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PubMed2002

Ras activation in T cells determines the development of antigen-induced airway hyperresponsiveness and eosinophilic inflammation.

The central role for Th2 cells in the development of Ag-induced airway hyperresponsiveness and eosinophilic inflammation is well documented. We have reported a crucial role for TCR-induced activation of the Ras/extracellular signal-regulated kinase mitogen-activated protein kinase cascade in Th2 cell differentiation. Here, we show that the development of both OVA-induced airway hyperresponsiveness and eosinophilic airway inflammation in a mouse asthma model are attenuated in transgenic mice by the overexpression of enzymatically inactive Ras molecules in T cells. In addition, reduced levels of IL-5 production and eosinophilic inflammation induced by nematode infection (Nippostrongylus brasiliensis or Heligmosomoides polygyrus) were detected. Thus, the level of Ras activation in T cells appears to determine Th2-dependent eosinophilic inflammation and Ag-induced airway hyperresponsiveness.

Animals↗

PubMed2004

IL-4 and IL-13 up-regulate intestinal trefoil factor expression: requirement for STAT6 and de novo protein synthesis.

The development of intestinal goblet cell hyperplasia/hypertrophy during nematode infection involves the Th2 cytokines IL-4 and IL-13 via STAT6 activation. This is thought to play an important role in host protective immunity against the infection. In this study we demonstrate that IL-4 and IL-13 up-regulate the specific goblet cell product trefoil factor-3 (TFF3) from the mucus-producing HT-29 CL.16E and HT-29 cells selected by adaptation to methotrexate. Up-regulation of TFF3 mRNA and protein levels occurred in a time- and dose-dependent fashion and was accompanied by up-regulation of the goblet cell product mucin 2 (MUC2). Addition of actinomycin D before IL-4/IL-13 stimulation led to decreases in TFF3 mRNA levels similar to those observed in controls without IL-4/IL-13. Furthermore, IL-4-mediated increased TFF3 transcription required de novo protein synthesis. Stable transfection of HT-29 CL.16E cells with a truncated dominant-negative form of STAT6 produced a cell line that was unresponsive to IL-4/IL-13. Although only one consensus STAT6 binding site is contained in the TFF3 gene, located in the intron 1, it did not operate as an enhancer in the context of an SV40 promoter/luciferase construct. Thus, STAT6 activation mediates a transcriptional enhancement of TFF3 by induction of de novo synthesized protein in goblet cells.

Goblet Cells↗

PubMed2006

Anaphylactic release of mucosal mast cell granule proteases: role of serpins in the differential clearance of mouse mast cell proteases-1 and -2.

The granule-derived mouse mast cell proteases-1 and -2 (mMCP-1 and -2) colocalize in similar quantities in mucosal mast cells but micrograms of mMCP-1 compared with nanograms of mMCP-2 are detected in peripheral blood during intestinal nematode infection. This differential systemic response was investigated both in vitro and in vivo. Bone marrow-derived mucosal mast cell homologs released similar quantities of mMCP-1 and-2 concomitantly with beta-hexosaminidase in response to calcium ionophore ( approximately 60% release) or IgE/DNP (25% release). In contrast, serum from mice sensitized by infection with Nippostrongylus brasiliensis 10 days earlier contained >1500-fold more mMCP-1 (10,130 +/- 1,609 ng/ml) than mMCP-2 (6.4 +/- 1 ng/ml), but, in gut lumen, the difference was approximately 8-fold. After OVA sensitization, >600-fold more mMCP-1 (7,861 +/- 2,209 ng/ml) than mMCP-2 (12.8 +/- 4.7 ng/ml) was present in blood 1 h after challenge, but, in gut lumen, there were relatively comparable levels of mMCP-1 and -2. To estimate the rates of systemic accumulation and clearance, 10 microg of mMCP-1 or -2 was injected i.p. Plasma levels of injected mMCP-2 peaked (1%) at 15 min then declined, whereas levels of mMCP-1 were maximal (approximately 25%) at 3 h. Inactivation of mMCP-1 with PMSF before injection resulted in mMCP-2-like kinetics, but inhibition of mMCP-1 by serum gave kinetics similar to that of native mMCP-1. mMCP-1 isolated from serum is complexed with serpins and we conclude that both the accumulation and the longevity of mMCP-1 in blood is due to complex formation, protecting it from a pathway that rapidly clears mMCP-2, which is unable to form complexes with serpins.

Anaphylaxis↗

PubMed1978

Counterimmunoelectrophoresis in the detection of antibodies to Schistosoma japonicum.

Counterimmunoelectrophoresis (CIE) was used to detect antibodies to Schistosoma japonicum soluble egg antigen in 118 sera from people living in a schistosomiasis endemic area in the Philippines. The sera were also tested for antibodies by the circumoval precipitin test (COPT); 53% were found positive by CIE and 48% positive by COPT. No significant differences were found between the tests (P = 0.18 by McNemar's test). Cross-reactions with sera from patients with intestinal capillariasis and monkeys with experimental angiostrongyliasis were not found and no false reactions were detected with sera from "normal" controls. The CIE test as used in the present studies was found to be comparable to the COPT in sensitivity and specificity as related to cross-reactivity with sera from nematode infections such as intestinal capillariasis and angiostrongyliasis. Results are usually available quickly with nearly 70% of any reactions occurring within 1 h. The test should be of value in seroepidemiologic surveys in schistosomiasis-endemic areas.

