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Biomedical subjects

R N Adams

Publications and source records attributed to R N Adams.

At least 73 records · Page 4Linked to original sources
PubMed1982

Treatment of ongoing experimental myasthenia gravis with short term high dose cyclophosphamide.

We have treated animals with an ongoing autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), using a strategy designed to eliminate the antibody-producing cells. During well-established EAMG, a single high dose of cyclophosphamide was given because of its known effectiveness against B-lymphocytes. To counteract the lethal effects of the drug, the rats were "rescued" by bone marrow cell transplantation. This treatment produced a rapid and sustained fall of antibody titers against both the immunizing antigen (Torpedo acetylcholine receptor) and the autoantigen (rat acetylcholine receptor). Immunologic memory, as measured by an anamnestic response to the antigen, was partially suppressed. Cyclophosphamide treatment produced improvement in the neuromuscular defect: treated animals had, on the average, twice as many acetylcholine receptors at neuromuscular junctions compared with untreated EAMG animals. This treatment method of short-term high doses of an immunosuppressive drug, such as cyclophosphamide, may eventually prove useful for human myasthenia gravis and other autoimmune diseases.

Animals↗
PubMed1981

Regional distribution of ascorbate in human brain.

A comprehensive mapping of ascorbate distribution in human brain was carried out by liquid chromatography analysis. The data agree with earlier literature values where comparable and provide new information on several brain regions, including a detailed distribution in the thalamus. While ascorbate concentrations tend to be high in regions rich in catecholamines, there is no real correlation between the two.

Amygdala↗
PubMed1981

In vitro and in vivo depolarization coupled efflux of ascorbic acid in rat brain preparations.

The depolarization-coupled efflux of endogenous ascorbate is demonstrated using rat synaptosome preparations and a rat cortical cup method. Ascorbate and catecholamines (monitored as a methodological control) were quantitated by high pressure liquid chromatography with electrochemical detection. In vitro potassium ion induces ascorbate efflux in a concentration-dependent, although calcium ion-dependent, manner. Veratridine also induces ascorbate efflux and its effect can be blocked by tetrodotoxin. In vivo, ascorbate efflux was likewise stimulated by increased potassium ion and by veratridine. In addition, electrical stimulation of medial lemniscus was accompanied by an increased efflux of ascorbate from somatosensory cortex. These results are intriguing in light of the recent evidence for the interaction of ascorbate with several neurotransmitter systems.

Animals↗
PubMed1980

Lymphocyte responsiveness to acetylcholine receptor in rats with experimental autoimmune myasthenia gravis.

We examined the time course of lymphocyte responsiveness to acetylcholine receptor (AChR) in rats with experimental autoimmune myasthenia gravis (EAMG). Rats were immunized with purified torpedo AChR. At intervals of one to eight weeks later, lymphocytes from the lymph nodes and spleen were cultured with purified torpedo AChR and rat muscle extract containing AChR. Lymphocyte responsiveness (stimulation index) was determined from uptake of 3H-labeled thymidine by the cultured cells. The response of lymphocytes to torpedo antigen began earlier and rose more rapidly than that to the homologous (rat) antigen. Lymph node cells responded more promptly than spleen lymphocytes. The stimulation indexes peaked at four to six weeks while antibodies to both antigen continued to rise. Delineation of this pattern of lymphocyte responsiveness sheds further light on the pathogenesis of the autoimmune response in EAMG and will be useful in the future design of immunotherapeutic strategies.

Acetylcholine↗
PubMed1980

Mechanisms of acetylcholine receptor loss in myasthenia gravis.

