Data on the existence ratio and social utility of Nash equilibria and of the Perfectly Transparent Equilibrium.

This dataset includes 204,350,000 games in normal form played by two agents that have the choice between three strategies each, as well as 100,000 games in normal form played by four agents that have the choice between three strategies each. The games are in general position, i.e.

Photonic crystal structures in ion-sliced lithium niobate thin films.

We report on the first realization of photonic crystal structures in 600-nm thick ion-sliced, single-crystalline lithium niobate thin films bonded on a lithium niobate substrate using adhesive polymer benzocyclobutene (BCB). Focused ion beam (FIB) milling is used for fast prototyping of photonic crystal structures with regular cylindrical holes. Unwanted redeposition effects leading to conically shaped holes in lithium niobate are minimized due to the soft BCB layer underneath.

UV second harmonic generation at 266 nm in He+ implanted beta-BaB2O4 optical waveguides.

We report on the second harmonic generation of deep UV light in beta -BaB(2)O(4) (BBO) waveguides pumped by a frequency-doubled continuous-wave Nd:YAG laser. An output power of 0.32 mW at 266 nm has been achieved for an internal pump power of 670 mW.

Detection of an mRNA polymorphism by differential display.

Differential display technology was utilized to compare programs of gene expression in primary cultures of human skin fibroblasts from normal volunteers and patients diagnosed with melancholic depression. Polymorphic transcripts of a single gene differing by one tandem repeat sequence of four nucleotides (TGAT) in the 3' noncoding region were detected.

Differential expression of pentraxin 3 in fibroblasts from patients with major depression.

In this study, differential display technology was used to compare gene expression in cultured fibroblasts from patients with major depression, melancholic subtype vs nonmelancholic depressives and normal volunteer controls. Genes differentially expressed in depressives and normals included an overexpressed 269 bp sequence tag showing approximately 95% identity with the Homo sapiens long pentraxin 3 (PTX3) gene sequence in the 3' noncoding region. The 269 bp complimentary DNA probe hybridized with the 1.

The role of CREB and other transcription factors in the pharmacotherapy and etiology of depression.

Psychiatric diseases are genetically complex and consequently, altered programs of gene expression have been hypothesized as the molecular basis of psychopathology. Since transcription factors represent the final communicative link between receptor activation and the orchestration of programs of gene expression, they are prime targets for studies on both the pharmacotherapy and the etiology of depression. The cyclic AMP response element binding protein (CREB) and the glucocorticoid receptor (GR) are altered by chronic treatment with antidepressants.

Noradrenergic antidepressants: does chronic treatment increase or decrease nuclear CREB-P?

Chronic administration of noradrenergic antidepressants causes a desensitization of the beta adrenoceptor coupled adenylate cyclase system. In the present studies, we attempted to answer the question of whether or not this deamplification is reflected beyond the second messenger system. Nuclear CREB-P was determined in frontal cortex of rats following acute and chronic administration of desipramine (DMI) or reboxetine and in human fibroblasts following incubation for 48 hours with DMI, reboxetine or venlafaxine.

Detection of an mRNA polymorphism by differential display.

Differential Display (DD) technology was utilized to compare programs of gene expression in primary cultures of human skin fibroblasts from normal volunteers and patients diagnosed with melancholic depression. Polymorphic transcripts of a single gene differing by one tandem repeat sequence of four nucleotides (TGAT) in the 3' noncoding region were detected.

Cross-talk between PKA and PKC in human fibroblasts: what are the pharmacotherapeutic implications?

Background: The present study was designed to confirm or refute in human fibroblasts the hypothesized cross-talk elicited via neurotransmitter transduction cascades at the level of protein kinase mediated phosphorylation of the nuclear transcription factor CREB.

Methods: Human fibroblasts from normal control subjects were subcultured and incubated at confluency after five growth passages with isoproterenol (stimulation of PKA mediated phosphorylation) and/or phorbol 12-myristate 13-acetate (PMA) (stimulation of PKC mediated phosphorylation) followed by the determination of nuclear CREB-P by immunoblotting, enhanced chemiluminescence and quantitation of the autoradiograms by laser densitometry.

Results: Using the nuclear transcription factor CREB as a target, both the activation of the cyclic AMP-PKA pathway by isoproterenol and the activation of the PKC pathway by PMA caused phosphorylation of nuclear CREB.

Cyclic AMP-dependent protein kinase in subtypes of major depression and normal volunteers.

We have shown a reduction in beta adrenoceptor-linked, cyclic AMP-dependent protein kinase [protein kinase A (PKA)] activity in fibroblasts of patients with major depression with melancholic features relative to normal volunteers. We evaluated a group of 35 patients with major depression subtyped by DSM-IV criteria as melancholic, atypical, and those not meeting either subtype designation ('non-subtyped') and 21 normal volunteers to ascertain whether or not the PKA activity abnormality was specific to melancholia. The melancholics showed marked reduction in cyclic AMP-stimulated PKA activity relative to normal volunteers.

