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Biomedical subjects

O Abramsky

Publications and source records attributed to O Abramsky.

At least 145 records · Page 8Linked to original sources

Acute and chronic demyelinating inflammatory polyradiculoneuropathy. Association with autoimmune diseases and lymphocyte response to human neuritogenic protein.

Of 66 patients (31 female and 35 male) with demyelinating inflammatory polyradiculoneuropathy (DIP), 12% (8/66) had a chronic relapsing and/or progressive course (CR-DIP) and 88% (58/66) had an acute monophasic illness (acute Guillain-Barré syndrome or GBS). Ten (15%) of the 66 had one or more associated putative autoimmune diseases; of these ten, five had CR-DIP and five had GBS. Cell-mediated immune responsiveness (CMI) of 30 cases with DIP was tested in vitro by lymphocyte transformation. Peripheral nervous system neuritogenic protein (NP) and central nervous system encephalitogenic myelin basic protein were the challenge antigens. Eighteen (60%) of the 30 patients had CMI to NP of human peripheral nervous system origin when a stimulation index (SI) of 2 or more was evaluated as positive; eight 27% (1) had CMI to NP when a positive SI was 3 or more. Of the 44 control patients with other neuropathies, only two (4.6%) demonstrated CMI to NP (SI, greater than or equal to 2). The in vitro response of patients with DIP to myelin basic protein (7/30) was not significantly different from that of the control population (16/44). The high incidence of DIP associated with autoimmune diseases and the CMI to NP in this group suggest that DIP may be an autoimmune disease with NP as one possible major antigen.

Acute Disease↗

Appearance of Guillain-Barré syndrome in patients during corticosteroid treatment.

Three patients developed acute Guillain-Barré syndrome while on steroid treatment. The first patient suffered from ulcerative colitis and developed Guillain-Barré syndrome when the steroid dosage was being tapered. Another patient with long-standing multiple sclerosis received steroids during relapse and the Guillain-Barré syndrome appeared while treatment was reduced. The third patient, with aqueductal stenosis and ventriculoatrial shunt, who received steroids when malfunction of the shunt was suspected, developed Guillain-Barré syndrome while steroids were being tapered. Based on the putative immune pathogenesis of inflammatory demyelinating polyneuropathy, the occurrence of the syndrome in these patients could have been due to a selective effect of low-dose steroids on a specific, maybe suppressor lymphocyte subpopulation.

Adrenal Cortex Hormones↗

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↗

Inhibition by alpha-fetoprotein fractions of hemagglutination reactions between A and B antigens of human red blood cells and specific antisera.

It is shown that fetal alpha-fetoprotein (AF)-rich fractions, isolated by chemical methods, can inhibit the agglutination reaction of human AB red blood cells (RBC) with specific antisera. Hemagglutination was not inhibited by other amniotic fluid or umbilical cord serum proteins in equivalent concentrations or by other pregnancy-associated hormones. The inhibitory effect is related to the amount of antibodies and AF fractions. It seems that AF interferes with the interaction between the antibody and the cell-surface antigens by preventing the binding of the antibodies to the cells. It is suggested that the ability of AF to inhibit hemagglutination reactions in vitro may play a role during pregnancy on the immune reaction between anti-A and anti-B antibodies and the corresponding RBC antigens, as well as on the manifestations or hemolytic disease of the newborn.

ABO Blood-Group System↗

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↗

Guillain-Barré syndrome after epidural anesthesia: direct nerve root damage may trigger disease.

Guillain-Barré syndrome (GBS) appeared in four patients 1 to 2 weeks after epidural anesthesia. In all patients, clinical diagnosis was confirmed by CSF findings and nerve conduction velocity studies. Although epidural anesthesia has not been listed as an antecedent event in GBS, evidence for the relationship has been previously reported. Interaction between the anesthetic agents and peripheral nervous system myelin or local trauma to roots may initiate a cascade of immunologic events that result in the demyelinating neuropathy.

Adult↗

Treatment of experimental allergic encephalomyelitis in rabbits with alpha-fetoprotein.

We studied the ability of alpha-fetoprotein (AFP) to suppress experimental allergic encephalomyelitis (EAE) in rabbits. Animals were treated with daily injections of 50 micrograms of AFP following the onset of neurological signs. Clinical status, anti-myelin basic protein (MBP) antibody titers, and histopathological changes in the CNS were determined. Treatment with AFP significantly improved the clinical scores of the affected rabbits and inhibited the binding of anti-MBP antibodies to MBP in vitro. However, there was no significant difference in the titers of anti-MBP antibody, and no amelioration of histopathological changes between treated and control animals. We conclude that AFP is effective in improving the clinical status of animals with EAE, even after the appearance of clinical signs.

Animals↗

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↗

Human alpha-fetoprotein-rich fraction inhibits galactocerebroside antibody-mediated lysis of oligodendrocytes in vitro.

