The regulation of CD95 (Fas) ligand expression in primary T cells: induction of promoter activation in CD95LP-Luc transgenic mice.

The interaction between CD95 (Fas) and CD95L (Fas ligand) initiates apoptosis in a variety of cell types. Although the regulation of CD95L expression on activated T cells is an area of intense study, knowledge related to the induction of CD95L promoter activity in primary T cells is lacking. In this report we describe the generation of a novel transgenic mouse strain, CD95LP-Luc, in which murine CD95L promoter sequence controls the expression of a luciferase reporter gene.

Effects of cholinergic agonists and antagonists on interleukin-2-induced corticotropin-releasing hormone release from the mediobasal hypothalamus.

In previous research we found that interleukin-2 (IL-2)-induced corticotropin-releasing hormone (CRH) release in vitro is mediated by cholinergic activation of nitric oxidergic (NOergic) neurons. The NOergic neurons release nitric oxide that stimulates CRH release. To further characterize the mechanism of IL-2-induced CRH release, the possible role of nicotinic as well as muscarinic receptors in IL-2-stimulated CRH release was evaluated.

Enhanced propagation of epileptiform activity through the kindled dentate gyrus.

Extracellular recordings were performed in combined hippocampal-entorhinal cortex (HC-EC) slices obtained from control and commissural kindled rats to investigate the propagation of epileptiform activity from the entorhinal cortex (EC) to the hippocampus (HC) after chronic epilepsy. Lowering extracellular Mg2+ concentration in control slices induced epileptiform activity consisting of spontaneous epileptiform bursts in area CA3 and of electrographic seizures in the EC. In contrast, the CA3 region of HC-EC slices obtained from kindled rats displayed significantly longer lasting epileptiform bursts and electrographic seizures.

Effects of luteinizing-hormone-releasing hormone, alpha-melanocyte-stimulating hormone, naloxone, dexamethasone and indomethacin on interleukin-2-induced corticotropin-releasing factor release.

Our previous studies have shown that the microinjection of interleukin (IL)-2 into the third ventricle of conscious rats evokes the release of adrenocorticotropin hormone (ACTH) and that its incubation with hemipituitaries in vitro was also effective in releasing ACTH. In the present experiments, we evaluated the effect of IL-2 on the release of corticotropin-releasing factor (CRF) from medial basal hypothalami (MBHs) incubated in vitro and studied the effect of other agents, whose release is altered in stress, on CRF release. IL-2 significantly stimulated CRF release at concentrations of 10(-13) and 10(-14) M, whereas increasing the concentration to 10(-12) to 10(-10) M did not produce significant release of CRF.

An interleukin-1-alpha-like neuronal system in the preoptic-hypothalamic region and its induction by bacterial lipopolysaccharide in concentrations which alter pituitary hormone release.

We studied the effect of intravenous injection of lipopolysaccharide (LPS) (30-250 micrograms) on the release of several anterior pituitary hormones as indicated by changes in their concentrations in plasma. Within 30 min after intravenous injection of LPS there was a dose-related stimulation of ACTH release; prolactin (PRL) release was induced only by the highest LPS dose injected (250 micrograms). Even the lowest dose of LPS (30 micrograms) decreased plasma growth hormone (GH) by 60 min.

Alpha-melanocyte-stimulating hormone inhibits corticotropin-releasing factor release by blocking protein kinase C.

Cytokine-induced release of corticotropin-releasing factor (CRF) from hypothalamic explants in vitro can be inhibited by femtomolar concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH). Because the mechanism of the anticytokine action of alpha-MSH remains unknown, we examined if the peptide inhibits CRF release by interference with various steps in the activation of CRF release. Previous studies have shown that CRF release is induced by activation of phospholipase A2 (PLA2).

