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V K Ghanta

Publications and source records attributed to V K Ghanta.

At least 55 records · Page 3Linked to original sources
PubMed1987

Regulation of natural immunity (NK activity) by conditioning.

A paradigm is described for the conditioning of the NK response. Mice were exposed to a classical conditioning procedure in which saccharin and lithium chloride (LiCl) served as the conditioned stimulus (CS) paired with an injection of either poly I:C or cytoxan, the unconditioned stimulus (US). Poly I:C was used as the US for enhancement and cytoxan served as the US for suppression. Subsequent exposure to the CS either enhanced or suppressed the NK activity in the conditioned animals. Our studies showed that only one association was needed for the learning to take place, training to consumption of water was not necessary, and the conditioned (enhanced) response could be recalled as soon as 7 days after pairing of the US and CS.

Animals↗
PubMed1987

Modulation of immune response. A possible role for murine salivary epidermal and nerve growth factors.

Both epidermal growth factor (EGF) and nerve growth factor (NGF) were found to moderate the reactivity of mouse spleen cells in an in vitro model of immune response. Blastogenic response was suppressed by EGF and potentiated by NGF. Both proteins are present in mouse, but not human, saliva in quantities equal to or greater than those affecting blastogenic response in our assay. Immune response occurring in the mouse periodontium may be affected by the presence of these factors in the saliva.

Animals↗
PubMed1986

Induction of the plateau phase and rescue of MOPC 104E by nonspecific immunization.

The enhancement of MOPC 104E myeloma growth by nonspecific immunostimulation with C. parvum or immunization with sheep red blood cells and levan mixture was evaluated in BALB/c mice. We observed increased levels of serum MOPC 104E IgM and early mortality in the tumor-bearing mice following treatment with C. parvum or antigenic stimulation. The enhancement of tumor growth observed was due to the production of lymphokine mitogenic factors produced in response to the nonspecific immunostimulation.

Animals↗
PubMed1986

In vitro effect of monoclonal anti-idiotype antibodies (anti-M104E) on MOPC 104E myeloma cells.

We investigated the effect of three monoclonal anti-idiotype antibodies (anti-M104E) on various functions of MOPC 104E myeloma cells in vitro. The antibodies used were N-20-2 [immunoglobulin M (IgM), BALB/c], SJL18-1 [IgM, BALB/c X SJL F1], and CD3-2 [immunoglobulin G1 (IgG1), BALB/c X A/J F1]. The two IgM antibodies were very efficient in blocking surface M104E IgM as shown by rosette inhibition, whereas the IgG1 isotype was not very effective. The reexpression of surface M104E IgM was different from antibody to antibody. The secretion of M104E IgM by MOPC 104E cells was partially blocked by the two IgM antibodies, but the IgG1 antibody had no effect. All three anti-idiotype antibodies inhibited the stem cell renewal activity of MOPC 104E cells assayed by colony formation assay. On the other hand, in suspension culture, the two IgM antibodies inhibited the growth of MOPC 104E cells in the absence of complement or effector cells of antibody-dependent cellular cytotoxicity, but IgG1 antibody had no effect. The starting tumor inoculum size was critical in the observations of the effects seen on both the growth and the colony-forming activity of MOPC 104E cells. The results of this study show the functional differences between various monoclonal anti-idiotype antibodies and also indicate that some anti-idiotype antibodies can inhibit the growth of MOPC 104E myeloma cells directly without any help of complement or effector cells of antibody-dependent cellular cytotoxicity.

Animals↗
PubMed1985

Establishment of growth factor-dependent MOPC 104E cell line in vitro.

The MOPC 104E cell line has been adapted to grow in vitro using a combination of feeder layer and growth factor(s). The growth of this myeloma cell line is dependent on the presence of growth factor(s). Growth-promoting activity generated from T-cell-mitogen-stimulated, Corynebacterium parvum-stimulated spleen cell culture supernatant, and peritoneal adherent cell culture supernatants gives dose-dependent proliferation. Generation of growth factors in the serum-free bovine serum albumin-substituted media and a rapid assay system based on [3H]thymidine uptake for the quantitation of growth promoting activity are described.

