Search PubMed⌕ Search

Biomedical subjects

J Crosbie

Publications and source records attributed to J Crosbie.

49 records · Page 3Linked to original sources
PubMed1991

Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens.

The long-standing hypothesis that tolerance to self antigens is mediated by either elimination or functional inactivation (anergy) or self-reactive lymphocytes is now accepted, but little is known about the factors responsible for initiating one process rather than the other. In the B-cell lineage, tolerant self-reactive cells persist in the peripheral lymphoid organs of transgenic mice expressing lysozyme and anti-lysozyme immunoglobulin genes, but are eliminated in similar transgenic mice expressing anti-major histocompatibility complex immunoglobulin genes. By modifying the structure of the lysozyme transgene and the isotype of the anti-lysozyme immunoglobulin genes, we demonstrate here that induction of anergy or deletion is not due to differences in antibody affinity or isotype, but to recognition of monomeric or oligomeric soluble antigen versus highly multivalent membrane-bound antigen. Our findings indicate that the degree of receptor crosslinking can have qualitatively distinct signalling consequences for lymphocyte development.

Animals↗
PubMed1991

Induction of self-tolerance in T cells but not B cells of transgenic mice expressing little self antigen.

Self-tolerance to a transgene-encoded protein, hen egg lysozyme, was examined in the T and B cell repertoires of a series of lines of transgenic mice that expressed different serum concentrations of soluble lysozyme. T cells were tolerant in all lines in which lysozyme was expressed irrespective of the antigen concentration, whereas B cell tolerance did not occur when the serum lysozyme concentration was less than 1.5 nanograms per milliliter (0.1 nM). Induction of elevated transgene expression could restore B cell tolerance. These findings support the hypothesis that autoimmune disease may in some instances arise through a bypass of T cell tolerance.

Animals↗
PubMed1990

Gastric paraganglioma: an immunohistological and ultrastructural case study.

This is a report of the immunohistochemical and ultrastructural features of a case of paraganglioma of the stomach in a 61-year-old woman who presented with melaena. The typical 'Zellballen' arrangement of epithelial cells with granular cytoplasm was present and the tumour was highly vascular. The polygonal epithelial cells stained strongly for neuron specific enolase and the intervening elongated sustentacular or support cells were positive for S100 protein and vimentin. Many dense core granules were present within the epithelial cells while the elongated support cells contained plentiful diffuse intermediate filaments. No hybrid cells or ganglion cells were present in the tumour. This is the sixth recorded case of gastric paraganglioma and the first to be studied in detail by immunostaining and electron microscopy.

Female↗
PubMed1989

Induction of self-tolerance in mature peripheral B lymphocytes.

In transgenic mice, mature peripheral B lymphocytes in lymphoid follicles, like immature B cells, are rendered tolerant by encounter with self-antigen, provided receptor occupancy by self-antigen exceeds a critical threshold. The tolerant state of the B cell is closely correlated with down-regulation of membrane IgM but not IgD antigen-receptors. Identical changes in antigen-receptor expression occur in a subset of follicular B cells in nontransgenic mice, suggesting that clonally silenced self-reactive cells are common in the peripheral B-cell repertoire.

Animals↗
PubMed1989

Neuraminidase pretreatment of donor lymphocytes and graft-versus-host disease.

Treatment of murine CBA splenocytes with Vibrio cholerae neuraminidase (VCN) prior to engraftment into cyclophosphamide (CY) immunosuppressed Balb/c x CBA mice reduced the incidence of acute lethal graft-versus-host disease (GvHD) and delayed mortality in the later phase of the disease. In the same model, pretreatment of donor splenocytes with VCN also reduced splenomegaly. Engraftment of F1 mice with CBA cells was clearly demonstrated at day 30 after infusion. Treatment of spleen cells with VCN did not compromise their ability to protect mice against irradiation-induced lethality. Furthermore, enzyme treatment was found to have no adverse effects on helper (TH-) and B-cell activity or on suppressor (TS-)cell function in adoptive transfer assays. Therefore, whereas the mechanism of the effect of the VCN preparation remains to be established, it is clear that the treatment provides protection against GvHD.

Animals↗
PubMed1988

Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice.

Immunological tolerance has been demonstrated in double-transgenic mice expressing the genes for a neo-self antigen, hen egg lysozyme, and a high affinity anti-lysozyme antibody. The majority of anti-lysozyme B-cells did not undergo clonal deletion, but were no longer able to secrete anti-lysozyme antibody and displayed markedly reduced levels of surface IgM while continuing to express high levels of surface IgD. These findings indicate that self tolerance may result from mechanisms other than clonal deletion, and are consistent with the hypothesis that IgD may have a unique role in B-cell tolerance.

Animals↗
PubMed1988

A fixed interval momentary sampling method for assessing on-going behaviours induced by dopamine receptor agonists.

1. An observational recording procedure for the objective measurement of unconditioned behaviour is described. 2. During an observation period an auditory cue (e.g. the click of a metronome) spaced at regular intervals (e.g. every 10 seconds) signals the observer to rate the presence or absence of target behaviours at the precise instant of the cue. 3. Practical and methodological considerations of the use of this technique are discussed. 4. This method has been used to compare behaviours elicited by the dopamine agonists apomorphine, LY-171555 and SK&F-38393. 5. These behaviours were also assessed using a stereotypy rating scale and these results are contrasted with those obtained using the time-sample method.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1981

High colloidal uptake in axillary nodes with metastatic disease.

Axillary lymphoscintigraphy using 99Tcm antimony sulphide colloid has been carried out in 29 patients with suspected breast cancer and was correlated with histology. Of the 23 with proved tumour, axillary node metastases were found in 19 and, although 10 did have diminished uptake on the side of the lesion, 5 had an equal uptake in both sides and 4 had an increased uptake on the side of the lesion. Further, some of the nodes in which the high uptake had occurred were those heavily infiltrated by tumour. It is concluded that: a, lymphoscintigraphy with antimony sulphide colloid is not a reliable technique for the detection of metastatic disease in the regional nodes; b, any lymphoscintigraphy with this or any other agent requires more meticulous histological correlation than hitherto before it can be assumed to have any proved clinical value.

Antimony↗