The distribution of the human endogenous retrovirus (HERV)-K genome was investigated by Southern-blot analyses using a HERV-K-env DNA probe. With the exception of one DNA-sample, obtained from a Chinese individual in whom an amplification of HERV-K was detected, Southern-blot analyses yielded identical hybridization patterns with DNA from peripheral blood lymphocytes of 37 normal healthy blood donors, with DNA from six tumor cell lines, or with 23 DNA samples prepared from various carcinoma tissues. To elucidate whether the integration of HERV-K genomes into the primate lineage occurred as a single event or as an integration with later expansion, we further examined the evolutionary history of HERV-K by Southern blot analyses with DNA samples from different primate species. We detected HERV-K genomes in Macaca mulatta and Macaca silenus, which represent Old World monkeys, but not in prosimians (Galago demidovii) and New World monkeys, represented by Saguinus fuscicollis, Saguinus oedipus, and Callithrix iacchus. Thus, we assume that the infection of the primate lineage with HERV-K had occurred after the divergence of New World and Old World monkeys, but before the evolutionary expansion of large hominoids. In contrast to the apparent lack of HERV-K-env sequences in DNA from tissue of the New World monkey Saguinus oedipus (cotton-top marmoset), we found HERV-K-DNA in the B95-8 cell-line, which is a Saguinus oedipus leukocyte cell-line, immortalized in vitro by Epstein-Barr virus (EBV) and cultivated in human cells. It may be speculated that HERV-K-DNA or HERV-K-particles were introduced into these cells during in vitro transformation with EBV.

We amplified, via PCR, DNA segments from intron 1 of the tyrosine hydroxylase gene (TH01) and intron 40 of the von Willebrand factor gene (VWA) in ten nonhuman primate genera. In humans both introns contain polymorphic microsatellites with tetrameric repeats. Compared to the allelic ranges in human populations relatively short repeat arrays could be detected for the nonhuman primates typed, presumably reflecting an ancient precursor state at both microsatellite loci. Furthermore, our results provide evidence for an association of the average number of repeats present in different primate genera and their divergence time from man. DNA sequencing of VWA orthologues revealed a relatively high variability in the arrangement of repeats in the 5'-repeat arrays, the generation of which could probably be explained by polar mutational events.

Six marmosets (Callithrix jacchus), 20 months to 16 years old, died from a disease characterized by weakness and paralysis of the hind legs, weight lose, anemia and transient diarrhea. The lesions most prominent at necropsy were subacute to chronic tubulointerstitial nephritis, subacute to chronic pancreatitis, and generalized hemosiderosis. Chronic protein deficiency is believed to be the underlying pathogenic mechanism, since the diet contained no more than 15% animal protein during the last two years, and increasing the amount of protein was accompanied by disappearance of the syndrome.

No abstract

Spontaneous IgM-mediated mesangioproliferative nephropathy was detected in 91% of tamarins and marmosets over 6 months old. The disease remains silent for long periods but is progressive. It is responsible for, or is at least related to, the cause of death in 20% of animals. Morphological characteristics are those of mesangial hyperplasia accompanied by subacute to chronic interstitial inflammation. The immunopathological demonstration of early accumulation of IgM within the mesangial cells and matrix, followed by interstitial deposition of C3, suggests that the lesion is mediated by immunological mechanisms.

Renal tissues of callitrichids with IgM nephropathy were immunohistochemically examined for the participation of IgA in pathogenesis. In 58 histopathologically nephropathy-positive kidneys, IgM predominated in 20 cases and IgA in 7 cases, and in 31 cases both immunoglobulins were rated to be approximately equally involved. The disease, therefore, might be described as IgM/IgA nephropathy. The renal tissues and sera were also tested for nutritional antigens or antinutritional antigen antibodies, using immunohistochemistry and Western blots (tissues) and enzyme-linked immunosorbent assay (sera). Evidences of nutritional antigens in the renal tissues were inconclusive, although circulating IgG class antibodies against cereals, milk, and egg proteins were present in quite a number of sera. Particular consideration was paid to IgA-antigliadin antibodies, which were statistically significantly associated with nephropathy as were IgA rheumatoid factors. The findings are discussed in relation to human IgA and IgM nephropathies.

Twenty-six gastrointestinal tumors were observed in twenty-three nonhuman primates during routine necropsies at the German Primate Center, Göttingen. The majority (15 cases) were colorectal mucoid adenocarcinomas in cotton-top tamarins (Saguinus oedipus), which in two animals were associated with gastric adenomas. Three cases of small intestinal mucoid adenocarcinomas occurred in common marmosets (Callithrix jacchus). One colonic leiomyoma was observed in a dwarf galago (Galagoides demidovii) and another one in a cotton top tamarin. Singular findings were a tubular adeno-carcinoma of the ileo-caecal valve in a saddle-backed tamarin (Saguinus fuscicollis) and a lymphosarcoma of jejunum, ileum, and colon in another saddle-backed tamarin. Multiple tubular adeno-carcinomas of the colonic diverticles occurred in an aged rhesus monkey (Macaca mulatta). The findings are discussed in comparison to the situation in man.

The ultrastructural and histochemical alterations during different stages of spontaneously occurring IgM nephropathy in Callitrichidae were determined. Callitrichid IgM nephropathy was classified according to the light microscopic sequence of the mesangial lesions in the individual glomeruli. In minimal disease and axial proliferation mesangial cells and mesangial matrix were symmetrically increased, whereas in panmesangial disease matrix deposition exceeded the cellular responses. However, ultrastructural matrix changes such as deposition of electron-dense particles, dilatation of the matrix channel system, and slightly increased collagen fiber expression were present also in minimal disease and axial proliferation. Histochemically collagen I and III phenotypes could only be verified in glomerular sclerosis, at that time accompanied by diminution of collagen IV The mesangial cellular lesions, in contrast, were very limited. The numerical increase in mesangial cells was associated with increased bleb formation and increased heterolysosome contents, whereas the amount of micro filaments was never increased.