Animals↗
PubMed1985

Tumor burden, chemotherapy, and cell kill in osteosarcoma model.

The complex relationships among tumor cell burden, dose and schedule of chemotherapy, and efficacy were investigated in a murine osteosarcoma model in which an easily measured marker provided an accurate, dynamic estimate of host tumor cell burden. Cytoxan (200 mg/kg) produced a 93.2-99.997% tumor cell kill in animals with a pretreatment tumor burden of 0.6-3% body weight. In animals with a pretreatment tumor burden of 5.1-10.24% body weight, however, the same dose of cytoxan produced less than 1 order of magnitude tumor cell kill (31-71%). A schedule utilizing three doses q12 days in animals with a moderate burden of tumor (up to 5% body weight) produced a cell kill of six or more orders of magnitude with some cures, an event which was more frequent with added immunostimulation. A schedule utilizing two doses q20 days in animals with a larger body burden (5-10% of body weight) was essentially ineffective. These results suggest that a small initial body burden (low stage) and an aggressive schedule of treatment are necessary for optimum results in cancer treatment. Small delays in initiation of treatment and prolonged intervals between doses can convert an effective drug to an ineffective one without the need to invoke biochemical mechanisms of resistance.

Alkaline Phosphatase↗
PubMed1985

Host regulation of MOPC 104E plasmacytoma after reduction of tumor burden by total body irradiation.

Radiation-sensitive BALB/c MOPC 104E plasmacytoma was studied to investigate the effectiveness of total body irradiation in reducing tumor burden and preventing tumor regrowth. Also noted were the effects of such radiation on host immunity. BALB/c mice bearing 7-day-old occult tumors were not rendered free of disease when treated with radiation of 300 or 500 rad. However, all of the mice treated with 800 rad were cured. When mice bearing large tumors (24-days-old) were similarly treated, no cures were observed in the group treated with 300 rad. Of mice treated with 500 rad, 44% were cured, as were 100% given 800 rad of treatment. The percent reduction in serum MOPC 104E IgM increased with increasing radiation doses for the "large tumor" group. These observations show that total body irradiation may result in tumor elimination in an experimental animal multiple myeloma model. At lower radiation doses, host immunity appears to play an important role in achieving cure.

Animals↗
PubMed1985

Neural and environmental influences on neoplasia and conditioning of NK activity.

The effects of physical restraint and poly I:C treatment on the growth of MOPC 104E myeloma and murine osteosarcoma and survival of animals bearing such tumors were investigated. Our studies show that in the Balb/c mice with MOPC 104E myeloma the effects of restraint stress were detrimental and lead to early death of the mice. When the restraint was combined with poly I:C, during the early course of the disease, restraint stress neutralized the beneficial effects of the poly I:C treatment. These studies show that under certain circumstances, restraint stress can negate the effects of therapy. On the other hand, restraint stress produced an opposite effect in C3H/He mice with murine osteosarcoma tumor treated in the same fashion. In mice with osteosarcoma, restraint stress delayed tumor growth and increased the median survival time. When restraint stress was combined with poly I:C treatment, the mean tumor size was smaller and median survival was substantially increased over the control group. Because poly I:C therapy delayed tumor growth and increased survival in both models, efforts to strengthen this response were tested by conditioning. Our studies show the response to poly I:C as measured by elevation of the NK activity could be conditioned with camphor smell. Conditioning of the host to raise immune activity to alter the outcome of disease is a new area yet to be explored and has important clinical significance. These studies, we believe, are important because they explore the connection between mind and body and resistance to disease.

Animals↗
PubMed1984

NMR study of in vivo RIF-1 tumors. Analysis of perchloric acid extracts and identification of 1H, 31P and 13C resonances.

