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Biomedical subjects

R C Ting

Publications and source records attributed to R C Ting.

At least 37 records · Page 2Linked to original sources
PubMed1984

Location of human T-cell leukemia virus (HTLV) p19 antigen on virus-producing cells.

Mouse monoclonal antibody to HTLV p19 was used to locate HTLV p19 on the surface of cells and virions by immunofluorescence microscopy (IFM) and immunoelectron microscopy (IEM). When HTLV-producing cells HUT 102 (B2 clone), MT-2 and strain A were used as target cells, HTLV p19 was detected on the surface of cells and virions as spots or small sectors by both IFM and IEM. Cells infected with animal type-C retroviruses, e.g., gibbon ape leukemia virus, simian sarcoma virus, feline leukemia virus, and Gross murine leukemia virus, were completely negative for HTLVp19 expression. Other human T cells not producing HTLV, including HUT78 and HSB2-0, immature or pre-T cells (Molt-3) derived from leukemia patients, and fresh peripheral blood T cells from healthy persons, were also negative. In addition, B cells including Rob-B, IM-9, Raji, and BT-1 did not react with the monoclonal antibody to HTLV p19. In the light of the presence of HTLV p19 in the periphery of acetone-fixed HTLV-producing cells as shown by IFM, it seems most likely that HTLV p19 is an internal antigen of HTLV with part of its structure protruding out of the viral and cell membrane. The monoclonal antibody to HTLV p19 did not lyse HTLV-producing cells in the presence of complement, as expected, because the antibody is an IgG1. Antibody-dependent cell-mediated cytotoxicity was also studied by the 51Cr-release assay. No cytotoxicity was observed. Although HTLV p19 does not contribute to the destruction of malignant T cells for treatment and/or virions for prophylaxis, this protein is an important marker for diagnosis of HTLV infection. The patterns of HTLV p19 expression described above were exactly the same for American HTLV-producing HUT 102 (B2 clone), for strain A cells and for Japanese HTLV-producing MT-2 cells. These results further substantiate the close relationship of the Japanese and American HTLV isolates.

Antibodies, Monoclonal↗
PubMed1982

Effect of type C viral expression and cellular karyotype on human B-lymphoblast tumorigenicity in nude mice.

Cultured human hematopoietic cells from several normal and leukemic sources, including those cells initiated after exposure to primate type C retroviruses were tested for their capacity to induce tumors in young athymic BALB/c (nu/nu) mice after sc inoculation. An attempt was made to correlate these results with virus expression and chromosome patterns. Progressively growing tumor formation was observed in 5 of 18 normal diploid B-lymphoblast lines from normal peripheral blood and in one of three diploid B-lymphoblast lines from leukemic donors established after infection with primate type C viruses (gibbon ape leukemia virus or simian sarcoma virus). In contrast, none of eight spontaneously transformed B-lymphoblast lines with normal diploid karyotypes formed progressively growing tumors, although one formed a tumor that remained the same size (0.5 cm) for several months. Progressive tumor formation occurred in four of seven previously established cell lines of different cell types that had abnormal karyotypes. Of the normal diploid B-lymphoblast cultures exposed to type C viruses, 12 were tested for the presence of viral RNA and structural proteins (p12, p30, gp70), and this information was correlated with tumorigenicity. Four of the six cultures expressing viral RNA or proteins were tumorigenic, whereas only one of six cultures that did not express virus information was positive. The results of this study suggest that expression of type C viral RNA and proteins by human B-lymphoblasts increases their tumorigenicity in nude mice. It is also apparent that caution must be used in attempts to correlate cell tumorigenicity and chromosome abnormalities in nude mice.

Animals↗
PubMed1981

Induction of differentiation of human promyelocytic leukemia cells (HL-60) by nucleosides and methotrexate.

