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Biomedical subjects

S Grey

Publications and source records attributed to S Grey.

13 recordsLinked to original sources
PubMed2000

Insulin-like signaling in yeast: modulation of protein phosphatase 2A, protein kinase A, cAMP-specific phosphodiesterase, and glycosyl-phosphatidylinositol-specific phospholipase C activities.

Previously, we have described significant effects of human insulin on glucose metabolism in the yeast Saccharomyces cerevisiae under conditions of growth limitation. These regulations apparently rely on a transmembrane receptor capable of binding human insulin and responding by tyrosine/serine phosphorylation of a specific set of polypeptides [Müller, G., Rouveyre, N., Crecelius, A., and Bandlow, W. (1998) Biochemistry 37, 8683-8695; Müller, G., Rouveyre, N., Upshon, C., Gross, E., and Bandlow, W. (1998) Biochemistry 37, 8696-8704; Müller, G., Rouveyre, N., Upshon, C., and Bandlow, W. (1998) Biochemistry 37, 8705-8713]. To characterize the molecular link between the initial steps in insulin-like signaling in yeast and the changes in the activities of glycogen synthase and glycogen phosphorylase, we examined here the effects of human insulin on a set of key regulatory enzymes of glycogen metabolism, protein phosphatase 2A (PP2A), cAMP-specific phosphodiesterase (cAMP-PDE), and protein kinase A (PKA). PP2A was activated about 2-fold by insulin in spheroplasts and in intact cells, whereas the fraction of active PKA was significantly reduced in a cAMP-independent manner as well as through a subsequent up to 3-fold increase in particulate cAMP-PDE activity accompanied by a 50% decrease in cytosolic cAMP levels. In addition, glycosyl-phosphatidylinositol-specific phospholipase C (GPI-PLC), which in isolated rat adipocytes is activated by insulin, was stimulated to up to 5-fold by glucose and 10-fold by glucose plus insulin in both yeast spheroplasts and intact cells leading to a concentration-dependent leftward shift of the glucose-response curve for activation of the GPI-PLC. GPI-PLC was most pronouncedly stimulated by authentic human insulin compared to various insulin analogues and insulin-like growth factor I. In addition to lipolytic cleavage by GPI-PLC, the GPI anchor of the cAMP-binding ectoprotein, Gce1p, was secondarily processed by a rapid proteolytic event. As the GPI-PLC reaction is rate limiting, the efficiency of the two-step anchor cleavage was significantly increased when insulin was present together with glucose as compared to glucose alone. The insulin concentrations effective in modulating PP2A, PKA, cAMP-PDE, and GPI-PLC activities correlate well with those required for half-saturation of the specific binding sites as well as for stimulation of protein phosphorylation and glycogen accumulation. The data suggest that mammalian insulin-sensitive cells and yeast share (part of) the key regulatory mechanism (consisting of PP2A, PKA, cAMP-PDE, and GPI-PLC) involved in the transduction of the insulin signal from the respective receptor systems to glycogen synthase and phosphorylase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Effects of training on interpretation of emotional ambiguity.

In four experiments we investigated whether interpretative biases found in anxious patients and high-trait anxious individuals can be induced by training in unselected volunteers. Repeated exposure to emotionally valenced (threatening) meanings of homographs during training was followed by relatively faster resolution of word fragments and faster lexical decisions for targets that matched the trained valence. Similar effects were found whether participants generated the meanings themselves, or verified a particular meaning of the homograph. Finally, comparison with a baseline condition confirmed that systematic exposure to threatening--but not non-threatening--resolutions of ambiguous words led to generally faster access times for congruent meanings, thus resembling the interpretative bias seen in anxiety states.

Adult↗
PubMed1999

Behavioral effects of corticosteroids in steroid-sensitive nephrotic syndrome.

OBJECTIVES: The objective of this study was to define the frequency and severity of steroid-related behavioral side effects in children with steroid-sensitive idiopathic nephrotic syndrome (SSNS) during treatment for relapse. STUDY DESIGN: We conducted a prospective, repeated- measures study in which 10 children with SSNS underwent behavioral assessment using the Child Behavior Checklist at baseline and during high dose prednisone therapy for relapse. RESULTS: Of the 10 children, 8 had normal behavior at baseline. Of these 8 children, 5 had Child Behavior Checklist scores above the 95th percentile for anxious/depressive behavior and/or aggressive behavior during relapse. Such scores are in the range normally considered appropriate for referral to a mental health provider. The 2 children who had abnormal behavior at baseline also experienced a worsening of their behavior during relapse. The behavioral changes occurred almost exclusively at prednisone doses of 1 mg/kg every 48 hours or more. Regression analysis showed that prednisone dose was a strong predictor of abnormal behavior, especially increased aggression. CONCLUSION: Children with SSNS often experience serious problems with anxiety, depression, and increased aggression during high-dose prednisone therapy for relapse.

Aggression↗
PubMed1998

Regulated and endothelial cell-specific expression of Fas ligand: an in vitro model for a strategy aiming at inhibiting xenograft rejection.

BACKGROUND: Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL. METHODS: Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter. RESULTS: Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells. CONCLUSION: This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.

Animals↗
PubMed1998

Regulation of monocyte tissue factor activity by allogeneic and xenogeneic endothelial cells.

The regulation of tissue factor (TF) activity by the cell associated tissue factor pathway inhibitor (TFPI) during monocyte (Mo) and endothelial cell (EC) interactions is not fully understood. This report describes co-ordinate induction of TF antigen (TF-Ag) and membrane-associated TFPI-Ag on human Mo following coculture with human aortic (HAEC) or porcine aortic EC (PAEC) or after stimulation with TNFalpha. We show that both allo- and xenogeneic EC induce human Mo-TF antigen in short-term culture. However, the TF activity of TNFalpha-primed Mo is suppressed when these cells are cocultured with HAEC [by 40.3 +/- 6.3% (p<0.02)] or PAEC [by 50.5 +/- 10.6% (p<0.001)]. Antibody (Ab) blocking studies confirm that TFPI is the principal anticoagulant associated with this suppression of TF-activity. Our data indicate that anti-TF activity originates, at least in part, from the activated human Mo in the coculture; additionally, specific generation of TFPI by Mo is observed under the xenogeneic culture conditions. As Mo associated TF, induced by allo- or xenogeneic EC interactions, is regulated by cell-associated TFPI, we propose that infiltrating Mo may modulate the thrombotic process at sites of vascular injury in association with both allo- and xenograft rejection.

Animals↗
PubMed1990

What do opiate addicts and cigarette smokers mean by "craving"? A pilot study.

There is general agreement that the term 'craving' requires clarification. This present report presents a pilot study in which groups of opiate addicts and cigarette smokers completed a brief rating scale to describe the frequency and intensity with which they had certain feelings while craving for their own drug of dependence. Craving was reported as being a dysphoric state and opiate addicts described more frequent and more intense dysphoric feeling while craving. Despite the difference in mean scores there were some similarities in the overall profile of scores in the two groups. Implications of these findings are discussed.

Adult↗
PubMed1990

Technique for occipito-cervical fusion in osteopenic patients.

A technique for occipito-cervical fusion in patients with upper cervical spine abnormalities and osteopenia is described and illustrated. This technique combines the use of autogenous bone graft and a polymethylmethacrylate (PMMA)-wire construct.

Aged↗