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I Chanarin

Publications and source records attributed to I Chanarin.

At least 19 recordsLinked to original sources
PubMed1997

A clinically significant anti-HLA-A2 detectable by extended incubation cytotoxicity and flow cytometric techniques but not by a standard NIH lymphocytotoxicity test.

A previously transfused female patient, known to have a platelet defect, was transfused with platelets prior to surgery. After the 18th unit she felt unwell, developed fever, rigor, became nauseous, and vomited. Her blood pressure decreased from 140/90 to 80/50 mm Hg. Passive transfer of donor granulocytes or red cell antibodies were excluded as a cause. Therefore, a serum sample from the patient was investigated for the presence of antibodies to human leukocyte antigens (HLA) using a standard National Institutes of Health (NIH) lymphocytotoxicity test, but antibodies were not detected. However, an extended incubation cytotoxicity test demonstrated the presence of an anti-HLA-A2, and indirect immunofluorescence flow cytometry showed the presence of an IgG1 antibody reacting with 50 percent of cells in a random pool of lymphocytes. One week later, multispecific HLA antibodies were detectable by both NIH and extended incubation cytotoxicity tests. Flow cytometry showed a 16-fold increase in the amount of IgG antibodies and the appearance of an IgM component. Such clinically important HLA antibodies can be detected by extended incubation cytotoxicity and flow cytometric assays prior to becoming reactive in a standard NIH cytotoxicity technique.

Journal Article↗
PubMed1994

Adverse effects of increased dietary folate. Relation to measures to reduce the incidence of neural tube defects.

Folate given in the periconceptional period reduced the numbers of births with neural tube defects (NTD) by 75%. Extension of these observations to all those at risk requires an increase in dietary folate, which can only be achieved by fortification of food. This will result in increased folate consumption by the whole population. Folate in excess of 1 mg daily can have adverse effects in patients with untreated cobalamin deficiency, usually undiagnosed pernicious anaemia (PA). In such patients, the anaemia is ameliorated with a return of normoblastic haemopoiesis, but in about half the patients neuropathy progresses or will develop for the first time. If continued long enough, such neuropathy is not reversed by subsequent cobalamin therapy. The lowest dose of folate that proved effective in preventing NTDs was 0.36 mg daily. This amount, added to a diet that already supplies about 0.2 mg folate, will give an average folate intake of 0.56 mg daily. To avoid exceeding this amount of folate significantly, folate should no longer be added to multivitamin preparations or the amount added should be considerably curtailed. Close surveillance should be set up to determine whether adverse effects are produced as a result of folate fortification of food. This surveillance should identify patients developing cobalamin neuropathy in the absence of anaemia and usually with a normoblastic marrow, a situation that is rare at the present time.

Anemia, Pernicious↗
PubMed1992

Pernicious anaemia.

Explore the source record for details and available documents.

Anemia, Pernicious↗
PubMed1990

Enhancement of recovery from psychiatric illness by methylfolate.

41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.

Adult↗
PubMed1990

Methylthioadenosine serves as a single carbon source to the folate co-enzyme pool in rat bone marrow cells.

[ribose-U-14C]Methylthioadenosine (MTA) was prepared by incubating methionine with [14C-U]ATP in the presence of methionine adenosyltransferase and the resulting S-adenosylmethionine was heated to release MTA. Labelled [14C]MTA, when incubated with rat bone marrow cells, yielded [14C]formate which was used in the synthesis of adenine and guanine. Unlike 14C from sodium, formate, serine and glycine, there was no decline in 14C utilization from MTA with bone marrow cells from rats in which cobalamin had been inactivated by exposure to nitrous oxide. It was concluded that methionine via MTA is a significant contributor of single-carbon units at the formate level of oxidation and that this pathway is maintained in cobalamin 'deficiency'.

Adenine↗
PubMed1990

Cobalamin inactivation induces formyltetrahydrofolate synthetase.

Loss of cobalamin function produces profound changes in the metabolism of formate. There is impaired synthesis of formyltetrahydropteroylglutamate synthetase (CHO-H4PteGlu), accumulation of endogenous formate and impaired utilization of [14C]formate. There are contradictory reports on the effect of cobalamin inactivation on CHO-H4PteGlu synthetase. This study confirms a significant increase in synthetase activity following cobalamin inactivation.

Analysis of Variance↗
PubMed1990

Cobalamin neuropathy. Is S-adenosylhomocysteine toxicity a factor?

