The effects of hypoxia on serial response time.
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Biomedical subjects
Publications and source records attributed to B Fowler.
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Three experiments were conducted to examine the effects of 35% N2 O (nitrous oxide) on human memory and auditory perception. In Experiment I, dichotic listening performance was found to be impaired. Experiment II used the same technique but was controlled for attenuation of sound transmission in the middle ear. No impairment was found. The perceptual effect found in Experiment I was peripheral, not central, and N2O did not impair short-term memory (STM). Experiment III used one-trial free recall of a word list. The shapes of the serial position curves were interpreted as indicating that N2O impairs long-term memory (LTM) but not STM. Experiment III provided no evidence, using cued recall, that the LTM deficit was due to impaired retrieval. Comparing these results with those for compressed air led to the conclusion that both N2O and hyperbaric nitrogen display an identical pattern of effects. A reason for the decrement found in some N2O STM studies may have been confounding the measurement of STM with that of LTM.
Up to the end of 1978 the Willink Biochemical Genetics Unit had screened 506821 babies for metabolic abnormalities over 10 years--98-99% of the children born in the region. Sixty-nine cases of phenylketonuria (PKU), 42 cases of histidinaemia, and six cases of homocystinuria were detected. As well as treating affected children, the staff of the unit have concentrated on providing full support for their families and maintaining good communications with parents, general practitioners, health visitors, and midwives. A clinic liaison sister has provided valuable support for health visitors and an important link between the unit and community services. A study of the costs of screening and treating cases of PKU for the year 1978 showed that this was cheaper, by pound 569000, than the costs of looking after patients with untreated PKU.
Cystathionine beta-synthase has been purified from human liver more than 3000-fold by a series of steps including high speed centrifugation, ammonium sulfate fractionation, chromatography on hydroxylapatite and DEAE-cellulose, gel filtration, preparative polyacrylamide gel electrophoresis, and glycerol density gradient centrifugation. The enzyme obtained is homogeneous as judged by polyacrylamide gel electrophoresis in four different systems: native, isoelectric focusing, in sodium dodecyl sulfate, and in 8 M urea. The native enzyme has an estimated molecular weight of 94,000 and is composed of two apparently identical subunits of 48,000. The pure enzyme has a specific activity of 160 units/mg of protein and contains tightly bound cofactor, pyridoxal 5' -phosphate. It is possesses serine sulfhydrase as well as cystathionine synthase activity. It has a broad pH optimum from 8.4 to 9.0, apparent Km values for L-serine of 1.15 mM and for L-homocysteine of 0.59 mM, and a pI of 5.2 The enzyme is stable over a pH range from 6.5 to 8.0 in phosphate buffers and can be stored in 40% glycerol at -15 degrees C for at least 1 month.
We have compared in vivo pyridoxine responsiveness with in vitro cystathionine beta-synthase activity in extracts of confluent fibroblasts from 14 synthase-deficient patients. Enzyme activity was measured with and without addition of its cofactor, pyridoxal-5'-phosphate, using a radioisotopic assay which detects as little as 0.25% of control activity. Six of seven lines from responsive patients had measurable activity without the added cofactor (0.6-15% of mean control). Two of these lines showed a five- and sevenfold stimulation of cystathionine beta-synthase activity with added pyridoxal-5'-phosphate; in the other four, the cofactor addition increased activity only modestly, as in controls. Two of seven lines from nonresponsive patients had measurable activity (each 3% of mean control) which increased two- and fivefold with the added cofactor. Cystathionine beta-synthase activity was undetectable in one line from a responsive patient and in five lines from nonresponsive ones. To characterize control and mutant synthase further, dissociation constants for pyridoxal-5'-phosphate were estimated and thermostability (54 degrees C) was studied in two control and five mutant lines. In one mutant, both parameters were normal; in the others, the affinity for the cofactor was reduced 3-to 11-fold and thermostability was much impaired. We conclude that at least three general classes of cystathionine beta-synthase mutants exist: those with no residual activity; those with reduced activity and normal affinity for pyridoxal-5' phosphate; and those with reduced activity and a reduced affinity for the cofactor. Pyridoxine responsiveness in vivo cannot be correlated simply with the presence or absence of residual synthase activity in vitro or with stimulation of in vitro enzyme activity by cofactor.
The purpose of this review is to examine the validity of change in the cortical evoked response as a measure of inert gas narcosis in humans. Three criteria are defined which must all be met if a nonbehavioral measure is to be accepted as an indicator of narcosis. The evoked response is assessed in terms of these criteria. Two classes of experiments which have used the evoked response in hyperbaric ocnditions are identified. The first class allows the evoked response to be assessed against more than one of these criteria. The outcome of every experiment in this class supports the view that the evoked response is not a valid measure of narcosis. The second class of experiment assumed that the evoked response is a measure of narcosis and were not designed to assess validity appropriately. Arguments by Kinney and associates in support of the assumption of validity are shown to be unsound. Possible explanations for inability to demonstrate validity are discussed and it is suggested that factors other than narcotic potency of the breathing gas mixture determine or at least play a major role in determining amplitude of the evoked response.
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Three experiments are reported which investigated the effects of hyperbaric air on long-term memory. In the first, word lists were learned at 1 and 8.6 ATA using a variable input-free recall paradigm. It was found that learning was affected but not clustered memory organization, and it was concluded that disorganization of memory is not a factor contributing to the learning deficit found with hyperbaric air. In the second and third experiments it was found that the recall of words, which had been learned when non-narcotic, was disrupted at 10 ATA by hyperbaric air and that this disruption was not overcome by providing memory-cues at the time of recall. Two possible explanations for these results are discussed. A hypothesis is put forward to reconcile the results of various hyperbaric memory experiments by pointing out that a relationship between stress and learning found with nitrous oxide could be applicable to these studies also.
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