Various purine and pyrimidine analogs and methotrexate were tested to determine whether they induce morphologic and functional myeloid differentiation in HL-60, a human promyelocytic leukemia cell line. Functional maturity was assessed by nitro blue tetrazolium reduction assays. 3-Deazauridine caused nearly all of the cells to differentiate during 6 days of treatment. Pyrazofurin, virazole, puromycin aminonucleoside, and the tricyclic nucleoside 3-amino-1,5-dihydro-5-methyl-1-beta-D-ribofuranosyl-1,4,5,6,8-pentaazaacenaphthylene induced maturation in 44-64% of the cells, whereas 5-azacytidine, 5-bromo-2'-deoxyuridine, 5-iodo-2' deoxyuridine, thymidine, and the antimetabolite methotrexate induced maturation in 28-36% of the cells. In terms of effective concentration, the most potent inducer was methotrexate (10-8 M). The predominant cell types after treatment with all of these compounds were the metamyelocyte and banded neutrophilic granulocyte.

Cell Differentiation↗
PubMed1979

Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors.

In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts.

Animals↗
PubMed1978

Differences in the capacity of simian virus 40 (SV40) tumor antigens on cells, membranes and in soluble form to induce transplantation immunity in hamsters and mice.

The immunogenicity of the SV40 tumor-specific transplantation antigen (TSTA) on cells, cell particulates and solubilized membranes was studied in mice and in Syrian hamsters. Immunizations were done with various concentrations of tissue-culture-passaged, non-virus-releasing transformed cells, purified cell membranes and in some cases purified nuclei and papain-solubilized membranes obtained from several species, including the mouse, hamster, man, and sheep. All transformed cell lines were T-antigen-positive. The immunosensitive mKSA line of BALB/c mice and the immunosensitive SV34 cell line of the hamster were used for tumor challenge. All materials, regardless of source and of type of preparation, were strikingly immunogenic in the mouse but only SV40 virus and SV34 (hamster) cells provided protection against tumor cell challenge in the hamster. Also, in a limited study, BKV-transformed hamster cells and purified cell membranes and JCV-transformed hamster cells were found to be immunogenic by the tumor rejection assay in the mouse but not in the hamster. SV40 immunization did not protect the hamster against BKV- and JCV-transformed hamster cells. These results are discussed in terms of possible different specificities resident on the TSTA molecule.

Animals↗
PubMed1978

Polyoma virus-human cell interactions: persistence of T-antigen in two cell lines with and without transformation.

The interaction of polyoma virus and human cells was investigated. Abortive infection as evidenced by the synthesis of T-antigen was observed in normal fibroblast and abnormal (transformed) cells but not in normal epithelial cells. A high percentage of simian virus 40-transformed WI-18 Va2 and spontaneously transformed BE skin cells produced T-antigen after high-multiplicity infection, but most of the cells rapidly lost antigen-producing capacity upon cell passage, and the cultures became negative by passage 3. All fibroblast cells displayed varying degrees of susceptibility to infection, but most of the cell lines became negative for T-antigen except for two. In one, T-antigen persisted in a small percentage of the cells throughout the lifetime of the culture, without cellular transformation occurring. In the other, the entire culture became morphologically transformed and eventually consisted of 100% T-antigen-positive cells. This is the first time that normal diploid human fibroblast cells have been transformed by polyoma virus.

Animals↗
PubMed1977

Survival of human cells in the aggregate form: potential index of in vitro cell transformation.

The ability of cell populations to survive in the aggregate form was compared to colony formation in soft agar and tumorigenicity in nude mice. Nontumorigenic human osteogenic sarcoma (HOS) cells, which formed colonies in soft agar, could not survive in the aggregate form. Tumorigenic HOS cell lines, which also formed colonies in soft agar, survived and proliferated in the aggregate form. Other cell types were tested with the same results. This approach, based on cell survival in the aggregate form, may provide an additional, reliable method for predicting the tumorigenic status of a cell population.

Animals↗
PubMed1977

Induction of simian virus 40 (SV40) transplantation immunity in mice by SV40-transformed cells of various species.

Specific tumor rejection was obtained with the use of simian virus 40 (SV40)-transformed cells from several species including man, rat, ape, sheep, and hamster. Growth of the syngeneic sarcoma mKSA in BALB/c mice was strikingly inhibited following a single immunization with as few as 10(3) intact, viable cells. Non-SV40-transformed cells did not induce tumor rejection activity nor did SV40-transformed lines induce immunity against the 3-methylcholanthrene-induced sarcoma Meth A, syngeneic with BALB/c mice. A close relationship existed between the tumor rejection antigen, the tumor-specific transplantation antigen (TSTA) located on the plasma membrane, and the intranuclear tumor antigen (T-ag). Both were associated with the DNA sequence of the early region of the SV40 genome, and TSTA activity was found in the nucleus. However, we did not observe a close parallelism between T-ag activity and TSTA. Neverthesless, the results strongly suggested that TSTA, like T-ag, was encoded by the virus.

