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S Sheridan

Publications and source records attributed to S Sheridan.

11 recordsLinked to original sources

The source of early IFN-gamma that plays a role in Th1 priming.

When naive CD4 T cells are primed, they rapidly differentiate into polarized Th1 and/or Th2 phenotypes. A major factor in producing such polarization is the early production of cytokines (IL-12 and IFN-gamma in the case of Th1 cells and IL-4 in the case of Th2 cells). One issue that remains unresolved is the source of the early IFN-gamma that synergizes with IL-12 to fully polarize CD4 T cells into Th1 cells. We have examined this question by injecting mice with anti-CD3 and examining cells from normal and various MHC-knockout mice. We found that IFN-gamma is induced rapidly in a small subset of CD8 T cells. This subset is absent in mice that lack beta2-microglobulin, but not in K(b)D(b)-double-knockout mice, indicating that these CD8 T cells are dependent on nonclassical MHC class Ib molecules. The early burst of IFN-gamma polarizes CD4 T cells toward Th1 cells, in part by stimulating the release of IL-12 from APC. We also use TAP- and CD1-knockout mice to show that such cells are not CD1-restricted NK T cells, nor are they dependent on TAP-1 transport for surface expression of the relevant MHC class Ib molecule. Therefore, they arise on MHC class Ib molecules that do not depend on TAP-1 transporters.

Animals↗

The fluorescent Congo red derivative, (trans, trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB), labels diverse beta-pleated sheet structures in postmortem human neurodegenerative disease brains.

A novel Congo red-derived fluorescent probe (trans, trans),-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) that binds to amyloid plaques of postmortem Alzheimer's disease brains and in transgenic mouse brains in vivo was designed as a prototype imaging agent for Alzheimer's disease. In the current study, we used BSB to probe postmortem tissues from patients with various neurodegenerative diseases with diagnostic lesions characterized by fibrillar intra- or extracellular lesions and compared these results with standard histochemical dyes such as thioflavin S and immunohistochemical stains specific for the same lesions. These data show that BSB binds not only to extracellular amyloid beta protein, but also many intracellular lesions composed of abnormal tau and synuclein proteins and suggests that radioiodinated BSB derivatives or related ligands may be useful imaging agents to monitor diverse amyloids in vivo.

Adult↗

Temperature changes in bovine mandibular bone during implant site preparation: an assessment using infra-red thermography.

OBJECTIVES: Changes in bone temperature during the sequence of drilling for implant site preparation using the Branemark technique were monitored using infra-red thermography. METHODS: Bovine mandibles were used to provide cortical bone of a similar quality to human mandibular bone. To ensure the consistency in the drilling procedure, one operator used a conventional dental handpiece with a motor provided by Nobelpharma. The manufacturer's specifications were followed during the implant site preparation, except that no irrigation was employed since infra-red radiation does not transmit through water. Thermal images were recorded using the Thermovision 900 system. A sequence of images was recorded during implant site preparation. Three drills were examined in terms of temperature changes during drilling over the entire area involved. The three drills used were a round bur, which determines the site of the fixture, a spiral drill (2 mm twist drill) which establishes the direction of the implant and finally a pilot drill (3 mm) which progressively increases the diameter of the site. RESULTS: Average values (n = 10 drill sequences) for maximum recorded temperature (Max T degrees C), change in temperature (delta T degrees C) from baseline and the area of involvement (mm2) for each drill in the 10 drill sequences were as follows: round, spiral (2 mm) and pilot (3 mm) drills gave maximum temperatures of 82.7 degrees C, 130.1 degrees C and 126.3 degrees C, respectively. The changes in temperature, delta T degrees C, were 45.7 degrees C, 79.0 degrees C and 78.9 degrees C for the round, 2 mm twist and 3 mm pilot drill, respectively. The average areas recorded for the round, spiral and pilot drills were 49 mm2, 140.1 mm2 and 273.0 mm2, respectively. CONCLUSIONS: It is concluded that the methodology employed accurately recorded temperature changes at and around the dental implant site, and provided preliminary baseline data against which the cooling efficacy of different irrigant systems may be compared.

Animals↗

Contractile responses to sumatriptan in isolated bovine pulmonary artery rings: relationship to tone and cyclic nucleotide levels.

We examined responses to the 5-hydroxytryptamine 1D (5-HT1D)-receptor agonist sumatriptan in bovine pulmonary artery rings (2-3 mm ID). The effects of agonist-induced tone and agents that alter intracellular cyclic AMP [cyclic AMP]i or [cyclic GMP]i on responses to sumatriptan were investigated. At resting tension, responses to sumatriptan were slight or not evident. In the presence of tone induced by U46619, responses to sumatriptan (1 nM-30 mM) were greatly potentiated, as were responses to the alpha2-adrenoceptor agonist UK14304. Responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) were potentiated only slightly. In the presence of U46619, addition of the adenylyl cyclase activator, forskolin (1 nM-0.1 microM or isoprenaline (ISO 1 microM) induced relaxations and increases in [cyclic AMP]i and resulted in further potentiation of the contractile response to sumatriptan. Addition of 0.1 microM sodium nitroprusside (SNP) inhibited sumatriptan-induced contractions. Whereas sumatriptan alone did not significantly affect [cyclic AMP]i, in the presence of U46619 it decreased [cyclic AMP]i. This effect of sumatriptan was further enhanced in the presence of forskolin. Sumatriptan increased [cyclic GMP]i. Using a nitric oxide (NO) synthase inhibitor and vessels denuded of endothelium, we showed that the increased [cyclic GMP]i in response to sumatriptan was endothelium-dependent and mediated by NO. This increase in [cyclic GMP]i was not observed in the presence of U46619. By measuring cyclic AMP and cyclic GMP phosphodiesterase (PDE) levels, we demonstrated that the point of "cross-talk" between cyclic nucleotides may not be at the level of total PDE activity. These results highlight the important role of [cyclic AMP], [cyclic GMP]i, and endothelium function in the control of 5-HT1D receptor-mediated vasoconstriction, which is dependent on a decrease in [cyclic AMP]i in the absence of an increase in [cyclic GMP]i.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