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Biomedical subjects

J D Johnston

Publications and source records attributed to J D Johnston.

At least 19 recordsLinked to original sources

Smokers have less dense bones and fewer teeth.

Women and men who smoke are more slender than their non-smoking counterparts and have a bone density appropriate to their degree of slenderness. As a result, they are more likely to sustain a fracture than their non-smoking counterparts. The lower bone density found in smokers may arise because of less stress and strain imposed on the skeleton by a slim physique. Smokers have poorer oral hygiene and less teeth than their non-smoking counterparts. The relationship between smoking and tooth pathology remains unclear: smoking may either act via a direct mechanism based on the toxicity of tobacco smoke or indirectly through body weight (ie the effect on teeth is part of a wider effect on bone structure).

Adult

Reproductive and developmental hazards and employment policies.

The task of informing workers of hazards in the workplace is seldom more difficult than with the subject of reproductive and developmental hazards. Occupational health staff and physicians are faced with a paucity of relevant medical information. Workers, kept aware of the thalidomide spectre with every media report of the latest descriptive epidemiology study, are anxious to know more. Employers, knowing that few agents are regulated on the basis of reproductive hazards, are encouraged to lessen workplace exposure to all agents but need guidance from government and scientists in setting priorities. Understandable ethical and scientific limitations on human studies require researchers to study animals and cells. The difficulties of extrapolating the results of this research to humans are well known. The scientific, medical, and workplace difficulties in dealing with reproductive and developmental hazards are mirrored in the regulatory positions found in North America. Some regard fetal protection policies as sex discrimination whereas others consider such policies as reasonable. Guidelines are provided to allow employers and medical practitioners to consider this difficult problem.

Abortion, Spontaneous

The mechanism of Ca2+ stimulation of citrulline and N-acetylglutamate synthesis by mitochondria.

ATP-driven citrulline synthesis by mitochondria treated with oligomycin, uncoupler and Ca2+ ionophore is stimulated more than 2-fold by an increase in extramitochondrial free [Ca2+] in the range 1-5 microM. Stimulation increases with the length of preincubation of mitochondria with Ca2+. EGTA prevents stimulation if added at the start of the preincubation period, but is without effect if added at the end, suggesting that Ca2+ acts indirectly on citrulline synthesis via the accumulation of an intermediate. Neither carbamoyl-phosphate synthase (ammonia) nor ornithine carbamoyltransferase are stimulated by up to 50 microM free Ca2+ in mitochondrial extracts, but N-acetylglutamate synthase is stimulated about 30% by 10 microM free Ca2+. We propose that an increase in the activity of N-acetylglutamate synthase in response to an increase in free [Ca2+] in the mitochondrial matrix may contribute to hormonal stimulation of the urea cycle.

Acetyltransferases

Sub-micromolar concentrations of extramitochondrial Ca2+ stimulate the rate of citrulline synthesis by rat liver mitochondria.

1. In the presence of physiological concentrations of Na+ and Mg2+, the rate of citrulline synthesis by isolated rat liver mitochondria respiring on a range of substrates was stimulated by up to 60% when the extramitochondrial Ca2+ concentration was raised from 130 pM to 770 nM. 2. Our findings suggest that hormonal stimulation of the urea cycle may be mediated by Ca2+.

Animals

The surreptitious observation design: an experimental paradigm for distinguishing artifact from essence in hypnosis.

Administered a hypnotic induction and 5 standard hypnotic suggestions twice via audiotape to a group of high-hypnotizable subjects and a group of low-hypnotizable simulators. During the first administration, subjects were led to believe that they were alone. However, their behavior was surreptitiously recorded on videotape and observed on a video monitor. The second administration occurred in the presence of an experimenter who had not been informed of group assignment. When unaware that they were being observed, simulators were significantly less responsive to suggestions than they were when openly observed. In contrast, the behavior of nonsimulating subjects was not affected by the presence of an experimenter. These data indicate that the responses of highly hypnotizable subjects to standard hypnotic suggestions cannot be accounted for in terms of simple compliance with experimental demand.

Humans

Stimulation of the respiration rate of rat liver mitochondria by sub-micromolar concentrations of extramitochondrial Ca2+.

1. The respiration rate of rat liver mitochondria was stimulated by up to 70% when the extramitochondrial Ca2+ concentration was raised from 103 to 820 nM. This occurred when pyruvate, 2-oxoglutarate, or threo-(Ds)-isocitrate was employed as substrate, but not when succinate was used. 2. Ruthenium Red prevented the stimulation of mitochondrial respiration by extramitochondrial Ca2+, showing that the effect required Ca2+ uptake into the mitochondrial matrix. 3. Starvation of rats for 48 h abolished the stimulation of mitochondrial respiration by extramitochondrial Ca2+ when pyruvate was used as substrate, but did not affect the stimulation of 2-oxoglutarate oxidation by extramitochondrial Ca2+. 4. Our findings are in accord with proposals that oxidative metabolism in liver mitochondria may be stimulated by Ca2+ activation of intramitochondrial dehydrogenases.

