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Biomedical subjects

M Janowski

Publications and source records attributed to M Janowski.

At least 37 records · Page 2Linked to original sources
PubMed1986

Retroviruses in radiation-induced lymphomas.

The nucleotide sequence of RadLV/VL3 (T+L+), the thymotropic and leukemogenic entity of the in-vitro propagated radiation leukemia virus complex (RadLV/VL3), is that of a recombinant retrovirus. The gag, pol and most of the env gene are very similar to the homologous regions of Akv MuLV. The 3' end of the env gene and the LTR appear to have derived from a xenotropic MuLV. However, the LTR has acquired a feature shared by other lymphomagenic MuLVs. This feature consists in sequence rearrangements resulting in the generation of presumed enhancer elements. RadLV/VL3(T+L+)-specific proviral sequences were found adjacent to the c-myc gene in several virus-induced thymic lymphomas of the rat, suggesting that the enhancer elements might play a role in lymphomagenesis. However, we found that the presence of a provirus at a specific DNA site can lead to an in-vitro growth advantage and to clonal cell selection independently of a lymphomagenic process. We conclude from this observation that clonal appearance of an integrated provirus in cultured radiogenic lymphoma cells does not necessarily reflect a viral induction of radiation-induced leukemogenesis.

Animals↗
PubMed1986

Oncogene involvement in radiation- and virus-induced mouse osteosarcomas.

Internal irradiation of mice using bone seeking radionuclides results in the activation of endogenous retroviruses and in the subsequent development of bone tumors. Genomic DNA from an osteosarcoma cell line, derived from an 90Sr-induced bone tumor, was cotransfected with the plasmid pSV2-neo into NIH/3T3 cells and G418-resistant transfectants gave rise to colonies in soft agar. Southern blot analysis of these first cycle transformants revealed the presence of extra copies of c-ras. We have analysed the arrangement of ecotropic murine leukemia proviral sequences in seven 90Sr-induced bone tumors and one osteosarcoma cell line of CF1-mice. Integration of ecotropic and/or ecotropic recombinant proviruses seems to be involved in rearrangements of 3' provirus cellular junction fragments occurring in all tumor DNAs analysed, but no indication for site-specific integration was found. We also determined the primary structure of FBR-MuSV, a transforming retrovirus able to induce bone tumors in newborn mice. FBR-MuSV contains sequences from all four exons of the murine c-fos gene, but lacks sequences encoding the first 24 and the last 98 amino acids of the c-fos gene product. The coding region of FBR-MuSV has also undergone two small in frame deletions. Thus, the v-fosFBR-MuSV retains 236 amino acids of the 380 amino acids of the murine c-fos product. In FBR-MuSV-transformed cells two fos-containing mRNAs have been detected: a 3.3-kb full-size genomic RNA and a 2.2-kb subgenomic mRNA as revealed by both fos- and MuLV-hybridization probes.

Animals↗
PubMed1985

Nucleotide sequence of the envelope gene of radiation leukemia virus.

The nucleotide sequence and the predicted amino acid sequence of the envelope gene (env) of RadLV/VL3 (T+L+) has been determined. RadLV/VL3 (T+L+) is a highly thymotropic (T+) and leukemogenic (L+) murine recombinant retrovirus continuously produced at high titer by BL/VL3 cells, a line established in culture from a radiation leukemia virus (RadLV)-induced C57BL/Ka mouse thymic lymphoma. The envelope gene is strikingly similar (92% homologous) to that encoded by the ecotropic Akv-MuLV. Among the differences, 134 scattered, although unevenly distributed point mutations (6.4%), two 9-bp deletions as well as a 6-bp insertion were observed (which result in 49 amino acid changes in the env gene of RadLV/VL3 (T+L+)).

Abelson murine leukemia virus↗
PubMed1985

Proviral genome of radiation leukemia virus: molecular cloning of biologically active proviral DNA and nucleotide sequence of its long terminal repeat.

