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V Altanerova

Publications and source records attributed to V Altanerova.

13 recordsLinked to original sources
PubMed2005

Cancer stem cells.

There is an increasing evidence supporting the cancer stem cell hypothesis. Normal stem cells in the adult organism are responsible for tissue renewal and repair of aged or damaged tissue. A substantial characteristic of stem cells is their ability for self-renewal without loss of proliferation capacity with each cell division. The stem cells are immortal, and rather resistant to action of drugs. They are able to differentiate and form specific types of tissue due to the influence of microenvironmental and some other factors. Stem cells divide asymmetrically producing two daughter cells -- one is a new stem cell and the second is progenitor cell, which has the ability for differentiation and proliferation, but not the capability for self-renewal. Cancer stem cells are in many aspects similar to the stem cells. It has been proven that tumor cells are heterogeneous comprising rare tumor initiating cells and abundant non-tumor initiating cells. Tumor initiating cells -- cancer stem cells have the ability of self-renewal and proliferation, are resistant to drugs, and express typical markers of stem cells. It is not clear whether cancer stem cells originate from normal stem cells in consequence of genetic and epigenetic changes and/or by redifferentiation from somatic tumor cells to the stem-like cells. Probably both mechanisms are involved in the origin of cancer stem cells. Dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. Isolation and identification of cancer stem cells in human tumors and in tumor cell lines has been successful. To date, the existence of cancer stem cells has been proven in acute and chronic myeloid leukemia, in breast cancer, in brain tumors, in lung cancer and gastrointestinal tumors. Cancer stem cell model is also consistent with some clinical observations. Although standard chemotherapy kills most cells in a tumor, cancer stem cells remain viable. Despite the small number of such cells, they might be the cause of tumor recurrence, sometimes many years after the "successful" treatment of primary tumor. Growth of metastases in distinct areas of body and their cellular heterogeneity might be consequence of cancer stem cell differentiation and/or dedifferentiation and asymmetric division of cancer stem cells. Further characterization of cancer stem cells is needed in order to find ways to destroy them, which might contribute significantly to the therapeutic management of malignant tumors.

Animals↗
PubMed2004

Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndrome.

Two mutations on the same allele of RET gene were revealed in a family with predisposition to multiple endocrine neoplasia (MEN) type 2A. The first mutation changes codon 634 from cysteine to serine. The second, a novel mutation in codon 641, changes alanine to serine in the transmembrane domain of the RET protein. Two mutations were present in close proximity in both the patients' germline and tumor DNA and were absent in DNA isolated from healthy family members and control blood donors. All MEN 2A affected family members suffered from medullary thyroid carcinoma and two of ten patients for pheochromocytoma. No parathyroid gland alterations were observed in patients with two RET gene mutations. Analysis of four genetic polymorphisms in the RET gene showed higher incidence of polymorphisms of exons 11 and 15. The observed allelic imbalance in favor of mutated allele in pheochromocytoma corresponded to higher expression of the RET gene. These observations confirm the multifactorial process leading to development of MEN 2A syndrome.

Adrenal Gland Neoplasms↗
PubMed1999

Bovine leukemia virus structural gene vectors are immunogenic and lack pathogenicity in a rabbit model.

Infection with a replication-competent bovine leukemia virus structural gene vector (BLV SGV) is an innovative vaccination approach to prevent disease by complex retroviruses. Previously we developed BLV SGV that constitutively expresses BLV gag, pol, and env and related cis-acting sequences but lacks tax, rex, RIII, and GIV and most of the BLV long terminal repeat sequences, including the cis-acting Tax and Rex response elements. The novel SGV virus is replication competent and replicates a selectable vector to a titer similar to that of the parental BLV in cell culture. The overall goal of this study was to test the hypothesis that infection with BLV SGV is nonpathogenic in rabbits. BLV infection of rabbits by inoculation of cell-free BLV or cell-associated BLV typically causes an immunodeficiency-like syndrome and death by 1 year postinfection. We sought to evaluate whether in vivo transfection of BLV provirus recapitulates pathogenic BLV infection and to compare BLV and BLV SGV with respect to infection, immunogenicity, and clinical outcome. Three groups of rabbits were subjected to in vivo transfection with BLV, BLV SGV, or negative control DNA. The results of our 20-month study indicate that in vivo transfection of rabbits with BLV recapitulates the fatal BLV infection produced by cell-free or cell-associated BLV. The BLV-infected rabbits exhibited sudden onset of clinical decline and immunodeficiency-like symptoms that culminated in death. BLV and BLV SGV infected peripheral blood mononuclear cells and induced similar levels of seroconversion to BLV structural proteins. However, BLV SGV exhibited a reduced proviral load and did not trigger the immunodeficiency-like syndrome. These results are consistent with the hypothesis that BLV SGV is infectious and immunogenic and lacks BLV pathogenicity in rabbits, and they support the use of this modified proviral vector delivery system for vaccines against complex retroviruses like BLV.

