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At least 19 recordsLinked to original sources

Alpha-fetoprotein, alpha-1-antitrypsin, and transferrin in gonadal yolk-sac tumours.

Since gonadal yolk-sac tumour in pure form or as a component of mixed germ cell tumour is in the majority of patients highly malignant, its histological recognition is of great prognostic importance. Yolk-sac tumour may assume various different histological guises, which have hitherto caused considerable terminological confusion; the present paper is aimed at correlating these morphological diversities with biochemical features which are consistent with yolk-sac differentiation. Using an enzyme-bridge immunoperoxidase technique, a series of 16 gonadal germ cell tumours with a yolk-sac component were screened for the presence of alpha-fetoprotein, alpha-1-antitrypsin, and transferrin. These proteins, normally produced by human yolk sac, were demonstrable in all the morphological patterns of yolk-sac tumour we have previously described. Six malignant non-germ cell tumours were submitted to the same investigations, and no evidence of the three protein markers was found in five; one tumour, however, an oat cell carcinoma of the bronchus, stained positively for transferrin.

Adolescent↗

Purification of canine alpha-fetoprotein and alpha- fetoprotein values in dogs.

Canine alpha-fetoprotein (AFP) was purified by a two step method. Anti-dog AFP antiserum was produced by immunizing rabbits with canine fetal serum proteins that failed to bind to an anti-dog whole adult serum affinity column. Canine AFP was then purified from amniotic fluid using affinity chromatography with anti-dog AFP antiserum. The bound protein was then eluted and further purified by passage through an anti-dog whole adult serum column. The non-binding protein's purity and specificity was confirmed by immunoelectrophoresis, double-diffusion, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and cross-reactivity with anti-human AFP. The molecular weight of canine AFP was approximately 66,000 by SDS-PAGE. Normal adult dogs had serum AFP levels of 7-63 ng ml-1. Levels of AFP were not altered by pregnancy but did show a small peak 2 days following parturition. Newborn puppies had serum AFP levels of 14.08 +/- 5.94 mg ml-1 at birth. By 1 week of age, serum AFP had fallen to 0.766 +/- 0.758 mg ml-1. AFP values in newborn puppies are thus considerably higher than those previously reported in humans, pigs and cattle.

Amniotic Fluid↗

T cell responses to HLA-A*0201-restricted peptides derived from human alpha fetoprotein.

alpha fetoprotein (AFP)-derived peptide epitopes can be recognized by human T cells in the context of MHC class I. We determined the identity of AFP-derived peptides, presented in the context of HLA-A*0201, that could be recognized by the human (h) T cell repertoire. We screened 74 peptides and identified 3 new AFP epitopes, hAFP(137-145), hAFP(158-166), and hAFP(325-334), in addition to the previously reported hAFP(542-550.) Each possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent class I binding assay. The peptides were stable for 2-4 h in an off-kinetics assay. Each peptide induced peptide-specific T cells in vitro from several normal HLA-A*0201 donors. Importantly, these hAFP peptide-specific T cells also were capable of recognizing HLA-A*0201(+)/AFP(+) tumor cells in both cytotoxicity assays and IFN-gamma enzyme-linked immunospot assays. The immunogenicity of each peptide was tested in vivo with HLA-A*0201/K(b)-transgenic mice. After immunization with each peptide emulsified in CFA, draining lymph node cells produced IFN-gamma on recognition of cells stably transfected with hAFP. Furthermore, AFP peptide-specific T cells could be identified in the spleens of mice immunized with dendritic cells transduced with an AFP-expressing adenovirus (AdVhAFP). Three of four AFP peptides could be identified by mass spectrometric analysis of surface peptides from an HLA-A*0201 human hepatocellular carcinoma (HCC) cell line. Thus, compelling immunological and physiochemical evidence is presented that at least four hAFP-derived epitopes are naturally processed and presented in the context of class I, are immunogenic, and represent potential targets for hepatocellular carcinoma immunotherapy.

Adenoviridae↗

Cellular and genetic restrictions in the immunoregulatory activity of alpha-fetoprotein. II. Alpha-fetoprotein-induced suppression of cytotoxic T lymphocyte development.

Alpha-fetoprotein (AFP), a major component of fetal and newborn sera, was shown to exert significant immunosuppressive activity on the in vitro generation of cytotoxic T lymphocytes (CTLs). This suppression proved independent of the suppressibility of the mixed leukocyte culture activation phase, since strain combinations whose proliferative responses were refractive to AFP-induced suppression also failed to develop demonstrable CTLs in the presence of AFP. Several strain combinations were also found in which normal generation of CTLs occurred in cultures containing AFP. This refractive nature correlated with the presence of nonsuppressible lymphocyte-stimulating alloantigenic systems on the stimulating cell population. These data provide the basis for proposing several possible mechanisms for AFP-induced suppression of T-cell-mediated cytotoxicity, as well as suggesting that the primary target of this suppression is the proliferating helper T cell precommited to respond towards the major histocompatibility complex-associated lymphocyte-activating determinants.