The proviral genome of a leukemogenic and thymotropic C57BL/Ka mouse retrovirus, RadLV/VL3(T+L+), was cloned as a biologically active PstI insert in the bacterial plasmid pBR322. Its restriction map was compared with those, already known, of two nonthymotropic and nonleukemogenic viruses of the same mouse strain: the ecotropic BL/Ka(B) virus and the xenotropic constituent of the radiation leukemia virus complex. Differences were observed around the gag-pol gene junction, in the pol gene, and in the env gene. Moreover, the nucleotide sequence of the RadLV/VL3(T+L+) long terminal repeat revealed the existence of two copies of a 43-base-pair sequence, of which BL/Ka(B) possesses only one copy.

Animals↗
PubMed1984

Integrity of glycoprotein complex sugars is required for homing but not for several other membrane-mediated functions.

In order to correlate the biochemistry of cell surface carbohydrates with cell function, we have treated cells with swainsonine and followed the biochemical and functional modifications induced by this compound. After treatment with swainsonine, surface glycoproteins had a lower apparent molecular weight and a higher isoelectric point. This is compatible with the replacement of complex carbohydrates by hybrid or high-mannose carbohydrates. Several functional tests were unaffected. However, swainsonine-treated cells displayed an altered pattern of in vivo homing, suggesting that carbohydrates play a role in this process.

Alkaloids↗
PubMed1984

[Isolation and characterization of retroviruses expressed in murine osteosarcomas induced by 90Sr].

The induction of osteosarcomas with 90Sr in CF1 mice is associated with the expression of ecotropic type-C RNA viruses devoid of sarcomatogenic activity. In contrast, the FBR murine osteosarcoma virus complex, isolated from a 90 Sr-induced osteosarcoma of a X/Gf mouse [M. Finkel et al. (1)], causes the rapid appearance of osteosarcomas in newborn mice and transforms fibroblasts in vitro. The transforming capacity of FBR murine sarcoma virus has been associated as an oncogene homologous to v-fos.

Animals↗
PubMed1984

[West Nile virus meningomyeloencephalitis--value of interferon assays in primary encephalitis].

A 68 year-old woman contracted West Nile fever after a stay of one month in Israel. Mild encephalitis and severe myelitis, resembling the "polio syndrome", developed, with important sequelae. Specific antibodies against West Nile fever virus progressively increased in the patient's serum. Epidemiological and clinical data about neurologic aspects of this infection are reviewed. Meningoencephalitis is not unusual, but only one previous case of acute anterior myelitis has been described in humans although this pathology is well known in experimental and veterinary diseases. Very few studies concern interferon and arbovirus infections in humans. Interferon assays in our patient's serum and cerebrospinal fluid showed its presence and persistence: this is in relation with the replication of the virus in the central nervous system, as it has been demonstrated in other primary viral encephalitis.

Aged↗
PubMed1983

Surface proteins of radiation-induced and radiation leukemia virus-induced thymic lymphosarcomas in mice.

Thymic lymphosarcomas (TLS) were induced in C57BL mice by X-rays or by Radiation Leukemia Virus (RadLV) and their surface glycoproteins (gps) compared after cell-surface radioiodination and polyacrylamide gel electrophoresis (SDS-PAGE). All lymphocytic antigens tested (T200, 170/100, Thy-1) and proteins with apparent molecular weight (Mr) around 120,000 and 100,000 were present on all tumours, as well as retrovirus--encoded proteins but considerable variation in the Mr of several serologically-related proteins was observed. Therefore, the TLS in C57BL mice form a heterogeneous group, suggesting that T cells can be transformed at different stages of maturation. The possibility that transformation allows or even triggers differentiation is also entertained.

Animals↗
PubMed1982

Common proviral integration sites in C57BL mouse lymphomas induced by radiation leukemia virus and absence of novel virus-related sequences in radiogenic lymphoma DNA.

