites, enlargement of the gall bladder, and severe anaemia at presentation. Clinical differentiation from other liver disorders in the same age group was clear in advanced cases but unreliable in earlier cases. Four asymptomatic siblings with hepatomegaly had a benign course. The need for non-invasive methods to diagnose early cases in the community is demonstrated. The other major diagnostic categories were: unresolved hepatitis (12); chronic active hepatitis (7); cryptogenic cirrhosis (6); neonatal hepatitis and biliary atresia (8).

Bhave, S A; Pandit, A N; Pradhan, A M; Sidhaye, D G; Kantarjian, A; Williams, A; Talbot, I C; Tanner, M S

1982-01-01

352

Lipotoxicity in the liver  

PubMed Central

Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21st century. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes, recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids, and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors, channels and transporters. However, it also induces endoplasmic reticulum stress via novel sensing mechanisms of the organelle’s stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis. This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses.

Zambo, Veronika; Simon-Szabo, Laura; Szelenyi, Peter; Kereszturi, Eva; Banhegyi, Gabor; Csala, Miklos

2013-01-01

353

LIVER PARENCHYMAL CELL INJURY  

PubMed Central

Iodoform, a relatively water-insoluble yellow solid, chemically reactive in free-radical reactions, produces early hepatocellular injury qualitatively similar to that of carbon tetrachloride. 2 hr after administration of radioactively labeled iodoform, nonvolatile 14C is preferentially recovered in microsomal lipid and protein. By 30 min microsomal properties are profoundly affected: oxidative demethylation decreases abruptly; increased lipoperoxide decomposition products are detected; and amino acid incorporation into liver protein is depressed. By 1 hr glucose-6-phosphatase is suppressed centrolobularly and increased stainable calcium is present in the midzone. Increased cell sap RNA contents are observed by 2 hr. Morphologically, the biochemical and histochemical changes are associated with progressive dispersion, vacuolation, and degranulation of the granular endoplasmic reticulum. Calcium-associated masses accumulate within the mitochondrial matrix, and mitochondria become progressively pleomorphic. Golgi components dilate and disperse. Membranous components of the cytoplasm of parenchymal cells conglomerate into labyrinthine tubular aggregates. Lipid accumulates in cytoplasmic droplets. Ultimately, centrolobular necrosis ensues. The close cytochemical and morphological similarities between the cellular injury produced in the liver by iodoform and that produced by carbon tetrachloride suggest common pathogenetic mechanisms associated with damage to membranes.

Sell, David A.; Reynolds, Edward S.

1969-01-01

354

Liver transplantation today.  

PubMed

In summary, liver transplantation has truly come of age. To put things in perspective, the recipient waiting list at the University of Pittsburgh never includes fewer than 200 suitable candidates, and it continues to grow in spite of the fact that we are now doing essentially one transplant per day. There are many excellent transplant centers throughout the United States and Europe, the only limiting factor being the supply of donors. Orthotopic liver transplantation is now covered by most major health insurance carriers, and some form of government coverage is anticipated for the indigent. As the supply of donors increases with aggressive education programs, the need for transplantation centers will also increase. However, this should not be uncontrolled growth. Mandatory training in transplantation surgery will surely be required as a prerequisite to the establishment of transplant centers in the future. The field of organ transplantation is the newest and most dynamic in medicine today. The results are encouraging and acceptable and offer the only hope to many persons dying of end-stage organ failure. With improvements in immune modulation at hand, organ transplantation will soon become a commonplace procedure offering a completely normal life expectancy. PMID:3550767

Marsh, J W; Makowka, L; Todo, S; Gordon, R D; Esquivel, C O; Tzakis, A; Iwatsuki, S; Starzl, T E

1987-04-01

355

What Happens After Treatment for Liver Cancer?  

MedlinePLUS

... 1-800-227-2345. Follow-up after a liver transplant A liver transplant can be very effective at both treating the cancer and replacing a damaged liver. But this is a major procedure that requires ...

356

What's New in Liver Cancer Research?  

MedlinePLUS

... can I learn more about liver cancer? What`s new in liver cancer research? There is always research ... cancer cases worldwide. Finding liver cancer early Some new blood tests are being studied to see if ...

357

Drug-induced liver injury  

Microsoft Academic Search

Drug-induced liver injury (DILI) accounts for 9.5% of all suspected adverse drug reactions (ADRs) and for a significant proportion of fatal ADRs. DILI may be a direct toxic effect or an immunological reaction to either the drug or an active metabolite. Drugs can cause a diverse array of liver injury, which may be acute or chronic. Adaptation to injurious effects,

Adam D. Farmer; Alison Brind

2011-01-01

358

Haemobilia following blunt liver injury.  

