Primary cultures of adult mouse sensory neurons maintained for 8 days in vitro (8 div), in both the presence of non-neuronal cell (NNC) outgrowth and in NNC-reduced cultures, were exposed to doses of ...ethanol, propanol, acetaldehyde and acrolein. The effects on cell viability were monitored: LD50's of 600 microM acrolein and 100 mM propanol were obtained after 24 h exposures and after 48 h with 1 mM acetaldehyde and 500 mM ethanol. Morphological effects were evident by scanning electron microscopy with sub-acute doses for each agent, using both lower concentrations and shorter exposures. Membrane pitting of the perikaryon and a reduction in the proportion of neurons bearing neurites were common signs of toxic insult. The neurites of treated cells were thicker and more irregular than those of untreated cells; this proved a good indicator of specific neurotoxicity rather than merely a cytotoxic response. Fetal calf serum in the medium lessened the response of neurons to ethanol treatments. Comparison with other in vitro studies suggests these primary cultures are a more sensitive system than established cell lines of neuronal origin for use in neurotoxicity testing.
The probability that in utero exposure to filarial antigens may influence the outcome of a subsequent infection has been investigated using a laboratory model whereby BALB/c mice are implanted with ...adult, female Acanthocheilonema viteae in order to generate a high-level, long lasting microfilaraemia. When infected using this procedure, BALB/c and (BALB/c x B10) F1 mice can be defined as susceptible and resistant respectively in terms of the microfilaraemia produced. By using microfilaraemic BALB/c mice as mothers, BALB/c and F1 offspring were exposed to the possibility of in utero infection. The finding of microfilariae in foetal tissues and their presence in the blood of two week old mice confirmed the transplacental transmission of parasites in both cases, BALB/c and F1 progeny born to microfilaraemic mothers failed to support a full infection from the L3 stage; similarly, progeny implanted with female worms were as sus-ceptible and resistant respectively as unexposed BALB/c and F1 controls. Spleen cells from in utero exposed, two week old BALB/c and F1 mice recognised filarial antigens in lymphocyte proliferation assays, as did their microfilaraemic mothers. In Western Blot studies, sera from such mice and from foetal, in utero exposed BALB/c mice recognised the same spectrum of A. viteae antigens as their mothers, which strongly suggests the transplacental transfer of maternal antibody. These results demonstrate that the A. viteae-mouse model may be useful in studying transplacental transmission and prenatal sensitisation in experimental filariasis.
A series of experiments were carried out to further characterize the previously discovered
Heligmosomoides polygyrus, adult worm homogenate (AWH), superantigen. AWH, in contrast to staphylococcal ...enterotoxin B (SEB) superantigen, was totally unable to stimulate naive thymocytes, in either the presence or the absence of exogenous accessory cells (AC). Experiments using AC from B10 congenic mice failed to indicate a requirement for a specific MHC haplotype for successful presentation of the AWH superantigen and also indicated that the presence or absence of the H-2,E molecule on AC did not affect AWH stimulation of T cell hybridamos. Furthermore, AWH was found to require the presence of MHC Class I-positive AC in order to stimulate T cell hybridomas, while, in contrast, the absence of MHC Class II on AC did not affect the superantigenic properties of AWH. Initial characterization of the T cell hybridomas stimulated by the AWH superantigen, indicated that all were CD4-positive and that three of them expressed TCR V
β8.1. Hence AWH superantigen can stimulate TCR V
β8.1/CD4-positive T cells only in the presence of MHC Class I-positive AC.
The documented in vitro response of mouse T cells to parasite antigens is typically anamnestic and H-2 restricted. As yet, there have been no confirmed reports of the existence of a ...non-H-2-restricted, superantigen type of response to the antigens of metazoan parasites. Reported here are data which show that antigens produced by the adult stage of the nematode parasite Heligmosomoides polygyrus (= Nematospiroides dubius) can stimulate naive T cells in vitro to proliferate and produce IL-2. A series of T cell hybridomas has been used to show that adult worm homogenate of H. polygyrus can stimulate parasite antigen naive T cells. This response is independent of the H-2 haplotype of the antigen-presenting accessory cells and does not appear to be influenced by the presence or absence of an H-2 E molecule. However, successful presentation of the H. polygyrus superantigen does require the presence of metabolically active accessory cells and fixation of the accessory cells with paraformaldehyde abrogates the response of the target cells. This discovery has important implications for the study of the role of superantigens in host/parasite interactions and will also help to expand current knowledge about the relationship between chronic intestinal nematodes and the host immune system.
The frequency of abnormal glucose tolerance in the first 12 months after gestational diabetes was found to be 33.3%, which is much higher than previously accepted. Women with gestational diabetes ...(Group 1 = 54 requiring insulin, Group 2 = 32 treated with diet alone) attending a metropolitan teaching hospital over a 3 1/2 year period were followed-up after delivery to determine their subsequent glucose tolerance. Of 86 seen 3 months after delivery, 2 had developed insulin-dependent diabetes mellitus (IDDM) and 2 noninsulin dependent diabetes mellitus (NIDDM), diagnosed by glucose tolerance testing. Another 38 returned for follow-up glucose tolerance testing at 12 months; of these 3 had impaired glucose tolerance (IGT), 7 had NIDDM, and one who had had NIDDM at 3 months now showed IGT after 9 months dietary treatment. Thus, 12 months after delivery, the cumulative prevalence of abnormal glucose tolerance was 14/42 (33.3%), 10 of the 42 being frankly diabetic (26%). Of the remaining 44 patients, 21 have not yet reached 12 months or were pregnant again, and 23 did not attend for glucose tolerance testing. Although the trend was for gestational diabetes mellitus (GDM) to recur earlier and more severely in subsequent pregnancies, in 3 instances the diabetes did not recur. Major congenital malformations occurred in 4 of the 86 babies (4.7%); minor malformations were found in a further 13 (15%) with no difference in frequency between Group 1 and Group 2.
PDF