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Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 307 records · Page 17Linked to original sources
PubMed1981

Circadian rhythms in serum and CSF cortisol of rhesus monkeys, and their modulation by timed injections of L-5-hydroxytryptophan.

Levels of in serum and cerebrospinal fluid have been studied in male and female rhesus monkeys. Untreated animals showed circadian rhythms of cortisol in both compartments, highest values occurring at 08.00 h and lowest at 20.00 h, but the decline following the morning peak was slower in cerebrospinal fluid (CSF) than in serum. Both levels and CSF/serum ratios (c. 0.017-0.027) were similar in males and females. The ratio between highest and lowest points on the circadian rhythm was greater for CSF (males: 2.50; females: 2.63) than for serum (1.69 and 1.78). There were significant correlations between CSF and serum levels in individual monkeys at each of the four time points studied. No circadian rhythm in CSF homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5-HIAA) was found, nor any correlation between these monoamine metabolites and cortisol levels. Injecting cortisol once daily in the evening (18.00h) resulted in greater proportional elevation in the CSF than in serum cortisol in samples taken two hours later, and the values in the two compartments were no longer correlated at this time. There was no effect on CSF 5-HIAA levels, Injecting L-5-hydroxytryptophan (L-5-HTP) (2.5 mg/kg) at four different time points produced abnormal daily patterns of cortisol secretion, the peak following the injection of L-5-HTP. The distortion of the normal circadian rhythm thus induced was greater in the CSF than in he serum, and CSF/serum ratios were increased one hour following L-5-HTP administration. The data suggested, but did not prove, that L-5-HTP injection may have produced the least Proportional elevation of cortisol at 08.00 h (at the time of normal daily maxima). 5-HIAA, but not HVA, was elevated one hour after L-5-HTP to 2-3 ties normal . A dose of 0.2 mg dexamethasone at 23.00 h suppressed cortisol levels in serum examined at 08.00 h the next day. This suppression was partially reversed by giving L-5-HTP one hour before taking the next morning's sample. Rhythmic and episodic changes in serum cortisol thus have a proportionally greater effect on the daily pattern of cortisol level in the CSF (and hence the cerebral compartment) than that in the vascular compartment, and thus the exposure of cortisol-sensitive tissues in the two compartments to cortisol may differ.

5-Hydroxytryptophan↗
PubMed1981

Postmortem changes of amino compounds in human and rat brain.

Contents of 35 amino acids and related compounds were measured in whole rat brain, and in superficial areas of biopsied and autopsied human brain, after incubation for various intervals at temperatures simulating those likely to occur in cadavers under mortuary conditions. These data should aid interpretation of values for amino compounds determined in autopsied brain from patients with neurological or psychiatric disorders. The contents of glutamic acid, glutamine, taurine, phosphoethanolamine, cystathionine, and homocarnosine remain unchanged for long periods in human brain. Aspartic acid content is stable for 4 h after death, but thereafter rises rapidly. Glycine content rises rapidly, as do the contents of most amino acid components of proteins. Glutathione content drops rapidly in human brain after death. GABA content is stable for about 30 min, and rises to a maximum 2 to 3 h after death, after which it remains unchanged for at least 24 h. In rat brain, GABA content rises more rapidly, aspartate content rises more slowly, homocarnosine content decreases progressively, and glycerophosphoethanolamine content decreases more rapidly than in human brain.

Amines↗
PubMed1981

Elevation of brain GABA content by chronic low-dosage administration of hydrazine, a metabolite of isoniazid.

When gamma-aminobutyric acid aminotransferase (GABA-T) activity was measured in vitro in rat brain, neither isoniazid (INH) nor for of its known metabolites (isonicotinic acid, acetylisoniazid, acetylhydrazine, diacetylhydrazine) inhibited the enzyme in concentrations (5 mM) far higher than those likely to be achieved when INH is administered to man. In contrast, hydrazine (5 micrometers) caused a 50% inhibition of GABA-T without inhibiting glutamic acid decarboxylase (GAD). Rats were injected daily for 109 days with hydrazine (0.08 or 0.16 mmol/kg/day), after which amino acid contents and enzyme activities were measured in their brains. Both hydrazine doses caused significant elevations of whole brain GABA content and reductions of GABA-T activity, but did not affect GAD activity. Chronic administration of hydrazine at these doses did not reduce weight gain or alter rat behavior, nor did it produce any irreversible pathologic changes in liver or alterations in hepatic aryl hydrocarbon hydroxylase activity. However, hydrazine treatment caused changes in the contents of many brain amino acids besides GABA, and markedly increased concentrations of ornithine, tyrosine, and alpha-aminoadipic acid in rat plasma. Inhibition of GABA-T activity and the other biochemical alterations observed in patients given high doses of INH probably result from hydrazine formed in the metabolic degradation of INH. Thus administration of hydrazine might be a more direct means of elevating brain GABA content in patients where this seems indicated, and might not entail a greater risk of adverse effects.