Binding of anti-inflammatory alpha-melanocyte-stimulating-hormone peptides and proinflammatory cytokines to receptors on melanoma cells.

alpha-Melanocyte-stimulating hormone (alpha-MSH1-13), a peptide derived from proopiomelanocortin, has remarkable anti-inflammatory and antipyretic activities. This peptide and a tripeptide that forms the COOH-terminal portion of the molecule (alpha-MSH11-13; Lys Pro Val) inhibit inflammation when given centrally or peripherally. Because of the similarity in their actions, the tripeptide has been presumed to be the amino acid message sequence underlying the effects of alpha-MSH1-13.

Blockade by interleukin-1-alpha of nitricoxidergic control of luteinizing hormone-releasing hormone release in vivo and in vitro.

Nitric oxide (NO) synthase (NOS), the enzyme that converts arginine into citrulline plus NO, the latter a highly active free radical, occurs in a large number of neurons in the brain, including certain neurons in the hypothalamus. Our previous experiments have shown that norepinephrine (NE)-induced prostaglandin E2 (PGE2) release from medial basal hypothalamic explants (MBH) is mediated by NO. Because release of luteinizing hormone (LH)-releasing hormone (LHRH) is also driven by NE and PGE2, we hypothesized that NO controls pulsatile release of LHRH in vivo, which in turn induces pulsatile LH release.

Cyclosporin A inhibits interleukin-2-induced release of corticotropin-releasing hormone.

Cyclosporin A (CSA), a potent immunosuppressive drug, has recently been shown to bind with high affinity to the immunophilin, cyclophilin. Calcineurin, the calcium-dependent protein phosphatase, binds the cyclophilin/CSA complex, rendering it inactive and blocking dephosphorylation of phosphoproteins. Very high concentrations of cyclophilin have been reported in the brain with a localization identical to that of calcineurin.

Alpha-melanocyte-stimulating hormone abolishes IL-1- and IL-6-induced corticotropin-releasing factor release from the hypothalamus in vitro.

Alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH), peptides derived from the precursor proopiomelanocortin, share amino acid homology at the aminoterminus of ACTH, occur within the pituitary and the brain and are potent antipyretic compounds in cytokine-mediated fever. Because alpha-MSH and ACTH act within the hypothalamus to block leukocytic pyrogen- or cytokine-mediated fever, we hypothesized that these compounds might also be capable of blocking the action of interleukin-1 (IL-1) and interleukin-6 (IL-6) to stimulate corticotropin-releasing factor (CRF) release from the hypothalamus. Mediobasal hypothalami (MBH) were incubated in vitro.

Role of nitric oxide in interleukin 2-induced corticotropin-releasing factor release from incubated hypothalami.

Stimulation of corticotropin-releasing factor (CRF) release from the hypothalamus by interleukin 2 (IL-2) was recently demonstrated. Cytokines induce nitric oxide synthase (NOS), an enzyme that converts L-arginine into L-citrulline and nitric oxide (NO). NO is believed to be responsible for the cytotoxic action of these agents.

Nitric oxide mediates norepinephrine-induced prostaglandin E2 release from the hypothalamus.

Nitric oxide (NO), formed by conversion of arginine to citrulline and NO by NO synthase, mediates relaxation of vascular smooth muscle. NO synthase has been demonstrated by immunocytochemical methods in neurons in various parts of the central nervous system including the hypothalamus. The latter finding suggested to us that NO might play a role in controlling the release of hypothalamic peptides.

Effect of thymosin alpha 1 on hypothalamic hormone release.

Thymosin alpha 1 (T alpha 1) is a well-characterized immunopotentiating polypeptide originally isolated from calf thymus. We have recently shown in vivo, probable hypothalamic effects of T alpha 1 to decrease the release of the pituitary hormones, TSH, PRL and ACTH from the pituitary gland. Therefore, in the present study we evaluated the effect of the peptide on the release of hypothalamic regulatory hormones: thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), as well as somatostatin (SRIH), from medial basal hypothalamic (MBH) fragments incubated in vitro.

Involvement of arachidonic acid cascade pathways in interleukin-6-stimulated corticotropin-releasing factor release in vitro.