Animals↗
PubMed1997

In vivo study of genetically simplified bovine leukemia virus derivatives that lack tax and rex.

Genetically simplified derivatives of complex retroviruses that replicate in animal models are useful tools to study the role of the complex regulatory genes in virus infection and pathogenesis and were proposed as a novel approach toward the development of vaccines against complex retroviruses. Previously we developed genetically simple derivatives of bovine leukemia virus (BLV) that can replicate in tissue culture independently of the BLV regulatory proteins, Tax and Rex, and the RIII and GIV open reading frames (K. Boris-Lawrie and H. M. Temin, J. Virol. 69:1920-1924, 1995). These derivatives are encoded on novel, hybrid retrovirus genomes that contain transcriptional control sequences of a simple retrovirus and gag-pol or env genes of the complex BLV. The first-generation simple BLV derivatives replicate as complementary viruses (coviruses) by using separate gag-pol or env genomes, and therefore virus spread is limited to cells that are infected with both covirus genomes. Here we describe a second-generation simple BLV derivative that is encoded on a single hybrid genome. We show the virus to be replication competent by successive passage on D17 target cells and by analysis of viral RNA and proteins in the infected cells. Furthermore, we evaluate the immunogenicity and infectivity of the simple BLV derivatives in a BLV animal model. Small groups of rats were injected either with virus-producing cells or with proviral DNA. Western immunoblot analysis revealed that antibodies against the major viral antigenic determinants are induced in response to either method of introduction and that seroconversion is sustained in most of the rats for at least 6 months (the duration of the study). The magnitudes of the antiviral responses were similar in rats infected with the first-generation simple BLV coviruses, the second-generation replication-competent derivative, or wild-type BLV. Wild-type BLV typically infects peripheral blood mononuclear cells (PBMC), and the simple BLV derivatives were also found to infect PBMC as demonstrated by PCR amplification of proviral sequences and reverse transcriptase PCR amplification of viral RNA in treated rats. These results establish that simple BLV derivatives lacking tax and rex are infectious and immunogenic in rats. These viruses will be useful tools in comparative studies with BLV to evaluate the role of tax and rex in maintenance of virus load and in disease outcome.

Animals↗
PubMed1993

Envelope glycoprotein gp51 of bovine leukemia virus is differently glycosylated in cells of various species and organ origin.

The carbohydrate moiety of the envelope glycoprotein gp51 of bovine leukemia virus, American strain, was studied. The virus was grown in ovine, bovine, porcine, bat and rat cells of various organ specificities. The gp51 was purified by immunoaffinity chromatography from virions of ten different virus-producing cells derived from various body organs of different species. Highly purified glycoproteins (single band in PAGE) were compared for their electrophoretic mobility, for the presence of epitopes by a battery of monoclonal antibodies, and for the glycosylation pattern by lectin blot analysis. Electrophoretic analysis of all tested glycoproteins deglycosylated by glycopeptidase F detected the same polypeptide backbone according to PAGE. The glycoproteins produced in rat cells migrated faster in PAGE, as detected in cells or in virions, than those produced in ovine cells. The pattern of their glycosylation was found to be dependent on the type of cells used for virus production. The differences in glycosylation were most pronounced when comparing the glycoprotein produced in ovine cells versus bat or rat cells. Changes in epitope expression were also detected. The differences in the patterns of glycosylation and in the accessibility of epitopes owing to the virus production in various kind of cells are discussed from virus infectivity and vaccine points of view.

Animals↗
PubMed1993

Two immunodominant regions revealed by monoclonal antibodies on the main structural protein p24 of bovine leukemia virus.

Eleven different monoclonal antibodies (Mabs) directed against the main structural protein p24 of bovine leukemia virus (BLV) were prepared. All Mabs reacted with p24 in Western blot and in radioimmunoprecipitation. Competition antibody binding assays with the prepared Mabs distinguished three independent groups of Mabs. Two immunodominant regions (IDRs) of p24 BLV were defined by these Mabs. The Mabs were induced preferentially against two immunodominant regions on the native form of p24 BLV (BLVp24 IDR-1 and BLVp24 IDR-2). Mab of the third group was directed against a different immunogenic epitope of p24 BLV. A model of the IDRs based on the differences in the fine epitope specificity of Mabs defining these immunodominant regions is proposed.

Animals↗
PubMed1991

Protective vaccination against bovine leukaemia virus infection by means of cell-derived vaccine.

