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Evolutionary and structural relationships among the group-specific component, albumin and alpha-fetoprotein.

The group-specific component (Gc) is a plasma protein that binds vitamin D. Recent characterization of human Gc cDNA demonstrated homology with serum albumin and alpha-fetoprotein. This study compares the sequences of the three proteins and demonstrates a strong evolutionary relationship. Albumin, alpha-fetoprotein and Gc evolved from an ancestral gene containing an intragenic triplication. Comparison of the amino acid sequences and patterns of double disulfide bonds suggests that the Gc gene may have diverged from an ancestral gene earlier in evolution than the genes encoding albumin and alpha-fetoprotein. Analysis of the amino acid and nucleotide sequences of the three internal domains of Gc revealed 19-23% amino acid sequence identity and the localization of three homology blocks with 40-44% nucleotide sequence identity. The deduced amino sequence of Gc furnished data for comparing its molecular configuration based on the predicted secondary structure with those predicted for human albumin and alpha-fetoprotein. Utilization of Gc cDNA has also led to the identification of its genomic DNA and detection of a human DNA polymorphism.

Albumins

Tissue sites of alpha fetoprotein synthesis by the rat during pregnancy and hepatoma growth.

The tissue sites of alpha1 fetoprotein (AFT) synthesis by the rat during gestation and hepatoma growth were determined by specific incorporation of a radiolabeled amino acid precursor into AFP by tissue cultures in vitro. During gestation, AFP were produced by the yolk sac, the fetal liver, and in small amounts by the fetal gastrointestinal tract; there was no synthesis by maternal rat tissues. During growth of a transplantable hepatoma, only the hepatoma tissue synthesized AFP; the nontumor tissue of the host contained AFP but did not produce it.

Animals

Regional prevalence of hepatitis B, delta, and human immunodeficiency virus infection in southern Africa: a large population survey.

Although hepatitis B infection is endemic in southern Africa, a changing epidemiology of the disease has recently been documented in the region. The authors surveyed migrant southern African male mineworkers during 1986 to establish the prevalence of chronic hepatitis B and D (delta) infection in their areas of origin. Hepatitis B surface antigen (HBsAg) was tested in 29,312 adult male mineworkers from 18 geographic regions, encompassing the diverse tribal and linguistic groups in the region, as well as in expatriate mineworkers from neighboring southern African countries. The same cohort was also tested for antibody to human immunodeficiency virus (HIV). Selected hepatitis B carriers were also tested for hepatitis B virus deoxyribonucleic acid (DNA), antibody to hepatitis D (anti-HD), and alpha-fetoprotein. The overall prevalence of HBsAg in this survey was 9.9%. However, the prevalence varied from 5.5% to 14% in different ethnic groups. A minority of carriers (4.9%) had replicative hepatitis B infection and were hepatitis B virus DNA-positive. Only 0.6% of tested carriers were anti-HD-positive. Alpha-fetoprotein determinations were abnormal in 1.2% of hepatitis B-positive men. These data show that although chronic hepatitis B infection remains widespread in southern Africa, carrier rates vary significantly from region to region. In contrast, hepatitis D co-infection remains extremely uncommon. These baseline seroprevalence data also establish that HIV infection was, in 1986, a rare infection in the indigenous population of South Africa.

Acquired Immunodeficiency Syndrome

Alpha-Fetoprotein levels in normal males from seven ethnic groups with different hepatocellular carcinoma risks.

Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.

Adult