Biochemical effects in man and rat of three drugs which can increase brain GABA content.
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Biomedical subjects
Publications and source records attributed to S Hansen.
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The numbers of functioning motor units and the parameters of the electrically evoked motor unit potentials in the extensor digitorum brevis muscles of 30 patients on chronic haemodialysis for renal failure were obtained using recently introduced quantitative electrophysiological techniques. Measurements of the distal motor latencies and motor nerve conduction velocities in the lateral popliteal nerves of the same patients are also presented. The results support the presence of a "dying back" type of neuropathy in uraemia, with a preferential involvement of the fastest conducting motor axons. Collateral reinnervation and compensatory increase in size of surviving motor units is relatively impaired in uraemic neuropathy in comparison with a similar study on diabetic neuropathy. The significance of paranodal and segmental demyelination in producing abnormalities of conduction velocity in these neuropathies is discussed.
Thirty-two patients with motor neurone disease were investigated using quantitative electrophysiological techniques. Estimates of the number of surviving motor units in the extensor digitorum brevis muscle and measurements of the electrophysiological parameters of these units are present along with the values for motor nerve conduction velocities. The results indicate that reinnervation in motor neurone disease is sufficient to compensate completely for the loss of up to 50% of the motor neurone pool supplying the muscle. The capacity for reinnervation is greater than we have found in a number of neuropathies but the efficiency of reinnervation decreases as the number of surviving motor units falls. Reinnervation appears to cease when 5% or less of the motor units remain viable. There is no electrophysiological evidence of a preferential loss of fast conducting axons, of pathological slowing of conduction nor of a dying-back process affecting the motor axon. Comparison of the electrophysiological parameters in progressive muscular atrophy and amyotrophic lateral sclerosis shows no significant differences. The underlying pathophysiological mechanisms are discussed in terms of the results.
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Ovariectomized rats, pre-implanted with elastomer capsules containing oestradiol, became sexually receptive after exposure to progesterone (implanted in elastomer capsules) for 4-6 h. Implantation of progesterone capsules facilitated receptivity in oestradiol-implanted rats independently of both previous exposure to progesterone implants and the presence of progesterone at the time of implantation. The duration of sexual receptivity in ovariectomized rats implanted with oestradiol and progesterone capsules was dependent upon the length of both the oestradiol and progesterone capsules, but the decline in sexual behaviour of receptive rats was independent of the continued presence of either oestradiol or progesterone. Repeated implantation of progesterone capsules at 6 hourly intervals prevented the decline of sexual receptivity.
Ovariectomized rats were implanted with oestradiol-filled elastomer capsules which were removed at various times after implantation. Sexual receptivity was tested after implantation of a progesterone-filled elastomer capsule 42 h after the onset of treatment with oestradiol. Exposure to oestradiol for about 32 h was required for induction of receptivity. Intact rats with regular 4 day oestrous cycles, and exposed to oestradiol-filled elastomer capsules for 6 h, showed sexual receptivity 24 h after the onset of oestradiol treatment. The behavioural effects of oestradiol in both ovariectomized and intact rats depended on when during the light-darkness (LD) cycle stimulation with oestradiol occurred; maximum effects were seen only if the oestradiol capsules were implanted at 16.00 h (4 h after lights off in the 12 h L : 12 h D cycle). The behavioural effect of progesterone implants, however, did not depend on the phase of the LD cycle. The LD-dependent rhythm in oestradiol sensitivity was eliminated by lesions in the suprachiasmatic nuclei of the hypothalamus.
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Amino compounds were measured with an amino acid analyzer in the fasting plasma of 34 patients with childhood psychoses (28 having infantile autism) and 40 control children, and in the cerebrospinal fluid (CSF) of 19 of the psychotic children and 23 control children. Organic acids were determined by gas chromatography in urine, plasma, and CSF of the psychotic patients. The mean concentration of ethanolamine in CSF was significantly higher in psychotic children than in control subjects. A subgroup of autistic children may possibly have a brain disorder involving ethanolamine metabolism. None of the known inherited diseases of organic acid metabolism was found in any of the psychotic children, but future studies utilizing sophisticated gas chromatography--mass spectrometry--computer techniques might disclose abnormal organic acid content in the CSF of such patients.
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The bacteriophages T3 and T7 are not modified and restricted by E. coli strains with different host specificity (E. coli B, K, O) in vivo. The phages code for a gene product with the ability to overcome classical restriction (ocr): ocr- mutants are subject to modification and restriction via DNA methylation vs cleavage. The T3 genome possesses recognition sites for the restriction endonuclease R.EcoB which, unless the DNA is B-specifically modified, trigger 5-7 DNA cleavages. The ocr gene function of T3 and T7 is located within the gene 0.3 region of these phages and is not identical with the sam (SAMase) function of T3. The mechanism of ocr protection remains unclear, while it is certain that this protection by the gene 0.3 protein is exerted in the infected cell and not through "over-all" modification in the preceding growth cycle of the phage.
When passaging phage T7 and SAMase-negative T3 mutants between E. coli strains with identical (EcoB) or without (EcoO) DNA host specificity, phenotypically a host-controlled modification and restriction is observed. This phenomenon is not due to "classical" modification and restriction of the bacteriophage DNA but depends on the reversibly altered adsorption capacity of the phages on the different host strains.
A girl with 46, XX, del (11) (q23), inv (9) (p13, q13) is described. The patient shows many dysplastic signs mainly of the face and skull. The pericentric inversion of chromosome 9 has been inherited from the mother (46, XX, inv (9) (p13, q13)).
The intracellular growth of the phages T3 and T7 is restricted in the presence of the Escherichia coli prophage P1. Phage T3 has a higher ability to express its genome and to damage the host cell than T7. This partial protection of T3 against P1 restriction is due to the T3-coded SAMase, an enzyme which degrades S-adenosylmethionine, the cofactor of the P1 restriction endonuclease. Since we did not observe DNA cleavage in vivo, we conclude that the in vivo action of the P1 nuclease is limited to a SAM-dependent repressor-like binding to T3 and T7 DNA, while further reactions with the DNA (modification vs cleavage) are blocked.
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The motor unit content and the dimensions of individual motor unit action potentials were studied in 17 patients with acute idiopathic polyneuritis from one week to 9 1/2 years after the onset of the illness. An initial decrease in motor unit numbers is followed by a progressive increase with the passage of time from the onset of the illness. The latencies, areas, amplitudes, and durations of individual motor unit potentials were increased above normal values. The results suggest the presence of significant axonal damage in the majority of cases of acute idiopathic polyneuritis. The intramuscular nerve fibres are the site of most severe electrophysiological dysfunction in this study.
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