Three C57BL/Ka mice were inoculated with RadLV/VL3, a thymotropic and leukemogenic virus population released by the permanent BL/VL3 cell line, which was derived from a C57BL/Ka lymphoma induced by radiation leukemia virus (RadLV). The neoplastic thymus and bone marrow cells from these mice were grown until the cultures became permanently established, and their DNAs were examined for the presence of virus-related sequences by restriction enzyme analysis. All six cell lines displayed identical EcoRI and BamHI restriction fragments, not found in control C57BL/Ka DNA and accounting for the presence of more than one novel provirus. The primary and secondary tumors were thus clonal and, even though they were obtained from different animals, possessed identical integration sites. The BL/VL3 cell line also displayed the clonal appearance of novel proviral sequences, partly identical, with respect to location and BamHI restriction pattern, to those found in the RadL/VL3-induced tumor cell lines. Neither radiation-induced tumors, nor cloned cell lines derived therefrom, whether producing leukemogenic virus (BL/RL12-P) or not (BL/RL12-NP), displayed the presence of novel virus-related sequences when compared with control tissues. Our results strongly suggest not only that, as described in the case of avian leukosis virus-induced tumors of the chicken, RadLV-induced leukemogenesis might be a consequence of cellular gene activation by promotor insertion, but also that more than one integration site might be involved. Radiation-induced tumorigenesis might be initiated by a comparable mechanism, not requiring the participation of a virus.

Animals↗
PubMed1982

[Aspects of megakaryocytic viral production in relation to lymphocytic leukemia in the rat].

Two viral populations BL/F (EL) and BL/F (SL) were derived from RadLV-Rs by propagation in rats where they induced respectively a generalized lymphoma in 5-6 weeks or a thymic lymphoma killing the animals in 5-6 months. In both cases, 10 days after inoculation of viral extract, numerous viral particles are present in the megakaryocytes (MKC) of the bone marrow and the spleen. Our results suggested a production rather than a passive accumulation of those particles by the MKC. The kinetics of blood platelet level for both leukemias showed a thrombocytopenia corresponding with the macroscopic development of the tumor. Therefore the evolution of the blood platelet level is not related to the MKC viremia. This suggests a lack of direct effect of virus BL/F on the MKC metabolism.

Animals↗
PubMed1982

[Common proviral integration sites in C57BL mouse lymphoma induced by mouse radiation leukemia virus and absence of novel proviral sequences in DNA from radiation-induced lymphoma].

Radiation leukemia virus (RadLV)-induced lymphomas of C57BL mice display the appearance of novel proviral sequences at common sites of their DNAs. These results are compatible with the hypothesis of viral oncogenesis by promotor insertion. Radiation-induced tumors do not acquire detectable novel provirus, suggesting that activation of a transforming gene proceeds by a mechanism distinct from the former.

Animals↗
PubMed1980

[Ultrastructural characterization of a retrovirus of mice (BL/F) producing leukemia in rats].

Two distinct leukemogenic viral subpopulations, BL/F (EL) and BL/F (SL) were derived from RadLV-Rs by propagation in rats. They were purified from the serum and studied by thin section and negative stain electron microscopy. Their ultrastructural organizations were not found to differ significantly from each other or from other murine leukemia viruses for which a detailed model now exists. Our work constitutes to our knowledge a first indepth study of viruses associated with radiation leukemia. It confirms the MuLV model built hitherto exclusively on observations from in vitro grown viruses.

Animals↗
PubMed1980

[Kinetics of the propagation of a murine virus (C57Bl mice) in the lymphoid system and bone marrow of rats (study using electron microscopy)].

Either a Slow (SL) or Early (EL) type of leukemia are respectively induced in rats by the RadLV-Rs derived BL/F (SL) and BL/F (EL) viral populations. The kinetics of virus propagation was studied comparatively in the thymus, spleen, lymph nodes and bone marrow of rats infected either with BL/F (EL) or BL/F (SL). During the first days after inoculation with BL/F (SL), the viral population increased rapidly in all tissues, reaching a peak at day 8 to 10, except in the lymph nodes which were almost devoid of viral particles. A very different pattern was shown by the EL leukemia, indicating the importance of the early distribution of viruses amongst the lymphoid tissues in view of the further development of the disease. The large amount of viruses observed inside the megakaryocytes and budding from these cells confirm that they play a role in the leukemogenesis.

Animals↗