Search PubMed⌕ Search

Biomedical subjects

N Haran-Ghera

Publications and source records attributed to N Haran-Ghera.

At least 37 records · Page 2Linked to original sources
PubMed1991

Prevention of spontaneous AKR T cell lymphomagenesis by 24-666, a virus isolated from an AKR B cell lymphoma.

Injection of a nonlymphomagenic ecotropic virus 24-666 isolated from a B cell lymphoma of AKR origin into young AKR mice (1-60 days old) inhibited spontaneous T cell lymphoma development. The reduction in T cell lymphoma incidence (16/106-15%) was accompanied with the appearance of B cell lymphomas (16/106-34%) in older mice (500 days mean latency). Infection of newborn to 60-day-old AKR mice with 24-666 prevented changes in thymus subpopulations and expression of MuLV-related cell surface antigens, normally observed in the thymus of 5- to 6-month-old AKR mice prior to lymphoma development. Thymuses of 24-666-infected 9- to 12-month-old mice lacked recombinant dual tropic virus (DTV) expression and retained the thymus pattern of 2-month-old AKR mice. At 12 months after 24-666 administration a striking decrease in Thy1.1 level and in the CD4+ CD8+ population and an increase in CD4- CD8- cells and in mu+ B cells, predominantly Ly1+, were observed. The presence of B cells in these thymuses was also reflected in the high response of thymocytes to LPS blastogenesis accompanied by a decreased response to PHA. Although T cell lymphoma development was markedly reduced by 24-666 administration, the establishment of potential lymphoma cells (PLC) was not affected. Transfer of lymphoid cells from 12-month-old grossly normal 24-666-infected mice to the appropriate recipients resulted in a high incidence (64-80%) of B cell lymphoma development. Thus, 24-666 seems to act through interference with the establishment of DTV in the thymus, thereby preventing PLC promotion to overt T cell lymphomas. Lack of the favorable microenvironment for PLC development in the T cell pathway enables PLC development in the B cell pathway in older mice.

Aging↗
PubMed1991

Prevention of spontaneous AKR T cell lymphomagenesis by elimination of potential lymphoma cells with antibody to specific gp 71 determinants.

AKR mice, highly susceptible to spontaneous T cell lymphomagenesis, were protected from developing the disease by a course of daily treatment with antibody 18-5 to gp 71 determinants (administered from birth to 10 days). Potential lymphoma cells (PLC) identified among bone marrow cells of untreated AKR mice since birth (using the transplantation bioassay method) were eliminated following treatment with antibody 18-5. Namely, transplantation of bone marrow cells and thymocytes of 250-day-old untreated AKR mice into (AKR/J x DBA/2)F1 and/or AKR recipients yielded 86-93% T cell lymphoma of AKR origin at a short mean latent period of 38-42 days. In contrast, transfer of lymphoid cells from 18-5-treated mice at a matching age caused only 7-13% T cell lymphoma of AKR origin. The accelerating effect of MCF 247 on lymphoma development in untreated AKR mice was not effective in 18-5-treated mice, probably due to lack of PLC that are promoted by MCF 247 to overt T cell lymphoma. The characteristic changes in thymus subpopulations preceding lymphoma development and coinciding with PLC identification in the thymus of untreated mice was prevented by 18-5. It is suggested that prevention of lymphoma development in AKR mice by passive antiviral immunotherapy involves elimination of PLC representing the initial tumorigenic phase in AKR lymphomagenesis.

Aging↗
PubMed1991

Validity of the in vitro system as a correlate of the in vivo model of RadLV lymphomagnesis.

Adult BL/6 mice are highly sensitive to lymphomagnesis by the radiation leukemia virus variant A-RadLV (80-100% T-cell lymphoma incidence after a latency of 70-110 days). This study shows that the in vivo elimination of T-cell subsets (including suppressor and cytotoxic T-cells) achieved by the repeated administration of cyclophosphamide, cyclosporin A, anti CD4 or anti CD8 mAb shortly after virus infection did not interfere with the lymphomagenic pathway. No reduction in the high lymphoma incidence or tumor latency was observed following the different treatments. Thus the suggestion on the basis of in vitro studies that the early phase of A-RadLV lymphomagenesis is associated with suppressor T-cells which abrogate a potential anti-tumor immune response has not been confirmed in these studies.

Animals↗
PubMed1990

Characteristics of potential lymphoma-inducing cells in mice sensitive or resistant to lymphomagenesis by radiation leukemia virus variants.