PubMed

Blunt liver trauma is commonly managed by non-operative measures. We report a case of an American Association for the Surgery of Trauma grade III liver injury and its complications, successfully managed by a combination of minimally invasive interventions. PMID:23217557

Laing, Grant Llewellyn; Clarke, D L; Ferndale, L; Reitz, D; Manchev, V

2012-11-01

359

Transdifferentiation of pancreas to liver  

Microsoft Academic Search

Transdifferentiation is the name used to describe the direct conversion of one differentiated cell type into another. Cells which have the potential to interconvert by transdifferentiation generally arise from adjacent regions in the developing embryo. For example, the liver and pancreas arise from the same region of the endoderm. The transdifferentiation of pancreas to liver (and vice versa) has been

Chia-Ning Shen; Marko E. Horb; Jonathan M. W. Slack; David Tosh

2003-01-01

360

White liver disease in lambs.  

PubMed

An outbreak of white liver disease in lambs in Western Australia is described. The disease affected 2- to 3-month-old lambs and was characterised by liver damage, severe ill-thrift, depression, serous ocular discharge, photosensitization, and a high mortality rate. Transient central nervous system signs occurred. A positive response to vitamin B12 therapy was demonstrated. PMID:7340780

Richards, R B; Harrison, M R

1981-12-01

361

Malignant rhabdoid tumor of liver  

PubMed Central

Malignant rhabdoid tumor (MRT) is a rare, but aggressive tumor commonly arising from the kidney in young children. Extrarenal MRT has been reported in the literature in various other sites including the liver, pelvis, CNS, abdomen, heart and other soft-tissues. Reported herein are the presentation, radiology, histopathology, immunohistochemistry, treatment and outcome of a 6 month infant with primary MRT of liver.

Agarwala, Sandeep; Jindal, Bibekanand; Jana, Manisha; Bhatnagar, Veereshwar; Gupta, Arun Kumar; Iyer, Venkateshwar K.

2014-01-01

362

Bioartificial Liver Support Anno 2001  

Microsoft Academic Search

Despite maximal intensive care, mortality of acute fulminant hepatic failure is high: 60%–75% in several studies. In addition patients with chronic liver insufficiency suffer from a bad quality of life: all patients suffer from fatigue; symptoms of hepatic encephalopathy, jaundice, and itching are often present. Analogous to artificial kidney treatment in patients with renal failure, an artificial liver assist device

Robert A. F. M. Chamuleau

2002-01-01

363

Diagnosis of canine liver disease  

Microsoft Academic Search

LIVER disease is relatively common in dogs, but its diagnosis presents a challenge. The liver's large reserve capacity means that many dogs show no clinical signs until late in the disease process and signs are often non?specific. Findings on blood tests and diagnostic imaging are also relatively non?specific and a biopsy is often required for definitive diagnosis. This article outlines

Nick Bexfield; Penny Watson

2006-01-01

364

The Liver, Regulator of Nutrition.  

ERIC Educational Resources Information Center

The purpose of this theme issue is to review the basic physiological, nutritional, and pathological facts pertaining to the liver. It is an educational tool through which university teachers and people in charge of training may enhance their teaching programs. The main liver diseases seen in young children and pregnant women in tropical regions is…

Dillon, J. C.

1995-01-01

365

Magnetic resonance elastography of liver: clinical applications.  

PubMed

Magnetic resonance elastography (MRE) has been successfully implemented in the assessment of diffuse liver diseases. Currently, MRE is the most accurate noninvasive technique for detection and staging of liver fibrosis with a potential to replace liver biopsy. Magnetic resonance elastography is able to differentiate isolated fatty liver disease from steatohepatitis with or without fibrosis. Potential clinical applications include the differentiation of benign and malignant focal liver masses and the assessment of treatment response in diffuse liver diseases. PMID:24270110

Venkatesh, Sudhakar K; Yin, Meng; Ehman, Richard L

2013-01-01

366

Multiphoton analysis of normal and diseased livers  

NASA Astrophysics Data System (ADS)

Diseases associated with the liver, a major internal organ, can lead to serious health problems. In this work, we present multiphoton images of normal and diseased liver specimens and we will characterize the changes to pathological liver specimens. In particular, we will focus on the physiological changes associated with liver fibrosis. Our results show that multiphoton microscopy is a useful technique for distinguishing normal and diseased liver tissues and that it has potential applications for in vivo diagnosis of liver diseases.

Liu, Yuan; Fwu, Peter T.; Chen, Hsiao-Ching; Chiou, Ling-Ling; Huang, Guan-Tarn; Lo, Wen; Lee, Hsuan-Shu; Dong, Chen-Yuan

2005-03-01

367

Magnetic Resonance Elastography of Liver: Clinical Applications  

PubMed Central

Magnetic resonance elastography (MRE) has been successfully implemented in the assessment of diffuse liver diseases. Currently, MRE is the most accurate noninvasive technique for detection and staging of liver fibrosis with a potential to replace liver biopsy. Magnetic resonance elastography is able to differentiate isolated fatty liver disease from steatohepatitis with or without fibrosis. Potential clinical applications include the differentiation of benign and malignant focal liver masses and the assessment of treatment response in diffuse liver diseases.

Venkatesh, Sudhakar K.; Yin, Meng; Ehman, Richard L.

2014-01-01

368

Liver disease, HIV and aging.  

