The substrate for folate polyglutamate biosynthesis in the vitamin B12-inactivated rat.
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Animals↗
Biomedical subjects
I Chanarin
Publications and source records attributed to I Chanarin.
Characterization of endogenous folate and incorporation of labelled folates into the brain of the South African fruit bat.
Folate in the brain of the South African fruit bat consists of 10-formyltetrahydropteroyglutamic acid and the tri-, tetra- and penta- forms of 5-methyltetrahydropteroylglutamic acid. Following parenteral injection, only 5-[3H]-methyltetrahydropteroylglutamic acid was taken up by the brain, but none of a dose of 14C-labelled tetrahydropteroylglutamic acid was detectable. Only trace smounts of the 5-methyltetrahydropteroylglutamic acid were converted into the formyl compounds and a small amount of methyltetrahydropteroyltriglutamic acid appeared after 96 h. There was no significant difference in vitamin B-12-deficient animals.
Animals↗
Fluxes of plasma transcobalamins following saturating doses of vitamin B12 in man.
The three vitamin B12 binding proteins in plasma were saturated with vitamin B12 by an intravenous injection of 57Co-vitamin B12. All three unsaturated vitamin B12 binding proteins reappeared in plasma in detectable amounts within 15 min of the clearance of unbound vitamin B12 from plasma.
Aged↗
Mean cell volume in a working population: the effects of age, smoking, alcohol and oral contraception.
The effects of mean cell volume (MCV) of age, smoking habit, alcohol consumption, menopausal status, and use of oral contraceptives have been studied as appropriate in 1596 white men and 892 white women in working populations in North-West London. In men, increasing age, smoking and alcohol consumption each make an independent contribution to MCV. In women, the effect of smoking is similar to that in men; the effect of alcohol is less obvious, possibly because of the low stated alcohol intake in women. The effect of alcohol on MCV in the population studied is not as marked as in hospital patients who admit to excessive alcohol consumption; this may partly be due to differences in methods of eliciting intake. There is a small increase in MCV following the menopause. Women on oral contraceptives show a rise in MCV with increasing age; this is not seen in women not on oral contraceptives. There is a strong inverse association between MCV and red blood cell count, which may be part of a mechanism to ensure constant oxygen carrying capactiy.
Adolescent↗
Familial erythrocytosis.
Erythrocytosis was found in 3 generations of an English family. The red cell mass was only moderately increased in some of the affected members but was accompanied by an unusually low plasma volume. Oxygen affinity of Hb was normal. Changes in serum and urinary erythropoietin showed an essentially normal pattern throughout a series of venesections. Venesection produced some transient clinical benefit in the older patient but there was no obvious change in the younger ones.
Adult↗
Selective inactivation of vitamin B12 in rats by nitrous oxide.
Exposure of rats to nitrous oxide rapidly inactivated the cytosol enzyme, methionine synthetase, but the mitochondrial enzyme, methylmalonyl CoA mutase, seemed to be unaffected, although both enzymes require vitamin B12.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
Evidence for intestinal origin of transcobalamin II during vitamin B12 absorption.
The plasma binding of newly absorbed, radioactively labelled vitamin B12 was studied during a urinary excretion (Schilling) test. Vitamin B12, after being absorbed from the gut, enters blood attached to transcobalamin II, which seems to be derived from the ileal enterocyte. The absorbed B12 re-enters the blood stream after the transcobalamin II-B12 complex is cleared by the liver and it is then excreted into the urine during the Schilling test.
Aged↗
Inhibition of intrinsic factor secretion by cimetidine.
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Cimetidine↗
Nitrous oxide and vitamin B12.
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Anemia, Megaloblastic↗
Folate-dependent serine synthesis in lymphocytes from controls and patients with megaloblastic anaemia: the effect of therapy.
The utilization of [14C]formate for serine synthesis by lymphocytes was impaired in all the patients with pernicious anaemia and in 70% of other patients with megaloblastic anaemia. In pernicious anaemia this was corrected by vitamin B12 therapy in 48 h but not by folate therapy although patients given folate showed a satisfactory haematological response.
Anemia, Macrocytic↗
Effect of phenytoin on DNA synthesis by human bone marrow.
Diphenylhydantoin (phenytoin) when incubated with human marrow interfered with the synthesis of deoxyribosenucleic acid (DNA) by those cells. This interference was dose related but was present at all concentrations, 25 microgram/ml to 100 microgram/ml. Cells unable to complete DNA synthesis would die in the marrow, lead to ineffective haemopoiesis and an increased folate requirement.