The fundamental abnormality affecting the neuromuscular junctions of myasthenic patients is a reduction of available AChRs, due to an autoimmune attack directed against the receptors. Antibodies to AChR are present in most patients, and there is evidence that they have a predominant pathogenic role in the disease, aided by complement. The mechanism of antibody action involves acceleration of the rate of degradation of AChRs, attributable to cross-linking of the receptors. In addition, antibodies may block AChRs, and may participate in producing destructive changes, perhaps in conjunction with complement. The possibility that cell-mediated mechanisms may play a role in the autoimmune responses of some myasthenic patients remains to be explored. Although the target of the autoimmune attack in myasthenic patients is probably always the acetylcholine receptors, it is not yet clear which of these immune mechanisms are most important. It is likely that the relative role of each mechanism varies from patient to patient. One of the goals of future research will be to identify the relative importance of each of these mechanisms in the individual patient, and to tailor specific immunotherapeutic measures to the abnormalities found.

Acetylcholine↗
PubMed1979

Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry.

The possibility of using in vivo voltammetry to monitor 5-hydroxytryptamine (5-HT) release from brain tissue in freely moving unanaesthetized rats has been examined. A potential (+0.2 to +1.0 V) was applied to a micrographite electrode stereotaxically placed within a specific brain region and current changes following the oxidation of electroactive compounds in the vicinity of the electrode tip were recorded. Administration of p-chloroamphetamine (5 mg/kg) produced a large increase in current in the striatum and this could be prevented by pretreatment with p-chlorophenylalanine (150 mg/kg X 2) to deplete brain 5-HT or Fluoxetine (10 mg/kg) which prevents the uptake of p-chloroamphetamine by 5-HT neurones. Fluoxetine (10 mg/kg) caused a small but long lasting increase in current. Stimulation of the median raphe nucleus produced a marked and rapid rise in current in the hippocampus but a much smaller one in the striatum. This response could also be prevented by 24 h pretreatment with p-chlorophenylalanine (150 mg/kg). Seven days after p-chlorophenylalanine administration raphe stimulation again produced an increase in current. Rats under barbiturate anaesthesia showed no clear increase in current either after p-chloroamphetamine or raphe stimulation, indicating that barbiturates may affect neurotransmitter release. The results suggest that 5-HT release can be monitored in the freely moving unanaesthetized rat using in vivo voltammetry, and that a moderate decrease in brain 5-HT concentration leads to a substantial inhibition of drug or stimulation induced release of 5-HT.

Animals↗
PubMed1978

In vivo voltammetry: monitoring of dopamine metabolites in CSF following release by electrical stimulation.

An in vivo electrochemical system which continuously records the concentration of metabolites of biogenic amines in small animal CSF is described. A small electrode, immersed in lateral ventricle CSF through a guide cannula, measures the amine metabolites by voltammetric oxidation. The detailed results of HVA release following electrical stimulation of the nigrostriatal pathway in rats are presented and compared with previous perfusion data. All the electrochemical results are verified by independent liquid chromatographic (chemical) analysis.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Lateralization of norepinephrine in human thalamus.

Norepinephrine has a strongly lateralized distribution in the human thalamus. In the pulvinar region the left hemisphere is rich in norepinephrine, whereas in the somatosensory input area the right hemisphere has a higher concentration of this catecholamine. Such naturally occurring left-right differences in concentration of a neurotransmitter represent a new aspect of hemispheric specialization.

Dopamine↗
PubMed1978

Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation.

The decrease of acetylcholine receptors at neuromuscular junctions of myasthenic patients has been attributed to an antibody-mediated autoimmune process that accelerates receptor degradation. We studied the mechanism of this process in skeletal-muscle cultures, using intact antibodies and antibody fragments. Addition of myasthenic IgG or its divalent fragment, F(ab')2, to cultures accelerated the rate of acetylcholine-receptor degradation threefold. By contrast, the monovalent fragment, Fab, from myasthenic serum had no effect on degradation, although it bound to acetylcholine receptors. Addition of a second, "piggyback" antibody to cross-link the Fab:receptor complexes resulted in a threefold increase of the degradation rate. Similarly, when acetylcholine receptors with bound alpha-bungarotoxin were cross-linked by the addition of specific antibody against alpha-bungarotoxin, the degradation rate increased approximately threefold. The effect of myasthenic patients' antibodies in accelerating degradation of acetylcholine receptors is attributed to their ability to cross-link the receptors.

Autoantibodies↗