VARIANTS OF Α-Fetoprotein

Purves, Langley R.; Merwe, E Van der; Bersohn, I

doi:10.1016/s0140-6736(70)90076-0

Cited by 39 publications

(17 citation statements)

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“…Purves found an average serum level of 15 ng/ml on Bantu miners [14] R uoslahti and Seppala [19], found 32 normal adult sera levels averaging 7.6 ng/ml. i.e.…”

Section: Discussionmentioning

confidence: 96%

“…They may differ biochemically. Several workers have described molecular variants of AFP, [14,20]. P urves et al [14] insisted on the different anti genic activity of these variants.…”

Section: Discussionmentioning

confidence: 99%

“…Several workers have described molecular variants of AFP, [14,20]. P urves et al [14] insisted on the different anti genic activity of these variants. Even with the same molecular form, the preparation used for calibration may still be impure, or it may be partly denatured by the processing.…”

Section: Discussionmentioning

confidence: 99%

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Radioimmunoassay of α-Fetoprotein. I. Technique and Serum Levels in the Normal Adult

et al. 1974

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“…Purves found an average serum level of 15 ng/ml on Bantu miners [14] R uoslahti and Seppala [19], found 32 normal adult sera levels averaging 7.6 ng/ml. i.e.…”

Section: Discussionmentioning

confidence: 96%

“…They may differ biochemically. Several workers have described molecular variants of AFP, [14,20]. P urves et al [14] insisted on the different anti genic activity of these variants.…”

Section: Discussionmentioning

confidence: 99%

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Radioimmunoassay of α-Fetoprotein. I. Technique and Serum Levels in the Normal Adult

et al. 1974

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“…One might argue that these differences reflect denaturation of hepatoma HAFP by our isolation procedures; however, precisely the same techniques were used for isolation of both proteins. Differences in primary amino acid sequence or in carbohydrate side chains could also be responsible for this difference in biologic potency (3,(25)(26)(27)), but we could elicit no evidence for such alterations by electrophoretic behavior or immunologic characteristicst (28), and others have found the amino acid and sugar composition of fetal and hepatoma HAFP to be almost indistinguishable (11,29). The possibility remains that the greater inhibitory effects of fetal versus hepatoma HAFP may be due to some low-molecular-weight molecule bound to fetal HAFP that emerges from a different biological environment …”

Section: Discussionmentioning

confidence: 99%

Demonstration of the inhibitory effect of human alpha-fetoprotein on in vitro transformation of human lymphocytes.

Yachnin¹

1976

Proc. Natl. Acad. Sci. U.S.A.

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We have studied the effects of human alphafetoprotein (HAFP), isolated from the serum and ascitic fluid of a hepatoma-bearing patient, on the in vitro transformation of human peripheral blood lymphocytes by a variety of mitogenic stimuli. At a concentration of 2.5 mg/ml, HAFP inhibited the Iymphocyte response to phytohemagglutinin, concanavalin A, and rabbit anti-human thymocyte serum, but failed to inhibit the response to pokeweed mitogen. HAFP Until recently, little was known of the biological role of the alpha-fetoprotein (1), although it was regarded as an embryonic serum albumin (2, 3) and was shown to possess estrogen hormone-binding properties (4). Our report on the inhibition of human lymphocyte transformation in vitro by fetuin (5), a bovine alpha-fetoprotein, and the simultaneous observations by Tomasi and his coworkers that murine alpha-fetoprotein suppresses murine lymphocyte responses in vitro to both mitogenic and antigenic stimuli (6, 7), suggest an immunoregulatory role for alpha-fetoproteins during fetal development. This paper presents experimental data that demonstrate the inhibitory effects of human alpha-fetoprotein (HAFP) on lymphocyte responses in vitro to a variety of mitogenic stimuli which include the one-way mixed lymphocytes culture. The results suggest that this effect may be due primarily to an inhibition of thymus-derived lymphocytic (T-lymphocyte) function. MATERIALS AND METHODSThe techniques for isolating, culturing, and harvesting cultures of human lymphocytes were previously described (5,(8)(9)(10). A 1 ml culture system was employed throughout, and all experiments with cultures were performed in triplicate. The effect of preexposure with HAFP on the viability of human lymphocytes was determined by trypan blue exclusion (5), and their ability to undergo subsequent transformation when subjected to a mitogenic stimulus was assessed. Lymphocytes (25-35 X 106), in a total volume of 2.0 ml of RPMI medium and 12.5% of human type AB serum, were incubated for 18 hr in the presence of 2.2 mg/ml of HAFP or HSA, with conditions identical to those used for lymphocyte cultures. A portion (4 X 106) of the lymphocytes was removed from the cell suspensions, spun down, and used for the determination of viability by the trypan blue method. The remainder of the cell suspension was diluted with 5 ml of Amos A gelatin (9) buffer and centrifuged at 150 X g for 15 min. The cell buttons were washed once more with 7 ml of Amos buffer, resuspended in culture medium, and used for transformation studies.The ability of HAFP to inhibit E-rosette formation by Ficoll-Hypaque-isolated human lymphocytes was determined by means of the E-rosette formation procedure, carried out in the presence of 2.5 mg/ml of HAFP . This procedure was similar to one already described (13), except that heat-inactivated human serum (type AB), previously absorbed with sheep red blood cells, was used in place of fetal calf serum.In addition to the effect of HAFP in the mixed lymphocyte culture (MLC), the effect of HAFP on l...

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“…In addition, an increased concentration of AFP in amniotic fluid was found to be a reliable indicator of congenital malformations of the fetus and especially of open malformations of the central nervous system [13], AFP produced by different fetal organs and under various pathologic conditions is immunologicaly identical. However, hetero geneity of AFP can be demonstrated by some electrophoretic techniques and especially by starch gel electrophoresis [ 14] and isoelectric focusing [15,16], To a large extent this het erogeneity might depend on binding of charged molecules by the AFP. Another form of AFP heterogeneity (microhetero geneity) can be demonstrated in its reaction with lectins [17][18][19][20], Two lectins which so far have proven to be most useful for studies of AFP microheterogeneity are concanavalin A (Con A) and Lens culinaris agglutinin (LCA).…”

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Microheterogeneity of Human Alphafetoprotein

Bręborowicz¹

1988

Tumor Biol

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The data available so far on the microheterogeneity of human AFP are reviewed. Molecular and developmental bases for the microheterogeneity of human AFP are discussed. Special attention is paid to the application of the studies on AFP microheterogeneity for the prenatal diagnosis of developmental malformations and for the differential diagnosis of some cancers. The results obtained using different methods are compared with special reference to lectin affinity electrophoresis and lectin affinity chromatography. In addition, a self-explanatory nomenclature of AFP variants is proposed in order to simplify the comparison of results obtained by different investigators. This has already been accepted by several investigators. The eventual simplification of methods applicable for clinical purposes and especially the difficulties encountered in experiments with monoclonal antibodies are also discussed.

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VARIANTS OF Α-Fetoprotein

Cited by 39 publications

References 10 publications

Radioimmunoassay of α-Fetoprotein. I. Technique and Serum Levels in the Normal Adult

Radioimmunoassay of α-Fetoprotein. I. Technique and Serum Levels in the Normal Adult

Demonstration of the inhibitory effect of human alpha-fetoprotein on in vitro transformation of human lymphocytes.

Microheterogeneity of Human Alphafetoprotein

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