Cobalamin neuropathy was produced in cape fruit bats (Rousettus aegyptiacus) by a cobalamin-free diet combined with intermittent exposure to nitrous oxide, which inactivates cobalamin. There were no significant differences in S-adenosylmethionine/S-adenosylhomocysteine ratios in the central nervous system of cobalamin-deficient and cobalamin-replete bats. Taken with other data there are no grounds of support for a hypothesis that cobalamin neuropathy is the result of impaired methylation, however produced.

Animals↗
PubMed1990

Red cell folate concentrations in psychiatric patients.

Red cell folate and vitamin B12 estimations were performed on 243 successively admitted in-patients at a District General Hospital Psychiatric Unit and 42 out-patients (29 attending a lithium clinic). Patients were classified into five diagnostic groups. The mean ages of the manic and schizophrenic patients were lower than of the depressed or euthymic patients but age was not correlated with red cell folate or serum B12 levels in any group. There were 89 (31%) patients with red cell folate below 200 ng/ml and 35 (12%) with concentrations below 150 ng/ml. Significantly more of these low-folate patients were in-patients than out-patients. The mean red cell folate in the depressed patients was significantly lower than in the euthymic, manic and schizophrenic groups. Alcoholics had a similar mean red cell folate to depressed patients which was not quite significantly lower than the other groups. The mean serum B12 level in the alcoholics was, however, significantly raised. There were no significant differences in red cell folate or serum B12 between lithium-treated and untreated euthymic patients. The highest proportions of values below 200 ng/ml and 150 ng/ml were found in depressed and alcoholic patients. Endogenous depressives had the highest percentage of values below 150 ng/ml (folate-deficient) of all psychiatric groups and alcoholic patients. The significance of these findings is discussed.

Adolescent↗
PubMed1990

Formate metabolism in the cobalamin-inactivated rat.

Endogenous formate levels in blood and liver were assayed in rats both after inactivation of cobalamin (Cbl) by exposure to N2O as well as in air-breathing controls. The uptake of [14C]formate by tetrahydrofolate (H4folate) in bone marrow cells and liver homogenate and the incorporation of [14C]formate into purine, pyrimidine, methionine, serine and choline, was measured. There was a significant accumulation of endogenous formate following Cbl inactivation. There was impaired utilization of [14C]formate for single unit carbon (C1 unit) transfers mediated by folate in Cbl-inactivated tissues, other than for synthesis of adenine. The impairment was not accompanied by any accumulation of labelled methylH4folate indicating that methylfolate trapping played no part in impaired single carbon unit transfer. The effect of Cbl lack was a failure to form formylH4folate so that formate accumulated. The reason for this is not known.

Animals↗
PubMed1990

Methylation of DNA in megaloblastic anaemia.

Methylation of cytosine residues in DNA samples, collected before and serially after cobalamin treatment from patients with cobalamin deficiency, was studied using restriction endonucleases Hpa II and Msp I and an epsilon globin gene probe. There was no evidence of hypomethylation in any of the samples. It was concluded that although hypomethylation of metabolites such as choline occurs, that of DNA is preserved in megaloblastic anaemia.

Anemia, Macrocytic↗
PubMed1989

Oxidation of 5-methyltetrahydrofolate in cobalamin-inactivated rats.

Rats were exposed to nitrous oxide, which inactivates cob(I)alamin (Cbl). As in air-breathing rats methionine administration led to the conversion of hepatic 5-methyltetrahydrofolate (MeH4 folate) into formyltetrahydrofolate. The recovery of MeH4 folate levels in liver after its oxidation initiated by methionine was noted and the rate compared with that for air-breathing rats. Oxidation of MeH4 folate was less complete and occurred more slowly in Cbl-inactivated rats as compared with controls. However, recovery of MeH4 folate levels was more rapid in Cbl inactivation. S-Adenosylmethionine did not produce a significant change in MeH4 folate levels in Cbl-inactivated rats, whereas it did so in air-breathing animals.

Animals↗
PubMed1989

Regulation of 5-methyltetrahydrofolate synthesis.

After an intraperitoneal injection of 100 mumol of methionine to rats, there is rapid oxidation of the methyl group of hepatic 5-methyltetrahydrofolate to formate and CO2. Recovery of the methylfolate level starts 2.5 h after the methionine injection, when the hepatic methionine level and the S-adenosylmethionine/S-adenosylhomocysteine ratio have returned to baseline values. S-Adenosylmethionine concentration is still elevated at this time.

Animals↗