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Biomedical subjects

H Ovadia

Publications and source records attributed to H Ovadia.

At least 73 records · Page 4Linked to original sources
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

Dopamine receptors on isolated membranes of rat lymphocytes.

Using [3H]-dopamine (DA) as the ligand of choice, we have shown that rat lymphocytes possess DA binding sites. The binding of [3H]-DA was specific, saturable, and of high affinity. The specific binding in membranes obtained from Con A-activated lymphoblasts was greater than the binding in respective unactivated lymphoid cells, and displaced by lower concentrations of unlabeled ligand. [3H]-DA was displaced specifically by DA, norepinephrine, and apormorphine. The binding sites were insensitive to neuroleptic drugs such as sulpiride, bromocryptine, and haloperidol. On the basis of these findings, we have suggested that lymphocytes possess a receptor site for catecholamines and the receptor for DA might be a D-3 receptor type.

Animals↗
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

Multiunit electrical activity in conscious rats during an immune response.

Mechanisms by which the central nervous system may be influenced during the course of an immune response probably exist but remain obscure. In an attempt to determine any neurophysiological changes during such responses, we have employed a conscious animal model bearing chronically implanted recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Rats were sensitized to sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) increased significantly to a maximum 5 days after SRBC injection and correlated with the initial appearance of anti-SRBC serum antibodies. Significant decreases in PO/AH MUA were recorded on Days 3 and 8 following the sensitization. PVN MUA decreased significantly for the first 3 days following immunization and then returned to a basal rate before increasing on Day 6. On the ninth and tenth days following the SRBC injection, both PO/AH and PVN MUA levels had returned to those recorded before immunization. A further group of animals was examined for PO/AH MUA changes during induction of a secondary response to SRBC. Firing rates increased significantly between Days 4 and 9 following the injection, the maximum increase being on Day 6. The profile of this response was different from that recorded during the first response, with no decreases recorded. The results are discussed in terms of neuroimmunomodulatory mechanisms such as those influencing neuroendocrine secretory function.

Animals↗
PubMed1987

Dopamine receptors on isolated membranes of rat thymocytes.

Using [3H]DA as the ligand of choice, we have shown that rat thymocytes possess dopamine binding sites. The binding of [3H]DA was specific, saturable and of high affinity. [3H]DA binding was rapid and reversible; [3H]DA was totally displaced by low concentrations of dopamine, norepinephrine, and apomorphine. The binding sites were insensitive to neuroleptic drugs such as sulpiride, bromocriptine, and haloperidol. On the basis of these findings, we have suggested that thymocytes possess a D-3 receptor type.

Animals↗
PubMed1987

A neurophysiological correlate of an immune response.

In order to examine possible neurophysiological changes during an immune response, we have recorded neural activity in a conscious animal bearing chronic recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Male rats were sensitized with sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) was recorded as 14.7 +/- 2.1 Hz prior to sensitization and was seen to increase significantly to a maximum of 33.1 +/- 6.0 Hz (p less than 0.005) five days after SRBC injection. This increase correlated with the initial appearance of anti-SRBC serum antibodies at a mean antibody titer of 1:32. Also recorded were decreases in PO/AH MUA on days 3 and 8 after the sensitization (8.2 +/- 2.4 Hz, p less than 0.005); 7.1 +/- 3.3 Hz, p less than 0.005, respectively). Basal PVN MUA was recorded as 14.7 +/- 2.4 Hz. It decreased significantly for the first three days after immunization, and then returned to a basal rate before increasing to 25.9 +/- 8.4 Hz (p less than 0.005) on day 6. On the ninth and tenth days after SRBC injection PO/AH and PVN MUA levels returned to those recorded before immunization.

Animals↗
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

Growth of human oligodendrocytes in vitro on extracellular matrix.

Based on the successful use of a basement membrane-like extracellular matrix (ECM) as a physiological substrate for the growth of adult rat oligodendrocytes, we have applied the system to oligodendroglia of human origin. ECM is excreted and deposited on a culture dish by endothelia cells. Glial cells isolated from fresh human brains by a Percoll density gradient were maintained on ECM for several weeks in vitro. Cells identified as oligodendrocytes by anti-galactocerebroside (GalC) could be transferred and replated on ECM-coated plates. In one case, GalC-positive cells isolated from a biopsy of an 8-year old girl were able to incorporate [3H]thymidine as revealed by autoradiography. ECM can be used successfully for the growth and in vitro maintenance of human oligodendrocytes.

Autoradiography↗
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↗
PubMed1985

Differential structural requirements for the induction of cell attachment, proliferation and differentiation by the extracellular matrix.

The subendothelial extracellular matrix (ECM) mediates the attachment of both human Ewing's sarcoma and colon carcinoma cells. Attachment and flattening of the sarcoma cells was sensitive to heat treatment but not to periodate oxidation of the ECM, whereas the colon carcinoma cells attached and flattened over heated but not periodate-treated ECM. Such differential sensitivity to heat treatment and periodate oxidation was also observed using purified fibronectin and laminin, respectively, but the inhibition of cell attachment was greater than with a similarly treated ECM. It is therefore conceivable that fibronectin and laminin specifically mediate the attachment and flattening of Ewing's sarcoma and colon carcinoma cells to the ECM, but that other constituents may support this attachment either directly or via interaction and stabilization of adhesive glycoproteins in the ECM. The ECM-mediated morphological differentiation of adult rat oligodendrocytes was sensitive to periodate oxidation to a much higher extent than to heat treatment of the ECM. In contrast, both treatments had only a small effect on the ECM-induced proliferation of vascular endothelial cells. These results indicate that different constituents of the ECM may be held responsible for its effects on different parameters of cell behavior, and that various cell types respond differently to a given modification of the ECM.

