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Biomedical subjects

R Deacon

Publications and source records attributed to R Deacon.

At least 37 records · Page 2Linked to original sources
PubMed1986

Vitamin B12 neuropathy is not due to failure to methylate myelin basic protein.

It has been proposed that the biochemical lesion in subacute combined degeneration of the cord due to vitamin B12 deficiency, is impaired methylation of residue 107 (arginine) in myelin basic protein. We have examined myelin basic protein in brains of rats in which vitamin B12 was inactivated by exposure to nitrous oxide for up to 7 days. In addition brains of fruit bats in which vitamin B12 neuropathy had been produced by feeding washed, and hence vitamin B12-free fruit, were examined. There was no difference in the methylation of arginine 107 in myelin basic protein in these animals as compared to healthy control animals. Rats given an inhibitor of transmethylation reactions (cycloleucine) showed the expected fall in methylation of myelin basic protein.

Animals↗
PubMed1985

Effect of cobalamin inactivation on folate-dependent transformylases involved in purine synthesis in rats.

N2O oxidizes and inactivates cob[I]alamin, and animals exposed in this way serve as models for cobalamin 'deficiency'. Such animals show a fall in activity of glycinamide ribotide transformylase and a rise in that of 5-amino-4-imidazolecarboxamide ribotide transformylase. The fall in glycinamide ribotide transformylase activity was prevented by parenteral 5'-methylthioadenosine derived from methionine. Methylthioadenosine in turn is converted into formate. Activity of glycinamide ribotide transformylase recovers after 7 days despite continued N2O inhalation, and this is probably related to restoration of methionine synthesis by induction of betaine:homocysteine transmethylase.

Acyltransferases↗
PubMed1985

Folate polyglutamate synthetase activity in the cobalamin-inactivated rat.

Exposure to N2O inactivates cob[I]alamin and interferes with the activity of methionine synthetase, of which cob[I]alamin is a coenzyme. Less directly, it stops the formation of folate polyglutamate from tetrahydrofolates. Studies on the activity of folate polyglutamate synthetase in rat liver in vivo were carried out. The synthetase activity increased after exposure to N2O for up to 48 h, but longer exposure was accompanied by a return of activity to baseline values. The rise in synthetase activity was prevented by supplying methionine, 5'-methylthioadenosine or 5-formyltetrahydrofolate. The fall in folate polyglutamate synthetase activity after 48 h was accompanied by a restoration of hepatic synthesis of folate polyglutamate despite continuation of N2O exposure.

Amide Synthases↗
PubMed1985

Role of folate dependent transformylases in synthesis of purine in bone marrow of man and in bone marrow and liver of rats.

The activity of the two folate dependent enzymes supplying carbon 2 and carbon 8 of the purine nucleus was assayed in the bone marrow of rats and man, as well as in rat livers. The activity of both enzymes was several fold greater in marrow than in liver. Inactivation of cobalamin by exposure to nitrous oxide did not affect the enzymes in rat marrow cells, although an appreciable effect on hepatic enzymes was found. The depression of hepatic glycinamide ribotide (GAR) transformylase in rats exposed to nitrous oxide was prevented by supplying a formate precursor, methylthioadenosine. There was a considerable rise in the activity of GAR transformylase in human marrow cells from patients with megaloblastic anaemia due to cobalamin deficiency but no change in activity in marrow from patients deficient in folate.

Acyltransferases↗
PubMed1985

Turnover of the methyl moiety of 5-methyltetrahydropteroylglutamic acid in the cobalamin-inactivated rat.

The metabolism of the methyl group of 5-methyltetrahydrofolate was studied in rats in which cobalamin had been inactivated by exposure to nitrous oxide and in air-breathing control animals. Methylfolate labeled with [14C] in the methyl group and with [3H] in the pteridine-PABA portion was injected and the disappearance of [14C]H3- relative to [3H]folate was measured in liver. The half-time of the methyl group in the livers of control rats was two hours. There was no turnover of the methyl group for the first 72 hours after cobalamin inactivation. After 72 hours, there was a slow turnover of the methyl group, with a half-time of 43 hours. In control rats, it is assumed that the methyl group was metabolized by transfer to homocysteine to form methionine. In cobalamin-inactivated rats, it was shown that methylfolate was used as the substrate for forming folate polyglutamate, and analogues with 3, 4, and 5 glutamic acid residues were present. It is likely that oxidation of the methyl group by methylene tetrahydrofolate reductase occurs from folate polyglutamate containing six and seven glutamic acid residues, (Brody et al, Biochemistry 21: 276, 1982), since we were unable to demonstrate labeled methyl in longer chain analogues.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1983

Effects of nitrous oxide-induced inactivation of cobalamin on methionine and S-adenosylmethionine metabolism in the rat.