Perchloric acid extracts of radiation-induced fibrosarcoma (RIF-1) tumors grown in mice have been analyzed by multinuclear NMR spectroscopy and by various chromatographic methods. This analysis has permitted the unambiguous assignment of the 31P resonances observed in vivo to specific phosphorus-containing metabolites. The region of the in vivo spectra generally assigned to sugar phosphates has been found in RIF-1 tumors to contain primarily phosphorylethanolamine and phosphorylcholine rather than glycolytic intermediates. Phosphocreatine was observed in extracts of these tumor cells grown in culture as well as in the in vivo spectra, indicating that at least some of the phosphocreatine observed in vivo arises from the tumor itself and not from normal tissues. In the 31P-NMR spectra of the perchloric acid extract, resonances originating from purine and pyrimidine nucleoside di- and triphosphate were resolved. HPLC analyses of the nucleotide pool indicate that adenine derivatives were the most abundant components, but other nucleotides were present in significant amounts. The 1H and 13C resonance assignments of the majority of metabolites present in RIF-1 extracts have also been made. Of particular importance is the ability to observe lactate, the levels of which may provide a noninvasive measure of glycolysis in these cells in both the in vitro states. In addition, the aminosulfonic acid, taurine, was found in high levels in the tumor extracts.

Animals↗
PubMed1984

Regulation of MOPC 104E by T cells and growth factors induced by C. parvum stimulation.

Corynebacterium parvum, known for its ability to retard the growth of experimental neoplasms, was examined for its effect on the growth of murine plasmacytoma MOPC 104E in vivo and in vitro. Immunostimulation with C. parvum resulted in the accelerated growth of MOPC 104E in experimental animals, as measured by the tumor IgM production. The acceleration of plasmacytoma growth was seen in all cases where C. parvum was given before or at the time of tumor transplantation. Increased proliferation of MOPC 104E was also observed when MOPC 104E was co-cultured in the presence of spleen cells from C. parvum stimulated mice as compared to the normal spleen cells. Removal of T cells by in vivo anti-thymocyte serum treatment, followed by anti-Thy 1.2 and complement in vitro, resulted in the partial loss of stimulatory activity. Furthermore, the stimulatory activity was shown to be associated with soluble mediators, which were generated by splenic adherent cells and T cells, and were, at least in part, responsible for the growth of plasmacytoma. Normal spleen cells did not generate a significant amount of soluble factor, but were able to augment MOPC 104E growth in co-culture at high spleen to tumor cell ratio.

Animals↗
PubMed1984

Effects of orchiectomy on spleen cell mitogen response and on the thymus of aged mice.

Seven weeks after orchiectomy, 19 and 10 month old mice had mean thymic weight increases of 34 and 128%, respectively, compared to sham-operated controls. Peripheral WBC counts were greater (p less than .05) in castrates of both age groups. On a cell for cell basis, the mitogen response of castrate spleen cells was not significantly greater than controls, and in some instances was significantly less. Although individual cell function may not be augmented after castration, in vivo immune response may be potentiated due to an increase in absolute number of lymphoid cells.

Aging↗
PubMed1984

Inhibition of growth of MOPC 104E cells in immunosuppressed mice.

In this report we provide evidence that suggests that MOPC 104E may come under regulation in highly immunosuppressed hosts depleted of T cells. Mice that are adult thymectomized, total body irradiated, and transplanted with bone marrow cells were able to resist the growth of MOPC 104E cells. Spleen cells from such animals had low NK activity and no cytotoxicity against MOPC 104E, and poor response to Con A, PHA, and LPS. The animals were deficient in Lyt-1+ and Lyt-2+ cells. The growth of MOPC 104E cells was measured by using the circulating level of MOPC 104E IgM in vivo in mice treated by different modalities. We observed that inhibition of tumor growth in vivo varied with the treatment of the host. Growth was inhibited in the host in the following order: ATXBM greater than XBM greater than NORMAL greater than ATx mice.

Animals↗
PubMed1984

Reduction of tumor burden in a murine osteosarcoma following hyperthermia combined with cyclophosphamide.

