PubMed Health⌕ Search

Biomedical subjects

T Brenner

Publications and source records attributed to T Brenner.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Effect of intracerebroventricular injection of nicotinic acetylcholine receptor antibodies on ACTH, corticosterone and prolactin secretion in the male rat.

The aim of the present study was to investigate the involvement of CNS nicotinic receptors for acetylcholine in the secretory activity of the hypothalamo-hypophyseal-adrenal axis and prolactin (PRL). Adult male rats received a daily intraventricular injection of partially purified nicotinic acetylcholine receptor antibodies (anti-AChR) obtained from a female patient with myasthenia gravis, for 5 consecutive days. Control animals were treated similarly with immunoglobulins obtained from a healthy woman. Blood samples were withdrawn either under basal conditions or following ether stress. Treatment with anti-AChR increased basal ACTH and corticosterone (CS) levels (by approximately two-fold) but completely inhibited the responses of these hormones and PRL to ether stress. In control animals, normal basal and stress-induced responses of ACTH, CS and PRL were observed. This study demonstrated the importance for nicotinic acetylcholine receptors in the mediation of basal and stress-induced adrenocortical activity as well as for the mediation of PRL secretion in response to stress.

Adrenocorticotropic Hormone↗

Alpha-fetoprotein suppresses experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE), induced in guinea pigs by immunization with myelin basic protein (MBP) or whole CNS homogenate was successfully treated, as well as partially prevented, by daily administration of fetal alpha-fetoprotein (alpha FP). alpha FP which is produced in high quantities during pregnancy can inhibit both the cell-mediated immune response to MBP and the binding of MBP antibody to the antigen in vitro. It has a non-specific immunosuppressive effect on both the cellular and humoral responses. It is suggested that the ability of alpha FP to suppress an experimental autoimmune disease, as presented in this model of EAE, indicates that clinical remissions of human autoimmune disease during pregnancy may be attributed to the effect of this natural substance.

Animals↗

Binding of myasthenia gravis antibodies to different acetylcholine receptor preparations.

A group of myasthenia gravis (MG) patients was studied in order to demonstrate the differential ability of acetylcholine receptor (AChR) antibodies to bind to AChRs from different sources. Four different AChR sources were used: human muscle, denervated rat muscle, normal rat muscle and the electric organ of the electric ray, Torpedo californica. We demonstrated that AchR antibodies from MG patients tested reacted best with receptors from human muscle, and least with the electric ray receptor. The patients were classified into three categories, each representing an antibody level pattern. THe most common pattern was that in which the antibody level for human AchR is highest, followed by decreasing values for AchRs of denervated rat muscle, normal rat muscle, and that of the electric organ of the electric ray. No correlation was found between the patient-specific antibody pattern and a clinical description of the MG patient.

Animals↗

Antiacetylcholine receptor antibody in neonatal myasthenia gravis.

Maternal titers to antiacetylcholine receptor antibody (anti-AChR Ab) were higher in two mothers with myasthenia gravis (MG) who had infants with neonatal MG than the nearly normal values in two mothers with MG who had unaffected infants. In one unaffected infant, another IgG antibody crossed the placenta, but an IgM antibody did not. In neonates there seems to be a correlation between the concentration of anti-AChR Ab and the presence and severity of the neonatal syndrome. The absence of fetal symptoms of MG and the delayed onset or worsening of some cases of neonatal MG may be due to high fetal levels of alpha-fetoprotein and its decline in concentration in infants after birth.

Acetylcholine↗

Influence of alpha-fetoprotein on the in vitro and in vivo immune response to acetylcholine receptor.

Alpha-fetoprotein (AFP) derived from amniotic fluid and both maternal and umbilical cord sera but not from hepatoma, blocks the binding of serum acetylcholine receptor (AChR) antibody from patients with myasthenia gravis (MG) and animals with experimental autoimmune MG (EAMG) to AChR preparations as measured by a radioimmunoassay. AFP also inhibits the AChR and mitogen induced in vitro proliferative response of lymphocytes obtained from animals with EAMG. Laboratory animals repeatedly injected with AFP fail to develop EAMG in response to sensitization with AChR. Animals with established EAMG show clinical improvement in response to AFP treatment. AChR antibodies are suppressed in such AFP-treated animals. AFP is present in increased amounts during pregnancy and thus could contribute to remissions during the second half of pregnancy in patients with MG. The rapid decrease in levels of AFP during the post-partum period may also be partly responsible for relapses seen during this period. AFP may also be responsible for the appearance of transitory neonatal MG only sometime after birth and in only a minority of cases.

Amniotic Fluid↗

Polyclonal B-cell activity in myasthenia gravis.

Using a protein A-reverse hemolytic plaque assay, we found that some patients with myasthenia gravis have increased numbers of circulating immunoglobulin secreting cells (IgSC). This pattern was not related to drug therapy, age, sex, duration of symptoms, thymectomy, or serum levels of AChR antibody, although elevated IgSC values tended to occur in patients with active symptoms. The responses of peripheral blood mononuclear cells to pokeweed mitogen were normal. These data suggest increased in vivo polyclonal B-cell activation in some myasthenic patients, although in vitro polyclonal B-cell activation is normal.

Acetylcholine↗

Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis: II. Perfused rat liver.

Livers from rats with experimental hypoproteinemia induced by aminonucleoside-nephrosis or plasmapheresis were perfused with a [14C]-labeled amino acid mixture at physiological concentration. Compared to control rats, a significantly increased incorporation of the amino acid label was found in the apolipoproteins of the ultracentrifugally separated very low and high density lipoproteins (VLDL, HDL), and into albumin secreted into the perfusate. However, no increase in the amino acid-derived lable was detected in VLDL-or HDL-borne lipids in nephrosis or plasmapheresis. Perfusion with U-[14C]leucine as a lipogenesis precursor at < 10 times higher than physiological concentration resulted in 5-fold increase in the label incorporation into perfusate proteins in nephrosis but only in a slightly significant increase in perfusate lipids. In contrast, the incorporation of a preformed fatty acid, 9,10-[3H] oleate into VLDL and HDL lipids increased 3- to 4-fold in nephrosis. Both with leucine and oleate as precursors, the increments in the label appearing in perfusate proteins or lipids, respectively, were markedly greater than the increases in hepatic tissue proteins or lipids. The results indicate that amino acids are preferentially directed by the liver into the synthesis of circulating apolipoproteins and albumin in hypoproteinemia and do not seem to constitute an important precursor of the liporpotein lipids. The increased production of apolipoproteins is associated with an increased incorporation of preformed fatty acids into lipoprotein lipids in addition to the previously reported stimulation of hepatic de novo lipid synthesis from recursors other than amino acids.

Animals↗

Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein.

Acetylcholine↗

Inosiplex in the treatment of subacute sclerosing panencephalitis.

Six patients with subacute sclerosing panencephalitis were treated with the antiviral agent inosiplex. The clinical condition of four children continued to deteriorate in spite of the treatment, the condition of one remained unchanged, and that of another improved minimally. The effect of inosiplex in these patients is not evident since this group demonstrated a pattern of progression similar to that seen in subacute sclerosing panencephalitis without specific treatment.

Adolescent↗