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V Herbert

Publications and source records attributed to V Herbert.

At least 199 records · Page 11Linked to original sources

A foreword.

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Folic Acid↗

Release of vitamin B12--binding protein by human leukocytes in vitro.

Human granulocytes (G) contain a vitamin B(12)-binding protein (B(12)BP). There is evidence that chronic myelogenous leukemia leukocytes (CMLL) may synthesize B(12)BP. Our prior studies suggested that intact, living intravascular G synthesize and release such protein into extracellular compartments in vivo. In the present study, CMLL were incubated in Trisbuffered Hank's basal salt solution (pH 7.2) containing 0.1% human serum albumin to study release of B(12)BP into the medium. B(12)BP was released continuously and in increasing amounts over a 5 hr period at 37 degrees C; this release was inhibited almost completely when the cells were incubated at 4 degrees C and by about half as much in the presence of N-ethylmaleimide (1 mmole/liter). Cycloheximide (50 mug/ml) had no effect on the release of B(12)BP but significantly inhibited incorporation of leucine-(3)H into leukocyte protein. G incubated with 20 mg/ml of compound 48/80, an experimental histamine-releasing agent, had a 6-fold increase in release of B(12)BP over a 2 hr period. Subcellular fractionation studies of human granulocytes demonstrate that most of the B(12)BP is associated with the granular (20,000 g) layer with an excellent correlation observed between its subcellular distribution and that of acid phosphatase.These findings suggest that the release of B(12)BP from G is mediated by an active process and provide further evidence that granulocytes are secretory as well as phagocytic cells.

Chromatography↗

Defective DNA synthesis in human megaloblastic bone marrow: effects of homocysteine and methionine.

In B(12) deficiency, inadequate DNA synthesis seems due in large measure to a block of tetrahydrofolic acid (THFA) regeneration from 5-methyl THFA (via homocysteine transmethylation). In support of the above, homocysteine appears to facilitate and methionine to reduce de novo DNA synthesis. This was measured by the ability of deoxyuridine to suppress thymidine-(3)H uptake into DNA in human bone marrow cultures. The homocysteine effect in B(12)-deficient marrow supports the possibility that there is in man an additional B(12)-independent pathway for regeneration of THFA by methylation of homocysteine to form methionine. Among possible explanations for the methionine effect is end-product inhibition of the homocysteine transmethylase reaction, resulting in further accumulation of 5-methyl THFA. Homocysteine transmethylation may play an important role in the regulation of THFA availability and de novo DNA synthesis. In vitro and in vivo evidence suggests that methionine may be useful to potentiate and homocysteine to reduce methotrexate action.

Anemia↗