Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA fragment encoding the complete coding region of a 27-kDa protein (p27) of Dirofilaria immitis was cloned. Antibody to the recombinant p27 bound to hypodermal tissues of third (L3) and fourth stage larvae (L4) of D. immitis and to both the hypodermis and the cuticle of L3s of Onchocerca volvulus, as visualized by immunoelectronmicroscopy. The deduced amino acid sequence of the central and C-terminal regions of p27 (amino acids S83 to H222) is 18-36% identical to members of the sHsp/alpha-crystallin family of proteins. The homologous region is thought to be responsible for the molecular chaperone activity of members of this family. The p27 cDNA does not encode a hydrophobic signal peptide. At least two homologous yet distinct p27 genes were identified in the D. immitis genome by Southern hybridization using the p27 cDNA as a probe. The p27 transcript was 0.9 kb in length on Northern blots. The expression of p27 in L3s of D. immitis was neither upregulated by heat shock (43 degrees C) nor by incubation at the physiologic temperature of 37 degrees C. Pulse-labeling experiments of both D. immitis and Brugia malayi L3s during the L3-L4 molt in vitro showed that synthesis of p27 is also not upregulated during this developmental phase. However, p27 is expressed constitutively throughout the D. immitis L3-L4 molt and therefore by both larval stages. In addition, both female and male adult worms of this species express p27 constitutively. P27, or an allomorph thereof, was detected in each of nine species representing four nematode superfamilies, thus indicating that this molecule is ubiquitous within the phylum Nematoda. In view of the hypodermal localization of p27, its constitutive expression, and its retention among nematodes, the function of this protein in essential housekeeping roles such as that of molecular chaperone during the molting process is discussed.
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PMID:Dirofilaria immitis: ultrastructural localization, molecular characterization, and analysis of the expression of p27, a small heat shock protein homolog of nematodes. 865 49

Glutathione S-transferases (GSTs) are essential detoxification enzymes for virtually all cells and may additionally aid in parasite survival by counteracting host-induced damage. GSTs from parasitic nematodes have been identified as potential targets for both immuno- and chemotherapy. To more closely characterize a 31-kDa (OvGST1) and a 24.5-kDa (OvGST2) GST from the pathogenic human filarial parasite Onchocerca volvulus, immunolocalization by electron microscopy was performed using two distinct affinity-purified polyclonal antisera raised against the recombinant OvGST1 and OvGST2. The strongest immunogold staining for OvGST1 was identified in the body wall of adult worms, especially in protuberances of the cuticle which lie in pouches of the hypodermis and in the outer zone of the syncytial hypodermis, where the external plasma membrane forms series of lamellae. Gold particles were also observed on the epicuticle of the adults and in the region of the border between the cuticle and hypodermis of microfilariae. The larval stages L1, L2, and infective L3 were also immunopositive for OvGST1. There was no specific labeling in the longitudinal musculature, the intestine, or the uterine wall of the adult worm. In contrast to the results for OvGST1, immunogold labeling for OvGST2 was observed throughout the whole hypodermal cytoplasm. The epithelial cells of the uterine wall showed moderate labeling. These ultrastructural immunolocalization results are consistent with the molecular characterization of both enzymes, indicating that OvGST1 is secreted out of the hypodermis into the cuticle and is acting at the host-parasite interface, while OvGST2 functions as an intracellular cytosolic housekeeping enzyme.
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PMID:Onchocerca volvulus: ultrastructural localization of two glutathione S-transferases. 950 46

The search for appropriate vaccine candidates and drug targets against onchocerciasis has so far been confronted with several limitations due to the unavailability of biological material, appropriate molecular resources, and knowledge of the parasite biology. To identify targets for vaccine or chemotherapy development we have undertaken two approaches. First, cDNA expression libraries were constructed from life cycle stages that are critical for establishment of Onchocerca volvulus infection, the third-stage larvae (L3) and the molting L3. A gene discovery effort was then initiated by random expressed sequence tag analysis of 5,506 cDNA clones. Cluster analyses showed that many of the transcripts were up-regulated and/or stage specific in either one or both of the cDNA libraries when compared to the microfilariae, L2, and both adult stages of the parasite. Homology searches against the GenBank database facilitated the identification of several genes of interest, such as proteinases, proteinase inhibitors, antioxidant or detoxification enzymes, and neurotransmitter receptors, as well as structural and housekeeping genes. Other O. volvulus genes showed homology only to predicted genes from the free-living nematode Caenorhabditis elegans or were entirely novel. Some of the novel proteins contain potential secretory leaders. Secondly, by immunoscreening the molting L3 cDNA library with a pool of human sera from putatively immune individuals, we identified six novel immunogenic proteins that otherwise would not have been identified as potential vaccinogens using the gene discovery effort. This study lays a solid foundation for a better understanding of the biology of O. volvulus as well as for the identification of novel targets for filaricidal agents and/or vaccines against onchocerciasis based on immunological and rational hypothesis-driven research.
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PMID:Identification of potential vaccine and drug target candidates by expressed sequence tag analysis and immunoscreening of Onchocerca volvulus larval cDNA libraries. 1081 3