The relationship between the H-2-associated responsiveness of mice to radiation leukemia virus variants (A-RadLV and D-RadLV) lymphomagenesis and the characteristics of early occurring potential lymphoma-inducing cells (PLC) among thymus and bone marrow cells of these virus-infected mice was investigated. Sensitivity to virus-induced T-cell lymphomagenesis was shown to involve early occurrence of Thy-positive PLC, found predominantly among thymocytes, whereas resistance was rather related with early identification of PLC-Thy-negative cells mostly among bone marrow cells. PLC were further characterized in the sensitive (BL/6 + A-RadLV) and resistant (BL/6 + D-RadLV) situations by testing in parallel the tumorigenic potential (using the transplantation bioassay method) and type of thymus and bone marrow cell populations separated by different methods such as size fractionation by centrifugal elutriation, cytotoxic elimination of lymphocytes, or panning. The early occurring PLC among thymocytes of BL/6 mice 10-20 days following infection with A-RadLV were shown to be cortisone-resistant, Thy+, CD4+, and/or CD8+ medium size dividing thymocytes. PLC among thymocytes of BL/6 mice + D-RadLV, identified among the medium and large cell fractions, were shown to be cortisone-resistant Thy-, CD4-CD8- lymphocytes. High tumorigenic potential of PLC was demonstrated only among unseparated or separated (on size basis) bone marrow cells of BL/6 + D-RadLV (72-84%), whereas unseparated or separated fractions of bone marrow from BL/6 + A-RadLV had a low lymphomagenic potential (15-20%). The parallelism between the bone marrow fractions that induced optimal thymus cellularity following reconstitution of lethally irradiated mice and optimal lymphomagenicity stress the prothymocyte characteristics of PLC among bone marrow cells of BL/6 mice infected with D-RadLV. It is suggested that in resistant and sensitive haplotypes RadLV variants infect different cell populations and thereby induce PLC which differ in their capacity to present associative MuLV antigens with self H-2.

Animals↗
PubMed1990

Chromosomal mapping of the murine c-abl proto-oncogene by in situ hybridization.

Deletion and rearrangement of chromosome 2 were shown to be major cytogenetic characteristics of radiation-induced murine myeloid leukemias. Analysis of the localization of the murine protooncogene c-abl, previously assigned by Goff et al. to chromosome 2, was done using the in situ hybridization method. The c-abl was located close to the centromere, within bands 2A-2B. This site does not correspond to the common characteristic deleted segments (2C-2D) predominantly observed in radiation induced murine myeloid leukemias.

Animals↗
PubMed1988

Prevention of T-cell lymphoma in AKR/J mice.

Injection of a dual tropic virus (DTV) isolated from a T cell lymphoma AKR/J mice into the thymus of 14 day old AKR/J puppies accelerates lymphoma development; 90-100% of the injected mice develop the disease within 120 days. In contrast a cell free centrifuge CFC-666 prepared B cell lymphoma of AKR/J origin injected into the thymus of 14 day old AKR/J mice failed to accelerate T cell lymphomagenesis and actually prevented the spontaneous T cell lymphoma development. However, 50% of the treated mice developed B cell lymphoma with a latency of 417 + 18 days. DTV injection induces amplification of thymic expression of MuLV related antigens, besides changes in thymus subpopulation. Such changes emerge spontaneously in 5-6 month preleukemic AKR/J mice (at the time of spontaneous DTV formation in the thymus). These changes in the thymus were not observed following CFC-666 injection. We assume therefore that CFC-666 interferes with spontaneous DTV formation that contributes to T cell lymphomagenesis.

Animals↗
PubMed1988

Deletion of chromosome 2 is an early event in the development of radiation-induced myeloid leukemia in SJL/J mice.

In this study we have analyzed the chromosomal changes in the preleukemic phase in SJL/J mice treated with radiation and acute myeloid leukemias (AMLs) induced by radiation alone or with additional corticosteroid treatment. SJL/J mice exposed to 300 rad whole body irradiation developed a low incidence of AML (20-25%) that could be markedly increased (to 50-70%) by additional coleukemogenic treatment with corticosteroids. Partial deletion in one chromosome 2 was found in 100% of bone marrow and spleen cells of leukemic animals in both treatment modalities, whereas the age-matched controls exhibited a normal karyotype. Five types of deletion were observed according to site and size, but region D through G was the common missing part in all five types of chromosome 2 deletion. The occurrence of chromosome 2 deletion was also tested among bone marrow cells removed from 17 mice, 4 months after exposure to 300 rad whole body irradiation, long before the time when AML development is expected. About 80% of the mice tested had different levels of deleted chromosome 2 among their bone marrow population. Cytological and histological examination of bone marrow and spleen of most tested animals showed a normal hematologic picture. These results suggest that the marker chromosome is related to the process of radiation-induced initiation of AML in SJL/J mice.

