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Biomedical subjects

D McVicar

Publications and source records attributed to D McVicar.

9 recordsLinked to original sources
PubMed2000

Interaction of Ly-49D+ NK cells with H-2Dd target cells leads to Dap-12 phosphorylation and IFN-gamma secretion.

Murine Ly-49D augments NK cell function upon recognition of target cells expressing H-2Dd. Ly-49D activation is mediated by the immunoreceptor tyrosine-based activation motif-containing signaling moiety Dap-12. In this report we demonstrate that Ly-49D receptor ligation can lead to the rapid and potent secretion of IFN-gamma. Cytokine secretion can be induced from Ly-49D+ NK cells after receptor ligation with Ab or after interaction with target cells expressing their H-2Dd ligand. Consistent with the dominant inhibitory function of Ly-49G, NK cells coexpressing Ly-49D and Ly-49G show a profound reduction in IFN-gamma secretion after interaction with targets expressing their common ligand, H-2Dd. Importantly, we are able to demonstrate for the first time that effector/target cell interactions using Ly-49D+ NK cells and H-2Dd targets result in the rapid phosphorylation of Dap-12. However, Dap-12 is not phosphorylated when Ly-49D+ NK cells coexpress the inhibitory receptor, Ly-49G. These studies are novel in describing Ly-49 activation vs inhibition, where two Ly-49 receptors recognize the same class I ligand, with the dominant inhibitory receptor down-regulating phosphorylation of Dap-12, cytokine secretion, and cytotoxicity in NK cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer.

BACKGROUND: To avoid the late sequelae associated with cranial radiation therapy in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has found increasing application as a means of preventing the development of overt central nervous system disease in childhood acute leukaemia. However, acute and chronic neurotoxicity has been described following HDMTX therapy, and the long-term intellectual outcome in children treated in this way is inadequately documented. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain is a noninvasive, quantitative way of assessing aspects of cerebral metabolism, which has not previously been applied to the study of children undergoing central nervous system directed therapy. PROCEDURE: To evaluate the potential role of (1)H-MRS in the investigation of related neurotoxicity, 11 children who had received HDMTX (cumulative dose 6-96 g/m(2)) underwent localised (1)H-MRS, magnetic resonance imaging. Neuropsychological assessments were performed on the children who had more than 1 year of follow-up time since last methotrexate treatment. Control (1)H-MRS studies on 11 adult and 6 young volunteers were undertaken. Eight patients had spectra of adequate quality. Comparisons between (1)H-MRS metabolite ratios and normal controls were made. RESULTS: Patients had a low choline/water ratio compared to controls (P < 0.01). No differences between patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen. Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the patients (104.1) was in the normal range. CONCLUSIONS: It is postulated that choline depletion in the brains of these patients may reflect subclinical disturbances of myelin metabolism as a result of methotrexate therapy and may represent a possible avenue of treatment in patients with clinical chronic methotrexate-related neurotoxicity.

Adolescent↗
PubMed1999

Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.

T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are less clear. Combined deletion in mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk-/-itk-/- cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-gamma activation.

Animals↗
PubMed1995

Serum amyloid A induces calcium mobilization and chemotaxis of human monocytes by activating a pertussis toxin-sensitive signaling pathway.

We have previously reported that serum amyloid A (SAA) induces adhesion and chemotaxis of human monocytes and polymorphonuclear neutrophils, in vitro as well as in vivo. Since the mechanism of SAA signaling is unknown, we have investigated the possibility that SAA, like other chemoattractants such as the chemotactic peptide FMLP and chemokines, might induce migration of monocytes by G protein activation. We report here that preincubation of monocytes with pertussis toxin (PTx) inhibited SAA chemotaxis, while incubation with cholera toxin (CTx) did not. Staurosporine and H-7, both inhibitors of protein kinase C (PKC), significantly decreased rSAA-induced chemotaxis of monocytes, suggesting that PKC may be involved in the rSAA signaling pathway. Moreover, rSAA, at concentrations that were effective in chemoattracting monocytes, resulted in transient elevation of cytoplasmic calcium concentration ([Ca2+]i), and incubation of cells with PTx markedly inhibited the mobilization of Ca2+ in response to rSAA. This suggests that both chemotaxis and the rise in [Ca2+]i, are mediated by G proteins of the Gi class. The increase in [Ca2+]i, induced in monocytes by rSAA, was comparable to that elicited by FMLP, and was severalfold greater than that induced by optimal concentrations of chemokine beta-family members such as RANTES, MCAF/MCP-1, and MIP-1 alpha. The chemoattractants FMLP, RANTES, MIP-1 alpha, and MCAF/MCP-1, all failed to desensitize rSAA-induced Ca2+ influx and chemotaxis in monocytes. This suggests that SAA uses a distinct receptor that is coupled to PTx-sensitive G proteins.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Digital sialography: imaging and intervention.

Digital subtraction imaging (DSI) has been widely used in angiography but less commonly applied to sialography. Over a 3-year period 109 patients referred for sialography, 42 males and 67 females with a mean age of 44 years (range 8-85 years), were examined using a digital subtraction imaging technique. 13 patients went on to have an interventional procedure, stone removal or duct dilatation. The role of DSI imaging in sialography and its use in facilitating interventional procedures on the salivary glands are discussed.

Adolescent↗
PubMed1993

Resilient adolescents and interparental conflict.

Two groups of young adolescents, both experiencing high interparental conflict but differing in terms of cognitive competence, were examined for individual and family factors that might distinguish a resilient group. Adolescent self-esteem and relationship with the mother differentiated the two groups. A stress buffering model is proposed.

Adaptation, Psychological↗