Animals↗

Simultaneous determination of percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein and alpha-fetoprotein concentration using the LiBASys clinical auto-analyzer.

BACKGROUND: Lens culinaris agglutinin (LCA)-reactive alpha-fetoprotein (AFP-L3) percentage of total AFP concentration [(AFP-L3/total AFP)x100] has been used as an effective marker for earlier diagnosis, for assessment of therapeutic effects and for predicting the prognosis of hepatocellular carcinoma (HCC). METHODS: A new clinical automatic analyzer, the "LiBASys", and an assay kit for the simultaneous determination of AFP-L3 percentage and concentration of AFP in human serum were developed. LiBASys performed automatic re-measurement and also met stat samples. Both AFP-L3 percentage and AFP concentration were calculated simultaneously and printed out continuously every 3.4 min per test. RESULTS: A linear dose-response relationship was observed up to 1000 ng/ml AFP concentration. The detection limit and functional sensitivity of LCA-nonreactive AFP (AFP-L1) and AFP-L3 concentrations were 0.4 and 0.8 ng/ml, and 0.4 and 1.0 ng/ml, respectively. Interassay CVs of AFP-L3 percentage and AFP concentration ranged from 2.8% to 13.4% and 2.6% to 4.6%, respectively. Assay results exhibited good correlations with those of commercially available lectin-affinity electrophoresis (r=0.984) for AFP-L3 percentage and with the RIA method (r=0.999) for AFP concentration. CONCLUSIONS: This method simultaneously yields both qualitative and quantitative results for AFP-L3 percentage and AFP concentration.

Adult↗

The differential diagnosis of yolk sac tumor and seminoma. Usefulness of cytokeratin, alpha-fetoprotein, and alpha-1-antitrypsin immunoperoxidase reactions.

Yolk sac tumor and seminoma may have a similar appearance in focal areas. Small biopsies may therefore be difficult to interpret. The authors studied 20 yolk sac tumors and 21 seminomas to investigate the utility of immunohistochemical markers in this differential diagnosis. All yolk sac tumors stained positively for cytokeratin (CK) but so did 43% of seminomas. The CK positivity of yolk sac tumors was generally more diffuse and intense, however, there was an overlap in the spectrum of intensity of CK positivity in yolk sac tumor and seminoma. Alpha-fetoprotein (AFP) was a less sensitive (55%) marker for yolk sac tumor than CK, but AFP was quite specific in this differential diagnosis because no seminoma stained for AFP. Alpha-1-antitrypsin was not a very useful marker because of poor sensitivity and specificity. The interpretation of light microscopic patterns remains of paramount importance in the differentiation of solid yolk sac tumor from seminoma.

Diagnosis, Differential↗

Establishment of a human hepatoblastoma model in athymic nude mice. Producibility of fatty acid-binding protein, alpha-fetoprotein, and alpha 1-acid glycoprotein.

An athymic nude mouse model of human hepatoblastoma, designated HBL-2, was established. HBL-2 produced alpha-fetoprotein (AFP) and the serum level in tumor-bearing mouse was roughly proportional to the tumor weight. Reactivity of AFP to Concanavalin A and Lens culinaris lectins indicated that it contained predominantly fucosylated, non-bisecting N-acetylglucosamine as a sugar moiety. Alpha 1-acid glycoprotein (AAG) was also found in both HBL-2 tumor extract and sera of tumor-bearing mice. The serum level, however, was not proportional to either the tumor weight or the value of the tumor extract. In addition, fatty acid-binding protein (FABP) was detected in approximately 40% of tumor cells and in tumor extract with polyclonal antibody against liver FABP. Thus, HBL-2 is an unique model of human hepatoblastoma, in that it produces FABP in addition to AAG and AFP.

Animals↗

Elevated serum alpha fetoprotein and normal liquor alpha fetoprotein values in association with an abdominal pregnancy.

A case report is described in which abdominal pregnancy was misdiagnosed by ultrasound scanning as a pregnancy within a horn of a bicornuate uterus. Two serum alpha fetoprotein (SAFP) results were greatly elevated and an amniocentesis was performed, the liquor alpha fetoprotein (LAFP) and karyotype were normal. Elective Caesarean section was performed at 38 weeks for a persistent transverse lie and an abdominal pregnancy was found. The outcome was excellent for both the mother and child. This is the first reported case of amniocentesis and measurement of LAFP in an abdominal pregnancy and confirms abdominal pregnancy as a rare cause of an elevated SAFP.

Adult↗

Alpha-fetoprotein, prealbumin, albumin, alpha-1-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors.

According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.

Adolescent↗

Monoclonal antibodies against human alpha-fetoprotein more reactive to cell-surface alpha-fetoprotein than to free alpha-fetoprotein.