Polyclonal rabbit antiserum to galactocerebroside (anti-GalC) produces titer-dependent lysis of cultured Percoll-isolated bovine and rat oligodendrocytes. In this study anti-GalC produced complement-dependent lysis of 76% of the bovine cells and 65% of the rat cells maintained for 3 to 6 days in vitro. With the concomitant addition of human umbilical cord serum fractions containing fetal alpha-fetoprotein (AFP), lysis was decreased to 31% and 39%, respectively. Control antisera (anti-complete Freund's adjuvant/albumin) showed a cytotoxicity index of 15% for bovine cells and 23% for rat cells. Neither albumin, nor normal human serum, nor any of several pregnancy-associated hormones reduced the lysis produced by anti-GalC. AFP-rich fraction reduced oligodendrocyte lysis when mixed with anti-GalC or complement, but not when first incubated with the cells. Similar findings were obtained when AFP was assayed in specific oligodendrocyte radioimmunoassays utilizing anti-GalC antibody. Our experiments indicate that AFP activity may result from its binding to anti-GalC antibody; it is possible that the Fc portion of the antibody is involved. These data provide in vitro evidence of a possible immunosuppressive role of AFP in the central nervous system.

Animals↗

Activity of multiple sclerosis during pregnancy and puerperium.

The influence of pregnancy on multiple sclerosis was studied in 338 women by determining in each trimester of pregnancy and post partum the number of relapses and the corresponding relapse rate. Eighty-five relapses occurred in association with 199 pregnancies, most (65) in the postpartum period, and a low number of relapses (2) were recorded in the last trimester of pregnancy. Comparing the average exacerbation rate of the study group with that of patients with multiple sclerosis in Israel (0.28 relapses per person per year), we found a statistically significant decrease in the third trimester (0.04) and a high increase in the first three months post partum (0.82). This pattern of remissions at the end of pregnancy and exacerbations post partum is similar to that observed in other putative autoimmune diseases.

Adult↗

Pharmacokinetics of valpromide after oral administration of a solution and a tablet to healthy volunteers.

The pharmacokinetics of valpromide, a primary amide of valproic acid, was investigated in 6 healthy, adult male volunteers, each of whom was given 900 mg as a marketed, enteric-coated tablet and a solution. Valpromide was biotransformed to valproic acid after the administration of the tablet and the solution with a bioavailability of 0.79 +/- 0.24 and 0.77 +/- 0.12, respectively, relative to a marketed tablet of valproic acid. The absorption of valpromide was not rate-limited by dissolution. As a solid, nonhygroscopic, neutral prodrug of valproic acid, valpromide may be a good alternative to valproic acid and sodium valproate.

Adult↗

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↗

Prevention of experimental autoimmune myasthenia gravis in rats by fetal alpha-fetoprotein-rich fractions.

Rats immunized with Torpedo acetylcholine receptor (AChR) developed experimental autoimmune myasthenia gravis (EAMG) manifested by an early acute phase and a late chronic phase. In the animals the acute and the chronic diseases were prevented by the administration of alpha-fetoprotein (AFP)-rich fractions obtained from human amniotic fluid and umbilical cord serum. Both the clinical and the electromyographic manifestations of EAMG was affected by AFP treatment. The anti-AChR antibody level as well as the cellular immune response to AChR were also affected by AFP. Rats immunized with Torpedo AChR and treated with AFP-rich fractions showed low levels of antibodies to rat AChR, and an inhibited proliferation response of lymphocytes to the antigen AChR. The addition of AFP in vitro to the lymphocyte culture significantly inhibited the proliferative response to AChR and to the mitogen phytohemagglutinin. AFP is present in high amounts during pregnancy, and therefore the present findings suggest that clinical remissions of myasthenia gravis during the second half of pregnancy may be attributed to the immunosuppressive effect of AFP.

Acute Disease↗

Pharmacokinetics of valproic acid obtained after administration of three oral formulations to humans.

The pharmacokinetics and bioavailability of valproic acid (VPA) were compared in six healthy volunteers after oral administration of the drug as follows: 1 g in standard tablet form, 1 g in enteric-coated tablet form, and 0.8 g in gelatin-capsule form. Following the administration of standard tablets, VPA concentrations reached a peak mean +/- SD of 105.4 +/- 9.0 micrograms/ml at 1 h and declined monoexponentially, with a terminal half-life of 14.9 +/- 2.4 h. Following the administration of the capsule, the serum concentration reached a peak of 82.1 +/- 14.8 micrograms/ml at 4 h. Following the administration of an enteric-coated tablet, there was an average time lag of 2 h with a delayed peak serum concentration of 93.5 +/- 13.1 micrograms/ml at 6 h. An identical terminal half-life of VPA was obtained for the three oral formulations. The bioavailability of the three VPA formulations was not significantly different, and it may be concluded that these formulations are bioequivalent.

Administration, Oral↗

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↗