A radiation- and chemotherapy-resistant murine osteosarcoma was used to investigate the effect of local hyperthermia (42.5 +/-0.1 degrees, 30 min) alone and in combination with cyclophosphamide. The cytotoxicity of cyclophosphamide on murine osteosarcoma was established previously in our laboratory. Local hyperthermia (42.5 +/- 0.1 degree, 30 min) had little or no effect on the 16-day-old (206 X 10(6) osteosarcoma tumor cells/mouse) tumor as shown by the changes in the tumor cell marker, alkaline phosphatase. A 2.5 +/- 3.5% reduction in the number of tumor cells was seen. Large tumors treated at 21 days postimplantation (357 X 10(6) tumor cells) showed a reduction of 24 +/- 14%. The effect of combination treatment with cyclophosphamide and hyperthermia produced greater reduction in the numbers of tumor cells than did either treatment used alone.

Animals↗
PubMed1983

Tumor proliferation and chemotherapy in immunosuppressed mice.

The influences on host immunosuppression by treatment with cyclophosphamide (200 mg/kg), steroid (prednisolone, 12.0 mg/kg for seven doses or 235 mg/kg for one dose), and adult thymectomy on tumor growth were compared. Treatment with cyclophosphamide 24 hr prior to MOPC 104E tumor transplantation produced the greatest facilitation of tumor growth. The role of prednisolone in rendering the MOPC 104E cells more vulnerable to conventional chemotherapy was also investigated. The combination of prednisolone with melphalan added measurably to the cytotoxicity of the treatment and increased the percentage of disease-free survivors. The observed effects of prednisolone might have been due to the increase in the cycling of myeloma cells directly, or the drug may have facilitated growth of the myeloma by blocking host expansion of T-cell immunity. Alterations of the host by adult thymectomy and immunosuppression with cyclophosphamide or prednisolone led to growth facilitation of myeloma. The limited studies reported here point out the usefulness of facilitation of tumor growth to accomplish increased neoplastic cell kill and increased percentage of disease-free survivors.

Animals↗
PubMed1983

MOPC 104E plasmacytoma functional heterogeneity and maturational potential in culture.

MOPC 104E plasmacytoma secretes an immunoglobulin M (IgM) paraprotein which reacts specifically with dextran B-1355. We separated plasmacytoma cells into subfractions by density gradient centrifugation. The majority of cells isolated from the peritoneal washes 3 days following i.p. transplantation of tumor were in active cell cycle and had a density of 1.055 or 1.065 g/ml. Cells isolated from 9-day-old ascites were confined to the heavy-density fraction (1.085 g/ml). The majority of these cells were not in proliferative phase. Functional analysis of the fractions using rosette formation and plaque formation assays indicated that cells in active cell cycle had less surface IgM and secreted less IgM than did cells not in cell cycle. An attempt was made to establish a cultured cell line of MOPC 104E plasmacytoma. The majority of the cells of the continuously cultured cell line were in active cell cycle, had less surface IgM, and secreted less IgM. Cultured cells acquired more cell surface IgM and actively secreted IgM following their secondary colonization in 0.8% methylcellulose. These studies showed that the new line of MOPC 104E retained the properties of the original ascites tumor. An important feature of these studies is that the density of cells within a colony is a stable property and is probably not related to cell cycle.

Animals↗
PubMed1982

Antigenic determinants on lymphocytes from young and old C57BL/6 mice.

Antigenic differences between lymphocytes from young and old female C57BL/6 mice were studied using 3 techniques. In one-way mixed lymphocyte reactions significant responses were obtained in 7.7% of the young leads to young combinations, 13.5% of the young leads to old, 18.2% of the old leads to young and 23.7% of the old leads to old. Polyethylene glycol enhanced the weak syngeneic MLR responses in all groups. Young anti-old antiserum was raised in young animals by injecting with lymphoid cells from old mice. The serum was cytotoxic to spleen cells from 5 of 6 old mice aged in animal facilities at University of Alabama in Birmingham and from 2 of 12 mice aged at Charles River. Lymphocytes from young mice were sensitized to old lymphocytes in a mixed lymphocyte culture and their cytotoxicity toward old cells measured in a chromium-release assay. No cytotoxicity was observed with sensitized lymphocytes from 5 young mice under various conditions. These results do not support the hypothesis that altered anti-genic determinants are always or even usually present on the lymphocytes of old mice.

Aging↗