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

Eosinophil infiltration and degranulation around the tissue-invasive stages of several species of helminths have been observed. Release of eosinophil granule contents upon the worms is supported by localization of two of the major granule proteins, major basic protein (MBP) and eosinophil peroxidase (EPO), on and around species of trematodes, nematodes, and cestodes. In the case of filarial worms, MBP is deposited on degenerating microfilariae (mf) of Onchocerca volvulus. Here, we performed in vitro assays of the toxicity of four purified eosinophil granule proteins, namely, MBP, EPO, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), for the mf of Brugia pahangi and Brugia malayi. MBP, ECP, and EDN killed these worms in a dose-related manner although relatively high concentrations of EDN were necessary. EPO, in the presence of a H2O2-generating system and a halide, was the most potent toxin on a molar basis; here, the most potent halide was I- followed by Br- and Cl-. Surprisingly, EPO in the absence of H2O2 killed mf at concentrations comparable to those required for MBP and ECP. The toxicity of EPO + H2O2 + halide was inhibited by heparin, catalase, or 1% BSA, whereas the toxicity of EPO alone was inhibited only by heparin. Heparin also inhibited killing by both MBP and ECP. Despite the homology of ECP with certain RNases, placental RNasin, an RNase inhibitor, was unable to inhibit ECP-mediated toxicity. These results indicate that all of the eosinophil granule proteins are toxic to mf and they support the hypothesis that eosinophil degranulation causes death of mf in vivo.
 ...
PMID:In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins. 232 97

Persons exposed to Onchocerca volvulus express differences in manifestations of onchocerciasis ranging from hyporeactive (generalized) to hyperreactive (sowdah) forms; absence of disease is seen in endemic normal persons. Analysis of the IgG isotypic antibody response to O. volvulus extracts and nonparasite ubiquitous antigens in 92 West Africans revealed highest anti-O. volvulus IgG1 and IgG2 responses in sowdah, high levels in the generalized form, and low antibody levels in endemic normal persons. Nonexposed persons had no antibodies. A significant IgG3 antibody response was detected only in sowdah, while high IgG4 levels occurred in both polar groups but were absent in both control groups. Isotypic responses to antigens unrelated to O. volvulus were similar in all groups but showed higher IgG1 and IgG2 levels in sowdah. Sowdah patients had high levels of Ro/SS-A antibodies, circulating immune complexes, and eosinophil cationic protein. These results document a strong B cell response in African sowdah and indicate variations in immune responsiveness.
 ...
PMID:Strong IgG isotypic antibody response in sowdah type onchocerciasis. 793 Jul 41

Onchocercomata with a single live or dead worm were analyzed to elucidate the infiltration of eosinophils. Females were classified according to the presence or absence of microfilariae in their uteri and in the nodular tissues. Immunohistochemical staining was performed using antibodies against eosinophil cationic protein, peroxidase, and major basic protein. Very few eosinophils were detected in nodules containing females without microfilariae or male or dead worms only, whereas eosinophils were abundant in all nodules with females producing microfilariae. The occurrence of eosinophils was not related to the age of the worm. Occasionally, degenerated or dead microfilariae attacked by activated eosinophils were found. By examination of onchocercomata with or without microfilariae from the same patient, it was excluded that the occurrence of eosinophils was dependent mainly on the host's immune status. In conclusion, live adult Onchocerca volvulus do not elicit an invasion of eosinophils as long as they do not produce microfilariae. The absence of eosinophilia does not exclude onchocerciasis.
 ...
PMID:Dependence of eosinophil granulocyte infiltration into nodules on the presence of microfilariae producing Onchocerca volvulus. 882 5