Animals↗
PubMed1977

Lack of expression of type C hamster virus after neoplastic transformation of hamster embryo fibroblasts by benzo(a)pyrene.

Syrian hamster embryo fibroblasts transformed in vitro with benzo(a)pyrene were analyzed for the presence of type C viral components, including extra- and intracellular reverse transcriptase activity, intracellular type C hamster virus-related RNA, and cellular hamster virus group-specific antigen. No evidence could be obtained for the presence of any of these components, although they were easily detectable in hamster fibroblasts producing either B-34 virus (a hamster virus pseudotype of Harvey murine sarcoma virus which contains an excess of helper type C hamster virus) or Harvey virus itself. In addition, intracellular viral RNA could not be detected in normal hamster embryo fibroblasts, in hamster fibroblasts transformed with simian virus 40, or in newborn hamster kidney and liver. Thus the detectable expression of the indigenous hamster type C virus is not required to maintain the transformed phenotype of these cells.

Antigens, Viral↗
PubMed1977

Survival differences exhibited by normal and transformed rat liver epithelial cell lines in the aggregate form.

Normal and transformed rat liver epithelial cell lines exhibited differences in the ability to survive in the aggregate form. Normal rat liver epithelial cells in the aggregate form underwent a rapid decline in the number of viable cells, while counterpart transformed epithelial cells exhibited an ability to survive and proliferate in the aggregate form. This survival ability was found to correlate with colony formation in soft agar and tumorigenicity in nude mice. Cell survival in the aggregate form could possibly serve as a criterion for in vitro transformation of epithelial cells derived from rat liver.

Cell Aggregation↗
PubMed1976

Immunogenic properties of a nonproducer malignant tumor induced by murine sarcoma virus.

A cloned cell line H-11 (HP) derived from an MSV-induced neoplasm (a hemangiosarcoma) was found to possess virus-specific tumor rejection antigen(s). The specific nature of the immune response was established through the use of a polyoma virus-induced neoplasm no. 89 both in cross immunization and cross challenge experiments. Virus antigens or surface antigens associated with virus production are not responsible for tumor rejection since virus production could not be detected, nor were any viral fingerprints of MSV found by the several assays used.

Animals↗
PubMed1975

Effect of cordycepin on the replication of type-c RNA tumor viruses.

Cordycepin (3'-deoxyadenosine) was previously shown to inhibit virus production induced by iododeoxyuridine from murine fibroblasts (Wu et al., 1972). We now report that the inhibitory effect of cordycepin results in a reduction of the number of cells producing virus as measured by the infectious center assay and fluorescent antibody technique. Cordycepin has a much greater inhibitory effect on viral replication than on transformation of normal rat kidney cells by murine sarcoma virus since viral production was greatly reduced (seven- to 35-fold) with 5-10 mug/ml of cordycepin while viral transformation was only slightly inhibited (two-fold reduction in focus-forming units) with the same concentration of cordycepin. Inhibition of viral production is most effective if the compound is present during the first 24 h after injection.

Animals↗
PubMed1975

Comparison of drug effects on RNA tumor viruses and on transformed cells.

Attempts to develop in vitro methods to test inhibitors for replication of C-type RNA tumor virus are made at two levels of the life cycle of the virus: 1) Formation of the proviral DNA, and 2) transcription and processing of viral RNA. Compounds such as rifamycin derivatives were found to be effective in interfering with the first process and compounds such as cordycepin, a nucleoside analogue, blocked effectively the second process. On the other hand, a class of known anti-tumor agents, glucocorticoids, was found to stimulate (10 fold or more) the induction of C-type virus following 5-iodo-2'-deoxyuride (IDU) treatment of murine cells. This is an intriguing example of a multi-focal action of an anti-tumor agent. We are exploring the implication of this for relapse or retransformation following successful chemotherapy in leukemic mice. Attempts are being made to develop an in vitro animal cell model for quantitative cytotoxic assays for compounds active in the above system and for comparing their effects on both normal and virus transformed cells.

Animals↗