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Biomedical subjects

T Brenner

Publications and source records attributed to T Brenner.

At least 73 records · Page 4Linked to original sources

Further studies on the stimulatory action of nicotine on adrenocortical function in the rat.

The aim of the present study was to further characterize the site of action of nicotine-induced hypothalamo-hypophyseal-adrenal (HHA) activation. A systemic injection of nicotine in concentrations of 65-2,100 micrograms/kg elevated serum corticosterone (CS) concentrations in a time and dose-dependent manner. Serum ACTH levels were also significantly increased. Pretreatment with dexamethasone (40 micrograms/kg) or the nicotinic antagonist, mecamylamine (1 mg/kg), abolished the ACTH and CS secretory responses to nicotine. Intracerebroventricular administration of antinicotinic acetylcholine receptor antibodies, prepared from the serum of myasthenia gravis patients, completely inhibited the nicotine-induced HHA activation. Bilateral lesions of the paraventricular nucleus similarly inhibited the nicotine-induced adrenocortical activity. These results suggest that nicotine activates the HHA axis by a central mechanism which ultimately requires the integrity of the paraventricular nucleus. Moreover, these findings indicate that the nicotinic adrenocortical effect is mediated specifically through activation of central nicotinic cholinergic receptors.

Adrenal Cortex↗

Proliferative response of blood cells of patients with myasthenia gravis to purified mammalian acetylcholine receptor.

We employed a purified mammalian (fetal calf) acetylcholine receptor (AChR) preparation to compare proliferation of peripheral blood mononuclear cells (PBMC) of patients with myasthenia gravis (MG) (n = 8) and normal controls (n = 6). PBMC of patients with MG demonstrated an enhanced proliferative response to AChR when compared to controls (mean stimulation index (SI) of 4.2 +/- 1.5 (SD) vs. 1.1 +/- 0.6; p less than 0.01) but no difference in the response to tetanus toxoid (7.1 +/- 3.9 vs. 11.1 +/- 10.8). These results suggest that MG patients exhibit a presumptive T-cell response to purified mammalian AChR that is not found in normal subjects. The nature of the proliferating cell and the interaction with B cells producing anti-AChR antibodies remain to be determined.

Cell Division↗

Fulminant subacute sclerosing panencephalitis in association with pregnancy.

Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.

Adolescent↗

Differential adrenocortical responses to neural stimuli following intracerebroventricular injection of nicotinic acetylcholine receptor antibodies in rats.

The aim of the present study was to investigate the involvement of central nervous system nicotinic receptors for acetylcholine in the adrenocortical responses to neural stimuli. Adult male rats received a daily intraventricular injection of partially purified nicotinic acetylcholine receptor antibodies (anti-AchR), obtained from a patient with myasthenia gravis, for 5 consecutive days. Control animals were treated similarly with immunoglobulins obtained from normal human serum. Blood samples were obtained under basal conditions or following photic, sciatic nerve stimulation, and acoustic stress. Treatment with anti-AchR increased basal ACTH and corticosterone levels (by approximately twofold) but inhibited the response to acoustic stress. The response to photic and sciatic nerve stimulation stress was not affected. This study demonstrated that nicotinic acetylcholine receptors may be differentially involved in the mediation of adrenocortical responses to neural stimuli.

Acoustic Stimulation↗

Late neuropsychologic status after childhood head trauma.

A neurologic and neuropsychologic test battery was administered to a sample of 35 children drawn from all those in a defined geographic area who had been hospitalized for head trauma before age 7 during the years 1970-1976. Examination was performed 3 1/2 to 10 years after injury, at age 6-15. Twelve subjects had been diagnosed at the time of injury as suffering moderate insult and had been referred to the metropolitan neurosurgical center, while twenty-three with only mild injury had been retained for observation in a local pediatric ward. The twelve with more severe insult were significantly inferior to the other subjects on the Block Design and Coding subtests of the revised Wechsler Intelligence Scale for Children. The Koppitz score of the Bender Test, the WISC-R scatter, the Benton Visual Retention Test, the GATB Motor Speed Test and the Bourdon-Wiersma Vigilance Test showed less diagnostic power and failed to distinguish between the group with more severe injury and that with less. A detailed and carefully scored neurologic examination also failed to distinguish between the two groups. The findings suggest that relatively common traumatic injury may be associated with detectable late cognitive deficit, and that some WISC-R subtests may be among the best measures for detecting such deficit.

