A new interpretation of the involvement of serotonin in delayed-type hypersensitivity. Serotonin-2 receptor antagonists inhibit contact sensitivity by an effect on T cells

5-HT is a neuromediator and a vasoactive amine released by platelets and murine mast cells at sites of inflammation. A role for 5-HT has been proposed in murine DTH and has been attributed to its 5-HT2R-dependent vasoactive properties. We have tested the hypothesis that the role of 5-HT in DTH is related to an interaction of 5-HT with DTH effector T cells. In vivo treatment of sensitized mice with the 5-HT2R antagonists methysergide or ketanserin inhibited both their capacity to elicit DTH and the ability of their lymphoid cells to transfer DTH. In vitro treatment of lymphoid cells, or of nylon wool-purified T cells from sensitized mice, with 10(-7) to 10(-9) M of the 5-HT2R antagonists methysergide, ketanserin, ritanserin, or LY 53857, followed by three washings, inhibited as strongly their ability to transfer DTH, both systemically or locally. Systemic and local co-transfer experiments of 5-HT2R antagonist-treated and untreated cells indicated that this inhibition was not related to the induction of suppression. 5-HT2R antagonist treatment was nontoxic to T cells; did not affect the in vitro response of T cells to mitogen; selectively inhibited the efferent, but not the afferent limb of DTH; and in the efferent T cell cascade, affected the late-acting (24 h) inflammatory DTH T cells, but not the early-acting, DTH-initiating T cells. 5-HT2R selectivity was suggested by the absence of effect of an alpha-adrenergic R antagonist, and by prevention of the inhibitory effect of a 5-HT2R antagonist by prior incubation with the selective 5-HT2R agonist 1-(2,5-dimethoxy phenyl-4-methyl)-2 aminopropane. In summary, inhibition of DTH effector T cell function appeared sufficient, independently of any vascular effect, to account for the in vivo inhibitory effect of 5-HT2R antagonists on the elicitation of DTH. Our data suggest that late-acting DTH effector T cells might express functional 5-HT2R, and that these receptors might require in vivo activation in order for the T cells to locally produce the inflammatory lymphokine-dependent aspects of DTH.     

Effects of genetic and environmental host plant variation on the susceptibility of two noctuids toBacillus thuringiensis

TwoApium graveolens var.rapaceum (L.) cultivars that differ in their suitability for the survival and growth ofSpodoptera exigua (Hübner) andTrichoplusia ni (Hübner) were used to examine the effect of genetic and seasonal environmental variation in host plant suitability on the efficacy ofBacillus thuringiensis subsp.kurstaki (Berliner). The effects of host plant genotype andB. thuringiensis were generally independent, so thatB. thuringiensis efficacy was greatest on the resistant host plant cultivar. Host plant suitability varied within growing season for both insect species but, while host plant suitability decreased with increasing plant age forT. ni, the response ofS. exigua to plant age was not as clear. Within season variation in host plant suitability affectedB. thuringiensis efficacy and the interaction betweenB. thuringiensis and host plant cultivar forS. exigua but not forT. ni. Soluble protein and Folin-Denis phenolic concentrations of host plant tissue were not correlated with changes in host plant suitability to either insect species.     

Use of personal medical records for research purposes.

The established practice of doctors using medical records for research purposes is threatened by the recent proposed guidelines from the Department of Health, the BMA, and the European Commission. The European Commission has proposed that explicit consent should be obtained from each patient before his or her medical records can be used; the proposals from the Department of Health and the BMA would require all research that needs access to personal medical records to be submitted to an ethics committee. We believe that these proposals would seriously impair an entire category of research and suggest therefore that another set of guidelines, proposed by a Royal College of Physicians'' working group, should be used to modify the proposals. The guidelines of the working group encourage the use of medical records for research and ensure that such use can be made in a confidential manner without causing harm.     