Pharmacological actions of the antidepressant venlafaxine beyond aminergic receptors.

The present study examines the effects of the antidepressant venlafaxine, a dual amine reuptake inhibitor, on (a) in vivo regulation of the densities of high- and low-affinity dihydroalprenolol (DHA) binding sites in the cortex of normal and reserpinized Sprague-Dawley rats and (b) targets beyond the beta adrenoceptor. While venlafaxine (30 mg/kg i.p.

Human fibroblasts as a relevant model to study signal transduction in affective disorders.

Background: Previous studies have demonstrated a blunted beta adrenoceptor-linked protein kinase A (PKA) response in the 900xg supernatant fraction of human fibroblasts cultured from patients with major depression.

Results: Results of the present studies demonstrate a significant reduction in the B(max) value of [3H]cyclic AMP binding to the regulatory subunit of PKA in the supernatant fraction of fibroblasts from patients with major depression with no change in the K(d) values. The data are consistent with the previous observation that the maximal stimulation of PKA by cyclic AMP is reduced without a change in the EC(50) value.

Lack of beta adrenoceptor desensitization in brain following the dual noradrenaline and serotonin reuptake inhibitor venlafaxine.

Venlafaxine, a dual amine reuptake inhibitor, was utilized to delineate the role of the individual aminergic components of the 'serotonin/noradrenaline link' in modifying receptor-linked second messenger cascades. Venlafaxine (20 mg/kg i.p.

Increased synaptic availability of norepinephrine following desipramine is not essential for increases in GR mRNA. Short communication.

Male Sprague-Dawley rats were treated for 7 days with the norepinephrine (NE) uptake inhibitors desipramine (DMI) or (+)-oxaprotiline or the inactive (-)-enantiomer of oxaprotiline. DMI, as previously reported, significantly increased hippocampal glucocorticoid receptor (GR) mRNA while the equipotent NE uptake inhibitor (+)-oxaprotiline like the inactive (-)-oxaprotiline did not alter hippocampal levels of GR mRNA. The results indicate that an increase in the synaptic availability of NE as a consequence of uptake inhibition is not responsible for the action of DMI on GR gene expression.

Beta-adrenoceptor-linked protein kinase A (PKA) activity in human fibroblasts from normal subjects and from patients with major depression.

Human fibroblasts from normal subjects and from patients with major depression are cultured and their beta-adrenoreceptor-cyclic AMP-protein kinase A (PKA) system characterized. The results indicate that the beta-adrenoreceptor-mediated activation of PKA in the 900 g supernatant fraction of human fibroblasts is mediated via beta-adrenoreceptors. The activation of PKA by isoproterenol is very rapid with maximal stimulation occurring at 5 seconds.

cAMP-dependent protein kinase activity in major depression.

Objective: The author's intent was to evaluate the activity of the beta-adrenoceptor-linked, cAMP-dependent protein kinase (protein kinase A) in patients with major depression compared with a group of nondepressed volunteer subjects.

Method: Skin fibroblast samples were obtained by 2-mm punch biopsy from 12 patients (11 were women) who had major depression diagnosed according to the Structured Clinical Interview for DSM-III-R and from 10 nondepressed volunteers (seven were women). Fibroblasts were cultured in Dulbecco's modified Eagle medium.

Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant.

Desipramine (DMI), a tricyclic antidepressant drug used in the treatment of depression, has been shown to increase steady-state levels of glucocorticoid receptor type II (GRII) mRNA in vitro and in vivo. To determine whether this effect is secondary to norepinephrine (NE) reuptake inhibition i.e.

The 'serotonin/norepinephrine link' beyond the beta adrenoceptor.

C6 rat glioma cells were utilized as a model system to probe the 'serotonin/norepinephrine link' at the level of preproenkephalin (PPE) gene expression. The beta adrenoceptor mediated increase in PPE mRNA was attenuated by the selective beta 1 adrenoceptor antagonist metoprolol which blocked the isoproterenol induced cyclic AMP generation by 97%. The subtype nonspecific antagonist propranolol blocked both the isoproterenol induced increase in cyclic AMP and the increase in the PPE mRNA steady-state levels.

The beta-adrenoceptor-coupled adenylate cyclase system in rat C6 glioma cells. Deamplification by isoproterenol and oxaprotiline.