Inhalation of nitrous oxidises cobalamin and, in turn, inactivates methionine synthetase which forms methionine from homocysteine and which requires cob[I]alamin as a co-factor. This study was planned to determine the effect of virtual cessation of methionine synthesis via a cobalamin-dependent pathway, on tissue levels of methionine, S-adenosylmethionine and on related enzymes. The level of methionine in liver fell initially after exposure to N2O but was restored to pre-N2O levels after 6 days despite continuing N2O exposure. Brain methionine fell within 12 h of N2O exposure but the fall was not significant. The restoration of methionine levels is accompanied by an increase in activity of betaine homocysteine methyltransferase in liver but this enzyme was not detected in brain. The activity of methionine synthetase remained very low in both liver and brain as long as N2O inhalation was continued. There was an initial rise in liver S-adenosylmethionine levels followed by a steady fall to 40% of its initial level after 11 days of N2O exposure. However, there was no change in the level of S-adenosylmethionine in brain during this period. The data indicate that either brain meets its requirement by increased methionine uptake from plasma or that there are alternate pathways in brain for methionine synthesis other than those requiring a cobalamin coenzyme.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1983

Effect of nitrous oxide-induced inactivation of vitamin B12 on glycinamide ribonucleotide transformylase and 5-amino-4-imidazole carboxamide transformylase.

Exposure to nitrous oxide (N2O) in vivo is accompanied by oxidation of cob[I]-alamin to the inactive cob[III]alamin [1]. There is loss of methionine synthetase activity [2] and evidence of depressed supply of single carbon units at the formate level of oxidation [3,4,5]. We measured the effect of inactivation of B12 on the folate-dependent transformylases concerned in purine synthesis. After 24 h exposure to N2O there was a significant fall in glycinamide ribonucleotide transformylase (EC 2.1.2.2) and a significant increase in 5-amino-4-imidazole carboxamide transformylase (EC 2.1.2.3).

Acyltransferases↗
PubMed1983

Increased urinary excretion of formiminoglutamic acid in nitrous-oxide-treated rats and its reduction by methionine.

Inhalation of nitrous oxide oxidises cob(I)alamin and inactivates methionine synthetase of which cobalamin is a co-enzyme. The biochemical changes in the rat following exposure to nitrous oxide resemble in some detail the changes present in patients with untreated pernicious anemia due to deficiency of cobalamin. There is a marked increase in the excretion of formiminoglutamic acid in the urine following exposure to nitrous oxide. A significant decrease is produced, while on N2O, by giving methionine. The explanation for these findings is discussed in the light of recent data on the effects of cobalamin inactivation.

Animals↗
PubMed1983

Chronic cobalamin inactivation impairs folate polyglutamate synthesis in the rat.

Nitrous oxide, by inactivating cobalamin in vivo, produces a suitable animal model for cobalamin 'deficiency.' The synthesis of folate polyglutamate with tetrahydrofolate as substrate is severely impaired in the N2O-treated rat, but is normal with formyltetrahydrofolate as substrate. Methionine restores the capacity of the N2O-treated rat to utilize tetrahydrofolate the minimum effective dose being 16 mumol. S-Adenosylmethionine was somewhat less effective than methionine but 5'methylthioadenosine, a product of S-adenosylmethionine metabolism, was significantly more effective than methionine in correcting the defect in folate polyglutamate synthesis. 5'Methylthioadenosine is metabolised to yield formate. It is suggested that these compounds have their effect in correcting folate polyglutamate synthesis by supplying formate for the formylation of tetrahydrofolate. Formyltetrahydrofolate, at least in the cobalamin-inactivated animal, is the required substrate for folate polyglutamate synthesis. Cobalamin is concerned with the maintenance of normal levels of methionine and this in turn is a major source of formate through S-adenosylmethionine and 5'methylthioadenosine.

