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B Fowler

Publications and source records attributed to B Fowler.

At least 145 records · Page 8Linked to original sources

[Homocystinuria].

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Child, Preschool↗

Effects of inert gas narcosis on behavior--a critical review.

The effects of inert gas narcosis on behavior before unconsciousness are reviewed with particular attention to four issues. The first is whether the qualitative behavioral effects of all inert gases are identical. Evidence is limited but does not contradict an affirmative answer. This is consistent with the unitary hypothesis of narcosis at the physicochemical level. The second issue concerns the relative merits of four approaches to narcosis; (a) the descriptive model, (b) the hierarchical organization hypothesis, (c) the operant paradigm, and (d) the slowed processing model. It is concluded that the latter two are showing some promise. In particular, operant techniques allow more sophisticated measures of narcosis in animals than behavioral end points, such as loss of the righting reflex. The slowed processing model claims that the majority of performance deficits in humans are caused by a single fundamental deficit, slowing of information processing due to decreased arousal. This slowing is usually accompanied by alterations in task strategy. These alterations, in combination with cumulative slowing in working memory, are said to account for the various manifestations of narcosis on complex tasks. The third issue concerns adaptation to narcosis. There is some evidence that adaptation can occur but it is unclear whether the cause is learning specific to narcosis or development of a physiological tolerance. However, adaptation has not always been found and the variables controlling its presence or absence have yet to be identified. The fourth issue concerns the modifying effects of various factors, such as carbon dioxide and anxiety, on narcosis. Methodological and conceptual problems hinder interpretation of the evidence in this area but, contrary to some current views, there appears to be no conclusive evidence that any factor other than ethanol potentiates narcosis. Some implications of these conclusions for diving operations are discussed.

Amphetamine↗

The penetration of latamoxef disodium (moxalactam) into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease.

After pre-operative administration of 1 g, latamoxef disodium (moxalactam) levels were measured in peripheral venous blood, skeletal muscle and subcutaneous fat sampled from 29 patients during either arterial reconstruction or amputation undertaken for arterial occlusive disease. Tissue samples were taken from both proximal and distal levels in the amputated limbs. Levels of latamoxef disodium were above the minimum inhibitory concentration required for most commonly encountered Gram-positive and Gram-negative organisms. No patients developed toxicity or superficial wound infection but there was one vascular graft infection by Candida albicans. It has been shown that latamoxef disodium penetrates rapidly into the subcutaneous fat and skeletal muscle of relatively ischaemic limbs, achieving levels inhibitory to many common pathogens.

Adipose Tissue↗

Metabolism of cadmium, zinc and copper in the rat kidney: the role of metallothionein and other binding sites.

Studies were undertaken to determine the effect of host zinc deficiency upon the distribution of Cd, Zn and Cu between and within male rat kidney cytosol and unfractionated cell pellet. In the first experiment male rates were fed stock diets supplemented with 100 micrograms Cd/mL in the drinking water for 30 days. Then Cd-treated rats and controls were segregated into groups, which received semipurified diets adequate or deficient in zinc for 14 days. After this regimen there were comparable concentrations of total Cd and metallothionein bound Cd in cytosol and the supernatant of sonicated, unfractionated pellet on a microgram Cd/g protein basis. Although less than 5% of cytosolic Cd is not bound to metallothionein (MT), 3-5 times as much non-MT Cd is present in the particulate fraction. The zinc-deficient (Zn-) dietary regime increases the non-MT Cd in the pellet. Quantitations were done of the Cu and Zn distribution in high molecular weight, superoxide dismutase, and metallothionein regions of the profiles of metals from Sephadex G-75 chromatography. In animals exposed to Cd and fed a zinc-normal (Zn+) diet, supernatant and pellet metal contents only change in the MT fraction. Similarly, zinc deficiency affects primarily the complement of metals bound to metallothionein: zinc is markedly decreased and Cu is lowered to a smaller extent. Cadmium is unchanged. Control kidney, unexposed to Cd, normally contains a substantial amount of Zn,CuMT. Two-week zinc deficiency greatly reduces MT-Zn and -Cu content without altering the metal content of other cellular pools.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transsulphuration and methylation of homocysteine in control and mutant human fibroblasts.

The ability of human skin-fibroblasts in monolayer culture to carry out transsulphuration and remethylation of homocysteine has been tested. The conversion of homocyst(e)ine ot cyst(e)ine and methionine was studied in control and mutant cells by incubation for 16 h with L-[35S] homocystine. Labelled cysteic acid and methionine sulphone were found in hydrolysates of oxidized cell proteins. The quantities found were dependent on the time of incubation and were used as a measure of cyst(e)ine and methionine formation, respectively. In control cells, labelled cyst(e)ine and labelled methionine were found. In cystathionine beta-synthase-deficient cell lines, labelled cyst(e)ine formation was reduced, while labelled methionine formed was similar to that of controls, indicating the role of transsulphuration in the formation of cyst(e)ine observed in control cells. In a 5,10-methylenetetrahydrofolate reductase-deficient cell line, labelled methionine formation was reduced, indicating the role of N-5-methyltetrahydrofolate-requiring methylation of homocysteine in the formation of methionine observed in control cells.

Cell Line↗

Narcotic effects of nitrous oxide and compressed air on memory and auditory perception.

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.

Atmospheric Pressure↗

The Manchester regional screening programme: a 10-year exercise in patient and family care.

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.

Child↗

Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits.

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.

Adult↗

Homocystinuria. Evidence for three distinct classes of cystathionine beta-synthase mutants in cultured fibroblasts.

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.

Adolescent↗

Does the evoked response measure inert gas narcosis?

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.

Acoustic Stimulation↗