4-Aminobutyrate Transaminase↗
PubMed1981

Neurotransmitter amino acids in dominantly inherited cerebellar disorders.

We measured amino acid contents in the brains of 11 patients with dominantly inherited cerebellar disorders. Despite clinical similarities, three biochemically different disorders were found. One disorder, with demonstrated HLA linkage in one pedigree, was characterized by moderate reduction of aspartate and glutamate contents in cerebellar cortex alone. In a second disorder, aspartate and glutamate contents were reduced markedly in other brain areas as well as in cerebellar cortex. Aspartate and glutamate contents were normal in cerebellar cortex in the third disorder. GABA content in cerebellar cortex and dentate nucleus was reduced in some patients with each disorder, whereas cerebellar taurine content was normal in all patients. Aspartate deficiency in cerebellar cortex did not result from lack of aspartate aminotransferase or pyruvate carboxylase activity. These amino acid abnormalities probably imply loss of specific cerebellar neurons.

Amino Acids↗
PubMed1981

Amino acid abnormalities in epileptogenic foci.

We compared amino acid contents of 54 epileptogenic foci removed neurosurgically from temporal or frontal cortex of 35 patients with focal epilepsy with those of biopsies from the same cortical regions of 14 nonepileptic patients. Neither taurine nor GABA content was reduced in epileptogenic foci. Glycine content was elevated markedly in some foci, whereas aspartic acid content was normal. Mean glutamic acid content was significantly higher in epileptogenic foci than in control cortex, and six foci contained amounts of glutamate more than 2 SD above the control mean. Our findings do not support hypotheses that deficiencies of taurine or GABA are involved in the pathogenesis of focal epilepsy but do suggest a possible etiologic role for the excitatory neurotransmitter, glutamic acid.

Adolescent↗
PubMed1981

Suprachiasmatic lesions disrupt the daily rhythmicity in the sexual behaviour of normal male rats and of male rats treated neonatally with antioestrogen.

Male rats were treated daily with oil or 100 micrograms of the antioestrogen, ethamoxytriphetol (MER-25), for the first 10 days of life and, when adult, lesions were made in the suprachiasmatic nuclei (SCN) of the hypothalamus or control lesions were made above the SCN and the rats were tested for sexual behaviour. Treatment with MER-25 enhanced the daily rhythmicity in both mounting and lordosis behaviour and SCN lesions disrupted these behavioural rhythms and the rhythm in the mounting behaviour of oil-treated rats. Rats treated with MER-25 and with SCN lesions showed high levels of mounting and lordosis behaviour throughout the light : darkness cycle. These results support the hypothesis that sexual differentiation by perinatal androgen stimulation uncouples the central rhythm generator from the neural substrates of sexual behaviour in rats.

Animals↗
PubMed1981

Induction of sexual receptivity in ovariectomized rats by pulse administration of oestradiol-17 beta.

Constant-release implants filled with oestradiol-17 beta induced sexual receptivity in ovariectomized rats in response to progesterone treatment if they were implanted 32 h before behavioural testing. A 20 h period of exposure to oestradiol, by implantation 32 h before testing and removal of the implants 20 h later, was sufficient for induction of the behaviour. The exposure time necessary for behavioural responses could be further reduced to two 4 h periods, between 32 and 28 h and between 16 and 12 h, before testing. Serum levels of oestradiol were raised within 1 h of oestradiol implantation and declined rapidly after implant removal. A single injection of oestradiol benzoate was much more potent than a single injection of oestradiol in inducing sexual receptivity in ovariectomized rats, but this difference in potency was reversed if two appropriately timed injections were given. Oestrone- or oestriol-filled implants were relatively ineffective in inducing sexual receptivity. It is suggested that oestradiol has to be present at crucial time points to prepare an ovariectomized rat to respond behaviourally to progesterone treatment and that oestradiol is the principal oestrogen in the stimulation of sexual behaviour in female rats.