PubMed

The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed. PMID:22127037

Falade-Nwulia, Oluwaseun; Thio, Chloe L

2011-12-01

369

Liver stem cells.  

PubMed

The capacity of hepatocytes and cholangiocytes to contribute to their own maintenance has long been recognized. More recently, studies have indicated the presence of both intra-hepatic and extra-hepatic stem/progenitor cell populations. The intraorgan compartment probably derives primarily from the biliary tree, most particularly the most proximal branches, i.e. the canals of Hering and smallest ductules. The extra-organ compartment is at least in part derived from diverse populations of cells from the bone marrow. These three tiers of liver cell regeneration serve to maintain the normal organ and to regenerate damaged parenchyma in response to a variety of insults. The nature and extent of the insult determines the balance between these stem/progenitor compartments. PMID:19002950

Theise, Neil D

2003-03-01

370

Liver abnormalities and endocrine diseases.  

PubMed

The liver and its pleotropic functions play a fundamental role in regulating metabolism, and is also an inevitable target of multiple metabolic disorders. The numerous and constant relationships and feedback mechanisms between the liver and all endocrine organs is reflected by the fact that an alteration of one oftentimes results in the malfunction of the other. Hypo- and hyperthyroidism are frequently associated with hepatic alterations, and thyroid diseases must be excluded in transaminase elevation of unknown cause. Drugs such as propylthiouracil, used in the treatment of hyperthyroidism, may induce liver damage, and other drugs such as amiodarone, carbamazepine, and several chemotherapeutic agents can lead to both thyroid and liver abnormalities. Liver diseases such as hepatitis, hepatocellular carcinoma, and cirrhosis may cause altered levels of thyroid hormones, and alcoholic liver disease, both due to the noxious substance ethanol as well as to the hepatic damage it causes, may be responsible for altered thyroid function. Both excess and insufficiency of adrenal function may result in altered liver function, and adrenocortical dysfunction may be present in patients with cirrhosis, especially during episodes of decompensation. Again an important player which affects both the endocrine system and the liver, alcohol may be associated with pseudo-Cushing syndrome. Sex hormones, both intrinsic as well as extrinsically administered, have an important impact on liver function. While oestrogens are related to cholestatic liver damage, androgens are the culprit of adenomas and hepatocellular carcinoma, among others. Chronic liver disease, on the other hand, has profound repercussions on sex hormone metabolism, inducing feminization in men and infertility and amenorrhoea in women. Lastly, metabolic syndrome, the pandemia of the present and future centuries, links the spectrum of liver damage ranging from steatosis to cirrhosis, to the array of endocrine alterations that are features of the syndrome, including insulin resistance, central obesity, and hyperlipidaemia. Clinical practice must integrally evaluate the effects of the intricate and tight relationship between the liver and the endocrine system, in order to better address all manifestations, complications, and prevent deterioration of one or the other organ-system. PMID:24090942

Burra, Patrizia

2013-08-01

371

Liver Resection of Colorectal Liver Metastases in Elderly Patients  

Microsoft Academic Search

Background  The percentage of elderly patients with colorectal liver metastases (CLM) has increased. Liver resection remains the only\\u000a curative therapy; data evaluating the outcome in this age group is limited. Aim of the present study was to determine if postoperative\\u000a morbidity, mortality, and other independent predictors influence survival in patients ?70 years undergoing liver resection\\u000a for CLM.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Clinical data on primary tumor

U. Kulik; T. Framke; A. Großhennig; A. Ceylan; H. Bektas; J. Klempnauer; F. Lehner

372

Multiple cysts in the liver autosomal dominant polycystic liver disease.  

PubMed

A 45-year-old woman was admitted because of abdominal pain and a feeling of fullness. Ultrasound and CT scan of the abdomen showed a massively enlarged liver with hundreds of cysts and displacement of the right kidney. There were no cysts in the kidneys. Because several members of her family also had multiple cysts in the liver, the diagnosis of autosomal dominant polycystic liver disease (PCLD) was made. Genetic analysis demonstrated a protein kinase C substrate 80 K-H (PR KCSH) gene mutation (1338-2A>G) and confirmed the clinical diagnosis. A brief review of the genetics and possible treatments is given. PMID:16788219

Karimbeg, A A; Loffeld, R J L F

2006-06-01

373

[Focal liver lesion, incidental finding].  

PubMed

The differential diagnosis of incidentally found Focal Liver Lesions (FLL) is complex. Screening procedures so far are only defined for patients with liver cirrhosis. Characterization of a FLL begins as soon as it is detected. Taking patients history and thorough clinical examination are essential. An imaging procedure that is used to detect liver masses should also allow the examiner to determine whether the lesion is benign or malignant. Conventional B-mode US and colour Doppler imaging are effective at detecting and characterizing typical liver cysts and calcifications. Laboratory data, computed tomography, magnetic resonance imaging and imaging guided liver biopsy are complementary methods.Contrast Enhanced Ultrasound (CEUS) is a well established diagnostic imaging technique for a variety of indications and applications. One of the most important applications is in the liver where it is frequently a first-line technique for the detection and diagnosis (characterization) of focal liver lesions (FLL). In this setting the accurate differentiation of benign from malignant lesions is critical to ensure the patient undergoes the appropriate therapeutic option. This has been documented in recently published guidelines, in particular in terms of the enhancement patterns of the most common FLL hemangioma, focal nodular hyperplasia hepatocellular adenoma and their differentiation from malignant lesions. In this article the role of CEUS in the characterization of incidentally found FLL is described. PMID:23033169

Dietrich, C F; Jenssen, C

2012-10-01

374

Cellular therapy for liver disease.  

