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)

To elucidate the pathogenic mechanisms involved in onchocercal sclerosing keratitis in humans, we developed a model of onchocercal interstitial keratitis in guinea pigs. Onchocerca volvulus antigens injected intrastromally into corneas of preimmunized Hartley guinea pigs induced an intense stromal keratitis with corneal edema, neovascularization, and infiltration with acute and chronic inflammatory cells. This reaction subsided after two weeks. Repeated intrastromal injection resulted in an exacerbation of the keratitis and ultimately in residual scarring. These findings are consistent clinically and histopathologically with the chronic interstitial keratitis observed in humans. To define which antigens induce the corneal reaction, O volvulus antigens were separated by molecular sieve chromatography and injected intrastromally. The highest activity was shown to reside in the fraction containing molecules of intermediate molecular weight. This model will be useful in defining O volvulus antigens and their role in sclerosing keratitis as well as in elucidating the immune mechanisms involved.
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PMID:Experimental interstitial keratitis induced by Onchocerca volvulus antigens. 246 73

Sclerosing keratitis is the major cause of blindness due to onchocerciasis; its pathogenesis is poorly understood. We have previously reported an immune-mediated model of experimental interstitial keratitis in guinea pigs following intrastromal challenge with soluble antigens from Onchocerca volvulus. This model system is ideal for evaluation of pathogenicity of multiple purified antigen preparations; however, reagents necessary for detailed immunologic analysis of the inflammatory cellular infiltrate are not yet available for guinea pigs. Because of the ready availability of these reagents for mice, a mouse model has been developed. The inflammatory response observed in this model was analogous to that seen in human onchocercal sclerosing keratitis as well as in the guinea pig model of onchocercal sclerosing keratitis. Granulocytes were present in the acute inflammatory response, whereas the chronic response showed lymphocytes, plasma cells, and histiocytes. Neovascularization and scarring of the corneal stroma was also observed. This model will be helpful in examining the mechanisms of immunopathogenesis and the contribution of the host genetic background to the disease.
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PMID:Immune-mediated Onchocerca volvulus sclerosing keratitis in the mouse. 769 31

Sclerosing keratitis is the predominant cause of blindness due to onchocerciasis which is a major human parasitic disease caused by the filarial parasite Onchocerca volvulus. In the present investigation, native pathogenic antigens of O. volvulus which are particularly potent in causing interstitial keratitis were characterized utilizing a guinea pig model. Following demonstration of the protein nature of these antigens using pronase digestion, the crude O. volvulus antigen extract was subjected to stepwise procedures of protein purification. At each stage of purification, pooled antigen fractions were injected into one cornea of presensitized guinea pigs followed by clinical evaluation of stromal inflammation and vascularization at different intervals of time after intrastromal challenge. Initial purification of the pathogenic antigens was carried out in the following order: molecular sieve chromatography on Bio-gel A-5m. anion exchange chromatography on Mono Q followed by DEAE-Sepharose CL-6B and cation exchange chromatography on Mono S. Two out of six different pools from the Mono S column (pool a eluted unbound at 10 mM-NaCl and pool e eluted between 130 mM and 475 mM-NaCl) were found to be most pathogenic. Further purification of Mono S pool a and pool e separately by gel filtration chromatography using Superose 12 demonstrated that the fractions which were most potent in inducing interstitial keratitis contained proteins with approximate molecular masses between 100 and 200 kDa. These results show that minor subfractions of total crude antigens of O. volvulus are largely responsible for induction of experimental interstitial keratitis. We have demonstrated the presence of these antigens in O. volvulus microfilariae by their cross-reactivities with anti-microfilarial antibodies, and hence the relevance of the purified antigens to ocular onchocerciasis in man since sclerosing keratitis is associated with invasion of the cornea by O. volvulus microfilariae. Isolation of these two pathogenic antigen pools represents the practical limits of purification and subsequent animal experiments possible with the available amounts of native parasite material obtained from infected human individuals in the absence of a suitable non-human host or of an in vitro culture system for O. volvulus.
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PMID:Characterization of native pathogenic antigens of Onchocerca volvulus: identification of high molecular mass protein antigens eliciting interstitial keratitis in a guinea pig model. 778 15

