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S Waxman

Publications and source records attributed to S Waxman.

177 records · Page 10Linked to original sources
PubMed1970

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↗
PubMed1969

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↗
PubMed1968

Malabsorption of hemoglobin iron in pernicious anemia: correction with intrinsic factor--containing substances.

Hemoglobin iron absorption in patients with treated prenicious anemia (PA) and concomitant iron deficiency was low compared to absorption in patients with iron deficiency alone. Crude and purified hog intrinsic factor (IF) concentrates doubled the absorption of hemoglobin iron in these patients as did normal (neutralized depepsinized) human gastric juice. Hemoglobin iron absorption was not significantly enhanced by PA gastric juice. Absorption of heme iron, like that of hemoglobin iron, was enhanced by normal neutralized depepsinized gastric juice. No enhancement of hemoglobin iron absorption by these substances was obtained in the normal or iron-deficient non-PA control subjects. Preincubation of the hog IF concentrate with antisera to IF significantly reduced the enhancement of hemoglobin iron absorption due to the concentrate. In vitro studies suggest that heme complexes with a substance present in IF-containing materials. Whether a gastric glycoprotein similar to IF serves as an intestinal transport factor for heme, similar to transport of vitamin B(12), or whether normal gastric juice acts by another mechanism cannot be determined at this time.

Anemia, Hypochromic↗
PubMedDate not supplied

Benzyl alcohol alters the hemoglobin phenotype of mouse erythroleukemia cells.

The hemoglobin minor/hemoglobin major ratio expressed in mouse erythroleukemia (MEL) cells grown in vitro varies according to the differentiation inducer utilized. For example, butyrate and hemin induce higher hemoglobin minor/hemoglobin major ratios than do dimethyl sulfoxide (DMSO) or hexamethylene bisacetamide (HMBA). Benzyl alcohol in non-toxic concentrations was found to markedly reduce the hemoglobin minor/hemoglobin major ratio and to moderately reduce the total hemoglobin induced by DMSO or HMBA in MEL cells, while only slightly decreasing the ratio induced by hemin or butyrate. The addition of dexamethasone (another and more potent inhibitor of the induction of hemoglobin synthesis than benzyl alcohol) to the media during HMBA induction of differentiation increased the hemoglobin minor/hemoglobin major ratio. This is similar to other "inhibitory" treatments (i.e., treatments that result in sub-optimal hemoglobin production) that have been previously reported. Therefore, although benzyl alcohol and dexamethasone both partly inhibit the induction of total hemoglobin production, they have opposite effects on the induced hemoglobin phenotype: benzyl alcohol decreases the hemoglobin minor/hemoglobin major ratio while dexamethasone increases it. The mechanism(s) of the alteration in the hemoglobin phenotype is unknown as is the mechanism of induction by any of the various inducing agents or of the inhibition of induction by any treatment. However, it appears that if the signal for the induction of hemoglobin minor is sufficiently potent (as it is during butyrate or hemin induction), it cannot be overcome by benzyl alcohol at a "non-toxic" concentration.

Acetamides↗
PubMedDate not supplied

Inhibition of methionine transport by methotrexate in mitogen-stimulated human lymphocytes.

Mitogen stimulation of human lymphocytes was used to study the expression of several amino acid transport systems in response to cell growth. Resting lymphocytes possess detectable neutral amino acid transport systems which can be activated by the mitogen, phytohemagglutinin (PHA). Sodium-independent transport of 2-aminobicyclo (2,2,1) heptane 2-carboxylic acid was similar in resting and stimulated lymphocytes. However, sodium-dependent uptake of methyl aminoisobutyric acid and alpha-aminoisobutyric acid increased threefold to eightfold with stimulation by PHA. Methionine uptake was primarily sodium-independent in resting lymphocytes, whereas methionine uptake increased fourfold to eightfold in stimulated cells; most of this increase was attributable to sodium-dependent transport. Uptake of methotrexate (MTX) was minimal in resting lymphocytes but was maximal 72 hrs after stimulation with PHA; this increase in MTX uptake was accompanied by inhibition of sodium-dependent methionine transport. These results suggest that PHA activates sodium-dependent transport of methionine and that this activation is blocked by the folate antagonist, MTX.

Biological Transport↗
PubMedDate not supplied

Structural requirements for differentiation-induction and growth-inhibition of mouse erythroleukemia cells by isoflavones.

Isoflavones are natural plant phytoestrogens which have been shown to have anticancer proliferation, differentiation and chemopreventive effects. In order to determine structure-function requirements, we compared the effects of several isoflavone derivatives and one flavone on mouse erythroleukemia (MEL) cell growth and differentiation. All chemicals tested are closely related in structure to genistein (4',5,7-trihydroxyisoflavone), a known differentiation inducer and tyrosine protein kinase inhibitor. Genistein, daidzein (4',7-dihydroxyisoflavone) and genistin (7-glucoside of genistein) induced differentiation of MEL cells based on benzidine staining. Biochanin A (5,7-dihydroxy-4'-metho-xyisoflavone) and apigenin (4',5,7-trihydroxyflavone) had no differentiation inducing effect. The potency of these chemicals on cell growth inhibition was apigenin > genistein > genistin > biochanin A > daidzein. These results suggest that the isoflavone structure and 4'-hydroxyl group are essential for the differentiation induction effect, whereas trihydroxyl derivatives are good growth inhibitors. Daidzein is a potent differentiation inducer with the least cytotoxic effect.

Animals↗