PubMed

Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow-derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow-derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease. PMID:24582199

Huebert, Robert C; Rakela, Jorge

2014-03-01

375

Imaging of liver metastases: MRI  

PubMed Central

Metastases are the most common malignant liver lesions and the most common indication for hepatic imaging. Specific characterization of liver metastases in patients with primary non-hepatic tumors is crucial to avoid unnecessary diagnostic work-up for incidental benign liver lesions. Magnetic resonance (MR) is rapidly emerging as the imaging modality of choice for detection and characterization of liver lesions due to the high specificity resulting from optimal lesion-to-liver contrast and no radiation exposure. Improvements in breath-hold T1-weighted fast spoiled gradient echo and rapid T2-weighted single shot echo-train acquisition enable imaging of the liver in a single breath-hold with high spatial resolution. Most metastases are hypo- to isointense on T1 and iso- to hyperintense on T2-weighted images. MR contrast agents provide critical tumor characterization and can be safely used in patients with iodine contrast allergy and renal failure. Other agents, including newly developing gadolinium-chelates or iron oxide agents may provide additional benefits in selected applications. The degree and nature of tumor vascularity form the basis for liver lesion characterization based on enhancement properties. Liver metastases may be hypovascular or hypervascular. Colon, lung, breast and gastric carcinomas are the most common tumors causing hypovascular liver metastases, and typically show perilesional enhancement. Neuroendocrine tumors including carcinoid and islet cell tumors, renal cell carcinoma, breast, melanoma, and thyroid carcinoma are tumors most commonly causing hypervascular hepatic metastases, which may develop early enhancement with variable degrees of washout and peripheral rim enhancement.

Namasivayam, Saravanan; Martin, Diego R

2007-01-01

376

Selected infectious disease disasters for nursing staff training at Egyptian Eastern Border.  

PubMed

Infectious disease disasters are events that involve a biological agent, disease and that result in mass casualties, such as a bioterrorism attack, an emerging outbreak of infectious disease; all disasters pose a risk of infection transmission. But, infectious disease disasters pose the great-risk to illness or death from an infectious disease. This study raised the awareness and improved knowledge by educational program for Military Nursing Staff on selected infectious disease disasters acquired at Egyptian Eastern Border. The selected arthropod-borne diseases were Anthrax, Tick borne relapsing, Louse borne replasing fever and liver fluke; Clonorchis sinensis. An interventional study was used, for 125 staff nurse who accepted to participate. The tools dealt with four questionnaires: (1) Some sociodemographic characteristics data (2) Educational needs assessment a structured questionnaire. (3) Knowledge test (pre/post-test) and (4) Participants' reactions questionnaire. The results showed that educational intervention significantly improvements the nursing staff knowledge, which were achieved at the immediate post intervention phase, and retained via three months post-test phase. In the service training programs about infectious disease disasters at Egyptian Eastern Border must be established and continued on regular basis. This would improve their knowledge about the epidemiology of these infectious disease disasters. PMID:24961011

El-Bahnasawy, Mamdouh M; Labib, Nargis Albert; Abdel-Fattah, Magda Abdel Hameed; Ibrahim, Abeer Mohammad Abdallah; Morsy, Tosson A

2014-04-01

377

Cholangiocarcinoma: descriptive epidemiology and risk factors.  

PubMed

In theory, the term of cholangiocarcinoma is reserved for the tumours originating from the intrahepatic bile ducts. The problems of classification of the most frequent hilar tumours and the absence of histopathological confirmation in a large percentage of cases in cancer registries from many countries show the difficulty of establishing the specific epidemiologic behaviour of intrahepatic cholangiocarcinoma (ICC). There are clearly two types of ICC: the first one is the consequence of the recurrent infection of the biliary ducts by the parasites Opisthorchis viverrini and Clonorchis sinensis, and is only seen in the areas of Southeast Asia where liver flukes are endemic. In these areas, incidence and mortality rates of ICC are extremely high. Both parasites have been classified class I carcinogens by the International Agency for Research on Cancer. The other type of ICC is a cancer much rarer but present in the whole world. Some risk factors have been well-established (chronic inflammation of biliary ducts, hepatitis, thorotrast, etc) but many patients do not have any of these factors. An increase in incidence and mortality of this second type of ICC has been seen in recent years, mostly in developed countries. There is an ongoing discussion in the literature about its authenticity and potential causes. PMID:20202771

de Martel, C; Plummer, M; Franceschi, S

2010-03-01

378

Metagonimus yokogawai: a 100-kDa Somatic Antigen Commonly Reacting with Other Trematodes  

