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Biomedical subjects

O Abramsky

Publications and source records attributed to O Abramsky.

At least 109 records · Page 6Linked to original sources
PubMed1991

Regulation of proenkephalin A messenger ribonucleic acid levels in normal B lymphocytes: specific inhibition by glucocorticoid hormones and superinduction by cycloheximide.

Proenkephalin A (PEA) encodes a group of small peptides known to function as neurotransmitters, neuromodulators, and neurohormones in the nervous and neuroendocrine systems. This gene has been shown to be expressed in lymphoid cells, supporting the concept of bidirectional communication between the immune system and the central nervous system. In the present study, we investigated the effect of steroids and the inhibition of protein and RNA syntheses on the regulation of PEA expression in normal rat B cells. The transient expression of PEA messenger (m) RNA levels occurring normally in B cells was markedly inhibited by the presence of either 50 nM prednisolone or dexamethasone, both of which are glucocorticoids; other steroids, such as testosterone or the steroid-inactive metabolite androsterone, were ineffective. In the presence of cycloheximide, a protein synthesis inhibitor, PEA mRNA was superinduced by a factor of 15-fold. Sorting by flow cytometry of cycloheximide-treated cells followed by in situ hybridization analysis revealed that the expression of PEA mRNA was exclusively confined to a small fraction of B cells. These results indicate that the mechanisms regulating PEA gene expression in B cells differ from those previously described in cells of the neuroendocrine and the nervous systems.

Animals↗
PubMed1991

Effect of experimental autoimmune encephalomyelitis on pregnancy: studies in rabbits and rats.

The influence of experimental autoimmune encephalomyelitis (EAE) on the course and outcome of pregnancy, and the effect of pregnancy on EAE development, was investigated in rabbits and rats. Animals were immunized with encephalitogenic antigen in complete Freund's adjuvant (CFA) either before or during pregnancy. Abortion or fetal resorption was observed in most of the rabbits immunized before or during pregnancy, but not in pregnant rabbits injected with CFA or saline alone. Fetal loss was higher in those rabbits that developed clinical EAE. In rats, fetal loss occurred only when immunization was carried out during the first half of pregnancy. The appearance of EAE in pregnant rabbits, but not in rats, was delayed until after abortion or termination of pregnancy. The incidence of EAE in rabbits was lower, with milder severity and longer duration. Serum antibody levels to myelin basic protein, the autoantigen of EAE, was lower in pregnant rabbits, but not in rats, as compared to non pregnant animals. These results indicate that in species where pregnancy has a suppressive influence on the development of experimental autoimmune demyelinating disease, immunization with the neuroantigen induces a high rate of fetal loss.

Animals↗
PubMed1991

Acute inflammatory demyelinating polyneuropathy following bone marrow transplantation.

Acute inflammatory demyelinating polyneuropathy (AIDP) appeared in two patients following allogeneic bone marrow transplantation (BMT). In one transplanted patient (but not in the donor) T cells were sensitized against peripheral nervous system myelin. This could reflect a change in the T cell repertoire in a different milieu. In this context, AIDP might be part of graft-versus-host disease or another associated autoimmune disorder following BMT.

Adolescent↗
PubMed1991

Development of experimental allergic encephalomyelitis during steroid administration. Outcome of neurological immune-mediated disorders under immunosuppressive therapy.

Glucocorticoids are frequently employed as immunosuppressive agents. Following clinical reports of occurrence and exacerbation of neurological immune-mediated conditions in patients receiving steroids, we studied the course of experimental allergic encephalomyelitis (EAE) in rats receiving methylprednisolone prior to and during disease induction and after the appearance of clinical signs. High methylprednisolone dose given prior to EAE induction significantly increased disease duration and the number of days at maximal disability. When the drug was given prior to and during the induction phase, both moderate and high doses exacerbated the EAE course. In contrast, treatment with methylprednisolone after the onset of clinical disease had a markedly beneficial effect. Thus, time of initiation, dosage and duration of treatment may differentially affect the course of EAE. Moreover, the natural course of a neurological immune-mediated condition may be worsened when it is triggered while the patient is under steroid treatment.