Animals↗
PubMed1987

Cytogenetic studies on B-cell leukemias of AKR origin.

The karyotype of B-cell leukemias of AKR origin was studied by G-banding. In contrast to previous observations indicating trisomy of chromosome 15 in spontaneous and chemically-induced B-cell leukemias, 11 out of 15 tumors analyzed had normal diploid karyotypes. Four tumors with the modal number 39-41 had different chromosome markers specific for each tumor. The possible correlation between non-random chromosomal changes and the target cell involved in the initial transformation in AKR leukemogenesis is discussed.

Animals↗
PubMed1987

Recognition of T-cell murine leukemia by bacteriocin (colicin); correlation with transplantation experiments.

The presence of potential murine leukemia and overt leukemia cells in various organs at different phases of leukemogenesis was demonstrated by transplantation experiments and sensitivity to bacteriocin (colicin HSC10). Such correlation was found in three experimental models: AKR mice developing spontaneous T-cell leukemia and BL/6 mice infected with radiation leukemia virus variants inducing a high or low overt T-cell leukemia incidence. The sensitivity to bacteriocin was evaluated by testing the cell cycle perturbation following in-vitro incubation of lymphoid cells with colicin (or Tris buffer as controls) monitored by flow-cytometry. The analysis was based on measuring relative differences in fluorescence intensity of propidium iodide stained DNA in the individual cells. The interaction with colicin of leukemic cells and lymphoid cells containing potential leukemic cells (PLC) resulted in a reduction in the cell number of the G0/G1 and SG2M phases while cells accumulated in the "pre-G1" channels. In contrast, normal lymphoid cells exposed to bacteriocin did not show such changes in the DNA histograms. The distribution pattern of PLC in the thymus and spleen (in the models tested) obtained by transplantation studies coincided with sensitivity of spleen and thymus cells to colicin. However, in most instances, the PLC in the bone marrow were not recognized by colicin, but their leukemogenic potential was reduced following interaction with colicin as shown by PLC transplantation studies. It is thus suggested that colicin might be used for identification and eradication of transformed cells.

Age Factors↗
PubMed1987

Enhanced AKR leukemogenesis by the dual tropic viruses. I. The time and site of origin of potential leukemic cells.

The occurrence of potential leukemia cells (PLC) among bone marrow, spleen, and thymus of AKR mice during the preleukemic period was tested by an in vivo transplantation bioassay. The presence of PLC in 30- and 75-day-old AKR mice was demonstrated mostly among bone marrow cells, less in spleen, and was lacking in thymus. Occurrence of PLC in young AKR mice was shown to be thymus independent. However, progression of PLC from young donors (14-80 days old) into overt leukemia following transplantation into F1 recipients was shown to be dependent on specific host conditions including an intact thymus and an Fv-1nn allele. In contrast, PLC from 7-9-month-old AKR mice or frank leukemic cells when transplanted grew in any intact or thymectomized histocompatible host, thereby indicating their autonomous growth state. Infection of 2-week-old AKR mice with the dual-tropic virus DTV-70 induced characteristic changes in the thymus and accelerated leukemia development. DTV-70 inoculation into 14-day-old AKR mice did not change the spontaneous PLC distribution pattern in the tested host organs within 30 days postinfection, nor did it change PLC-specific host requirements for further progression into leukemic cells; however, it enhanced PLC transition to autonomous leukemic cells. The preferential cell tropism of DTV-70 for target cells (prothymocytes) among bone marrow and young spleen cells rather than for thymocytes was also demonstrated in an in vitro-in vivo test. The dual tropic virus may act as a promoter on preexisting PLC (present mostly among bone marrow cells) by enhancing their ability to progress into autonomous leukemic cells.

Animals↗
PubMed1987

Enhanced AKR leukemogenesis by the dual tropic viruses. II. Effect on cell-mediated immune responses.

We examined the relationship of the leukemia-accelerating properties of a dual-tropic virus (DTV-70) (when injected into the thymus of 14-day-old AKR mice) to its ability to impair T cell functions. Splenic lymphocytes from virus-infected AKR mice were found to have reduced T cell mitogenic responses; moreover, these cells suppressed phytohemagglutinin stimulation of cells from normal, uninfected AKR mice. The response to the B cell mitogen lipopolysaccharide was slightly enhanced at 15 days following DTV-70 infection and was unaffected at later ages. AKR mice infected with DTV-70 showed reduced ability to develop delayed-type hypersensitivity reaction and interleukin 2 production. In contrast, spleen cells from the virus-infected mice responded normally to allogeneic stimulation in mixed lymphocyte culture and mounted an almost normal graft versus host reaction. The data suggest that DTV-70 impairs certain T cell functions that could interfere with immune surveillance and thus permit progression of preleukemic cells into overt leukemia. These T cell functions are suppressed normally by 6 months of age, perhaps by spontaneously arising DTV.

