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H Ovadia

Publications and source records attributed to H Ovadia.

At least 19 recordsLinked to original sources
PubMed1992

Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation.

We examined the effect of acute immunosuppression with high dose cyclophosphamide (CY), followed by syngeneic T-cell-depleted bone marrow transplantation (SBMT) on chronic-relapsing autoimmune encephalomyelitis (CR-EAE) induced in SJL/J mice by immunization with mouse spinal cord homogenate (MSCH) in adjuvant. Treatment of mice on day 9 post immunization, before the appearance of clinical signs of the disease, delayed the onset of paralysis, but did not affect its clinical course. Treatment on day 2-3 after the first clinical signs led to complete regression of the disease. During a period of 3 months, only one of the 15 mice treated after the the onset of CR-EAE relapsed, as compared to a total of 21 relapses in the 15 untreated animals. A rechallenge with MSCH in adjuvant on day 78 after immunization induced a severe relapse in all untreated mice, with 78% mortality; in contrast, only 25% of mice treated with CY and SBMT relapsed when similarly rechallenged. Lymphocytes from mice treated with CY and SBMT showed reduced in vitro proliferative responses to myelin basic protein (GMBP) and PPD, even after the rechallenge with MSCH. Our results show that high dose CY for elimination of immunocompetent lymphocytes, followed by SBMT rescue, suppresses CR-EAE and induces tolerance to the immunizing antigens. These results may encourage attempts to apply a similar therapeutic principle in life-threatening human neurological autoimmune diseases.

Animals↗
PubMed1992

[Mathematical modelling of open-wedge tibial osteotomy and correction tables].

This study analyzes mathematically the orientation of the superior tibial epiphysis in frontal and sagittal planes for knees with genu varum arthrosis. The assessment of the opening is determined mathematically for the osteotomies; this leads to the establishment of tables which can be used in practise during upper tibial osteotomies.

Humans↗
PubMed1991

Expression of alpha-smooth muscle actin in murine bone marrow stromal cells.

Human fibrotic bone marrow (BM) stroma has been shown to contain alpha-smooth muscle actin (alpha-SMA)-positive cells. These closely resemble myofibroblasts that were described in other fibrotic tissues. We studied the expression of alpha-SMA in a series of murine BM-derived stromal cell lines to investigate the cellular origin and functional significance of myofibroblast-like cells in hematopoietic tissues. Although these cell lines differed in their biologic properties, most of them expressed alpha-SMA under certain conditions. Cells expressing alpha-SMA constituted a minor population in post-confluent, growth-arrested cultures. However, the incidence of cells expressing alpha-SMA increased significantly when cultures were transferred to nonconfluent conditions. A similar increase in alpha-SMA-positive cells occurred after a strip of cells was scraped away from the confluent cell layer; the cells of the affected area acquired alpha-SMA-positive contractile phenotype. The relationship between alpha-SMA expression and hematopoietic activity was studied using a cloned cell line of BM origin (14F1.1). The ability of these endothelial-adipocyte cells to support hematopoiesis in vitro was maximal under confluent conditions, whereas their expression of alpha-SMA under such conditions was residual. Moreover, in long-term BM cultures supported by confluent 14F1.1 cells, stromal areas associated with proliferating hematopoietic precursors, known as "cobblestone areas," were devoid of alpha-SMA-positive cells. These observations suggest that the expression of alpha-SMA is reversible and inversely related to hematopoietic activity.

Actins↗
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↗
PubMed1990

Selective facilitation of putative corticotropin-releasing factor-secreting neurones by interleukin-1.

The activity of single hypothalamic paraventricular nucleus (PVN) neurones was recorded in order to examine the mechanism by which the endogenous pyrogen interleukin-1 (IL-1) increases activity of the hypothalamo-hypophyseal-adrenocortical axis. IL-1 injected intravenously caused a rapid increase in the electrical activity of putative corticotropin-releasing factor (CRF)-secreting neurones located within the PVN. The activity of neighboring, electrophysiologically identified, vasopressin-secreting neurones was not altered by the stimulus, indicating a lack of involvement of this secretagogue of adrenocorticotropic hormone (ACTH) in this response to IL-1. These results support the concept of a rapid and specific activating effect of IL-1 upon hypothalamic CRF secretion as a part of a bidirectional communicating link between immune and central nervous systems.

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

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

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↗
PubMed1987

CSF myelin basic protein levels in leptomeningeal metastases. Relationship to disease activity.

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Adolescent↗
PubMed1987

Effect of hypothalamic lesions on experimental autoimmune diseases in rats.

The development of experimental autoimmune encephalomyelitis (EAE) was prevented in rats immunized with encephalitogenic antigen two weeks, but not twelve weeks, after stereotaxic electrolytic destruction of the anterior hypothalamus. Serum antibody level to the antigen myelin basic protein was decreased, and in vitro lymphocyte transformation response to a mitogen was increased. On the other hand, incidence and intensity of chronic experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor immunization were higher in rats with anterior hypothalamic lesion. In addition, expression of EAE in rats was inhibited when dopamine and norepinephrine in brain were depleted due to intraventricular injection of 6-hydroxydopamine or subcutaneous injection of reserpine. The study indicates hypothalamic modulatory effects on autoimmune response as well as possible involvement of neurotransmitters in this kind of neuroimmunomodulation.

Animals↗
PubMed1986

Experimental allergic encephalomyelitis: passive transfer of resistance during lactation.

Pregnant rats challenged with encephalitogenic antigen in complete Freund's adjuvant (CFA) during pregnancy, transferred a resistance to induction of experimental allergic encephalomyelitis (EAE) in encephalitogenic challenged offspring. The resistance to induction of EAE was transferred during the whole lactation period, until weaning, and not during pregnancy. Through the milk, anti-myelin basic protein antibodies were transferred to the newborn animals. The degree of protection against EAE decayed with age and was not influenced by EAE occurrence in the mothers. In addition, the course of EAE in the rats was not affected by pregnancy. We believe that such transfer of resistance and antibodies may serve as a model for the study of milk-transmitted maternal immunocompetent factors, as well as a model for the mechanisms involved in the resistance of EAE.

Animals↗
PubMed1979

Normal immunosuppressive protein inhibition of human and murine lymphoblastoid cell line proliferation.

Normal immunosuppressive protein, prepared from human plasma by DEAE-cellulose chromatography, inhibits DNA synthesis in human cell lines of lymphocytes of both T and B origin. It also inhibits [3H]thymidine incorporation in mouse cell lines. Normal immunosuppressive protein was able to inhibit the proliferation of these cells, although they were already transformed and had a high rate of DNA synthesis. On the other hand, it does not inhibit myeloid cells or fibroblasts.

Alpha-Globulins↗