Animals↗
PubMed1990

Alpha-interferon modifies cortical EEG activity: dose-dependence and antagonism by naloxone.

Activation of the immune system is believed to provide signals in the form of chemical messengers that are able to change neural activity in a variety of regions of the central nervous system. In studies designed to examine the effects of alpha-interferon (alpha-IFN) upon the central nervous system, recordings of cortical EEG were made following intracerebroventricular injection of various doses of the cytokine. Administration of 25 U of alpha-IFN increased the amount of wake and decreased the amount of desynchronized sleep in the first hour following injection; an increase in synchronization being seen in the third hour. alpha-IFN at 250 U increased the amount of synchronization and decreased the amount of desynchronized sleep in the EEG, principally in the second hour, with 2,500 U having similar but more potent effects, mostly in the first hour. The (mu) opiate receptor antagonist, naloxone, was found to decrease the amount of EEG synchronization and blocked the increases in synchronized sleep produced by 250 U alpha-IFN. The data suggest that alpha-interferon increases EEG synchronization in a dose-dependent and specific manner, probably via central mu-opiate receptors. The increased wake in the EEG following 25 U suggests, however, that another discrete effect of alpha-IFN may also exist.

Animals↗
PubMed1989

Regulated expression of proenkephalin A in normal lymphocytes.

The expression of proenkephalin A (PEA), a neuropeptide-encoding gene, was examined in normal rat lymphocytes. With the use of Northern blot hybridization analysis of total RNA, PEA mRNA was found in normal cells derived from spleen, lymph nodes, and bone marrow. Cell sorting of the two main fractions of B and T cells derived from the spleen revealed that PEA is expressed in normal B cells (sIg+). The expression of PEA mRNA was markedly enhanced after a short incubation (3 h) of cells with LPS or Salmonella typhimurium. This was not the case when these cells were incubated with Con A during the same period of time; whereas, in thymocytes the presence of PEA mRNA was exclusively dependent upon mitogenic stimulus (Con A) and could be detected after 24 h of in vitro incubation. Extracts of cells were also found to contain immune reactive enkephalins, indicating that the PEA mRNA is translated. These results support the concept that neuropeptides, such as enkephalins, have a role in the modulation of the immune response and may participate in the bidirectional communication between the nervous and immune systems.

Animals↗
PubMed1989

[Clinical trial of copolymer 1 in multiple sclerosis].

A synthetic copolymer of amino acids, copolymer 1 (Cop 1), proved to be very effective in suppressing experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). It is 1 of a series of synthetic amino acid copolymers which simulate the basic protein constituent of the myelin sheath and the autoantigen responsible for induction of EAE. It cannot induce EAE but it does suppress it in a variety of animals. The immunological cross-reaction between Cop 1 and the basic protein is the basis for this suppressive activity. In view of the resemblance between EAE and MS, clinical trials with Cop 1 in MS were started. The first preliminary clinical trial was at this hospital and involved 4 patients with severe MS. A double-blind, randomized placebo-controlled pilot trial was carried on for 2 years in 50 patients with the exacerbating-remitting form of MS but with a Kurtzke Disability Status Scale rating of no more than 6. There were statistically significant differences in the number of patients with exacerbations in the placebo group, 23, as compared to only 16 in the Cop 1-treated group. As to exacerbations per patient, the 2-year averages were 2.7 and 0.6, respectively. Side-effects of Cop 1 were minimal. These results suggest that Cop 1 may be beneficial when given early in the exacerbating-remitting form of MS. Further trials, necessary to establish its efficacy in MS, are being run at the Albert Einstein College of Medicine in NY.

Amino Acids↗
PubMed1989

Effect of interleukin-1 on adrenocortical activity in intact and hypothalamic deafferentated male rats.