Animals

The effects of ethanol on blood toluene concentrations.

The metabolism of toluene was found to be inhibited by a large dose of alcohol in seven volunteers exposed to 80 ppm of toluene under experimental conditions. When alcohol was taken during exposure, blood toluene concentrations were 42.5% greater on average than during exposure with no alcohol. This is probably due to competition for alcohol dehydrogenase which is required for the breakdown of both ethanol and toluene. In men exposed to toluene at work, it was found that blood toluene concentrations were lowest in those who drank regularly. These results suggest that continued alcohol intake increases the metabolism of toluene, presumably by inducing the microsomal oxidising enzyme system in the liver.

Adult

Steroid 21-sulfatase activity in human placenta.

Intravenously administered [3H]-deoxycorticosterone sulfate is not metabolized by way of deoxycorticosterone in men or non-pregnant women. Thus, it can be implied that steroid 21-sulfatase is not active in human tissues. On the other hand, evidence has accrued that deoxycorticosterone sulfate is hydrolyzed in human placenta. In the present investigation, we sought to ascertain if steroid 21-sulfatase activity were present in placenta and, if so, to characterize the enzyme activity in this tissue. Steroid 21-sulfatase activity was found to be present in microsome-enriched fractions prepared from human placental tissue; conditions of linearity of the reaction with time and protein concentration were established and the apparent KM of the enzyme for deoxycorticosterone sulfate was 100 microM. Thus, deoxycorticosterone sulfate, which is present in high concentration in plasma of the human fetus, may enter trophoblast wherein it could be hydrolyzed; the deoxycorticosterone formed could be secreted into the maternal circulation. Such a process, together with deoxycorticosterone formation from plasma progesterone in extraadrenal sites, could account for the high concentrations of deoxycorticosterone that are present in plasma of near-term pregnant women.

Dehydroepiandrosterone

A comparison of erythrocyte glutathione S-transferase activity from human foetuses and adults.

Glutathione S-transferase activity was measured in partially purified haemolysates of erythrocytes from human foetuses and adults. Enzyme activity was present in erythrocytes obtained between 12 and 40 weeks of gestation. The catalytic properties of the enzyme from foetal cells were similar to those of the enzyme from adult erythrocytes, indicating that probably only one form of the erythrocytes enzyme exists throughout foetal and adult life.

Chromatography, Gel

Partitioning of bile acids into subcellular organelles and the in vivo distribution of bile acids in rat liver.

1. The subcellular distribution of conjugates of cholic acid and chenodeoxycholic acid between cytosol, nuclei, mitochondria and microsomes in rat liver has been determined. 2. The partition coefficients for the distribution of these bile acids between subcellular fractions and buffer have been measured and used to construct a compartmental model of the amounts of conjugated bile acids present in the different subcellular organelles in vivo. 3. This model indicates that a large percentage of the bile acid in the rat liver is found in the nuclear fraction; 42% of the cholic acid conjugates and 27% of the chenodeoxycholic acid conjugates. Substantial amounts of bile acid are also present in microsomes and mitochondria suggesting that published estimates of the amounts of bile acids in these fractions are underestimates. 4. The model also allows the amount of bile acid which is in free solution in cytosol to be determined; 10.9% of the cholic acid conjugates and 4.1% of the chenodeoxycholic acid conjugates in rat liver were present in this fraction. Knowlege of the amount of free bile acid allows possible roles of the cytosolic bile binding proteins to be assessed.

Animals

Microscopic lysis of lumbar adhesive arachnoiditis.

The results of a long-term study of 28 patients operated on for adhesive lumbar arachnoiditis are presented. The technique involved was microscopic lysis of adhesions. The first case of surgery was performed in 1966 and the last, in 1970, with followup through 1976. Numerous observations are made regarding the clinical picture and the appearance of arachnoiditis at the time of surgery. Some conclusions are drawn regarding the causes of this condition with some emphasis on the role of Pantopaque, multiple surgeries, and other trauma. The conclusion is that surgical attack on arachnoiditis is a straightforward surgical exercise that, when carried out with appropriate caution, produces no further neurologic deficits and some short-term improvement. However, the authors feel that this procedure should not be performed at the present time because there does not appear to be a method for preventing the reaccumulation of the scar tissue and subsequent recurrence of the symptoms.

Adult