Sclerosing keratitis is the major cause of blindness due to onchocerciasis which results from chronic infection with the filarial parasite Onchocerca volvulus. Using a murine model of onchocercal sclerosing keratitis, we have demonstrated previously that predominantly (> 85%) CD3 + /CD4+ T-cells as well as the IL-2 receptor bearing cells infiltrate into the cornea in vivo during development and progress of the disease. The identification of CD4+ subsets TH1 and TH2 based on the cytokine secretion patterns of murine T-lymphocytes has been useful for understanding the immune basis of resistance and pathogenesis in murine models of several parasitic diseases. The present investigation was carried out to demonstrate whether the local immune response at the corneal lesion due to onchocercal interstitial keratitis correlated with such distinct patterns of cytokine production. For that purpose, mRNA was extracted separately from corneas obtained from the diseased eyes and the normal eyes of A/J mice with onchocercal interstitial keratitis, reverse transcribed and amplified by the polymerase chain reaction with four different cytokine specific primers. In corneas obtained from the eyes affected with onchocercal interstitial keratitis, mRNAs coding for IL-4 and IL-5 were up-regulated compared to the normal eyes having no lesions from the same animals. However, the levels of mRNAs for IL-2 and IFN gamma were found to be the same in the diseased and normal eyes. Taken together, these data suggest that IL-4 and IL-5 producing TH2-lymphocytes are active at the corneal lesion due to onchocercal interstitial keratitis.
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PMID:In vivo molecular analysis of cytokines in a murine model of ocular onchocerciasis. I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFN gamma mRNAs in the cornea due to experimental interstitial keratitis. 903 Sep 83

Onchocerciasis is a major cause of blindness. Although the World Health Organization has been successful in reducing onchocerciasis as a public health problem in parts of West Africa, there remain an estimated 17 million people infected with Onchocerca volvulus, the parasite that causes this disease. Ocular pathology can be manifested in any part of the eye, although disease manifestations are frequently characterized as either posterior or anterior eye disease. This review focuses on onchocerca-mediated keratitis that results from an inflammatory response in the anterior portion of the eye and summarizes what is currently known about human disease. This review also describes studies with experimental models that have been established to determine the immunological mechanisms underlying interstitial keratitis. The pathogenesis of keratitis is thought to be due to the host inflammatory response to degenerating parasites in the eye; therefore, the primary clinical symptoms of onchocercal keratitis (corneal opacification and neovascularization) are induced after injection of soluble O. volvulus antigens into the corneal stroma. Experimental approaches have demonstrated an essential role for sensitized T helper cells and shown that cytokines can regulate the severity of keratitis by controlling recruitment of inflammatory cells into the cornea. Chemokines are also important in inflammatory cell recruitment to the cornea, and their role in onchocerciasis is being examined. Further understanding of the molecular basis of the development of onchocercal keratitis may lead to novel approaches to immunologically based intervention.
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PMID:Pathogenesis of onchocercal keratitis (River blindness). 1039 75

One of the most significant contributions to tropical medicine and ophthalmology was made by Jean Hissette: African ocular onchocerciasis. During his extensive investigations in the Babindi country, he found numerous adults with river blindness. Their eye disease was caused by the filaria Onchocerca volvulus Leuckart. He noticed the signs of interstitial keratitis and band keratopathy, faint iritis or iridocyclitis, posterior synechiae and often a downward distortion of the pupil. He was the first to describe chorioretinal scarring of the fundus, what became known as the Hissette-Ridley fundus. People reported to him their entoptic phenomena which he unequivocally interpreted to be the images of microfilariae in the patient's own eye. During his stay in Belgium in 1932, he elucidated the pathogenesis of blindness since he was able to provide histological proof of the presence of microfilariae in various ocular tissues of an enucleated eye from a patient living near the Sankuru river. Like other serious health impairments, the severe inflammatory lesions in the eye occurred only after the microfilariae had died. Hence he realized that dying microfilariae play a key role in the mechanisms leading to blindness. Hissette's precise descriptions were the logical fruit of his outstanding observational abilities and enabled him as a man of great intuition to speculate about causal relationships. He evidently benefited from the fact that he took the native Africans seriously and asked them their opinion. In 1933, his friend and teacher Dr. De Mets in Antwerp already wrote on Hissette's discovery in the Belgian Congo: "This study is of exceptional value to specialists which is not only a tribute to its author, but to our common native country (Belgium)."
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PMID:The significance of some observations on African ocular onchocerciasis described by Jean Hissette (1888-1965). 1854 27