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Biomedical subjects

L Dmochowski

Publications and source records attributed to L Dmochowski.

At least 37 records · Page 2Linked to original sources

Viral type A and type B hepatitis: morphology, biology, immunology and epidemiology--a review.

Viral hepatitis is one of the most serious infectious diseases in the United States and is of great concern to the public health agencies, hospitals and research laboratories. Progress in our knowledge of this disease has been based on cooperation between specialists in many diverse scientific disciplines employing sophisticated scientific instruments and technics. Close cooperation between clinical pathologists and clinicians is of great importance in diagnosis. Biologic, immunologic, epidemiologic and morphologic studies have resulted in the demonstration that the disease is the result of infection with at least two different viruses, described as type A and type B hepatitis viruses. The first induces type A hepatitis (infectious or epidemic, or MS-2 strain) of longer incubation period, is transmitted parenterally and apparently by inhalation or ingestion of virus-containing material, by venereal means as well as by other means. Extremely sensitive methods are now available for the detection of hepatitis type B infection, based on the results of biochemical, biophysical and immunoelectronmicroscopic studies that resulted in our knowledge of structure and composition of type B virus, and our knowledge of host immune responses to the various components of this virus. Thus it is now known that two antigen-antibody systems are associated with viral hepatitis type B: hepatitis B surface antigen (HBsAg) and antibody (HBsAb) and hepatitis B core antigen (HBcAg) and antibody to it (HBcAb). The test for antibody to HBcAg appears to be a sensitive indicator of viral replication when only subdetectable amounts of HBsAg are circulated. Since the recent discovery and characterization of type A hepatitis virus, great progress has been made in our understanding of the relationship between type A and type B hepatitis viruses. There is no cross immunity between the two viruses, and as is now suspected, there may be at least another virus, described as type C virus, which may play an etiologic role in viral hepatitis. There is no doubt now that type A and type B hepatitis viruses can be transmitted to monkeys; type A to marmosets and chimpanzees, type B to chimpanzees and rhesus monkeys. The two viruses are serologically and immunologically distinct. This knowledge and the results of biologic experiments have laid a solid foundation of meaningful diagnostic procedures for the two types of viral hepatitis. Advances in biophysical and biochemical procedures of treatment of sera of hepatitis B patients have resulted in availability of viral material, noninfectious but immunogenic, for vaccination of chimpanzees. Protective efficacy trials of the vaccine in chimpanzees have demonstrated the vaccine to be fully protective against high doses of infectious hepatitis B virus...

Africa↗

Type-C virus particles in placenta of the cottontop marmoset (Saguinus oedipus).

Electron microscopy of near-term placentas of two cottontop marmosets (Saguinus oedipus) revealed, in one placenta, the presence of budding and mature C-type virus particles associated with the basal trophoblast. The particles were morphologically similar to those observed by other investigators in placentas of other primate species.

Animals↗

Quantitative nucleotide sequence relationships of mammalian RNA tumor viruses.

A molecular hybridization technique has been used to quantitatively measure the nucleotide sequence relationships of selected mammalian RNA tumor viruses. Reciprocal cross-hybridization tests were done in which a given radioactively labeled, viral genomic RNA species was annealed with an excess of unlabeled, complementary DNA product synthesized in endogenously instructed reverse transcriptase reactions. Hybrid formation was measured with pancreatic RNase A. Three representative mammalian RNA tumor virus groups were examined: murine viruses, simian viruses, and feline viruses. The results of reciprocal cross-hybridization testing have revealed that the murine viruses consist of four distinctly related subgroups: (i) the Friend leukemia virus/Rauscher leukemia virus subgroup, (ii) the Gross leukemia virus subgroup, (iii) the Moloney sarcoma virus subgroup, and (iv) the Kirsten sarcoma virus subgroup. Simian sarcoma virus, the only simian virus examined, appeared to share limited interspecies sequence relationships with members of the other virus groups and in particular with Kirsten sarcoma virus. Of the two members of the feline virus group tested, Rickard feline sarcoma virus and RD-114, each was placed in a separate, unrelated subgroup. Rickard feline sarcoma virus exhibited limited sequence relatedness with members of the other virus groups, whereas RD-114 exhibited none.

Animals↗

In vitro transformation of cells from human neoplasms.

The possible involvement of RNA tumor virus genomes in human cell transformation was investigated. Forty-nine cell cultures from neoplastic, normal, or embryo tissues were examined for transformation, following inoculation of murine leukemia virus (MuLV), feline leukemia virus (FeLV) grown in human cells, or bone marrow aspirates from leukemia patients. Five cultures exhibited transformation (1 after inoculation of MuLV grown in human cells; 4 after inoculation of human leukemic bone marrow), and 4 were established as cell lines. They were derived from giant cell tumor and fibrosarcomas. The established transformed cells formed colonies in soft agar, grew progressively in immunosuppressed mice, and carried antigens common to FeLV and MuLV. Although virus particles were not seen in these cultures, 68S RNA was detected in their media. Medium from nontransformed parent cultures also contained 68S RNA but in amounts about 15 times less than in transformed cultures. Transformed human cells passaged in mice produced both type C virus particles and 68S RNA. Antigens common to MuLV and FeLV were found in these particles. However, the results of biological and serological studies indicate their difference from conventional MuLV and FeLV. The relationship of this virus and 68S RNA found in transformed cultures remains to be determined.

