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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conjunctival lymphographies in patients infected with Onchocerca volvulus in Liberia showed normal or only slightly dilated lymphatics. The light-microscopical studies of conjunctival specimens revealed microfilariae predominantly in edematous dilated interstitial channels. Microfilariae in lymphatics and interstitial channels without endothelium of the conjunctivae were demonstrated by scanning and transmission electron microscopy. No signs of inflammatory cellular reaction were found in the vicinity of the parasites. In conclusion, the dilatation of lymphatics and interstitial channels as well as the pathways along which the microfilarial penetrated the cornea and the anterior segments of the eye are discussed.
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PMID:[Lymphographic and morphological studies of the conjunctiva in onchocerciasis patients in Liberia]. 686 55

To provide quantitative information on the epidemiology of infection with Onchocerca volvulus and to define the association between indicators of infection and onchocercal eye disease, skin snips were obtained and skin and ocular examinations were performed on 892 persons living on seven Guatemalan coffee plantations. Skin-snip positivity and the density of microfilariae in the skin increased with age, reaching highest levels at 15-19 years, and both were greater in males than females. A history of nodulectomy was given by 67% of long-term residents and this percentage also increased with age. Over 90% of skin-snip positive subjects and 39% of skin-snip negative subjects had previous or present nodules. Microfilariae were detected in the cornea of 35.1% and in the anterior chamber of 18.9% of all persons examined and the frequencies increased with age, reaching peak levels at 10-19 years. Onchocercal eye lesions were found in 52 persons, causing bilateral blindness in six. Skin-snip positivity, microfilarial skin density, number of nodules, eye infection, and onchocercal eye lesions all correlated significantly with each other. Onchocercal blindness in one or both eyes was found only on fincas with a high prevalence (greater than 80%) and intensity of infection (greater than 22 microfilariae/mg skin).
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PMID:Onchocerciasis in Guatemala. Epidemiology in fincas with various intensities of infection. 697 10

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 caused by the parasite Onchocerca volvulus. Although the importance of T cells in the pathogenesis of onchocerciasis has been suggested, their precise role in onchocercal sclerosing keratitis has not yet been defined. Using immunohistological techniques and a murine model of onchocercal sclerosing keratitis, we have performed a temporal analysis of the inflammatory T cells infiltrating into the cornea at Days 4, 7, and 21 following intrastromal challenge with soluble O. volvulus antigens into presensitized mice. The maximum number of CD3+ T cells were observed in the corneal stroma at Day 21 when sclerosing keratitis was most severe. The majority (> 85%) of the CD3+ T cells were CD4+ at all time points. A few infiltrating cells bore IL-2 receptors indicating possible activation of a small fraction of the T cells. These results suggest that CD4+ T cells play an important role in onchocercal sclerosing keratitis.
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PMID:Infiltration of CD4+ T cells into cornea during development of Onchocerca volvulus-induced experimental sclerosing keratitis in mice. 799 62

Onchocerciasis is commonly known as River Blindness and affects about 18 million people around the world. It is transmitted by black flies that breed in river and stream rapids and transmit the parasitic microfilariae, Onchocerca volvulus, to people who live and work near such rivers. Infection with the microfilariae results in blindness or visual impairment for 1 or 2 million people. The microfilariae migrate to superficial tissues and may invade any part of the eye and ocular structure. Living worms cause little damage, however, their death triggers a localized inflammation which can lead to blindness. Sclerosing keratitis, a severe corneal involvement, is the major cause of blindness from the disease. The World Health Organization (WHO) Expert Committee on Onchocerciasis has estimated that 9% of the disease is found in Africa, the rest occur in Yemen and Latin America. Treatment with ivermectin is contraindicated for pregnant and lactating women, children under 5 years of age, asthmatics, and people with other diseases. The WHO Onchocerciasis Control Program in 11 countries of West Africa has eliminated the risk of onchocerciasis by aerial spraying of black fly breeding sites only from 1 country. A single annual oral dose (150 mg/kg) of ivermectin can reverse early lesions in the cornea. Ivermectin must be taken annually to sustain protection against blindness, thus its incorporation into primary health care along with malaria, AIDS, trachoma, xerophthalmia, and cataract is most cost effective. Nigeria and Tanzania have optometry schools, and optometrists can play a significant role in onchocerciasis control and blindness prevention programs by training local health care workers to distribute invermectin in vision screening programs.
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PMID:Onchocerciasis and other eye problems in developing countries: a challenge for optometrists. 824 90