We have demonstrated that centrally administered interleukin-6 (IL-6) stimulates adrenocorticotropin (ACTH) secretion by a direct effect on corticotropin-releasing factor (CRF) release from the hypothalamus. Since metabolites of the arachidonic acid cascade (AAC) have been implicated in mediating actions of cytokines in different tissues and some AAC inhibitors were able to block pyrogenic effects of cytokines and suppress IL-1-induced ACTH secretion, we decided to examine the mechanism of IL-6 action on CRF release in vitro. After a 60-min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami (MBH) were preincubated for 30 min with dexamethasone (DEX), a phospholipase A2 (PLA2) inhibitor, to block arachidonic acid (AA) formation, or with inhibitors of AA metabolism: a cyclooxygenase inhibitor--indomethacin (IND); a lipoxygenase inhibitor--5,8,11-eicosatriynoic acid (ETI), and an epoxygenase inhibitor--clotrimazole (CLO).

Induction of adrenocorticotropic hormone release by interleukin-6 in vivo and in vitro.

Recent reports show that cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF) and intravenously administered interleukin-6 (IL-6) stimulate adrenocorticotropic hormone (ACTH) release. Both IL-1 and TNF are known to be potent inducers of IL-6, a monokine produced by activated monocytes and folliculo-stellate cells of the pituitary gland and released from the hypothalamus. To determine the site(s) of action of IL-6 in the control of ACTH release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats and measured ACTH by RIA.

The effect of interleukin-6 on pituitary hormone release in vivo and in vitro.

Intravenously administered interleukin-6 (IL-6), a monokine produced by activated monocytes and folliculostellate cells of the pituitary gland, has been recently reported to elevate plasma ACTH level and to stimulate PRL, GH and LH release from cultured pituitary cells. To determine the site(s) of action of IL-6 in the control of pituitary hormone release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats. Both 0.

The effect of nerve growth factor on DNA synthesis, cyclic AMP and cyclic GMP accumulation by mouse spleen lymphocytes.

Nerve growth factor (NGF), a trophic neuropeptide, is known to stimulate development, and to be important in the maintenance and survival of sympathetic and sensory neurons. Considering the presence of specific receptors on the surface of spleen cells, the effect of 2.5s nerve growth factor on 3H-thymidine uptake, cAMP and cGMP accumulation in mouse spleen lymphocytes has been studied.

Effect of amantadine on prolactin secretion, pituitary DNA synthesis and 3H-spiperone binding in male estrogen-treated rats.

Amantadine, a well-known antiviral agent, causing an increase in dopamine synthesis, release and the inhibition of re-uptake of noradrenaline and dopamine in central and peripheral catecholaminergic neurons, is successfully used in the treatment of Parkinson's disease. In the present paper, we have studied the effect of various doses of amantadine on in vivo prolactin secretion and the incorporation of 3H-thymidine and 3H-spiperone binding by the anterior pituitary gland of long-term diethylstilboestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstilboestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of 3H-thymidine by DNA anterior pituitary cells.

Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytes in vitro.

The effects of nimodipine (voltage-dependent calcium channel blocker), CGP 28392 and BAY K 8644 (novel dihydropyridine derivatives that are considered as calcium entry stimulators) on the spontaneous proliferation of mouse spleen lymphocytes were studied in vitro. [3H]-thymidine incorporation into DNA of lymphocytes was used as an sensitive index of the cell proliferation. It has been found that nimodipine (10(-4) M-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose dependent fashion with ED50 value of 2.

Pronounced increase of survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy.

During 1982-86, 43/137 patients with cardiomyopathy, Classes II, III and IV, had ejection fractions (EF) below 40%, and a mean EF of 25.1 +/- 10.3%.

Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro.

The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation.

Effective and safe therapy with coenzyme Q10 for cardiomyopathy.

Coenzyme Q10 (CoQ10) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, X-rays, electrocardiograms, echocardiography, and coronary angiography.