The present study was designed to elucidate the site of action of interleukin 1 (IL-1) modulation of the hypothalamic-hypophyseal-adrenal (HHA) axis. An intraperitoneal injection of recombinant human IL-1 beta (160 U/rat) significantly elevated serum levels of ACTH and corticosterone (CS). In rats with complete mediobasal hypothalamic deafferentation, the HHA response to IL-1 was inhibited. An intracerebroventricular injection of rIL-1 (2 U/rat) caused a marked increase in serum ACTH and CS. These results suggest that IL-1 activates the HHA axis by a direct effect upon the brain, and that intact neural connections between the mediobasal hypothalamus and extrahypothalamic brain regions are essential for IL-1-induced HHA responses.

Adrenocorticotropic Hormone↗
PubMed1989

Evidence for the involvement of the central adrenergic system in interleukin 1-induced adrenocortical response.

The role of central catecholamines in the mediation of adrenocortical activation, induced by interleukin 1 (IL-1), was investigated by measuring ACTH and corticosterone in serum. Adult male rats were injected with either vehicle or the neurotoxin 6-hydroxydopamine (6-OHDA) into the lateral ventricle or the ventral noradrenergic ascending bundle. In vehicle-injected rats, 2 U of IL-1, injected intraventricularly, produced a 5- and 15-fold increase in ACTH and CS, respectively, in serum, 120 min after the injection of IL-1. In contrast, 6-OHDA, injected either intraventricularly or into the ventral noradrenergic ascending bundle, abolished the response to an intracerebral injection of IL-1. In addition, in rats pretreated with the alpha 1-adrenergic antagonist, prazosin, IL-1 failed to activate the adrenocortical axis. In other rats pretreated with the beta-adrenergic antagonist, propranolol, the adrenocortical response did not significantly differ from that of vehicle-pretreated rats. These results suggest that central adrenergic transmission, originating at the ventral noradrenergic ascending bundle and acting through alpha 1-adrenergic receptors, is involved in the adrenocortical response to IL-1.

Adrenal Cortex↗
PubMed1989

In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis.

Peripheral blood lymphocytes and B-cells were obtained from patients with myasthenia gravis and stimulated in vitro with either pokeweed mitogen or Epstein-Barr virus (EBV), respectively. EBV stimulation of B-cells caused a production of antibodies to acetylcholine receptor in 15 of the 25 myasthenia gravis patients: the EBV stimulation of B-cells was more effective in this regard than the pokeweed mitogen stimulation of peripheral blood lymphocytes. The in vitro synthesis of anti-acetylcholine receptor antibodies was found to be positively correlated with both the patients' sera antibody titers and with the disease severity.

Autoantibodies↗
PubMed1989

Evidence for the involvement of the central adrenergic system in the febrile response induced by interleukin-1 in rats.

We have studied the effect of noradrenaline- and serotonin-depleting agents on the febrile response induced by an intracerebroventricular (i.c.v.) injection of interleukin-1 (IL-1) in rats. Pretreatment with an injection into the lateral ventricle of the catecholamine-depleting agent, 6-hydroxydopamine (6-OHDA), abolished the febrile response induced by IL-1. Injection of 6-OHDA into the ventral noradrenergic ascending bundle (VNAB) did not affect the pyrogenic effect of IL-1. Pretreatment with the serotonin-depleting agent, 5,7-dihydroxytryptamine (5,7-DHT), did not inhibit the febrile response to IL-1. In addition, pretreatment with a beta-adrenergic blocker (propranolol) but not an alpha-adrenergic blocker (yohimbine) attenuated the fever induced by an i.c.v. injection of IL-1. These results suggest that the integrity of the central catecholaminergic system is important in mediating the IL-1-induced fever in rats. The central serotonergic system, as well as noradrenergic neurotransmission at the hypothalamus, do not appear to participate in this endogenous pyrogen-induced febrile response.

5,7-Dihydroxytryptamine↗
PubMed1989

Characterization of opiate binding sites on membranes of rat lymphocytes.

