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Analysis Of The Proteomic Feature Of Guillain-Barré Syndrome-associated Campylobacter Jejuni

Posted on:2005-11-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Y TianFull Text:PDF
GTID:1104360125458249Subject:Neurology
Abstract/Summary:PDF Full Text Request
Guillain-Barré syndrome(GBS) is now the most common cause of acute flaccid paralysis worldwide in the post-polio era, it is clinically characterized by the progressive weakness, usually symmetrical, with or without paralysis of respiratory muscle and cranial nerves. Recent neurophysiological and pathological studies have led to a reclassification of GBS into acute inflammatory demyelinating polyneuropathy(AIDP),acute motor axonal neuropathy(AMAN),acute motor and sensory axonal neuropathy(AMSAN),Miller Fisher syndrome(MFS).About two-thirds of GBS are preceded by infections within 1-3 weeks of GBS onset, often suggestive of gastrointestinal enteritis or upper respiratory tract infection. Campylobacter jejuni(C.jejuni), which is a leading cause of acute enteritis, has become recognized as the most frequent antecedent pathogen for part of the GBS cases in recent years. Professor Li in our department isolated several strains of C.jejuni from GBS patients and chickens, and established the first animal model of AMAN worldwide by feeding or immunization with live C.jejuni strains and the purified lipopolysaccharide(LPS) fraction, therefore demonstrated that C.jejuni infection is an important pathogeny of GBS. The ratio of C.jejuni infection is high in the population, poultry and domestic animals in our country, but only certain C.jejuni strains with specific serotype are associated with development of GBS. There is a high incidence of GBS in northern China, the most frequently encountered pattern of GBS in northern China is AMAN with a relatively severe clinical course and a poor recovery. Therefore, it is very important to determine the strains capable of triggering GBS in susceptible hosts, and perform the risk-assessment studies and intervention of the pathogenic C.jejuni to reduce the incidence. The exact mechnism by which C.jejuni infection develops to GBS is still unclear , although the molecular mimicry between the core of LPS of certain strains of C.jejuni and gangliosides in peripheral nerves of human body is mostly considered to play an important role in the pathogenesis of GBS. Several investigators attempted to find the molecular characterization or specific markers of GBS-related C.jejuni at genic level, but did not draw a consistent conclusion. The lack of the molecular characterization of GBS-related C.jejuni hampers the performance of identification of the pathogenic C.jejuni strains, vacculation development and intervention. Following the rapid progress of genome, the functional genome, or post-genome is put forward. Protein is the production of gene expression and the final indicator of the function of gene, so proteomics has become one of the main contents of functional genome. Two-dimensional polyacrylamide gel electrophoresis (2DE) and mass spectrometry are the two key techniques of proteomics .Proteomics has increasingly been used to the studies of differentially expressed proteins related to diseases. Bacteria in different conditions and different strains can express different proteome. Finding the differentially expressed proteins between the pathogenic and normal cells helps to find the gene, proteins or the molecular marker related to diseases, thus helpful to the diagnosis, treatment and prevention for the diseases.Completion of C.jejuni genome and the development of the techniques in 2DE and mass spectrometry provide us with possibility of studying the molecular characterization of GBS-related C.jejuni highthroughputly at both phenotypic and genic level.The marker proteins of GBS-associated C.jejuni were analyzed by proteomics in this study. Since the stability and reproducibility of 2DE concern the reliability and inter-laboratory comparison of the data, we first established the 2DE system for C.jejuni and evaluated its stability and reproducibility, then analyzed the differentially expressed proteins between GBS-associated C.jejuni and non-GBS-associated C.jejuni strains and identified them by mass spectroscopy to find the marker proteins of GBS-associated C.
Keywords/Search Tags:Guillain-Barré syndrome, campylobacter jejuni, proteomics, polymerase chain reaction, sequence, wlaX, flagellin, flaA gene.
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