Animals↗
PubMed1985

Prevention of experimental allergic encephalomyelitis by anterior hypothalamic lesion in rats.

Bilateral electrical lesions were performed in the anterior hypothalamus (AH) and hippocampus (HC) of female Lewis rats. AH but not HC lesions were found to inhibit the appearance of clinical signs typical of experimental allergic encephalomyelitis (EAE). The incidence of EAE was 17.2% and the duration was 1.33 +/- 0.07 days after AH lesions compared with an incidence of 85% and duration of 4.81 +/- 0.6 days in the controls. Destruction of the AH was followed by decreased levels of antibodies to myelin basic protein and increased reactivity of splenic lymphocytes to concanavalin A, but did not affect the extent of mononuclear cell infiltration within the brain and spinal cord.

Animals↗
PubMed1984

Adult rat oligodendrocytes grown in vitro upon an extracellular matrix have the ability to proliferate.

The use of extracellular matrix (ECM) as a natural substrate for cell culture has markedly improved the growth and morphological differentiation of isolated adult rat oligodendrocytes. ECM-grown oligodendrocytes exhibited cyclic nucleotide phosphodiesterase (CNP)-activity which increased with time in culture and network formation. As much as 50-70% of the cells incorporated [3H]thymidine as visualized by the high labeling index of galactocerebroside (GalC)-positive cells. Chemical and enzymatic modifications of the ECM suggested that laminin in conjunction with other ECM constituents, plays a role in the induction of proliferation and/or differentiation responses in mature oligodendrocytes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1984

Binding of hormonal steroids to isolated oligodendroglia and astroglia grown in vitro on a naturally produced extracellular matrix.

The ability of glial cells, grown on extracellular matrix (ECM), to bind corticosterone (CS), dexamethasone (Dex), and testosterone (T) was investigated. Isolated oligodendrocytes were able to specifically bind CS as well as T. Bound [3H]CS was partially displaced by excess T, whereas no displacement of [3H]T was observed with excess CS. Oligodendrocytes were not able to bind [3H]Dex. Astrocytes derived from hippocampal or hypothalamic slices showed no binding of either [3H]CS or [3H]Dex. The results demonstrate that ECM-grown oligodendrocytes possess receptors for CS and T but not for Dex. Furthermore, the binding sites for CS were less specific than the comparable sites for T. These results substantiate the notion that oligodendrocytes are involved in the action of steroid hormones within the brain.

Animals↗
PubMed1983

Enhanced growth and morphological differentiation of isolated adult rat oligodendrocytes in vitro: use of a naturally produced extracellular matrix.

Attachment, growth and morphological differentiation of isolated adult rat oligodendrocytes cultured on a naturally produced basement membrane-like extracellular matrix (ECM) occurred much faster than on poly-L-lysine (PLL) coated tissue culture dishes. In each individual trial the cells cultured on ECM exhibited, within 3-5 days in culture, a massive outgrowth of long and branched cytoplasmic processes. Outgrowth to such an extent, using PLL or plastic tissue culture dishes, was not observed even after 2 weeks in culture. The successful high plating efficiency, rapid growth and network formation as well as its resemblance to the in vivo environment of cells make this naturally produced substrate a superior substitute for PLL and therefore more attractive for studying the behavior and function of oligodendrocytes in vitro.

Animals↗
PubMed1983

Role of macrophage-myelin basic protein interaction in the induction of experimental allergic encephalomyelitis in Lewis rats.

Stimulated peritoneal exudate cells (PEC) containing activated macrophages (M phi) of Lewis (Le) rats were exposed for 1 hr in vivo or in vitro to radioiodinated soluble myelin basic protein (MBP) or MBP incorporated into magnetic microspheres (MBP-microspheres). The uptake by M phi of the dose of microsphere-bound MBP averaged 6.2%, whereas the average uptake of soluble MBP was 0.17%. Naive rats were sensitized with M phi-associated MBP or M phi-associated MBP-microspheres via the hind footpads without the aid of conventional immunologic adjuvants. Draining lymph node cells (LNC) or spleen cells from sensitized rats were cultured for 3 days with guinea pig MBP (GPMBP) alone or in combination with concanavalin A (Con A), then injected i.v. into naive recipients. Clinical signs of experimental allergic encephalomyelitis (EAE) appeared 6 days after transfer of LNC or spleen cells, and typical CNS lesions were seen in recipients sacrificed 10 to 14 days after transfer. The challenge of MO-MBP-sensitized rats with MBP-CFA resulted in severe clinical signs of EAE marked by an accelerated onset of neurologic symptoms.

Animals↗
PubMed1983

Magnetic microspheres as drug carriers: factors influencing localization at different anatomical sites in rats.

Factors of practical expediency influencing magnetic fixation of circulating microspheres, known to be capable of carrying therapeutically effective drugs, were studied in three different anatomic sites in rats: the tail, the hind leg, and the head (including both soft tissues and brain). Specific localization of magnetic microspheres was achieved at these three sites, but only with varying degrees of success. Specific targeting of the microspheres within brain tissue could not be accomplished. Factors influencing and tending to restrict specific retention of circulating microspheres by an external magnetic force include: complex vasculature networks, subsurface depth, and tissue-vascular barriers. Even with magnets producing high magnetic field gradients, effective localization of microspheres would appear to be restricted to tissues relatively close to body surfaces.

Animals↗