Animals↗
PubMed1981

[Psychic development of children under conditions of longterm isolation (author's transl)].

Three children with severe combined immunodeficiency have been isolated for 19-22 months. Two of the children have been placed into the isolation system directly after delivery; on child entered the isolation system at the age of 5 months. The influence of this situation on the psychic development of the children was studied by the means of direct observation as well as by psychometric test methods. An additional child which has been isolated between the age of 6 and 32 months was retested at the age of 4 and 6 years. The reported observation which include those of the parents and the team allow the conclusion, that a normal development is possible under these extreme conditions, when an optimal clinical and psychological support is maintained.

Child Development↗
PubMed1980

Motor unit potential abnormalities in multiple sclerosis: further evidence for a peripheral nervous system defect.

We have recently reported abnormalities of single fibre EMG in patients with multiple sclerosis. The present study applies quantitative electrophysiological techniques to the same group of patients. The number of motor units in the extensor digitorum brevis muscle was measured and their characteristics recorded. Also the shortest distal motor latency and fastest motor conduction velocities were estimated. Abnormalities suggesting a patchy denervating/reinnervating process due to pathology in the intramuscular nerve network or at the endplate were found in a number of patients. There was a good correlation between patients with abnormal motor unit potentials and those with abnormal single fibre EMG "jitter".

Electromyography↗
PubMed1980

Quantitative electrophysiological study of alcoholic neuropathy.

Thirty-one chronic alcoholic patients were investigated using quantitative electrophysiological techniques. Estimates of the numbers of functioning motor units in the extensor digitorum brevis muscles and measurements of the parameters of the potentials of these units are presented along with the values for motor nerve conduction velocities in the innervating lateral popliteal nerves. Motor conduction velocities and sensory nerve action potential amplitudes were also measured in the ulnar nerves. The results and their inter-relationships lead us to conclude that the slowing of motor nerve conduction and reduction in sensory nerve action potential amplitudes in alcoholic neuropathy are a consequence of axon loss. We found no evidence of pathological slowing of conduction in surviving axons. Reinnervation by functioning motor axons is poor compared to a number of other neuropathic conditions. In our patients there was no evidence of preferential involvement of sensory axons. The results support a predominant axonal dysfunction in alcoholic neuropathy.

Action Potentials↗
PubMed1980

Failure of aminooxyacetic acid therapy in Huntington disease.

Seven patients with Huntington disease were treated with aminooxyacetic acid (AOAA), an inhibitor of gamma-aminobutyric acid aminotransferase (GABA-T), in an effort to alleviate symptoms by increasing brain GABA content. AOAA was given orally in a placebo-controlled crossover trial in which patients, relatives, and three of the evaluating physicians remained blind. Toxic symptoms occurred in all seven patients when AOAA dosage was increased beyond 2 mg per kilogram per day, and included drowsiness, ataxia, seizures, and psychotic behavior. In five patients who took AOAA for 4 months, no clinical improvement was observed. Biochemical monitoring showed that less inhibition of hepatic GABA-T enzyme activity was achieved than in patients treated with large doses of isoniazid. Results of this trial neither support nor exclude the possible therapeutic usefulness of increasing brain GABA content in Huntington disease.

Acetates↗
PubMed1980

Virus adaptation to host cells: the non-classical modification of phage T3.

Bacterial virus T3 undergoes host-controlled modification which is not based on "classical" processes of DNA modification and restriction. The adsorption and thus the growth of T3 on Escherichia coli W cells (E. coli K12 derivative) decisively depends on the host strain on which the virus was previously propagated. Depending on the modification conferred to the virus by its last host, its efficiency of plating (e.o.p.) on E. coli W varies by six orders of magnitude between 10(-7) and 10(-1). This does not reflect the appearance of T3 host-range mutants, but a fully reversible modification of genotypically unchanged T3 wild-type phage. The behaviour of T3 in the described host system constitutes a second case of so-called non-classical modification and restriction (KRUGER et al. 1977, Molec. gen. Genet. 153, 107-110) of bacteriophages. Non-classical modification (protein modification) is additive to and independent of DNA modification and restriction as demonstrated with the ocr- phage T3/R7. - Furthermore, our results suggest that the adsorption specificity of T3 is determined by at least two independent genetic factors; in both of these factors T3 differs from T7.

Adaptation, Physiological↗