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.

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.

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.

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.

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.

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.

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.

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.

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.

Cobalamin-folate interrelations.

Cobalamin deficiency leads to impaired folate function as demonstrated by markedly impaired single-carbon unit transfer into purine, thymidine and methionine. This occurs in the total absence of 'methylH4folate trapping'. In cobalamin deficiency there is impaired synthesis of formylH4folate and raised levels of endogenous formate in blood and liver.

The recovery of circulating progenitor cells after chemotherapy in AML and ALL and its relation to the rate of bone marrow regeneration after aplasia.

Peripheral blood levels of BFU-e, CFU-GM and CFU-mix were studied serially in nine patients with acute leukaemia in remission during the period of recovery that followed induction or consolidation chemotherapy. Following 23 courses of treatment in the nine patients, the values for all three classes of progenitor were found to be higher in ALL than in AML (mean peak CFU-GM levels 5.8 x 10(3)/ml and 0.

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.

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.

In vivo oxidation of the methyl group of hepatic 5-methyltetrahydrofolate.

Methionine given parenterally to rats caused rapid disappearance of methyltetrahydrofolate from the liver and a corresponding rise in tetrahydrofolate and formyl-tetrahydrofolate concentrations. When [14C]H3--H4folate was given, methionine caused an increased [14C]0(2) excretion, indicating that oxidation of the methyl group had occurred. Methionine was more effective than S-adenosylmethionine at causing oxidation, but serine was ineffective.

Vegetarian diet and cobalamin deficiency: their association with tuberculosis.

To determine whether the high incidence of tuberculosis among Asiatic Indians in the United Kingdom was due to impaired killing of Mycobacterium tuberculosis by macrophages from patients deficient in cobalamin, a nutritional survey was carried out among 1187 Indians and the incidence of tuberculosis determined from medical records. The question asked was whether tuberculosis was significantly more common among life-long vegetarians compared with omnivores. The incidence of tuberculosis in vegetarians was 133 in 1000 and that in subjects on mixed diets 48 in 1000.