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Biomedical subjects

J Abels

Publications and source records attributed to J Abels.

78 records · Page 5Linked to original sources
PubMed1967

Studies on antibody to intrinsic factor.

Sera from a group of 79 patients with pernicious anemia were studied for the presence of antibody to intrinsic factor. Two general types of antibody activity were found, and it was possible to distinguish three groups of pernicious anemia sera on the basis of their content of these types. Type I antibody blocks the binding of radioactive vitamin B(12) to intrinsic factor when added to intrinsic factor before the B(12); it is not detected on intrinsic factor when added after B(12). This antibody blocks intrinsic factor-mediated B(12) absorption in vivo when mixed in the sequence intrinsic factor + antibody I + B(12), but not when mixed in the sequence intrinsic factor + B(12) + antibody I. Type II antibody reacts with intrinsic factor when B(12) is attached. This antibody prevents the absorption of B(12) from intrinsic factor in pernicious anemia patients when mixed in the sequence intrinsic factor + B(12) + antibody II, and is thereby distinguished from antibody I.

Anemia, Pernicious↗
PubMedDate not supplied

Effects of 5-fluorouracil treatment of rat leukemia with concomitant inactivation of cobalamin.

The cytostatic activity of 5-fluorouracil (5-FU) can be modified by the addition of reduced folates, as well as antifolates. This is indicative of the complex involvement of folate metabolism in the effects of 5-FU. In the BN rat leukemia model, 5-FU treatment was combined with the inactivation of cobalamin (vitamin B12) by nitrous oxide (N2O). Exposure to nitrous oxide causes severe disturbance of folate metabolism through the inhibition of the cobalamin-dependent enzyme methionine synthetase, and leads to loss of folates from the cell. With regard to the effects on growth of leukemia, the addition of nitrous oxide did not antagonize 5-FU. On the contrary, therapeutic effects were enhanced by combined treatment, as was evident from a further reduction of leukemic infiltration in spleen and liver, from a decrease or even disappearance of leukemic cells in the peripheral blood, and from extended survival of rats. These findings were in accordance with metabolic studies in isolated leukemic cells of treated rats, in which combined treatment caused further impairment of thymidylate and DNA synthesis. Pretreatment with nitrous oxide, for a period of 3 days, was more effective than treatment after the administration of 5-FU. Folate levels, in plasma and intracellular, were reduced after combined treatment. It is concluded that in this leukemia, unlike observations in some models of solid tumors, the activity of 5-FU is enhanced with a depletion of folates. This effect is probably comparable to the combination of methotrexate pretreatment with 5-FU, and might be important to applications of 5-FU in combination chemotherapy of hematological neoplasms.

Animals↗
PubMedDate not supplied

5-Fluorouracil treatment of rat leukemia and a reappraisal of its application in human leukemia.

5-Fluorouracil (5-FU), an effective pyrimidine antimetabolite was evaluated in the BNML rat model of human acute myeloid leukemia. Single injections of 5-FU, 15-50 mg/kg i.p., caused a sharply dose-related reduction of leukemic growth as measured by liver and spleen weights and leucocyte counts. Similar results were obtained with three doses of 5-FU over a period of 10 days. No apparent toxicity was observed in these experiments. A schedule of 25 mg/kg every 5 days extended the survival time of leukemic rats to 156%, as compared to untreated controls. In the BNML model such an increase in lifespan is equivalent to a 10,000 fold reduction of the tumor mass. These results indicate a potential value of 5-FU treatment in human myeloid leukemia. 5-FU, however, is not used in the clinical treatment of leukemia. A review of the literature revealed that there have been very few relevant studies of this application of 5-FU, while the more unique activity of this drug against some solid tumors has been investigated extensively. Therefore, it can be concluded that there is no clear evidence of the ineffectiveness of 5-FU against leukemia, and that further investigations should find out whether the disregard of 5-FU in this respect is justified.

Animals↗