PubMed Central

This study was undertaken to characterize the properties of a 100 kDa somatic antigen from Metagonimus yokogawai. Monoclonal antibodies (mAbs) were produced against this 100 kDa antigen, and their immunoreactivity was assessed by western blot analysis with patients' sera. The mAbs against the 100 kDa antigen commonly reacted with various kinds of trematode antigens, including intestinal (Gymnophalloides seoi), lung (Paragonimus westermani), and liver flukes (Clonorchis sinensis and Fasciola hepatica). However, this mAb showed no cross-reactions with other helminth parasites, including nematodes and cestodes. To determine the topographic distribution of the 100 kDa antigen in worm sections, indirect immunoperoxidase staining was performed. A strong positive reaction was observed in the tegumental and subtegumental layers of adult M. yokogawai and C. sinensis. The results showed that the 100 kDa somatic protein of M. yokogawai is a common antigen which recognizes a target epitope present over the tegumental layer of different trematode species.

Park, Young-Jin; Park, Jeong-Hyun; Chai, Jong-Yil

2014-01-01

379

Metagonimus yokogawai: a 100-kDa Somatic Antigen Commonly Reacting with Other Trematodes.  

PubMed

This study was undertaken to characterize the properties of a 100 kDa somatic antigen from Metagonimus yokogawai. Monoclonal antibodies (mAbs) were produced against this 100 kDa antigen, and their immunoreactivity was assessed by western blot analysis with patients' sera. The mAbs against the 100 kDa antigen commonly reacted with various kinds of trematode antigens, including intestinal (Gymnophalloides seoi), lung (Paragonimus westermani), and liver flukes (Clonorchis sinensis and Fasciola hepatica). However, this mAb showed no cross-reactions with other helminth parasites, including nematodes and cestodes. To determine the topographic distribution of the 100 kDa antigen in worm sections, indirect immunoperoxidase staining was performed. A strong positive reaction was observed in the tegumental and subtegumental layers of adult M. yokogawai and C. sinensis. The results showed that the 100 kDa somatic protein of M. yokogawai is a common antigen which recognizes a target epitope present over the tegumental layer of different trematode species. PMID:24850966

Han, Eun-Taek; Yang, Hyun-Jong; Park, Young-Jin; Park, Jeong-Hyun; Chai, Jong-Yil

2014-04-01

380

3-Tesla MRI Response to TACE in HCC (Liver Cancer)  

ClinicalTrials.gov

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

2014-03-20

381

Liver transplantation in alcoholic patients.  

PubMed

Alcoholic liver disease is one of the most common causes of cirrhosis and indications for orthotopic liver transplantation in Europe and North America. The reluctance to transplant alcoholics stems in part from the view that alcoholics bear responsibility for their illness. There is also the perception that the alcoholic person is likely to relapse into alcohol use after transplantation and thereby damage the allograft. In this review, we considered the evaluation for and outcome of liver transplantation in alcoholics with special attention to the specific risks of alcohol relapse, to show that alcoholism should be considered like other co-morbid states rather than as a moral flaw. PMID:15819795

Burra, Patrizia; Lucey, Michael R

2005-05-01

382

[Liver involvement in systemic diseases].  

PubMed

Liver involvement is common in connective tissue disorders and usually asymptomatic. However, it may be symptomatic and cases of fulminant hepatitis have been reported. A diagnosis of specific hepatic involvement needs to rule out drug toxicity, viral hepatitis, or auto-immune liver disease. The large panel of auto-antibodies that is now available to the clinician is helpful to differentiate auto-immune hepatitis and specific liver involvement associated with connective tissue disease. In the latter, the outcome is generally favourable with immunosuppressive treatment. PMID:20934791

Geri, G; Saadoun, D; Cacoub, P

2011-08-01

383

Management of polycystic liver disease.  

PubMed

Polycystic liver disease (PCLD) is characterized by multiple cysts throughout the liver. Patients may develop chronic intractable symptoms that may be debilitating. Others may develop medical complications that necessitate intervention. There is a variety of nonsurgical and surgical treatment options for symptomatic or complicated PCLD, which range from cyst aspiration and fenestration to liver transplantation. Studies have described variable efficacy and morbidity. Currently, there are no guidelines for the management of PCLD patients and the optimal intervention is controversial. This article reviews the pathogenesis, classification and spectrum of treatment options for PCLD. PMID:15565206

Cheung, Justin; Scudamore, Charles H; Yoshida, Eric M

2004-11-01

384

Scaffolds for liver tissue engineering.  

