Search PubMed⌕ Search

Biomedical subjects

R Deacon

Publications and source records attributed to R Deacon.

At least 55 records · Page 3Linked to original sources
PubMed1981

Changes in tissue folates accompanying nitrous oxide-induced inactivation of vitamin B12 in the rat.

The anesthetic gas, nitrous oxide, oxidizes cob(I)alamin and thus inactivates methionine synthetase which requires cobalamin as a coenzyme. The effect on folates in liver, kidney, marrow, plasma, and brain in rats breathing a 1/1 nitrous oxide/oxygen mixture is described. There is loss of folate from tissues, most marked in liver, that affects folate polyglutamates to a greater extent than folate monoglutamates. Both methyl- and nonmethyl-analogues are affected. There is a transient rise in the levels of 5-methyltetrahydropteroylpolyglutamate in all tissues 8 h after starting nitrous oxide, which falls thereafter. In marrow and brain there is also a transient rise in methyltetrahydropteroylmonoglutamate. Plasma folate increased markedly throughout the period of exposure to nitrous oxide. It is suggested that these changes are due to the action of nitrous oxide in depressing tissue uptake of folate from plasma, in promoting loss of folate into urine and in inhibiting folate polyglutamate synthesis.

Animals↗
PubMed1981

Recovery of tissue folates after inactivation of cobalamin by nitrous oxide. The significance of dietary folate.

The anesthetic gas, nitrous oxide (N2O), oxidizes the cobalt moiety in the vitamin B12 molecule and in this way inactivates methionine synthetase which requires reduced cobalamin. In rats this is followed by a disappearance of folates from the tissues, this loss being most marked in the liver. Returning the animals to a normal atmosphere leads to restoration of most of the pre-N2O folate levels within 5 days. The plasma folate, which rises on exposure to N2O, falls within several hours. The restoration of tissue folates does not take place if the rats are placed on a low folate diet after withdrawal from an N2O environment. Thus the fall in tissue folate levels is due to loss from the body either by excretion or increased catabolism and not to redistribution of folate. Return of normal folate levels requires a dietary source of folate.

Animals↗
PubMed1981

Megaloblastic change is a feature of colonies derived from an early erythroid progenitor (BFU-E) stimulated by monocytes in culture.

The morphology of stained preparations of cells from human bone marrow and peripheral blood erythroid colonies cultured in methylcellulose, were examined by light microscopy. Although the morphology of 7 d erythroid colonies (CFU-E) was largely normoblastic, bone marrow and peripheral blood erythroid burst (BFU-E) showed a variable degree of megaloblastic and culture system and the deoxyuridine suppression test demonstrated active thymidine synthesis. Megaloblastic morphology was correlated with the growth induced by the addition of monocytes to erythroid progenitors. It was concluded that megaloblastosis was a feature of the erythroblasts derived from an early BFU-E which required monocytes for their development.

Bone Marrow Cells↗
PubMed1981

The effect of nitrous oxide-induced inactivation of cobalamin on plasma amino acid levels in the rat.

Rats were maintained in an atmosphere of equal volumes of oxygen/nitrous oxide (1/1) for up to 7 d and plasma levels of methionine, glycine, serine, histidine, homocysteine and S-methylcysteine were measured. There was a fall in plasma methionine and a rise in plasma serine levels. There were no significant changes in glycine and histidine levels. Homocysteine and S-methylcysteine were not detected in rat plasmas. The fall in plasma methionine was due to loss of cobalamin-dependent methionine synthetase activity. The rise in plasma serine may be due to decline in its metabolism via methenyltetrahydrofolate cyclohydrolase which is concerned in oxidizing the methenyl-carbon ( =CH-), initially derived as a methylene-carbon (-CH2-)from serine, to formate (-CHO).

Amino Acids↗
PubMed1981

Changes in plasma folate levels in rats inhaling nitrous oxide.

Inhalation of nitrous oxide, which inactivates vitamin B12, is followed by a rise in the plasma folate level. The concentration of plasma folate remains elevated throughout the period of exposure to nitrous oxide. Returning the rats to the air is followed by a fall to pre-exposure plasma folate levels within 24 h.

Animals↗
PubMed1980

Vitamin B12 regulates folate metabolism by the supply of formate.

