Anti-beta 2-glycoprotein I antibodies bind to central nervous system.

Anti-beta 2-GPI antibodies (a beta 2-GPI) were found in serum from patients with anti-phospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). Since a beta 2-GPI are often found in patients with anti-cardiolipin antibodies (aCL), their role in thrombosis as well as other central nervous system (CNS) manifestations in APS is unclear. We, therefore, investigated whether affinity-purified a beta 2-GPI bind the CNS. Astrocyte and neuron cell lines and histological sections were used as CNS substrates. Indirect immunofluorescence and/or streptavidin-biotin-peroxidase techniques revealed that astrocytes, neurons and vascular endothelium were bound by purified a beta 2-GPI (mouse monoclonal, rabbit polyclonal, human serum Ig a beta 2-GPI). This suggests a potential role for a beta 2-GPI in the CNS damage, as a beta 2-GPI might contribute to CNS pathology by either a direct interaction with astrocytes and neurons or an interaction with cerebral vascular endothelial cells. CNS immunoreaction was also demonstrated using six a beta 2-GPI-positive sera from patients (four with neurological manifestations). No binding to CNS was seen using a beta 2-GPI-negative sera, i.e. five from SLE patients (two with CNS involvement) and six healthy donors, or a monoclonal aCL without a beta 2-GPI immunoreactivity. Thus, the CNS reactivity by the a beta 2-GPI-positive sera appears specifically due to a beta 2-GPI and independent from aCL. Because of the presence of aCL in all patient sera, and the CNS involvement in three control patients, it is not possible to attribute a direct role for a beta 2-GPI in neurological diseases in this study

Dopamine receptor mRNAs in the rat lymphocytes

i.f. (2001) 1.75

Dopamine receptor mRNAs in the rat lymphocytes.

i.f. (2001) 1.75

Serum anti-beta(2)-glycoprotein I antibodies from patients with antiphospholipid antibody syndrome bind central nervous system cells

Sera from 20 patients with antiphospholipid syndrome (APS), primary or secondary to systemic lupus erythematosus (SLE), or with SLE, were assayed by immunoblot analysis for anti-beta(2)-glycoprotein I antibodies (a beta(2)-GPI), and by indirect immunofluorescence (IIF) technique for reactivity with astrocyte and neuron cell lines and with histological sections of human brain biopsies and monkey cerebellum. Six sera from healthy donors were studied as a control. Eleven out of the 20 patient sera contained a beta(2)-GPI and were immunoreactive with astrocytes and neurons, both in culture and in the histological sections, and with the endotheliocytes of the microvessels present in the histological sections. Cell localization and the pattern of immune reaction were similar to those obtained with a monoclonal antibody a beta(2)-GPI. Eight of the remaining patient sera, found a beta(2)-GPI(-), did not react with the nervous substrates (and the control sera), while one exhibited immunoreactivity analogous to the a beta(2)-GPI(+) sera. The interference of anticardiolipin antibodies (aCL) in the immunoreactivity with the nervous substrates was excluded since aCL were present in all patient sera and no immune reaction was observed in the histological sections incubated with a monoclonal aCL. Therefore, the binding of a beta(2)-GPI from patients to cells of the central nervous system (CNS) occurs independently from aCL. This issue may be relevant to further evaluate the potential pathogenetic role of a beta(2)-GPI in the CNS damage of APS-like conditions. (C) 1998 Academic Pres

Opioid-dopamine interaction in planaria: a behavioral study

The behavioral response of planaria to the exposure to selective opioid agonists was studied. The m agonist [d-ala2 , N-methyl-Phe4 ,Gly5 -ol]enkephalin (DAMGO) and the d agonist [D-Pen2 , D-Pen5 ]enkephalin (DPDPE) failed to alter motor activity at all doses tested. Low doses of the selective k agonist (9)-trans-U-50-trans-3,4-dichloro-N-methyl-N[2-(1-pyrrodinyl)- cyclohexyl]benzene acetamide methasulphonate (U50, 488) and bremazocine–HCl increased motor activity leading to C-like position (CLP) and screw-like hyperkinesia (SLH). These changes were identical to those seen previously with the exposure to D2 or D1 dopamine receptor agonists, respectively. Higher doses of k agonists produced the enhancement of CLP and SLH together with robust snake-like movements (SLM). This latter response, that was typical of stimulation of k opioid receptors, was blocked by co-exposure to naloxone or the selective k antagonist Nor-binaltorphimine (Nor-BNI). Finally, co-exposure to sulpiride or SH-23390 respectively blocked the CLP or SLH response produced by U50,488 or bremazocine. Our data indicate the presence of k opioid receptors in planaria and suggest the functional interaction between the opioid and dopamine system in this simple animal model

Neuropharmacology of cannabinoid system: from basic science to clinical applications.