PubMed

This review focuses on the expanding role for biomaterials and polymer scaffolds in liver tissue engineering. Studies are subdivided into in vitro and in vivo approaches. The in vitro section of the review discusses the challenges specific to liver tissue engineering, and how the choice of scaffold and its structure influences the success of the regenerative medicine strategy. The in vivo section evaluates early attempts to stimulate liver repair with cell and growth factor therapies, their failings and how current approaches aim to solve these problems. PMID:16359250

Hammond, John S; Beckingham, Ian J; Shakesheff, Kevin M

2006-01-01

385

Interventional Radiology in Liver Transplantation  

SciTech Connect

Radiology is a key specialty within a liver transplant program. Interventional techniques not only contribute to graft and recipient survival but also allow appropriate patient selection and ensure that recipients with severe liver decompensation, hepatocellular carcinoma or portal hypertension are transplanted with the best chance of prolonged survival. Equally inappropriate selection for these techniques may adversely affect survival. Liver transplantation is a dynamic field of innovative surgical techniques with a requirement for interventional radiology to parallel these developments. This paper reviews the current practice within a major European center for adult and pediatric transplantation.

Karani, John B., E-mail: john.karani@kingsch.nhs.uk; Yu, Dominic F.Q.C.; Kane, Pauline A. [King's College Hospital (United Kingdom)

2005-04-15

386

Role of liver biopsy in nonalcoholic fatty liver disease  

PubMed Central

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

Nalbantoglu, ILKe; Brunt, Elizabeth M

2014-01-01

387

Liver diseases in pregnancy: liver transplantation in pregnancy.  

PubMed

Pregnancy in patients with advanced liver disease is uncommon as most women with decompensated cirrhosis are infertile and have high rate of anovulation. However, if gestation ensued; it is very challenging and carries high risks for both the mother and the baby such as higher rates of spontaneous abortion, prematurity, pulmonary hypertension, splenic artery aneurysm rupture, postpartum hemorrhage, and a potential for life-threatening variceal hemorrhage and hepatic decompensation. In contrary, with orthotopic liver transplantation, menstruation resumes and most women of childbearing age are able to conceive, give birth and lead a better quality of life. Women with orthotopic liver transplantation seeking pregnancy should be managed carefully by a team consultation with transplant hepatologist, maternal-fetal medicine specialist and other specialists. Pregnant liver transplant recipients need to stay on immunosuppression medication to prevent allograft rejection. Furthermore, these medications need to be monitored carefully and continued throughout pregnancy to avoid potential adverse effects to mother and baby. Thus delaying pregnancy 1 to 2 years after transplantation minimizes fetal exposure to high doses of immunosuppressants. Pregnant female liver transplant patients have a high rate of cesarean delivery likely due to the high rate of prematurity in this population. Recent reports suggest that with close monitoring and multidisciplinary team approach, most female liver transplant recipient of childbearing age will lead a successful pregnancy. PMID:24282354

Hammoud, Ghassan M; Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat; Ibdah, Jamal A

2013-11-21

388

MODEL OF TOXICANT RESPONSE IN ENGINEERED LIVER  

EPA Science Inventory

This project proposes to: engineer a tissue to mimic liver behavior (a so-called 3-Dimensional or 3D liver model); simulate liver toxicity by exposing the 3D liver model to two known toxicants ( carbon tetrachloride and 1,2 dichloroethylene); and ...

389

Hepatitis B and Primary Liver Cancer  

MedlinePLUS

... Liver Biopsy Treatment of Liver Cancer Diagnosis and Management High Risk Groups Blood Tests Managing HBV HBV and Liver ... pain, weight loss, lack of appetite, weakness and fatigue, and finally the ... medical management. For those with chronic hepatitis B, primary liver ...

390

The role of adipokines in liver fibrosis  

Microsoft Academic Search

Liver fibrosis is a dynamic process consisting of the chronic activation of the wound healing reaction in response to reiterated liver damage, leading to the excessive deposition of fibrillar extracellular matrix into the liver and eventually, if the cause of injury is not removed, to liver cirrhosis. The term “adipokines” identifies a group of polypeptide molecules secreted primarily by adipose

Cristiana Bertolani; Fabio Marra

2008-01-01

391

MRI of Focal Liver Lesions  

PubMed Central

Magnetic resonance imaging, MRI has more advantages than ultrasound, computed tomography, CT, positron emission tomography, PET, or any other imaging modality in diagnosing focal hepatic masses. With a combination of basic T1 and T2 weighted sequences, diffusion weighted imaging, DWI, and hepatobiliary gadolinium contrast agents, that is gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB), most liver lesions can be adequately diagnosed. Benign lesions, as cyst, hemangioma, focal nodular hyperplasia, FNH or adenoma, can be distinguished from malignant lesions. In a non-cirrhotic liver, the most common malignant lesions are metastases which may be hypovascular or hypervascular. In the cirrhotic liver hepatocellular carcinoma, HCC, is of considerable importance. Besides, intrahepatic cholangiocarcinoma and other less common malignancies has to be assessed. In this review, the techniques and typical MRI features are presented as well as the new algorithm issued by American Association for the Study of the Liver Diseases (AASLD).

Albiin, Nils

2012-01-01

392

Liver Disease and Adult Vaccination  

MedlinePLUS

... for Adults Share Compartir Liver Disease and Adult Vaccination Vaccines are especially critical for people with health ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

393

Cholestatic liver disease in children.  