Brain Injuries↗

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↗

Ampicillin may aggravate clinical and experimental myasthenia gravis.

Ampicillin trihydrate aggravated the symptoms of two myasthenic patients. One patient had severe temporary weakness after an ampicillin sodium challenge. Ampicillin increased the preexisting electrical decrement in three rabbits with experimental autoimmune myasthenia gravis while the drug had no deleterious effects in less affected or normal animals. Myasthenic patients receiving ampicillin should be closely monitored for possible acute exacerbations.

Ampicillin↗

Evidence that central nicotinic-acetylcholine receptors are involved in the modulation of basal and stress-induced adrenocortical responses.

We investigated the involvement of central nervous system nicotinic-acetylcholine receptors in the secretory activity of the hypothalamic-hypophyseal-adrenal axis. Antiacetylcholine receptor antibodies derived from rabbits immunized with purified Torpedo-acetylcholine receptor or from myasthenia gravis patients were injected intracerebroventricularly into adult male rats for 5 consecutive days. Treatment with both preparations caused increased basal corticosterone concentrations, inhibition of the corticosterone response to ether stress, and neurological signs and motor dysfunctions. The adrenocortical response in experimental autoimmune myasthenia gravis Lewis rats with high circulating antiacetylcholine receptor antibodies was also tested. These rats exhibited a marked increase in basal corticosterone concentrations and a normal response to ether stress. The results showed that antinicotinic-acetylcholine receptor antibodies, either circulating or intraventricularly administered, can modulate both basal and stress-induced adrenocortical secretion.

Adrenal Cortex↗

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↗

A monoclonal antibody raised to corpus callosum extract reacts with 2',3'-cyclic nucleotide 3'-phosphohydrolase.

Monoclonal antibody against 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was generated by fusing mouse myeloma cells with spleen cells from BALB/c mice immunized with delipidated white matter from rat corpus callosum. The antibody was characterized by solid-phase radioimmunoassay, immunoblot of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoprecipitation from C6 glioma cells, and indirect immunofluorescence staining of monolayer cultures containing oligodendrocytes. The monoclonal antibody bound specifically to an intracellular antigen of oligodendrocytes, but not to Schwann cells, astrocytes, neurons, or fibroblast cytoplasm. The immunoblot of SDS-PAGE of CNS myelin showed that the antibody identified two protein bands at 48,000 and 50,000 molecular weight. These proteins were not identified in peripheral nervous system myelin. The monoclonal antibody immunoprecipitated CNP enzyme activity from extracts of C6 glioma cells. This monoclonal antibody should prove useful in further study of this myelin-specific enzyme in CNS myelin and in cells responsible for myelin production.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Astrocytes, oligodendrocytes, and Schwann cells share a common antigenic determinant that cross-reacts with myelin basic protein: identification with monoclonal antibody.

We have produced a monoclonal antibody against myelin basic protein that reacts with astrocytes, oligodendrocytes, and Schwann cells. This antibody was generated by fusion of mouse myeloma cells with spleen cells from BALB/c mice immunized with delipidated white matter from adult rat corpus callosum. The antibody was characterized via solid-phase radioimmunoassay, immunoblot of SDS-PAGE, and by indirect immunofluorescence staining of monolayer cultures containing oligodendrocytes, astrocytes, and Schwann cells. Myelin basic protein (MBP) was shown previously to be present only in myelin producing cells in CNS and PNS (oligodendroglia and Schwann cells) and not in astrocytes. The binding of this monoclonal antibody to all 3 cell types suggests that these cells share a common epitope. This epitope may be related to a common progenitor cell.

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↗

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↗

Survivors of severe traumatic brain injury in childhood. II. Late residual disability.

36 survivors of very severe traumatic childhood brain injury have been followed for a median period of 48 months after injury. One remains in a vegetative state and 35 have been discharged. 34 regained ambulation, and motor function became essentially normal in 14 of them. Ataxia and movement disorders were as common among the residua as was spasticity. Only one child remained aphasic, but 14 showed dysarthria. Six of the 36 showed major dementia and most of the rest showed very significant new impairment of cognitive and social function. This impairment was greater than expected from changes in the I.Q. Motor and speech function showed prolonged recovery while learning ability and social function did not. The overall degree of recovery seems not much better in these children than in adults.

Adolescent↗