A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average ~1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608±136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies. 相似文献
Prednisolone causes a dose-related inhibition of antigen-evoked histamine release from IgE-sensitized human skin in vitro. The effective concentrations are of the same order as are achieved in plasma therapeutically.
Analysis of prednisolone inhibition shows that it acts on the second histamine release stage, antigen—antibody combination being unaffected.
In contrast with the traditional view, our results show that, at least in human skin, glucocorticoids can inhibit antigen-evoked histamine release.
Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%). 相似文献
An inexpensive and easily constructed metabolic cage for mice is presented. This apparatus can reliably monitor food and fluid consumption, as well as urine and fecal output, in a relatively non-intrusive manner. 相似文献
Fos oncoprotein expression is a marker of neuronal activation following seizures. Here, using this method we examined the anatomical locations of muscimol-induced absence seizures in the rat forebrain. Six hours after a systemic injection of muscimol a massive Fos immunoreactivity appeared in the olfactory system, retrosplenial cortex and paraventricular thalamic nucleus, whereas other cortical areas contained low level of Fos expression. These results provide the first functional morphological evidence suggesting that these forebrain structures with Fos expression may play an important role in the pathophysiology of muscimol-induced absence seizures. 相似文献
Macrophage colony stimulating factor (M-CSF) is a microglial activator expressed at increased levels in the brain in Alzheimer's disease. In monotypic microglial cultures, M-CSF strongly augments amyloid beta (Abeta) induced microglial production of proinflammatory cytokines and nitric oxide. However, this augmentation could be due to strong autocrine and paracrine effects in monotypic cultures. We used hippocampal organotypic cultures to test M-CSF/Abeta augmentation in a system modeling intact brain. Combined M-CSF/Abeta treatment increased interleukin-1 (IL-1) and macrophage inflammatory protein 1-alpha expression by microglia, whereas inducible nitric oxide synthase (iNOS) expression was localized primarily to astroglia. Induction of cytokines and iNOS was also observed after lipopolysaccharide treatment of organotypic hippocampal cultures, but iNOS expression was localized mainly to microglia rather than astrocytes. Treatment with M-CSF/Abeta did not result in neuronal death. These results demonstrate that combined M-CSF/Abeta treatment results in a strong inflammatory response in the organotypic environment without inducing neurotoxicity. 相似文献
When systemic anaphylaxis has been induced in rats infected once with the nematode, Nippostrongylus brasiliensis, the gross pathological lesions are found in the small intestine (`early' anaphylaxis). When systemic anaphylaxis is induced in rats infected four times, these lesions appear predominantly in the lungs (`late' anaphylaxis). The reasons for the change in localization of the lesions have been studied.
Reaginic antibodies are involved in both `early' and `late' anaphylaxis but there was no difference in the physicochemical and biological properties of circulating reagins taken after one or after four infections. In particular, no differences in their preference for a distinct tissue structure was detected because, in rats given either `early' or `late' reaginic antibody, passive systemic anaphylaxis resulted in lesions restricted to the small intestine. The amount of `blocking' antibody increased after several successive infections and did not explain the decrease in sensitivity to systemic anaphylaxis which occurred in rats infected twice or three times.
Differences in the degree of anaphylactic sensitization of a given tissue were assessed by measuring titres of local reaginic antibody and concentrations of tissue histamine. Following an initial infection, anaphylactic sensitization is highest along the small intestine; following several successive infections, anaphylactic sensitization is especially high in lung tissue. It is suggested that the changes in the local site and degree of anaphylactic sensitization are due to the increase in immunity of the host which allows the parasite to migrate to the lungs but not to reach the intestine.