Aminoimidazole carboxamide ribonucleoside toxicity: a model for study of pyrimidine starvation

Aminoimidazole carboxamide ribonucleoside (AIC-R), a purine precursor, has biphasic effects on the growth of Chinese hamster fibroblasts. At 200 microM AIC-R cell growth is almost completely arrested, while at 50 and 700 microM AIC-R cell growth is comparable to that observed in the absence of nucleoside. The growth inhibition produced by AIC-R is the consequence of inhibition of the orotate phosphoribosyltransferase-orotidylic decarboxylase (OPRT-ODC) reactions, as evidenced by a 87% reduction in the intracellular concentrations of UTP and CTP, accumulation of orotate in the medium, and restoration of normal growth by inclusion of 100 microM uridine in the medium. Inhibition of pyrimidine nucleotide synthesis at 200 microM AIC-R is associated with an 82% reduction in the intracellular concentration of PP-ribose-P and a 150% increase in the concentration of purine nucleotides. Restoration of cell growth to a normal rate at 700 microM AIC-R--a condition under which PP-ribose-P remains depressed and purine nucleotide concentrations are also depressed (40% of control)--and absence of toxicity at 50 microM AIC-R--a condition under which purine nucleotide concentrations are increased by 150% and PP-ribose-P concentration is normal--suggest that the inhibition of OPRT-ODC observed at 200 microM AIC-R is caused by the combination of the reduction in PP-ribose-P and increase in purine nucleotides. These studies provide a better understanding of the control of the OPRT-ODC reactions in the cell and provide additional insight into the basis of pyrimidine starvation induced by purine nucleosides.     

Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations.

As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease.     

Methods in coccidiosis research: separation of oocysts from faeces.

Factors which may be important in the large-scale extraction of coccidial oocysts from faeces ha.ve been investigated with Eimeria tenella. Age of bird, inoculum, feeding status at the time of inoculation, period of collection, feeding status during collection, collection medium, homogenization and sieving, flotation, washing, sporulation and further purification have all been considered. The aim has been to establish a method to produce the maximum number of oocysts of a required degree of purity and viability, with the expenditure of the minimum amount of physical effort, time, animals and chemicals. In our method, groups of chickens 3-4 weeks of age are inoculated with 5000 oocysts of E. tenella and food is supplied ad lib. Over the period 5-8 days after inoculation, faeces are collected in trays containing 2% (w/v) potassium dichromate solution, while food intake is restricted. The faecal material is homogenized, passed once through 40 and 100 mesh sieves, centrifuged and the oocysts recovered from the sediment by 3 flotations in saturated salt solution. Following washing, oocysts are sporulated by forced aeration at 30 degrees C and may be further purified by hypochlorite treatment, or passage in 5% Tween 80 solution through a glass bead column followed by sucrose density gradient centrifugation. Routine passages along these lines over a 5 year period have given a recovery of 46% of the oocysts excreted by over 7000 birds.     

Susceptibility of Murine Norovirus and Hepatitis A Virus to Electron Beam Irradiation in Oysters and Quantifying the Reduction in Potential Infection Risks

Consumption of raw oysters is an exposure route for human norovirus (NoV) and hepatitis A virus (HAV). Therefore, efficient postharvest oyster treatment technology is needed to reduce public health risks. This study evaluated the inactivation of HAV and the NoV research surrogate, murine norovirus-1 (MNV-1), in oysters (Crassostrea virginica) by electron beam (E-beam) irradiation. The reduction of potential infection risks was quantified for E-beam irradiation technology employed on raw oysters at various virus contamination levels. The E-beam dose required to reduce the MNV and HAV titer by 90% (D₁₀ value) in whole oysters was 4.05 (standard deviations [SD], ±0.63) and 4.83 (SD, ±0.08) kGy, respectively. Microbial risk assessment suggests that if a typical serving of 12 raw oysters was contaminated with 10⁵ PFU, a 5-kGy treatment would achieve a 12% reduction (from 4.49 out of 10 persons to 3.95 out of 10 persons) in NoV infection and a 16% reduction (from 9.21 out of 10 persons to 7.76 out of 10 persons) in HAV infections. If the serving size contained only 10² PFU of viruses, a 5-kGy treatment would achieve a 26% reduction (2.74 out of 10 persons to 2.03 out of 10 persons) of NoV and 91% reduction (2.1 out of 10 persons to 1.93 out of 100 persons) of HAV infection risks. This study shows that although E-beam processing cannot completely eliminate the risk of viral illness, infection risks can be reduced.