Tests were performed to determine whether live mammalian cells producing env gene glycoproteins and main structural protein p24 of bovine leukaemia virus (BLV), heterologous to bovine species, could serve as an immunogen in cattle to prevent induction of bovine leukaemia. Ovine virus-non-producing clonal cells NP-2 were used as the immunogen. The NP-2 cells synthesized only the env gene products--glycoprotein gp51 and gp30 and main structural protein p24 of BLV. The NP-2 cells, inoculated into rats, induced an antibody response directed against envelope glycoproteins of BLV. The antibodies neutralized the infectivity of BLV as determined by the VSV/BLV pseudotype neutralization test. Similar results were obtained by vaccination of cattle with these cells. A dose of less than or equal to 2 x 10(6) live cells inoculated subcutaneously induced an antibody response in cattle, while a high dose of killed cells was ineffective. The antibodies in cattle were directed against env products of BLV. A group of 92 cows was vaccinated and followed up for 4 years. The antibody levels fluctuated slightly during the 4-year observation period, generally decreasing with time, but revaccination always increased the antibody titre. No transfer of seropositivity was observed to seronegative animals which were kept in contact with vaccinated ones. In a separate experiment a group of young heifers, after repeated vaccination, were challenged with a high dose of infectious virus and/or virus-producing cells. The response to BLV infection was followed by syncytial induction assay after co-cultivation of white blood cells with indicator cells CC81.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Induction of leukemia in chicken by bovine leukemia virus due to insertional mutagenesis.

Bovine leukemia virus (BLV) was inoculated into one-day-old chickens. In a small part of inoculated chickens leukemia developed during observation period of one year. Out of 88 birds inoculated, only 4 developed histopathologically verified leukemia. The induced leukemia was characterized by enlarged liver and spleen. The organs were infiltrated with leukemic cells. The DNAs of body organs of inoculated chickens were analysed by Southern blot hybridization for the presence of BLV specific sequences. Out of 9 suspicious chickens tested in 6 birds the BLV was found to be integrated into host DNA either as a complete viral genome or as a part corresponding to its 3'-end. The leukemic cells were monoclonal as regard to the integration site of the BLV provirus. Neither the expression of BLV provirus in chicken leukemic cells nor the antibody response to BLV antigens in inoculated birds was detected. The rearrangements and amplification of erb-B and myb loci of protooncogenes in leukemic cells was detected. There were no changes in loci of following protooncogenes: myc, sis, fes, fps, erb A, src and yes. All obtained data taken together suggest that the BLV induced leukemia in chickens is caused by insertional mutagenesis.

Animals↗
PubMed1989

Induction of immune deficiency syndrome in rabbits by bovine leukaemia virus.

Newborn rabbits were inoculated with bovine leukaemia virus (BLV). The majority of infected rabbits produced antiviral antibodies. All the seroconverted animals developed symptoms resembling AIDS and died several months after inoculation. The course of experimental infection of rabbits with BLV resembled in many respects the broad spectrum of clinical disorders associated with AIDS induced by HIV. Antibody response to virus proteins was followed by immune deficiency and signs of neuropathy, and the animals subsequently died of opportunistic infections. Virus transmission from infected babies to the mothers by contact was also observed. In some cases the virus was salvaged from lymphocytes of rabbits with the immune deficiency syndrome. The virus-specific sequences were found to be integrated at random in the DNA of haematopoietic cells and of some organs. Slight expression of viral RNAs in lymphocytes was found. Experimental infection of rabbits with BLV can be used in experiments to understand AIDS induction.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Infection of rats with bovine leukaemia virus: establishment of a virus-producing rat cell line.

Adult rats were infected with bovine leukaemia virus (BLV). Inoculated rats persistently produced antibodies directed against viral structural proteins. No major pathogenesis in infected rats was found during 2 years of observation. It was possible to recover the virus from rat spleen several months after infection. A cell line, R(BLV), was established from rat spleen; this contained integrated BLV provirus. R(BLV) cells kept for over 80 passages in vitro produced viral particles with the properties of BLV. Provirus reintegration and/or amplification occurred in R(BLV) cells. The cell line was found to be tumorigenic in rats, and the virus produced was immunogenic. R(BLV) cells represent the first described BLV-producing rat cell line. Proven persistent infection with BLV indirectly suggests that rats can serve as a reservoir of BLV in nature.

Animals↗
PubMedDate not supplied

Characterization of the RNA dependent DNA polymerase of bovine leukemia virus.

The reverse transcriptase-RNA dependent DNA polymerase of Bovine Leukemia Virus (BLV) was isolated and characterized. The enzyme has a molecular weight of about 80kd and the isoelectric point is 7.6. The enzyme prefers magnesium, as a divalent cation using synthetic homopolymeric template primer poly (C) oligo (dG). Monoclonal antibodies directed against reverse transcriptase of human immunodeficiency virus type I (HIV-I) did not crossreact with the isolated polymerase.

Antibodies, Monoclonal↗