In view of the importance of membrane receptors for the interconnection between the central nervous system and the immune system, we carried out a study to characterize opiate binding sites on membranes of rat lymphocytes. We found that mitogen-activated spleen cells, but not thymocytes, possess specific and displaceable binding sites for [3H]naloxone. The binding was equally effective and intense while using B-cell-depleted spleen cells. The binding showed two sites of saturation, one at 10 nM and the other at concentrations greater than 20 nM of [3H]naloxone. Computer analysis of the binding data obtained with the lowest concentrations of naloxone revealed a unique site with high affinity binding to opiates. Displacement was achieved with morphine sulphate and naloxone but not with opioid peptides. The binding of the antagonist, [3H]naloxone, was profoundly inhibited by the co-presence of 120 mM NaCl and up to 100 microM guanosine 5'-O-(3-thiotriphosphate (GTP gamma S). Other metal ions and cyclic nucleotides were not able to interfere with the specific binding. This specificity for GTP analogues is consistent with the hypothesis that a GTP-binding regulatory protein that couples receptors to adenylate cyclase is involved in the process of binding of opiates to lymphocytes. The existence of binding sites on lymphoid cells, analogous to receptors for agents known to affect brain functions, may be another link between the immune system and the central nervous system.

Animals↗
PubMed1989

Central administration of immunomodulatory factors alters neural activity and adrenocortical secretion.

This study was designed to examine the effects of intracerebroventricular administration of a variety of immunomodulatory factors upon cortical EEG, preoptic area/anterior hypothalamic (POA/AH) multiunit activity (MUA), and corticosterone secretion in conscious, freely moving rats. The substances tested were alpha-interferon (alpha-INF), thymic humoral factor (THF), histamine, and interleukin-1 (IL-1). Saline administration did not alter POA/AH MUA up to 45 min after injection but increased the total time and duration of synchronized EEG periods. alpha-INF and THF were found to significantly reduce POA/AH MUA and increased the amount and duration of synchronized EEG while decreasing basal plasma corticosterone levels. Histamine and IL-1 did not alter POA/AH MUA discharge but decreased EEG synchronization and evoked an increase in plasma corticosterone levels. These results demonstrate that some secretions of the immune system are able to alter EEG discharge and neural activity in an area of the brain known to modulate both immune and neuroendocrine secretory activity. The results also appear to be related to adrenocortical secretory activity, which was altered by the substances tested.

Adrenal Cortex↗
PubMed1989

Effect of interleukin-1 on ACTH and corticosterone secretion in dexamethasone and adrenalectomized pretreated male rats.

The present study was designed to investigate the role of glucocorticoids in mediating the stimulatory effect of interleukin-1 (IL-1) upon the adrenocortical (AC) axis. Intact male rats were injected with either vehicle or dexamethasone (DEX) (5-50 micrograms/100 g b.w.) and were subsequently exposed to ether stress or to an intracerebroventricular (i.c.v.) injection of 2 U recombinant human IL-1 beta. In addition, adrenalectomized (ADX) rats were injected i.c.v. with 2U IL-1; for comparison ADX rats were also exposed to ether stress and insulin-induced hypoglycemia. In intact rats, ether-stress-induced AC activation was much more sensitive to the DEX inhibitory effect than the IL-1-induced AC activation. In ADX animals, insulin-induced hypoglycemia and ether stress produced a significant increase in ACTH serum values whereas IL-1 administration failed to activate ACTH secretion. Glucocorticoid binding studies showed that an i.c.v. injection of 2 U IL-1, 3 h before sacrifice, markedly reduced the specific in vitro binding of 3H-corticosterone by the nuclear fraction of dorsal hippocampal tissue slices. These results suggest that IL-1 may activate the AC axis, at least in part, by interfering with the negative feedback effect of circulating glucocorticoids.

Adrenal Cortex↗
PubMed1989

Intraventricular interferon treatment for subacute sclerosing panencephalitis.

Three children with subacute sclerosing panencephalitis (SSPE) were treated with alpha-interferon. Medication was administered via an Ommaya reservoir into the cerebral ventricular system over a period of 13 to 24 months in increasing amounts up to 1.0 x 10(6) IU twice weekly. Mild clinical improvement in two children and a stable course in the third were associated with improvement of electroencephalographic recordings in all patients and a decrease in antimeasles antibodies in the cerebrospinal fluid of two. The small number of patients does not enable us to determine whether this course was the natural history of SSPE in our patients or whether it was induced by treatment, yet it seems that intraventricular interferon treatment can modify the course of SSPE.

Child↗