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)

Ocular onchocerciasis results from immune recognition of parasite proteins released into the eye by degenerating microfilariae. Previous studies have shown that pathology similar to human ocular onchocerciasis can be induced in sensitized mice by intracorneal injection with Onchocerca volvulus antigens. In the current study, we used this murine model to map the segments of O. volvulus protein disulfide isomerase (OvPDI) associated with the development of corneal pathology. Subclones of OvPDI were constructed encompassing one or more predicted T cell epitopes. Keratitis was induced in BALB/c mice after subcutaneous immunizations with OvPDI, followed by intracorneal challenge of OvPDI constructs. Truncated OvPDI proteins containing amino acids 450-481 of OvPDI were found to induce keratitis, whereas constructs that did not include this region did not induce corneal pathology. Consistent with this observation, two peptides derived from the 450-481 region stimulated T cell proliferation to a greater degree than control carrier protein. DNA sequence analysis of cDNAs encoding OvPDI from blinding and non-blinding strains of O. volvulus indicated no differences in the primary amino acid sequence of the 450-481 domain. Immunization of animals with OvPDI induced antibodies recognizing a 55 kDa host protein, identical to the predicted molecular weight of the mouse PDI homologue. Together, these data implicate specific antigenic epitopes of OvPDI in the development of O. volvulus mediated corneal pathology.
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PMID:Identification of an epitope of a recombinant Onchocerca volvulus protein that induces corneal pathology. 929 6

The objective of this study was to characterize a recombinant antigen of Ancylostoma caninum that had been identified by immunoscreening with selected antisera as described elsewhere. In vitro expression of clone Ac38-1 produced a protein with an apparent molecular mass of approximately 38 kDa, which reacted in Western blots with the antiserum from rabbits experimentally infected with L3 and also with affinity-purified antibodies against hydrophilic proteins of the cephalic glands obtained from the antiserum against the intestine, cephalic glands, and cervical glands of adult worms. It was recognized not by antisera from dogs percutaneously infected with 1,000 L3 of A. caninum but by antiserum from dogs infected with 100,000 L3 of A. caninum. DNA sequencing of clone Ac38-1 showed a cDNA fragment with a coding region of 1,014 bp. Comparison of clone Ac38-1 with the Genbank DNA data base revealed 78% identity with a 244-bp segment of the cm5b5 clone of the free-living nematode Caenorhabditis elegans coding for a protein disulfide isomerase gene. The deduced amino acid sequence of clone Ac38-1 showed 82% identity with a 334-amino-acid (aa) segment of the protein disulfide isomerase of C. elegans and 73% identity with a 334-aa segment of the protein disulfide isomerase aa sequence of Onchocerca volvulus.
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PMID:A recombinant protein disulfide isomerase homologue from Ancylostoma caninum. 976 8

The cuticle of parasitic nematodes consists primarily of a network of collagen molecules. The enzyme responsible for collagen maturation is prolyl 4-hydroxylase, making this enzyme a central activity in cuticle biosynthesis and a potentially important chemotherapeutic target. Adult and embryonic Brugia malayi are shown to be susceptible to inhibitors of vertebrate prolyl 4-hydroxylase, with exposed parasites exhibiting pathologies consistent with a disruption in cuticle biosynthesis. A full-length cDNA (Ov-phy-1) encoding a catalytically active alpha-subunit of Onchocerca volvulus prolyl 4-hydroxylase was isolated and characterized. The derived amino acid sequence of Ov-phy-1 encoded a peptide that was most similar to the two Caenorhabditis elegans prolyl 4-hydroxylase homologues and to the isoform II enzymes of vertebrates. Expressed sequence tag (EST) analysis and developmental polymerase chain reaction (PCR) studies demonstrated that Ov-phy-1 was expressed in L3 and adult parasites. The gene encoding the Ov-phy-1 open reading frame contained 11 introns, similar in structure to the gene encoding human prolyl 4-hydroxylase isoform I. Genomic Southern blot, EST and genomic PCR studies demonstrated that the O. volvulus genome contained between three and eight genes closely related to Ov-phy-1. Co-expression of Ov-phy-1 with the O. volvulus homologue of protein disulfide isomerase in a baculovirus system resulted in the production of enzymatically active O. volvulus prolyl 4-hydroxylase. In vitro production of enzymatically active O. volvulus prolyl 4-hydroxylase should facilitate identification of specific inhibitors of the parasite enzyme.
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PMID:Characterization and expression of enzymatically active recombinant filarial prolyl 4-hydroxylase. 1152 51