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M D Winter

Publications and source records attributed to M D Winter.

7 recordsLinked to original sources

Neuronal uptake of pesticides disrupts chemosensory cells of nematodes.

Low doses of the acetylcholinesterase-inhibiting carbamate nematicides disrupt chemoreception in plant-parasitic nematodes. Fluorescein isothiocyanate (FITC)/dextran conjugates up to 12 kDa are taken up from the external medium by certain chemosensory neurons in Caenorhabditis elegans. Similar chemoreceptive neurons of the non-feeding infective stage of Heterodera glycines (soybean cyst nematode) fill with FITC and the nuclei of their cell bodies selectively stain with bisbenzimide. The widely used nematicide aldicarb disrupts the chemoreceptive response of H. glycines with 50% inhibition at very low concentrations (ca 1 pM), some 10(-6)-fold lower than required to affect locomotion. Similarly, the anthelmintic levamisole had this effect at 1 nM. Peptides selected as mimetics of aldicarb and levamisole also disrupt chemoreception in H. glycines and Globodera pallida at 10(-3)-fold or lower concentration than required to inhibit locomotion. We propose an uptake pathway for aldicarb, levamisole, peptide mimetics and other soluble molecules by retrograde transport along dendrites of chemoreceptive neurons to the cell bodies and synapses where they act. This may prove to be a general mechanism for the low-dose effects of some nematicides and anthelmintics.

Aldicarb↗

Vaccination of young lambs against infection with Nematodirus battus using gamma irradiated larvae.

Helminthologically naIve 6-week-old Suffolk lambs were given 1-3 doses of 20000 gamma-irradiated infective larvae (L3) of the nematode Nematodirus battus at weekly intervals. Following an anthelmintic drench they were challenged with 50000 viable L3 at 10 weeks of age. Nematode worm burdens 14 days post-challenge showed a significant (P<0.01) 66% reduction in the single vaccine dose group. The two and three dose groups had mean worm burdens which were 30 and 42% lower than controls, respectively, although these were not statistically significant. There was little measurable stimulation of the immune system in the vaccinated lambs, suggesting that the repeatedly dosed animals may have developed immunological unresponsiveness to the parasite.

Animals↗

The effect of dexamethasone on resistance of older lambs to infection with Nematodirus battus.

Old lambs (8 months of age) infected with 50,000 L3 of Nematodirus battus had larvae developing normally in their tissues on day 4 post-infection (P.I.), but by day 8 P.I. there were only 4105 +/- 1044 worms left in the alimentary tract. Some of these worms contained crystals in their intestine. Eight-month-old lambs treated with dexamethasone and infected with 50,000 L3 of N. battus contained a mean worm burden of 7878 +/- 1262 on 18 days P.I. Untreated 8-month-old lambs similarly infected were virtually worm free by day 18 P.I. Peripheral eosinophilia became elevated in the untreated lambs over the course of infection and, at post-mortem, the tissue mast cell and eosinophil counts were much higher than in the dexamethasone treated group. Although the phenomenon of age resistance is thought to have a strong immunological component, there may also be other physiological factors, resulting in fewer nematodes and lower fecundity of the worms.

Aging↗

The mast cell and eosinophil response of young lambs to a primary infection with Nematodirus battus.

Helminthologically naive 8-week-old lambs were administered 50,000 infective-stage larvae of the trichostrongyle nematode Nematodirus battus. Initial mean adult worm burdens were significantly reduced (P < 0.01) at day 21 post-infection (p.i.). Peripheral blood eosinophil counts showed a significant increase (P < 0.001) by day 25 p.i. when compared with uninfected control animals. Sections of small intestine taken at post-mortem from the area of adult worm establishment over the course of infection showed a significant increase in mucosal eosinophil and mast cell numbers during the period of adult worm rejection, when compared with uninfected control animals. These results show that young lambs develop significant increases in the numbers of cells associated with an inflammatory reaction in the intestine during the development of a partially protective immune response to this parasitic nematode.

Animals↗

The serum immune response of young lambs to a primary infection with Nematodirus battus.

Young lambs (6-8 weeks of age) were infected with 50000 infective stage larvae of the trichostrongyle nematode Nematodirus battus. Initial mean adult worm burdens of 23884 +/- 1678 (S.E.M.) at day 14 post-infection (p.i.) were reduced significantly (P < 0.01) to a mean burden of 5383 +/- 1397 by day 21 p.i. Blood samples were taken and serum analysed using ELISA and Western blotting techniques for IgG antibodies specific for N. battus. Pre-infection serum from young naive animals showed IgG recognition of adult and larval N. battus whole worm homogenate. Recognition of adult antigens became reduced during the first 14 days after infection, followed by a subsequent increase beginning between days 14 and 18 p.i. and peaking at day 28 p.i. IgM recognition of N. battus antigens showed a single response peak, starting between days 14 and 18 p.i., without the pre-infection elevated titre as observed with IgG. These results show that young lambs can mount a significant serum response to a primary infection with N. battus during rejection of adult worms and that lambs receive from their dams IgG antibodies that are capable of recognizing adult and larval N. battus during the first few weeks of life.

Animals↗

The effect of Trichinella spiralis and Trichinella pseudospiralis on the mechanical properties of mammalian diaphragm muscle.

The isometric mechanical properties of diaphragm muscle were studied in mice infected with either Trichinella spiralis or Trichinella pseudospiralis. Measurements of muscle stress were taken at 15, 20, 30 and 40 days post-infection. Infected diaphragm muscle showed a significant (P < 0.001) reduction in muscle stress during both twitch and tetanic contractions when compared with muscle from control animals. T. spiralis caused a significant reduction in resistance to muscle fatigue. The consequences of these changes in muscle function to host pathology are discussed, and related to previous work on the effects of Trichinella on host biochemistry and the immune response.

Animals↗