Bone Marrow↗
The effect of homocysteine, methionine, serine and glycine on DNA synthesis by human normoblastic and megaloblastic bone marrow cells.
Both glycine and methionine, when added to a suspension of human bone marrow cells, impaired the utilization of deoxyuridine for DNA synthesis, using either the uptake of 3H-deoxyuridine or the subsequent uptake of 3H-thymidine as an index. Homocysteine reduced the uptake of both 3H-deoxyuridine and 3H-thymidine, indicating interference with DNA synthesis after the stage of thymidylate synthesis. Another explanation that the decreased uptake of both substances by homocysteine was due to cell damage caused in vitro was suggested by the trypan blue viability test. Serine generally did not produce significant effects. No difference could be detected between the results in normoblastic and megaloblastic marrow.
Bone Marrow Cells↗
Studies in chronic lymphocytic leukaemia. The kinetics of 51Cr-labelled lymphocytes.
1. 9 Studies of lymphocyte transport are reported in which the 51Cr labelling technique of Hersey (1971) was employed on 8 patients with chronic lymphocytic leukaemia (CLL) and 1 with lymphosarcoma. 2. A new approach to the analysis of the data was formulated employing the principles of impulse analysis. This allowed the quantitation of cell transport between various locations making the minimum number of assumptions. It was also possible to take account of the principal defect of this label, its tendency to elute from live cells. 3. In spite of marked lymphocytosis, numbers of cells moving between those tissues whose lymphocytes exchange relatively slowly and the bloodstream was found to be normal. The blood and lymph nodes may therefore accumulate lymphocytes in response to a transport defect which hinders the progress of these cells from one pool to another. 4. The finding that CLL lymphocytes fluxes are normal in certain locations casts doubt on the hypothesis that lymphocyte proliferation is uncontrolled in this disease. An alternative possibility is that cell proliferation is regulated so as to maintain these fluxes within the normal range.
Aged↗
Platelet Autoimmunity.
Autoimmunity to platelets was looked for by complement fixation, antiglobulin consumption, transformation and migration-inhibition techniques. Only the migration-inhibition method gave consistently positive results. The test was positive in nine out of 14 patients with idiopathic thrombocytopenic purpura and all five patients with glandular fever.
Autoantibodies↗
Deoxyuridine suppression test: a comparison of two methods and effect of thymidine on the incorporation of 3H-deoxyuridine into DNA in human bone marrow cells.
Deoxyuridine suppression tests have been performed by two different methods of six normoblastic and eight megaloblastic marrows. A good correlation was obtained between the results by the modified and the original methods. The simplified method was found to be applicable for a clinical purpose to diagnose megaloblastosis in the marrow. Uptake of 3H-deoxyuridine into DNA and effect of various concentrations of thymidine was studied on five normoblastic and six megaloblastic marrows. In megaloblastic marrows, a greater amount of thymidine was required to obtain the same rate of suppression of 3H-deoxyuridine incorporation into DNA than in normoblastic marrows. Impairment of thymidine incorporation into DNA in megaloblastic marrows was not revealed. Therefore, lower rate of suppression of 3H-deoxyuridine by thymidine in megaloblastic marrows may be due to impairment of the incorporation of deoxyuridine before the addition of thymidine.
Anemia, Megaloblastic↗
Lack of association of the development of anti-sperm antibodies and other autoantibodies as a consequence of vasectomy.
The possibility of autoantibodies--other than sperm antibodies--developing as a consequence of vasectomy has been investigated in 255 volunteers. During the first year after vasectomy no obvious increase was observed in the occurrence of any of these antibodies (rheumatoid factor, antinuclear antibodies and antibodies against smooth muscle, mitochondria, gastric parietal cell, thyroid microsomes and thyroglobulin). Ninety-nine of the patients were also examined for agglutinating and immunofluorescent antibodies to sperm to see if there was any relationship between the occurrence of anti-sperm antibodies and other autoantibodies. However, the prevalence of non-sperm autoantibodies did not differ in two nearly equal groups of patients with and without indications of autoimmune reactions to spermatozoa, respectively. Consequently the present results lend no support to the hypothesis that vasectomy could induce autoimmunity to other autoantigens than sperm-specific antigens.
Agglutinins↗