PubMed

Inherited syndromes of intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the prime indication for liver transplantation in children. Our understanding of the pathogenesis of these diseases has increased substantially by the discovery of genetic mutations in children with intrahepatic cholestasis and the findings that inflammatory circuits are operative at the time of diagnosis of biliary atresia. Building on this solid foundation, recent studies provide new insight into genotype-phenotype relationships and how mutations produce altered bile composition and cholestasis. New evidence exists that although liver transplantation is curative for patients with end-stage liver disease owing to cholestasis, some patients may develop recurrence of cholestasis because of the emergence of autoantibodies that disrupt canalicular function in the new graft. Progress is also evident in biliary atresia, with recent studies identifying candidate modifier genes and directly implicating lymphocytes and inflammatory signals in the pathogenesis of bile duct injury and obstruction. PMID:20425482

Santos, Jorge L; Choquette, Monique; Bezerra, Jorge A

2010-02-01

394

Cholestatic Liver Disease in Children  

PubMed Central

Inherited syndromes of intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the prime indication for liver transplantation in children. Our understanding of the pathogenesis of these diseases has increased substantially by the discovery of genetic mutations in children with intrahepatic cholestasis and the findings that inflammatory circuits are operative at the time of diagnosis of biliary atresia. Building on this solid foundation, recent studies provide new insight into genotype-phenotype relationships and how mutations produce altered bile composition and cholestasis. New evidence exists that although liver transplantation is curative for patients with end-stage liver disease owing to cholestasis, some patients may develop recurrence of cholestasis because of the emergence of autoantibodies that disrupt canalicular function in the new graft. Progress is also evident in biliary atresia, with recent studies identifying candidate modifier genes and directly implicating lymphocytes and inflammatory signals in the pathogenesis of bile duct injury and obstruction.

Santos, Jorge L.; Choquette, Monique

2010-01-01

395

Liver Biopsy in Human Leptospirosis.  

National Technical Information Service (NTIS)

Liver biopsies of proved human cases of leptospirosis showed partial disappearance and/or distortion of bile ductules and sinusoidal pole microvilli. The more severe cases showed definite mitochondrial pathology. Enlargement of the intercellular spaces wa...

T. de Brito

1967-01-01

396

Drugs Approved for Liver Cancer  

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

397

Liver disease in cystic fibrosis.  

PubMed

The survival of patients with cystic fibrosis (CF) has progressively increased over recent decades, largely attributable to early diagnosis through newborn screening and advances in nutritional and respiratory care. As the life expectancy of patients with CF has improved, non-respiratory complications such as liver disease have become increasingly recognized. Biochemical derangements of liver enzymes in CF are common and may be attributed to a number of specific hepatobiliary abnormalities. Among them, Cystic Fibrosis-associated Liver Disease (CFLD) is clinically the most significant hepatic complication and is believed to have a significant impact on morbidity and mortality. However, there remains much conjecture about the extent of the adverse prognostic implications that a diagnosis of CFLD has on clinical outcomes. The purpose of this review is to give an overview of the current knowledge regarding liver disease in children with CF. PMID:23769887

Leeuwen, Lisette; Fitzgerald, Dominic A; Gaskin, Kevin J

2014-03-01

398

Liver (Hepatocellular) Cancer (PDQ): Prevention  

MedlinePLUS

... with hepatitis A usually get better without treatment. Hepatitis B Hepatitis B is caused by contact with the ... factors may increase the risk of liver cancer: Hepatitis B and C Having chronic hepatitis B or chronic ...

399

Autoantibodies in chronic liver diseases.  

PubMed

177 patients with chronic liver disease, among 115 with chronic hepatitis and 61 with liver cirrhosis were subjected to the autoantibodies examinations (ANA, AMA, ASMA, APCA, LKM, ATA) by means of immunofluorescent method (IFA). 25% of cases showed autoantibodies of autoimmunological disease index titre (1:80). Autoantibodies occurred more frequently in woman (75%), mainly in the age of 40-60. Patients with hepatic cirrhosis revealed autoantibodies as frequently as other patients. Among patients infected with hepatotropic viruses (HBV, HCV) with chronic liver diseases, autoantibodies were present in 23-28% of cases and in patients with chronic liver diseases of non-infectious etiology, autoantibodies were observed in 25% of cases. PMID:11780553

Panasiuk, A

2001-01-01

400

Polycystic liver diseases.  