Nitrous oxide (N2O) inactivates the B12 coenzyme involved in methionine synthesis and interrupts formation of the folate coenzyme (folate polyglutamate). Normal synthesis of folate polyglutamate is restored in the N2O-treated rat when folate carrying a single carbon unit is supplied at the formate level of oxidation. The activity of the enzyme, formyl synthetase, which links formate to tetrahydrofolate, is increased after exposure to nitrous oxide. Formate is normally derived from the oxidation of methyl groups, methionine being an important source. It is suggested that failure of methionine synthesis leads to a paucity of formate and in turn to inadequate formylation of tetrahydrofolate. Formyltetrahydrofolate is the required substrate for the synthesis of folate polyglutamate, and impairment of this step in turn compromises general folate metabolism.

Animals↗
PubMed1980

The effect of nitrous oxide inactivation of vitamin B12 on rat hepatic folate. Implications for the methylfolate-trap hypothesis.

Rats exposed to N20 show a decrease in liver folate to about 25% of the initial value after 10 days. There is a transient increase in the amount of 5-methylterrahydropteroylpolyglutamate in the first 24 h, but thereafter the content decreases. The level of 5-methyltetrahydropterolymonoglutamate declines without any transitory increase. The transient accumulation of 5-methyltetrahydropteroylpolyglutamate is due to failure of methionine synthetase. Thereafter the decrease in the amount of methylfolate makes it improbable that trapping of methylfolate is the explanation for failure of folate metabolism in vitamin B12 deficiency.

Animals↗
PubMed1980

Globin chain biosynthesis in iron deficiency.

Globin chain synthesis was studied in seven severely iron-deficient patients before and after treatment with iron. There was no appreciable difference between the individual pre- and post-treatment alpha/beta specific activity ratios and the mean alpha/beta ratio for each group was 1.00+/-SD 0.04. In a further six untreated iron-deficient patients the mean alpha/beta ratio was 1.00+/-SD 0.04. There was therefore no evidence that iron deficiency caused a reduction in alpha/beta ratio. Three patients with beta thalassaemia trait and coexistent iron deficiency had lower alpha/beta ratios before treatment than after treatment with iron. It appeared that iron deficiency had caused reduced alpha chain synthesis in this group. Preliminary experiments have shown that the alpha/beta specific activity ratio of purified haemoglobin A is decreased in iron deficiency, indicating an increase in the size of the free alpha chain pool. It is suggested that iron deficiency may interfere with the proteolytic mechanism normally responsible for the destruction of excess alpha chains. In combined iron deficiency and beta thalassaemia trait, the resulting increase in free alpha chains might act by negative feedback to inhibit further alpha chain synthesis (Blum et al, 1970) thereby reducing the pre-treatment alpha/beta ratio.

Globins↗
PubMed1980

Marrow cells from patients with untreated pernicious anaemia cannot use tetrahydrofolate normally.

Folate analogues were added to human bone marrow cells to determine their effect on deoxyuridine utilization in the deoxyuridine suppression test. Formyltetrahydrofolates fully corrected the impairment of dU utilization in pernicious anaemia marrows but tetrahydrofolate was relatively ineffective. All these analogues were effective in megaloblastic marrows from folate deficient patients. Formyltetrahydrofolates also enhanced dU utilization by normal human marrows whereas methyltetrahydrofolate reduced its use. In terms of the methylfolate trap hypothesis, the expectation that cobalamin-deficient marrows would be able to use tetrahydrofolate normally was not realized.

Anemia, Megaloblastic↗
PubMed1980

Inactivation of methionine synthase by nitrous oxide.

Exposure of rats to a 50% N2O/oxygen mixture led to a rapid loss of methionine synthase activity in both liver and brain. This enzyme has vitamin B12 as a cofactor. There was impaired conversion of deoxyuridine to deoxythymidine by bone marrow cells and this defect followed loss of methionine synthase activity. There was no homocystinuria. Withdrawal of N2O was followed by a relatively slow recovery of methionine synthase activity over four days. The inactivation of vitamin B12 by N2O promises to be a valuable tool in the study of vitamin B12 metabolism.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1979

Analysis of variations in hospital use by Medicare patients in PSRO areas, 1974-1977.

A study of the use of short-stay hospitals in PSRO areas by Medicare enrollees aged 65 and over for the period 1974 through 1977 revealed that discharge rates increased, average length of stay (ALOS) decreased, and days-of-care rates remained relatively constant in nearly all of the PSRO areas. The data show large variations in hospital use in PSRO areas within States and HEW regions, and suggest that factors within the area are critical determinants of hospital utilization. This study presents important implications for PSRO program policy for it suggests that factors other than physician and hospital behavior should also be considered when setting objectives for reducing misutilization and improving the quality of health care.

Aged↗