Adenosine↗
PubMed1982

A peptide-containing fraction of plasma from schizophrenic patients which binds to opiate receptors and induces hyper-reactivity in rats.

A serum fraction from schizophrenic patients has been investigated for its effect on opiate receptor sites and on behaviour in rats. Serum from schizophrenic patients was ultrafiltered and fractionated on DEAE-Sephadex A-25. The concentration of peptide material eluting under 0.1 M HCl (fraction I) was further purified on Sephadex-G10 and four major peaks were identified (fractions II to V). When injected intracerebroventricularly in rats, fraction II produced a characteristic behavioural syndrome, which included hyperactivity associated with hyperemotionality. The effects were long lasting, bouts of hyperemotionality accompanied by analgesia were recorded over a two-week period. The same fraction from control non-patients produced a transient and much reduced, but qualitatively similar response. There was evidence that fraction III was also active. An in vitro opiate receptor binding test showed that fraction II from schizophrenic patients inhibited [3H]naloxone binding.

Adolescent↗
PubMed1982

A comparison of tetrahydrofolate and 5-formyltetrahydrofolate in correcting the impairment of thymidine synthesis in pernicious anaemia.

5-formyltetrahydrofolate and tetrahydrofolate were added to marrow cells from patients with untreated pernicious anaemia at 1, 5 and 50 nmol doses in the deoxyuridine suppression test. At all 3 dose levels formyltetrahydrofolate was significantly more effective in correcting the defect of thymidine synthesis in pernicious anaemia, than tetrahydrofolate. The data suggest that formylation of tetrahydrofolate is necessary for its normal utilization.

Anemia, Pernicious↗
PubMed1982

Comparison of independent randomised reading of radiographs with direct progression scoring for assessing change in asbestos-related pulmonary and pleural lesions.

Direct scoring of progression of pleural and parenchymal lesions was compared with change assessed by independent readings to the ILO classification among 155 men from HM Dockyard, Devonport, followed-up for 10 years. For pleural calcification the two methods agreed closely, whereas direct scoring yielded relatively too little progression of small opacities and too much progression of pleural thickening. The choice of method for assessing progression should depend on objectives.

Asbestos↗
PubMed1982

The rise in the incidence of hospitalizations for the aged, 1967 to 1979.

Since the beginning of the Medicare program in July 1966, the rate of hospitalization for persons age 65 and over has risen steadily. The rate grew more for the aged than for younger age groups. Because of concern about the appropriateness and cost of hospital care, this article examines the increase in hospitalizations for the aged and attempts to identify factors that may explain why the discharge rate rose more for the aged than for younger persons. The article shows that most of the increase in the discharge rate among the aged was associated with an increase in the percentage of persons using the hospital rather than with an increase in rate of multiple hospitalizations. There was also a large increase in the rate of hospital stays of short duration. Examination of changes in diagnostic and surgical case-mix showed that there was a large increase in vascular and cardiac surgeries. Changes in demographic composition and insurance coverage did not help explain the difference in the rate of growth of hospitalizations by age group. The increase in the rate of the aged being cared for in the hospital raises the question of the necessity and quality of the care they receive. Additional studies should focus on the nature and appropriateness of the hospital services rendered to the elderly.

Adolescent↗
PubMed1982

Urinary folate loss following inactivation of vitamin B12 by nitrous oxide in rats.

Rats were injected with [2-14C]H4PteGlu daily for 3 d and thereafter one group left in air and a second group in an atmosphere of nitrous oxide/oxygen (1/1). Nitrous oxide inactivates cobalamin. The N2O-treated rats excreted large amounts of L. casei-active folate into the urine. The urinary folate co-chromatographed with authentic 3H-labelled 5-methyltetrahydrofolate. Both groups of animals excreted 14C-labelled breakdown products in the urine but there was no evidence of increased folate catabolism in the N2O-treated rats. It was concluded that the folate deficiency that develops in the N2O-treated rat is due to massive urinary loss of folate. This appears to be secondary to impaired cellular uptake of folate which leads to a raised plasma folate level.

Animals↗