Antigens, Viral↗

Transformation of cells in human bone tumor cultures.

Two cell lines from tumors of 16 patients with osteosarcoma and two cell lines from 5 patients with giant cell tumor of bone showed conversion of cell type after 2 to 13 months in culture. Transformed cells of epithelial like morphology appeared in small focal areas and rapidly overgrew nontransformed cells. These cells were characterized by rapid growth, loss of contact inhibition, and growth in soft agar. Attempts to demonstrate virus(es) by electron microscopy, treatment with chemicals, or by inoculation of human cell lines were thus far unsuccessful. Antigens not present in parental cultures were observed in the transformed cells by fixed immunofluorescence test with sera of 13 and 20 osteosarcoma patients and 3 of 8 patients with giant cell tumor of bone. Absorption of positive sera with transformed cells of either osteosarcoma or giant cell tumor removed the reaction but not with absorption with heterophile material or mycoplasma. Presence of group-specific-like antigen (gs-3) in the transformed cells (but not in parent cultures) was shown by immunofluorescence. Fluids of transformed cultures contained heavy RNA similar to that of oncornaviruses. These findings suggest the presence of viral information in some human bone tumors.

Antigens, Neoplasm↗

Virus retrieval studies in human neoplasia.

Short- and long-term co-cultures of 49 cases of human osteosarcoma cells with bone marrow or peripheral blood cells of patients with different types of leukemia were studied. Morphological changes were observed in 7 of 13 long-term co-cultures resembling those induced by RNA tumor viruses. The changes were accompanied by appearance of cytoplasmic antigen as shown by fixed immunofluorescence test with sera from patients with osteosarcoma, leukemia, and of some apparently normal blood donors. Absorption with Forssman-like substances, whole human embryo cells or osteosarcoma cells demonstrated the reaction to be due to tumor antigen(s) in co-culture cells showing morphological changes. Electron microscopy showed a few type C virus particles in one co-culture. Cell-free filtrates of fluid from the transformed co-cultures induced morphological changes in 1 of 4 human embryo cultures. Uninoculated embryo cultures or those inoculated with filtrates from parental sarcoma or leukemia cultures showed no morphological changes. Human embryo cell cultures treated with fluid from parental leukemic bone marrow but not from parental sarcoma cultures showed appearance of cytoplasmic antigen by immunofluorescence test with sera of osteosarcoma and leukemia patients and of some apparently normal blood donors. Transformed human co-cultures showed the cytoplasmic antigen with 28 of 48 sera of osteosarcoma and leukemia patients tested, after absorption with Forssman-like material, human embryo, and mycoplasma suspensions. Fourteen of 49 sera of normal donors were also positive with the transformed co-cultures. Similar results were obtained in an earlier series of experiments with human embryonic cultures transformed by fluid from different osteosarcoma-leukemia co-cultures when examined by fixed immunofluorescence tests with sera of patients with osteosarcoma and leukemia. In 2 whole human embryo cell cultures showing morphological changes high molecular weight RNA was found, similar to that of RNA animal tumor viruses and in one of the cultures transient reverse transcriptase was detected.

Antigens, Viral↗

Sarcoma-negative leukemia-positive transformed cell culture established from a murine sarcoma virus-induced rat bone tumor.

Inoculation of the Soehner-Dmochowski isolate of the Moloney strain of murine sarcoma virus (MSV), designated MSV-SD, consistently leads to the development of bone tumors in the susceptible New Zealand black (NB) rats. Two separate cell cultures have been established from 2 individual MSV-SD-induced NB rat bone tumors. Cells of 1 bone tumor culture, designated RBT-E, are in early in vitro passages. These cells form colonies in agar medium and take up 2-deoxy-D-[3H]glucose at a greatly enhanced rate, 5 times that of normal nontransformed rat embryo cells. Cells of the RBT-E culture release both MSV and murine leukemia virus (MuLV) and therefore contain sarcoma-positive leukemia-positive transformed cells. The other rat bone tumor culture, designated RBT-L, produced MSV at early passages. RBT-L culture has been passaged over 130 times in vitro. Cells of the RBT-L culture form colonies in agar medium and take up 2-deoxy-D-[3H]glucose at an enhanced rate (3 times that of rat embryo cells), indicating the presence of transformed cells within the RBT-L culture. However, cells of the RBT-L culture at late passages (Passage 130 or more) produce only MuLV and no detectable MSV activity (as shown by the lack of tumor-inducing activity and the lack of focus-forming activities by direct assay or by infectious center assay). Attempts to rescue MSV activity from RBT-L cells by cocultivation with MuLV-producing mouse cells were not successful. The MuLV found in the RBT-L cells, however, is a competent helper virus capable of rescuing the MSV genome from MSV-SD-induced hamster bone tumor cells. All the available evidence supports the notion that late passages of the RBT-L culture contain transformed cells that do not produce conventionally detectable MSV. These cells are referred to as sarcoma-negative leukemia-positive cells. The sarcoma-negative leukemia-positive cells represent a different kind of MSV-induced transformed cells and provide a unique system for studies in search of MSV markers such as MSV-specific antigens and MSV-specific nucleotide sequences.

Animals↗