The beta-adrenoceptor-coupled adenylate cyclase system in rat C6 glioma cells displays many characteristics observed in brain tissue: using nonlinear regression analysis of agonist competition binding curves, we demonstrated that the bulk of beta-adrenoceptors show high nanomolar affinity for isoproterenol; like in brain tissue, Gpp(NH)p does not shift agonist competition binding curves to the right; and the agonist isoproterenol rapidly downregulates the number of beta-adrenoceptors and deamplifies the norepinephrine signal. However, unlike in brain tissue, where (-)-oxaprotiline fails to decrease the number of beta-adrenoceptors and to desensitize the cyclic adenosine monophosphate generating system, it desensitizes the beta-adrenoceptor-coupled adenylate cyclase system in C6 glioma cells. Determination of the relative steady-state levels of beta-adrenoceptor messenger ribonucleic acid (mRNA) by Northern blot analysis showed a twofold increase in the steady-state levels of the mRNA at 30 minutes following exposure to (-)-isoproterenol or (-)-oxaprotiline.

Ethidium bromide fluorescence of 28S ribosomal RNA can be used to normalize samples in northern or dot blots when analyzing small drug-induced changes in specific mRNA.

Quantitative analysis of Northern blots is frequently accomplished with the aid of an internal standard. Most common is probing for an additional message the steady-state levels of which do not change in response to the experimental conditions and the signal of which is sufficiently removed from that of the target gene after gel electrophoresis. However, this strategy is not always feasible.

Dose-dependent down-regulation of beta-adrenoceptors by isoproterenol in rat C6 glioma cells.

Nano- and micromolar isoproterenol concentrations were compared by studying cyclic AMP, beta-adrenoceptor density and beta 1-adrenoceptor mRNA in rat C6 glioma cells. 1 microM isoproterenol significantly changed all parameters at 15-30 min. The beta 1-antagonist metoprolol attenuated the response.

Characterization of the inducible serotonin-sensitive dihydroalprenolol binding sites with low affinity for isoproterenol.

The previous findings that the inducible [3H]-dihydroalprenolol (DHA) binding sites with low affinity for isoproterenol (RL) could be regulated by serotonin (5-HT) in vitro and by 5-hydroxytryptophan and the 5-HT uptake inhibitor fluoxetine in vivo, prompted the present pharmacologic characterization of these receptor sites, using nonlinear regression analysis of competition binding curves. If isoproterenol was used as the displacing agent, lesioning with 5,7-dihydroxytryptamine selectively increased [3H]-DHA binding sites with low micromolar affinity. By contrast, if 5-HT was used as the displacing agent, the receptor population with high agonist affinity showed a fourfold increase whereas the density of [3H]-DHA sites with low micromolar affinity for 5-HT was not altered.

Dual aminergic regulation of central beta adrenoceptors. Effect of "atypical" antidepressants and 5-hydroxytryptophan.

Nonlinear regression analysis of agonist competition binding curves reveals that the [3H]-dihydroalprenolol-labeled receptor population with low affinity for isoproterenol is increased by p-chlorophenylalanine (PCPA) and this increase is abolished by 5-hydroxytryptophan (5-HTP) in vivo. Desipramine (DMI) decreased the beta adrenoceptor population with high agonist affinity to the same degree in PCPA-treated animals as in control animals, thus explaining the reported discrepancy between beta adrenoceptor number and responsiveness of the beta adrenoceptor-coupled adenylate cyclase system. Mianserin also selectively reduced the beta adrenoceptor population with high agonist affinity in membrane preparations of normal animals, whereas fluoxetine selectively abolished the upregulation of the low affinity sites in reserpinized animals and had no effect on either receptor population from brain of normal animals.

New perspectives on the molecular pharmacology of affective disorders.

Research with antidepressants has emphasized the importance of a delayed deamplification of the linked serotonin (5HT)/norepinephrine (NE) receptor coupled adenylate cyclase system in brain. The basic phenomena of regulation of receptor number and function of the beta adrenoceptor linked adenylate cyclase system in brain are well established, with NE regulating beta adrenoceptors in the high agonist affinity conformation (linked to adenylate cyclase and down-regulated by antidepressants), and with 5HT regulating those receptors in the low agonist affinity conformation. The biochemical effector systems of NE and 5HT are discussed and it is concluded that the final common pathway of signal transduction is protein kinase mediated phosphorylation of cellular proteins.

Effects of thyroid alterations and carbamazepine on cortical beta-adrenergic receptors in the rat.

The effect of alteration in thyroid status on beta adrenergic receptors in the cortex of the rat was assessed. Normal animals were treated with large doses of thyroxine (T4) and triiodothyronine (T3) and thyroidectomized animals were treated with physiological replacement doses of T4 and T3 in order to assess the possible differential effects of these hormones. In addition, a group of rats was treated with a diet of carbamazepine (an anticonvulsant also used in the treatment of manic-depressive illness), which has been shown to reduce peripheral levels of thyroid hormone in humans.