Corneal inflammation similar to human onchocercal keratitis can be induced in mice by subcutaneous immunization of a soluble extract of Onchocerca volvulus (OvAg) followed by direct injection of OvAg into the corneal stroma. Previous studies have shown that corneal pathology is associated with increased systemic and corneal Th2 cytokine expression and that IL-4 gene knockout (IL-4-/-) mice develop less severe or no O. volvulus-mediated keratitis. The current study examined the contribution of Th2 cytokines to the diminished OvAg-induced corneal immunopathology observed in IL-4-/- mice. IL-4-/- mice (129Sv x C57B1/6), wild-type F2 littermates (IL-4+/+), and C57B1/6 mice were sensitized by repeated subcutaneous immunization with OvAg. Ten days after the final immunization, mice were sacrificed, spleens were removed, and cells were incubated with OvAg. Cells from immunocompetent C57B1/6 and IL-4+/+ mice produced IL-4 and IL-5, but no IFN-gamma, whereas cells from IL-4-/- mice had elevated IFN-gamma and no IL-4. Interestingly, cells from these animals produced levels of IL-5 protein equivalent to those of C57B1/6 and IL-4+/+ mice. To determine cytokine production in corneas during the onset of onchocercal keratitis, OvAg-immunized mice were injected intracorneally with OvAg, and cytokine gene expression in the cornea was determined by RT-PCR. Temporal analysis of cytokine gene expression in corneas of immunocompetent mice showed that the Th2-associated cytokines IL-4, IL-5, IL-10, and IL-13 were produced within 1 day of intrastromal injection, with sustained elevations for 10 days. Maximal IFN-gamma mRNA levels were not detected until Day 10. This was in contrast to IL-4-/- mice in which IFN-gamma appeared at Day 1 and remained elevated for at least 10 days. Moreover, in corneas from IL-4-/- mice, all Th2 cytokines with the exception of IL-4 were up-regulated and expressed with kinetics similar to that of IL-4+/+ littermates. Histologically, corneas from IL-4-/- mice were less edematous and contained fewer eosinophils and other inflammatory cells than those from immunocompetent controls. As there was no difference in peripheral eosinophil levels, these data indicate that the diminished severity of onchocercal keratitis in IL-4-/- mice is not due to failure to develop systemic or local Th2 cytokine responses or to produce eosinophils, but that IL-4 may be involved in recruitment of eosinophils and other inflammatory cells into the corneal stroma.
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PMID:Onchocerca volvulus-mediated keratitis: cytokine production by IL-4-deficient mice. 893 77

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

Invasion of the corneal stroma by neutrophils and eosinophils and subsequent degranulation disrupts corneal clarity and can result in permanent loss of vision. In the current study, we used a model of helminth-induced inflammation to demonstrate a novel role for Ab in mediating recruitment of these inflammatory cells to the central cornea. C57BL/6 and B cell-deficient (microMT) mice were immunized s. c. and injected intrastromally with Ags from the parasitic helminth Onchocerca volvulus (which causes river blindness). C57BL/6 mice developed pronounced corneal opacification, which was associated with an Ag-specific IL-5 response and peripheral eosinophilia, temporal recruitment of neutrophils and eosinophils from the limbal vessels to the peripheral cornea and subsequent migration to the central cornea. In contrast, the corneas of microMT mice failed to develop keratitis after intrastromal injection of parasite Ags unless Ags were injected with immune sera. Eosinophils were recruited from the limbal vessels to the peripheral cornea in microMT mice, but failed to migrate to the central cornea, whereas neutrophil recruitment was impaired at both stages. With the exception of IL-5, T cell responses and peripheral eosinophils were not significantly different between C57BL/6 and microMT mice. Taken together, these findings not only demonstrate that Ab is required for the development of keratitis, but also show that recruitment of neutrophils to the cornea is Ab-dependent, whereas eosinophil migration is only partially dependent upon Ab interactions.
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PMID:An essential role for antibody in neutrophil and eosinophil recruitment to the cornea: B cell-deficient (microMT) mice fail to develop Th2-dependent, helminth-mediated keratitis. 1052 1

Previous studies demonstrated that in the murine model of Onchocerca volvulus keratitis, neutrophils and eosinophils are recruited into the cornea in a biphasic manner in response to intrastromal injection. To determine if CD4(+) T cells regulate migration of neutrophils and eosinophils into the cornea, CD4(+) cells were depleted using monoclonal antibody GK1.5 before intrastromal injection of parasite antigens. Depletion of CD4(+) cells abrogated corneal opacification at later but not early stages of disease. Consistent with this observation, CD4 depletion significantly impaired recruitment of eosinophils to the cornea but had no effect on neutrophils. These data indicate that CD4(+) T cells mediate sustained O. volvulus keratitis by regulating eosinophil recruitment to the cornea.
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PMID:CD4(+) depletion selectively inhibits eosinophil recruitment to the cornea and abrogates Onchocerca volvulus keratitis (River blindness). 1094 84


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