Adolescent↗

PubMed1989

Ivermectin for human strongyloidiasis and other intestinal helminths.

Since ivermectin, a mixture of 2 closely related macrocyclic lactones, has proven highly effective against animal intestinal nematodes, trials were undertaken to determine its efficacy against human intestinal nematodes. We tested 110 patients with strongyloidiasis and 90 with enterobiasis; many had other intercurrent intestinal nematode infections. Stool examinations were done before and after patients were given a single dose of oral ivermectin capsules (50, 100, 150, or 200 micrograms/kg body wt); 55 recipients of 100 or 200 micrograms/kg doses received a second identical dose the next day. Kato and saline smears, ethyl acetate concentration, modified Baermann's technique, and Harada-Mori cultures were repeated; cure was defined as complete absence of eggs and/or larvae from stools tested 30 days after dosing. Ivermectin was well tolerated. Overall cure rates at all doses 30 days after therapy averaged 88% for strongyloidiasis, 100% for ascariasis, 85% for trichuriasis, and 85% for enterobiasis. Ancylostoma duodenale and Necator americanus were little affected.

Adolescent↗

PubMed1984

Liver pathology of yellow perch, Perca flavescens (Mitchill), infected with larvae of the nematode Raphidascaris acus (Bloch, 1779).

Larvae of the nematode Raphidascaris acus were found free or encapsulated in the liver of yellow perch. Blood vessels were distorted or destroyed during larval migrations and larvae were eventually encapsulated in a thick-walled whitish nodule. Successful walling-off of the parasite resulted in the formation of a collagenous nodule and a complete loss of the worm. No mortality of perch was associated with larval R. acus but the introduction of susceptible fishes into a lake harboring this parasite may be important in some stocking programs.

Animals↗

PubMed1999

[Hypersensitivity to Anisakis simplex: apropos of 36 cases].

The authors report a group of 36 cases of hypersensitivity to Anisakis simplex, a fish parasite. They examined 11 boys and 25 girls who attended the Allergy service of the Central Hospital Marques of Valdecilla in Santander (Spain), between 12th May 1997 and 26th June 1998, for history of acute urticaria, most often after an aggravation of an allergic pathology. All were given an immunological examination that was composed of: food investigation, prick test, measurement of total and specific IgE and blood eosinophilia. In conclusion, the authors emphasize an increase in hypersensitivity to Anisakis simplex, masked by a food allergy and in spite of a nematode infection. Blood eosinophilia was normal in most cases.

Aged↗

PubMed2001

A survey on anthelmintic resistance in nematode parasites of sheep in Lusaka, Zambia.

While surveys in Southern Africa indicate anthelmintic resistance of gastrointestinal nematodes to be common in small ruminants in South Africa, Kenya and Zimbabwe there have been no reports of resistance in Zambia. The objective of this study was to determine whether anthelmintic resistance occurs in Zambia, and to obtain information on nematode control practices in the country. During the rainy season six commercial sheep farms were selected in and around Lusaka and Chisamba. Worm control practices were gauged by means of a questionnaire, and the Faecal Egg Count Reduction Test was performed for assessing anthelmintic efficacy of albendazole, levamisole and ivermectin. On all farms anthelmintic treatment was the only approach used to control nematode infections. Frequency of treatment varied from twice a year to every 6 weeks and drugs of different anthelmintic groups were alternated within the same year. There was a wide range in faecal egg counts of individual sheep before treatment, with some individual counts of up to 87000. Larval identification showed that Haemonchus was almost the only genus recovered from the faecal cultures before and after treatment. Albendazole resistance was found on five of the six farms. On each of the four farms where ivermectin gave less than 95% reduction in egg counts, there was resistance to albendazole as well. Levamisole showed an efficacy of 95% or higher on all six farms.

Albendazole↗

PubMed1979

[Modern therapy of intestinal helminthiasis (author's transl)].

The modern chemotherapy of intestinal worm diseases is essentially based on niclosamide, thiabendazole and mebendazole. Thus an effective therapy with few side effects has become possible for these helminthiases. In infections with Taenia, Ascaris, Trichuris, Ankylostoma, Strongyloides, Trichostrongylus and Oxyuris, as the most frequently imported helminths, an elimination rate of over 90% of the parasites can be attained. Infections with nematode larvae as with Larva migrans and trichinoses are more problematic therapeutically because the anthelmintics are directed principally against the adult worms.

Benzimidazoles↗

PubMed2002

A bulk tank milk survey of Ostertagia ostertagi antibodies in dairy herds in Prince Edward Island and their relationship with herd management factors and milk yield.

The objective of this study was to quantify the relationship of the levels of antibodies to Ostertagia ostertagi in bulk-tank milk samples from Prince Edward Island (PEI) dairy farms to milk production and to herd-management practices potentially related to gastrointestinal nematode infections. The milk samples were obtained from 289 to 322 dairy farms during 2000; production and management data were available from 197 and 200 farms, respectively. Cow exposure to pasture and whole-herd anthelmintic treatment were the only herd management variables significantly associated with antibody levels in the fall of 2000. An increase in antibody levels from the observed 25th percentile to the 75th percentile (interquartile range) was associated with a drop in milk production of 1.2 kg/cow/day. The results of this study indicate that the enzyme-linked immunosorbent assay for O. ostertagi antibody is a potentially useful technique to measure parasite exposure in adult dairy cows and that parasite burdens in lactating cattle in PEI have an important impact on milk production.

Animal Husbandry↗

PubMed1953