Routine immunofluorescence for pruritic urticarial papules and plaques of pregnancy.
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Biomedical subjects
Publications and source records attributed to J Goodall.
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We generated Theiler's murine encephalomyelitis virus mutants resistant to several neutralizing monoclonal antibodies (MAbs) having their epitopes near a trypsin cleavage site of VP1. Neutralization and Western blot (immunoblot) studies suggest that two of the MAbs have identical epitopes that partly overlap the epitope of a third MAb. Sequencing of RNA of the mutants localized the epitopes to a site near the carboxyl end of VP1. The limited diversity of nucleotide changes seen in the mutants and the immunodominance of the site suggest that the carboxyl end of VP1 may have an important function.
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Null equations have been derived which allow quantification of the agonist properties of a compound that is able to modify the state of a tissue simultaneously by interacting with a particular type of receptor and by other means. Parameters can be estimated which separately characterize the agonist properties of the compound and its functional interactant effect. The null equations have been tested in a model system by using a mixture of papaverine (5 microM) and hexyltrimethylammonium bromide (30 microM) to mimic an agonist which also has functional antagonist properties. The values obtained for the various parameters measured directly and indirectly are in good general agreement, confirming the validity of the model.
The effects of the opioid receptor agonist RX783006 and of the opioid receptor partial agonist (+)-meptazinol have been examined on electrically induced twitch responses of the guinea-pig isolated ileum and of the mouse isolated vas deferens. Log10 concentration-tissue state curves were determined for (+)-meptazinol and RX783006, alone, in combination and in the presence of naloxone (30 nM). Analysis of these log10 concentration-tissue state curves using the null equations derived and tested in the preceding paper indicates that the opioid agonist action of (+)-meptazinol on mouse vas deferens is quantitatively similar to that on guinea-pig ileum. The results also suggest that (+)-meptazinol acts as a functional antagonist on the guinea-pig ileum as well as on the mouse vas deferens. The potency of (+)-meptazinol relative to RX783006 has been measured by an indirect method which should eliminate any functional antagonistic action of (+)-meptazinol. This method gives a relative potency of (+)-meptazinol in both tissues which is three to six times greater than that measured directly on guinea-pig ileum. This discrepancy may be due to experimental error but it may also indicate that direct measurements on guinea-pig ileum underestimate the agonist potency of this compound on opioid receptors.
The effects of the opioid receptor agonist RX783006 and of the opioid receptor partial agonist (+)-meptazinol have been examined on electrically-induced twitch responses of the guinea-pig isolated ileum and of the mouse isolated vas deferens. Log10 concentration-tissue state curves were determined for (+)-meptazinol and for RX783006, alone, in combination and, when appropriate, in the presence of naloxone (30 nM). Analysis of these log10 concentration-tissue state curves using the null equations derived and verified in the previous paper allows quantitation of the characteristics of the interaction of (+)-meptazinol with the opioid receptors in these tissues. The results indicate that the apparent differences in the actions of (+)-meptazinol on isolated electrically-stimulated guinea-pig ileum and mouse vas deferens can be accounted for without the need to postulate differences between mu-opioid receptors in these two tissues.
Both yohimbine (0.1 to 10 microM) and phentolamine (10 microM) increased the tritium overflow evoked by electrical stimulation (2.5 Hz, 1 ms, 15 V, for 90 s every 20 min) of mouse isolated vas deferens previously incubated with (-)-[3H]noradrenaline. At their maximally effective concentrations, phentolamine (10 microM) produced an effect that was sustained over the 2 h of the experiment while the effect of yohimbine (6 microM) decreased by about 60% over the first 40 min and was then sustained at a lower level. At higher concentrations of yohimbine, the increase in evoked tritium overflow was less marked and at the highest concentration tested (30 microM) evoked overflow was reduced below the levels seen before exposure to the drug. It is concluded that at concentrations maximally effective in inhibiting the presynaptic alpha-adrenoceptor-mediated mechanism controlling transmitter release, the known local anaesthetic effect of yohimbine may contribute to the overall effect on evoked transmitter overflow.
Electrically induced twitch responses of mouse vas deferens and guinea-pig ileum were inhibited by morphine, normorphine and the peptide opioid agonist RX783006; naloxone blocked the effects of all three opioid agonists yielding Ke values which were not significantly different and which were within the range (1-4 nM) expected for mu-type receptors. At concentrations between 0.1 and 10 microM (+)-meptazinol inhibited the twitch response of the ileum while (-)-meptazinol produced potentiation. Naloxone (20 nM) completely blocked the effect of (+)-meptazinol and further increased the potentiation produced by (-)-meptazinol. In the mouse vas deferens preparation neither isomer affected the electrically induced twitch response at concentrations below 5 microM and higher concentrations (10-300 microM) produced potentiation. Naloxone (20 nM) did not modify this effect. It is concluded that both isomers are opioid agonists on the mu-receptors in guinea-pig ileum but not in mouse vas deferens and that a cholinergic component, which may contribute to the action of meptazinol in-vivo, is present to a smaller extent in the (+)-isomer.
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Multiple sclerosis has been reported to have a high prevalence in the Orkney and Shetland Islands and in Caithness in comparison with the highlands of Scotland and the Outer Hebrides-the Western Isles. For this reason a survey was undertaken in the Outer Hebrides and 25 probable and 30 probable and possible patients with multiple sclerosis were found. This is an increase from eight and 11 respectively found in 1954. The present prevalence rate of 97.3 per 100 000 for probable and possible multiple sclerosis is not significantly different from that found in a recent study in the Grampian region in north-east Scotland. Repeated studies in small populations generally show increasing prevalence of multiple sclerosis because some patients are missed in the earlier studies, and over a long period of time there may also be some increase in survival time. This increase has been found in the Orkney and Shetland Islands, in north-east Scotland, and also in the Outer Hebrides.
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The background to social and emotional deprivation is discussed and applied to a study of kwashiorkor in East African children. A group of 107 children with kwashiorkor was compared with 111 controls. Age, sex and tribe were all found to have significances of their own: fifty of each group were therefore matched for these three factors. Ten other factors were found to be significant in the background of children with kwashiorkor, all of which could be associated with social or emotional deprivation or both (see Table 14). It is concluded that, in childhood, sustained personal care and affection are essential to normal growth.
Following the observation that many children with kwashiorkor had a deprived look in their eyes, the guardians of 107 children with kwashiorkor and 111 controls were interviewed about their home life, in a survey made at New Mulago Hospital, Kampala, between 1969 and 1972. A child's age, sex and tribe were found to have an influence on the nutritional state, therefore 50 of each group were matched for these variables. Ten significant associations were found which distinguished kwashiorkor patients from the control group. Children with kwashiorkor were more likely to be attended by someone other than the mother; to have changed attendants when ill; to have a pregnant mother; and to have separated parents. Further to these, singletons of split partnerships were at special risk; breast-feeding had stopped; weaning was begun for bad reasons; a child was more often living away from the parents and had been sent away coincident with weaning. The fathers tended to be poor. It is suggested that these 10 factors could be used as a social scoring system in assessing the risk of incipient kwashiorkor.