Age Factors↗
PubMed1985

High incidence of B cell lymphomas derived from thymectomized AKR mice expressing TL.4 antigen.

AKR mice, 6-12 mo after birth, display a high incidence of spontaneous T cell lymphomas that can be prevented by thymus removal at the age of 1-3 mo. We report here the presence of dormant preleukemic cells among bone marrow cells of 8-12-mo-old AKR mice that have been thymectomized when 40-60 d old. Transplantation of bone marrow cells from these thymectomized AKR donors into syngeneic or hybrid (AKR X DBA/2)F1 intact or thymectomized recipients resulted in lymphoma development of AKR origin in 80-100% of the recipients. Analysis, by flow microfluorometry, of the antigenic cell surface phenotypes of the developing lymphomas revealed that all tumors were B cell lymphomas, since the cells stained with class-specific anti-IgM reagents and other reagents specific for B cells (RA3-2C2, RA3-6B2, anti-I-A, and anti-Fc receptor), and were Thy-1-. All these B cell tumors also expressed two T cell differentiation antigens, TL.4, found exclusively on T cell lymphomas, and Lyt-1 antigen, previously shown (11) to be expressed on some B cell neoplasms. The surface markers mu, I-A, RA3-2C2, and TL.4 identified by immunofluorescence, were shown to be integral membrane components synthesized by the tumor cells, rather than passively acquired proteins.

AKR murine leukemia virus↗
PubMed1985

High incidence of acute myeloid leukemia in SJL/J mice after X-irradiation and corticosteroids.

SJL/J mice which developed a high incidence of spontaneous reticulum cell neoplasms, developed a low rate incidence (20-25%) of myeloid leukemia (ML) after X-irradiation. The possible effect of adrenal steroid imbalance to radiation-induced ML in SJL/J mice was tested. Intact and thymectomized animals were exposed to a single dose of 300 r whole body irradiation and treated with either hydrocortisone acetate, prednisone, metyrapone and adrenocorticotropin as coleukemogenic agents. Hydrocortisone and prednisone exerted a marked coleukemogenic effect, increasing the ML incidence to a similar rate of about 50-70%, at a mean latent period of 300 days. Prominent leukemic infiltration were observed in the bone marrow, spleen, lymph nodes and liver of the leukemic animals. Results of cytological and histological studies, including cytochemistry and ultrastructure, were all consistent with the diagnosis of acute myeloid leukemia (AML). Since AML is the type of human secondary leukemia which appears increasingly in patients treated with alkylating drugs and/or irradiation and corticosteroids for Hodgkin's disease or other neoplastic diseases, the experimental model of AML induced in SJL/J mice could be used for elucidation of mechanisms of leukemogenesis in secondary leukemia.

Adrenal Cortex Hormones↗
PubMed1985

Changes of H-2 antigen expression on thymocytes during leukemia development by radiation leukemia virus.

The expression of antigens encoded by the K and D region genes of the major histocompatibility complex on thymocytes of BL/6 mice infected with Radiation Leukemia Virus (RadLV) variants, A-RadLV to which they are sensitive or D-RadLV to which they are resistant, was investigated. Reduced thymus cellularity due to the thymolytic effect of both RadLV variants (30-40% cell reduction within 24 h after intrathymic virus injection) was accompanied with elevated H-2 expression on thymocytes. A high density of H-2D and to a lesser degree increased expression of H-2K were observed following infection with both virus variants. This elevated H-2 expression was maintained transiently for 6-7 weeks in the resistant situation and persisted in the sensitive situation until overt leukemia developed. The occurrence of A-RadLV transformed cells in 75% of the tested thymuses within 10 days after infection (vs 16% in D-RadLV treated mice) and their further expansion until overt leukemia developed could explain the continued expression of elevated H-2 expression on thymocytes in the sensitive situation. The majority (85%) of the primary A-RadLV induced leukemias tested expressed more H-2D/H-2K gene products than normal thymocytes. We conclude that leukemia development due to RadLV infection is not associated with the reduction or disappearance of H-2D/H-2K gene products.

Animals↗