This paper describes the finding of monoclonal antibody (MoAb) more reactive to cell-surface alpha-fetoprotein (AFP) than to free AFP by using a simple in vitro system. Twelve mouse MoAbs, ten IgG1, one IgG2a and one IgG2b, against human AFP from hepatocellular carcinoma were obtained by the cell fusion technique. Each hybridoma supernatant was assayed by enzyme-linked immunosorbent assay (ELISA) to solid-phase AFP. The assay results showed that two MoAbs, 67D and 80G, were most reactive to AFP. 80G had a higher affinity constant than 67D, while the both reactions were similarly difficult to inhibit by free AFP in ELISA. 67D and 80G reacted with AFP on the surface of ethanol-fixed cells from the human hepatoma cell line HuH-7 and this reaction was also difficult to inhibit by free AFP in Cell ELISA. Furthermore, Western blot analysis showed that 67D and 80G were more reactive to membrane-bound AFP than other antibodies. These findings first suggest that there could be anti-AFP MoAbs preferably binding to cell-surface AFP rather than to serum AFP.

Antibodies, Monoclonal↗

Immunohistochemical type distinction of alpha-fetoprotein in various alpha-fetoprotein-secreting tumors.

In order to clarify the histogenesis of alpha-fetoprotein (AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.

Female↗

Combined serum hepatoma-specific alpha-fetoprotein and circulating alpha-fetoprotein-mRNA in diagnosis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, its prognosis is poor, and early detection is of utmost importance. Although alpha-fetoprotein (AFP) is a useful marker for detecting and monitoring HCC development, the false-negative or false-positive rates with AFP alone may be as high as 30%-40% for patients with small HCCs. To enhance the specificity and accuracy of AFP measurements for HCC, we analyzed AFP expression states in livers, detected the hepatoma-specific AFP (HS-AFP) fraction and AFP-mRNA from peripheral blood mononuclear cells, and explored their clinical implications for HCC diagnosis. METHODS: AFP expression and hepatocyte distributions in liver specimens were investigated by an immunohistochemical assay. Total RNAs were extracted from circulating blood, synthesized to cDNA through random primers and reverse transcriptase, and fragments of the AFP gene were amplified by a nested-PCR assay. The HS-AFP fraction was separated by lectin-affinity chromatography and its level was detected by radioimmunoassay. RESULTS: The incidence of AFP was 73.3% in HCC tissues and its expression in HCCs with moderate or low differentiation was significantly stronger than that of HCCs with high differentiation (P<0.05). The incidence of AFP gene fragments was 100% in HCCs, and 60% in paracancerous tissues (P<0.01). In the HCC and liver cirrhosis groups, the incidence of HS-AFP was 91.7% and 18% (P<0.01), and of AFP-mRNA was 56.7% and 16% (P<0.01), respectively, and neither was found in controls. HS-AFP or AFP-mRNA was not significantly related to size or number of HCC, but to its differentiation, metastasis, and relapse (P<0.05). CONCLUSIONS: Different AFP expression is present in different parts of HCC tissues. HS-AFP and AFP-mRNA fragments improve sensitivity and specificity, and both are useful markers to diagnose HCC or monitor metastasis and relapse.

Adult↗

Screening for multiple pregnancy. Determination of human chorionic gonadotropin (hCG), alpha-fetoprotein (alpha-FP) and human placental lactogen (hPL) in blood during the second trimester of pregnancy.

The value of single determinations of serum hCG, hPL, and alpha FP for the detection of multiple pregnancy was investigated in a consecutive series of 992 women between the 14th and 24th week of pregnancy. With the 90th percentile as referent value, all twin pregnancies (n = 10) were detected by the combined results of the three determinations. Considered separately, hPL proved to be the most useful indicator of multiple gestation; the sensitivity of hPL alone was 70% and the predictive value of hPL concentrations above the 90th percentile was 8.1.

Chorionic Gonadotropin↗

Doppler velocimetry of the umbilical artery as a predictor of pregnancy outcome in pregnancies characterized by elevated maternal serum alpha-fetoprotein and normal amniotic fluid alpha-fetoprotein.

OBJECTIVE: Women with elevated maternal serum alpha-fetoprotein (MSAFP) and normal amniotic fluid alpha-fetoprotein (AFAFP) are at an increased risk of an adverse pregnancy outcome. Such MSAFP elevations are probably the consequence of transplacental leakage caused by placental abnormalities. These may result in disturbed bloodflow through placental vessels. The purpose of this study was to assess whether measurement of such disturbances by Doppler velocimetry of the umbilical artery has a predictive value for pregnancy outcome. STUDY DESIGN: The study group consisted of 85 patients, in whom the only finding was elevated maternal serum alpha-fetoprotein. Systolic/diastolic (S/D) ratios were calculated using a continuous wave Doppler measurement of the umbilical artery, performed at 6 to 8-week intervals. Serial results for each individual were incorporated into a single 'Velocimetry Score'. RESULTS: In group B (14 patients) with an abnormally elevated umbilical S/D ratio, a higher incidence of intrauterine growth retardation (42.9%), preterm deliveries (78.6%), and fetal loss (42.9%) was noted, as compared with group A (71 patients) with a normal S/D ratio. CONCLUSIONS: Umbilical artery Doppler velocimetry may serve as a predictor of pregnancy outcome in the high-risk group characterized by elevated MSAFP.

Adult↗