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Biomedical subjects

I Chanarin

Publications and source records attributed to I Chanarin.

At least 109 records · Page 6Linked to original sources
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

Effect of anticonvulsants on the uptake of 5-methyltetrahydrofolic acid by the choroid plexus in rabbits.

1. The isolated choroid plexus of the rabbit takes up 5-methyltetrahydrofolate from the incubation medium. 2. Other folate analogues (pteroylglutamic acid, methotrexate, 5-formyltetrahydrofolate = folinic acid) inhibited the uptake of 5-methyltetrahydrofolate. 3. The uptake of 5-methyltetrahydrofolate was inhibited by low temperature, anaerobic conditions and dinitrophenol. 4. The anticonvulsant drugs, diphenylhydantoin and phenobarbital, had no effect on 5-methyltetrahydrofolate uptake. 5. The inhibitory effect of pteroylglutamic acid on the uptake of 5-methyltetrahydrofolate by the choroid plexus may explain the effect of long-term folic acid therapy in aggravating vitamin B12 neuropathy in pernicious anaemia.

Animals↗
PubMed1977

Reversal of ineffective erythropoiesis in pernicious anaemia following vitamin B12 therapy.

Ineffective erythropoiesis was quantitated in a series of patients with pernicious anaemia at different times in relation to vitamin B12 therapy by measuring the incorporation of [15N]delta aminolaevulinic acid and [15N]glycine into early labelled bilirubin. Prior to therapy ineffective erythropoiesis was grossly increased but this was reversed within 24 h of giving vitamin B12, suggesting that most of the existing megaloblasts are enabled to mature into circulating red cells.

Aged↗
PubMed1977

Abnormal folate polyglutamate ratios in untreated pernicious anaemia corrected by therapy.

The relative amounts of folate compounds having 1--3--, 4--, 5-- and 6--glutamic acid residues in the molecule were measured in red blood cells. The results were expressed in relation to methyltetrahydrofolate pentaglutamate (5-glutamic acid residues) which is the analogue present in highest concentration. When the concentration of pentaglutamate is given a value of 100 the relative concentration of folates with 1--3--, 4--, 5-- and 6--glutamic acid residues in control subjects are 48, 48, 100 and 50 respectively. In folate deficiency there is a fall in the relative amount of the short chain glutamic acid chain compounds in addition to having an overall fall in the amount of folate present, the values for 1--3, 4, 5 and 6 chain folates being 16, 14, 100 and 39. By contrast, in untreated pernicious anaemia there is an accumulation of the short chain folates as well as an overall fall in polyglutamate concentration and the relative concentrations were 72, 44, 100 and 30. Folate polyglutamate appears to be the active coenzyme and the reltive amounts of glutamic acid residues may serve to regulate the rate of enzyme activity. In pernicious anaemia the amount of enzyme is reduced and on this hypothesis the regulatory function impaired.

Anemia, Pernicious↗
PubMed1977

The effect of anticonvulsant drugs on thymidine and deoxyribosenucleic acid synthesis by human marrow cells.

An abnormal deoxyuridine suppression test was found in treated epileptic patients that did not correlate with other evidence of abnormal folate metabolism. Diphenylhydantoin at a level of 100 microgram/ml interfered with the incorporation of [3H]thymidine into DNA. It is suggested that anticonvulsants may exert their effect at a stage of DNA synthesis beyond that at which folate coenzymes operate. Folate deficiency may then arise as a result of death of cells in vivo causing an increased folate requirement.

Anticonvulsants↗
PubMed1977

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↗
PubMed1977

The physiological macrocytosis of pregnancy.

Sixty-four healthy women were followed during normal pregnancies in which they took supplements of iron or iron+folate or an inactive placebo. The red cell size increased in those patients receiving iron alone or iron+folate. The group on the inactive placebo who received no supplemental iron had red cells of constant size and a falling serum iron. Nineteen women not included in the trial developed macrocytosis during pregnancy:marrow samples from these showed normoblastic erythropoiesis in 18 and minor megaloblastic changes in one. Macrocytosis developing during pregnancy is a physiological change in the majority of cases.

Adult↗
PubMed1977

Congenital dyserythropoietic anaemia: response to splenectomy and quantitation of ineffective erythropoiesis.

The clinical and haematological features of an unusual case of congenital dyserythropoietic anaemia are described. There was a pronounced haemolytic component to the anaemia, with a mean cell life of five days, and a remarkable response to splenectomy. Measurement of the incorporation of 15N glycine into the haem of circulating red cells and into bilirubin showed that haem turnover due to ineffective erythropoiesis was increased 45 times compared with a control group (11.63 mg/kg/day, NR = 0.26 + 0-10) and represented 51% of total erythroid haem turnover.

Anemia↗