PubMed

Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal or recessive dominant pattern of inheritance and is characterized by the progressive development of multiple cysts, isolated or associated with polycystic kidney disease, that appear more extensive in women. Cholangiocytes have primary cilia, functionally important organelles (act as mechanosensors) that are involved in both normal developmental and pathological processes. The absence of polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia, represent a potential mechanism leading to cyst formation, associated with increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal cell-matrix interactions, and alterations in cell polarity. Proliferative and secretive activities of cystic epithelium can be regulated by estrogens either directly or by synergizing growth factors including nerve growth factor, IGF1, FSH and VEGF. The abnormalities of primary cilia and the sensitivity to proliferative effects of estrogens and different growth factors in PCLD cystic epithelium provide the morpho-functional basis for future treatment targets, based on the possible modulation of the formation and progression of hepatic cysts. PMID:20138815

Onori, P; Franchitto, A; Mancinelli, R; Carpino, G; Alvaro, D; Francis, H; Alpini, G; Gaudio, E

2010-04-01

401

Polycystic liver diseases  

PubMed Central

Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal or recessive dominant pattern of inheritance and is characterized by the progressive development of multiple cysts, isolated or associated with polycystic kidney disease, that appear more extensive in women. Cholangiocytes have primary cilia, functionally important organelles (act as mechanosensors) that are involved in both normal developmental and pathological processes. The absence of polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia, represent a potential mechanism leading to cyst formation, associated with increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal cell–matrix interactions, and alterations in cell polarity. Proliferative and secretive activities of cystic epithelium can be regulated by estrogens either directly or by synergizing growth factors including nerve growth factor, IGF1, FSH and VEGF. The abnormalities of primary cilia and the sensitivity to proliferative effects of estrogens and different growth factors in PCLD cystic epithelium provide the morpho-functional basis for future treatment targets, based on the possible modulation of the formation and progression of hepatic cysts.

Onori, P.; Franchitto, A.; Mancinelli, R.; Carpino, G.; Alvaro, D.; Francis, H.; Alpini, G.; Gaudio, E.

2010-01-01

402

Radiology of liver circulation  

SciTech Connect

This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions.

Hermine, C.L.

1985-01-01

403

IL-13 Signaling in Liver Fibrogenesis  

PubMed Central

Liver fibrosis is the final common pathway of chronic liver diseases irrespective of etiology. However, etiology deeply impacts progression and characteristics of liver fibrogenesis. IL-13 is the dominant pro-fibrotic cytokine in Schistosomiasis associated liver fibrogenesis. In vitro, IL-13 directly induces expression of fibrosis-associated genes, e.g., collagens or connective tissue growth factor, in hepatic stellate cells. Recently, potential effects of IL-13 in non-Schistosomiasis associated liver fibrosis have been uncovered. This review summarizes the potential roles of IL-13 in chronic liver disease of different etiologies, and the downstream events mediating IL-13 signaling in liver fibrogenesis.

Liu, Yan; Munker, Stefan; Mullenbach, Roman; Weng, Hong-Lei

2012-01-01

404

Comparative Study of Human Liver Ferritin and Chicken Liver by Mössbauer Spectroscopy. Preliminary Results  

NASA Astrophysics Data System (ADS)

A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Mössbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Mössbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

2004-12-01

405

Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology  

Microsoft Academic Search

Background\\/Aims: The significance of abnormal liver function tests in the absence of diagnostic serology is unclear. The aim of this study was to report liver biopsy findings in a large group of patients with unexplained abnormal liver biochemistry. Methods: Histological findings were examined in 354 patients who underwent liver biopsy to investigate abnormal liver function tests. Results: Six percent of

Maeve M. Skelly; Peter D. James; Stephen D. Ryder

406

Model for end-stage liver disease (MELD) and allocation of donor livers  

Microsoft Academic Search

Background & Aims: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease

Russell Wiesner; Erick Edwards; Richard Freeman; Ann Harper; Ray Kim; Patrick Kamath; Walter Kremers; John Lake; Todd Howard; Robert M. Merion; Robert A. Wolfe; Ruud Krom

2003-01-01

407

Liver Transplantation for Alcoholic Liver Disease: A Consideration of Reasons For and Against  

PubMed Central

Orthotopic liver transplantation is a clinical procedure that has been accepted widely as the treatment of choice for individuals with advanced chronic liver disease. As such, its application to the important clinical problem of alcoholic liver disease is inevitable. The arguments for and against liver transplantation for individuals with advanced alcoholic liver disease are presented.

Van Thiel, David H.; Gavaler, Judith S.; Tarter, Ralph E.; Dindzans, Vincents J.; Gordon, Robert D.; Iwatsuki, Shunzaburo; Makowka, Leonard; Todo, Satoru; Tzakis, Andreas; Starzl, Thomas E.

2010-01-01

408

Ablative therapy for liver tumours  

PubMed Central

Established ablative therapies for the treatment of primary and secondary liver tumours, including percutaneous ethanol injection, cryotherapy, and radiofrequency ablation, are discussed. Newer techniques such as magnetic resonance imaging guided laser interstitial thermal therapy of liver tumours has produced a median survival rate of 40.8 months after treatment. The merits of this newly emerging technique are discussed, together with future developments, such as focused ultrasound therapy, which holds the promise of non-invasive thermoablation treatment on an outpatient basis.

Dick, E A; Taylor-Robinson, S D; Thomas, H C; Gedroyc, W M W

2002-01-01

409

Energy Metabolism in the Liver  

PubMed Central

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial ? oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic s