Biomedical subjects
Publications and source records attributed to R Hehlmann.
Three elderly patients are reported, in whom serologically confirmed recent infectious mononucleosis is followed by fatal lymphoproliferation (case 1), by acute monocytic leukemia (case 2), and by acute probably monocytic leukemia (case 3).
In three patients arthropathy was the earliest symptom of hemochromatosis. Two of these patients had a precirrhotic stage of hemochromatosis. The liver histology of the third patient showed a beginning cirrhosis. The serum iron ranged from 212 to 260 micrograms/dl. The transferrin saturation was 95-100%. Serum iron and transferrin should be determined in all patients with arthralgias, since arthropathy may be the first clinical sign of hemochromatosis.
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The enzyme-linked immunosorbent assay (ELISA) technique was applied to the detection and quantification of simian sarcoma-associated virus (SiSV)-glycoprotein gp70 in virus preparations and cells and compared to the RIA competition technique. By detecting 0.1 ng of retroviral glycoprotein, its sensitivity is comparable to that of the RIA technique. It was further shown that the antibodies used recognize the protein and not the sugar components of the glycoprotein.
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As a contribution to the solution of the etiological question of human neoplasias, human leukemias, lymphomas and sarcomas were shown to contain viral structures and/or virus-like particles that resembled analogous animal RNA tumor viruses or their structures. The human particles possess 1. a single stranded, high molecular weight 70s RNA, 2. a RNA-dependent DNA-polymerase, 3. a characteristic density of 1.16--1.19 g/cm3, and 4. a base sequence of their RNA related to the RNA of analogous animal RNA tumor viruses. Although a biological activity of these particles has not been shown, their similarity with analogous animal viruses, their presence in certain neoplasias, and their absence in normal, non-embryonal tissues make some function of these particles in human carcinogenesis likely.
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Virus particles with the biochemical properties of C-type retroviruses appeared transiently in bone tissues of (C3H x 101) f1 hybrid mice early after treatment with 224 Radium; such particles were then again detected in the bones of the irradiated animals at the onset of osteosarcoma formation and in the osteosarcomas. Antibodies against a murine retrovirus isolated from a 224 Ra-induced osteosarcoma were produced and detected in the serum of the 224 Ra-treated animals within a month after treatment began. The antibody levels plateaued to a maximum after about 2 months and remained elevated until the tumors started to develop. The antibody concentration in the serum of these irradiated animals decreased then progressively to reach levels similar to those observed in untreated controls. It thus appears that the imminence of osteosarcoma development can be predicted by monitoring the anti-C-type virus antibody levels in the serum of the irradiated mice. These experiments also strongly suggest that treatment with 224Radium induces expression of endogenous viruses in the animals.
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The detection and quantification of retroviral proteins in cells, tumors, and sera by an enzyme immunoassay technique (enzyme-linked immunosorbent assay [ELISA]) is described. The ELISA technique has been applied to three viral systems: murine leukemia virus, baboon endogenous virus, and simian sarcoma virus. By detecting 0.1 nf of retroviral antigen, the sensitivity of the ELISA is comparable to that of the competition radioimmunoassay technique.
The mouse melanoma B16 contains particles encapsulating a high molecular weight RNA of 60--70S size associated with a reverse transcriptase. The particles possess a density of 1.14--1.18 g/cm3. The RNA shares sequences with the 70S RNAs of several mammalian C-type RNA tumor viruses. The nuclear DNA of the mouse melanoma B16 possesses particle-related sequences not present in the genome of normal C57BL mice.
The mouse melanoma B16 contains particles encapsulating high molecular weight RNA of 60--70S size associated with a reverse transcriptase. The [3H]DNA synthesized by these particles possesses homology with RNA isolated from a hamster melanoma and from three human malignant melanomas.
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A high-molecular-weight RNA encapsulated with an RNA-instructed DNA polymerase in particles possessing the density characteristic of the RNA tumor viruses has been detected in 13 out of 14 human malignant melanomas. The [3H]DNA synthesized by these particles in an endogenous reaction hybridizes to RNA extracted from the human melanoma particulate structures, but not to RNA from normal skin. Similar particles containing RNA and enzyme have been found in basal cell and squamous cell carcinomas of the skin. The RNA of the melanoma particles is easily distinguishable by hybridization from the RNAs found in the particles of the basal and squamous cell carcinomas.