The involvement of eosinophils in the host reaction to microfilariae (mf) of Onchocerca volvulus was studied by immunohistochemistry and immunoelectron microscopy. Skin biopsies were obtained from patients after transepidermal administration of the microfilaricide amocarzine. At 20-28 h after the application of amocarzine, mf were degenerated or dead and a marked eosinophil-parasite adherence (EPA) reaction was seen, with intense staining for intra- and extracellular eosinophil granule proteins such as eosinophil cationic protein (ECP) surrounding the mf. Immunoelectron microscopically the eosinophil granule matrix in intact and necrotic eosinophils was specifically labeled, whereas granules whose matrix had dissolved showed no specific gold particle binding. As specific labeling was seen on lowly electron-dense material adjacent to matrix-depleted granules, the material was regarded as released eosinophil granule matrix material. Intact and necrotic eosinophils, matrix-containing as well as matrix-depleted eosinophil granules, and released eosinophil granule matrix material were observed on the surface of damaged mf and between collagen fibers. The coincidence of mf degeneration, EPA reaction, and release of eosinophil granule matrix material on damaged mf and collagen fibers indicated a role of eosinophils and eosinophil granule matrix protein in the host reaction to mf after amocarzine application.
 ...
PMID:Immunoelectron microscopic evidence for release of eosinophil granule matrix protein onto microfilariae of Onchocerca volvulus in the skin after exposure to amocarzine. 974 32

Eosinophils, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN/EPX), myeloperoxidase (MPO) and IgE were measured in blood, serum and/or urine in Schistosoma haematobium- and Onchocerca volvulus-infected Guineans and O. volvulus- and S. haematobium-negative Guineans coinfected or infected with intestinal nematodes. The number of eosinophils and levels of eosinophil granule proteins but not of MPO were found to be strongly elevated in all Africans as compared to European controls. The highest serum ECP and serum and urinary EDN/EPX levels were observed in the hyperreactive form of onchocerciasis (sowda). Onchocerciasis patients and O. volvulus-negative Africans coinfected or infected with intestinal nematodes (hookworm and/or Ascaris lumbricoides) revealed higher serum granule protein concentrations and/or absolute eosinophil counts and urinary ECP than those without nematode infections. Statistical differences between both sections were found for the absolute eosinophil counts and for serum EDN/EPX and IgE in generalized onchocerciasis, and for urinary ECP in sowda, indicating stimulation of the eosinophil potential of O. volvulus-positive patients by coexistent hookworm infection. This worm species, in contrast to A. lumbricoides, causes especially high eosinophil counts and EDN/EPX and IgE levels. From these results it is concluded that in nematode diseases, ECP and EDN/EPX levels reflect the degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates. Serum ECP and serum and urinary EDN/EPX may, therefore, serve as parameters to monitor helminth infection. Urinary ECP may be a marker of eosinophiluria secondary to urogenital manifestation of S. haematobium. It is elevated in hyperreactive onchocerciasis activated by intestinal nematodes.
 ...
PMID:Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin in serum and urine of patients with onchocerciasis coinfected with intestinal nematodes and in urinary schistosomiasis. 1020 16

Onchocercosis or riverblindness, caused by the filaria ochnocerca volvulus, is endemic in many countries of central and Western Africa. Symptoms of the disease can occur years after the infection, chronic itching dermatitis is the first sign, without treatment blindness may develop after years. Onchodermatitis is a hyperreactive course of onchocercosis with massive eosinophilia and elevated IgE, which suppresses a microfilarial spread through the body. Here, we report about the case of an 9-year-old girl who immigrated from the republic of Congo at the age of seven and has been living in Germany for more than two years. Presumably she suffered from onchodermatitis. She presented papular, indurated and itching skin lesions with pigmentary changes, predominantly located at the limbs. Remarkable results of blood tests were 11,000/microl (60 %) eosinophils and IgE 28 000 KU/l, ECP > 200 mg/l, without a history of atopic diseases. HIV, Strongylosis and Loa Loa were excluded. Anti filaria antibodies were detected in a concentration of 51 AKE, microscopy of skin samples failed to detect the parasites. After a single dose of Ivermectin the dermatitis improved, after two weeks the itching was absent, results of repeated blood tests tend to normalize in the following months. Due to the long lifespan of filaria in humans, the disease occurs years after infection in endemic areas. The differential diagnosis for itching skin lesions with high eosinophils in children from developing countries should include onchocercosis.
 ...
PMID:[Dermatitis and eosinophilia in a 9-year-old girl from Congo: putative onchodermatitis]. 1643 76

Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes.
 ...
PMID:Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels. 2458 58