Cannabis is not only a widely abused drug, but also has the potential for the development of useful agents for the treatment of emesis, anorexia and several neurological disorders. In this article we will review the biology of endogenous cannabinoid system and the effects of modulation of transmitter release by cannabinoids in the nervous system. During the past decade, two cannabinoid receptors, named CB1 and CB2, were identified. Putative endogenous ligands at these receptors were discovered as anandamide and 2-arachidonoylglycerol, and several research tools were identified, including receptor agonists and antagonists, antibodies, antisense oligodeoxynucleotides, and CB1 and CB2 receptor knockout mice. CB1 receptor is negatively coupled to adenylate cyclase and is either negatively or positively associated to ion channels. The localization of CB1 receptors justifies the effects of cannabinoids in the central nervous system, including the control of movement, memory impairment, analgesia and addiction. The main function of the endocannabinoid system is to regulate synaptic transmission in excitatory and inhibitory pathways in the brain. In this respect, it is relevant that the majority of cannabinoid receptors is located presynaptically on neurons where their activation causes the inhibition of the release of the respective neurotransmitter, an action that is shared in common with opioid receptors. CB1 receptor-mediated inhibition of transmitter release might explain the reinforcing properties and memory impairment caused by cannabinoids. Moreover, it may be relevant to the therapeutic potentials of cannabinoids

Effects of gonadal steroids on the growth of human pituitary adenomas in vitro

The effects of testosterone (T), dihydrotestosterone (DHT) and methyltrienolone (R 1881) on cell proliferation of eight human pituitary tumors in culture wre assessed by [3H]thymidine incorporation and compared to those of progesterone (Pg) and 17 beta-estradiol. Receptors for androgens (AR), estrogens (ER) and progesterone (PgR) were characterized. AR had a significant inhibitory effect on all AR-positive tumors, whatever their hormonal content. Inhibitory effects of either T and DHT < R1881 < Pg were observed in tumors co-expressing AR and PgR. The inhibitory effect of R 1881 on a PgR-positive/AR-negative tumor suggested that R 1881 action was partially PgR-mediated. The effects of either T or the nonaromatizable DHT and R 1881 were unrelated to ER expression. We conclude that AR can modulate the growth of human pituitary tumors through direct receptor-mediated intracellular pathways which may be common to various pituitary cell types

Serum mitogenic activity on in vitro glial cells in Neurofibromatosis type 1

Glial mitogenic effect was investigated in sera from the following groups of subjects: group (1) 31 patients clinically and genetically affected by Neurofibromatosis type 1 (NF1) belonging to different families; group (2) 42 patients without family history of NF1 affected by sporadic neoplasms of the same histogenetic origin as the proliferative lesions that are present in NF1; group (3) 51 healthy volunteers without family history of NF1 nor of neoplastic disease; group (4) 54 clinically healthy relatives of the NF1 patients included in the first group. All NF1 patients and 3/54 healthy relatives had alterations of exons 31 or 32 of NF1 gene. Glial proliferation, measured by [H-3]thymidine incorporation, was significantly increased by sera from all NF1 patients and from 23/54 of clinically healthy relatives, as compared to sera from healthy volunteers. This serum mitogenic activity strongly suggests the existence of soluble glial proliferating molecules in NF1 families. The molecular weight (3-30 kDa), the heat- and freeze-stability and the specificity for glial cells, suggest that the molecules responsible for this mitogenic effect are different from the growth factors previously described in NF1-associated tumor extracts and from lymphokines. Within each NF1 family, the maximal serum dilution stimulating glial proliferation was similar both in affected members and in their clinically healthy relatives. Since none of the clinically healthy relatives showing serum mitogenic activity was positive for the NF1 mutation analysis and, conversely, those having altered exons 31 or 32 of NF1 gene did not show any mitogenic activity, these results suggest that the phenotype expression of NF1 might depend not only on the NF1 mutations per se, but also on other genetic or epigenetic factors, such as serum glial proliferating molecules. (C) 1998 Elsevier Science B.V. All rights reserved