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Biomedical subjects

V K Ghanta

Publications and source records attributed to V K Ghanta.

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

Effect of thymic hormone treatment on several immune functions of nude mice.

Studies of the effect of short-term, intense treatment with thymic hormone on mitogen response, cytotoxicity to EL-4 lymphoma and natural killer cell (NK) activity was investigated Balb/c nude mice (about 12-16-week-old) were treated 5 times per week for 3 weeks with: Facteur Thymic Serique (FTS) and Thymopentin (TP5, Thymopoietin 32-36) at 1 microgram and 10 ng; TM4 1 ng (an enzyme resistant variant of FTS); Thymosin Fraction V (TF5), 10 and 1 microgram; and 0.1 ml saline, and killed 2 days after the last treatment. The animals were monitored for changes in weight, hematocrit, peripheral blood lymphocyte (PBL) and spleen mitogen response. Additional groups of nude mice were immunized with 1 x 10(7) 5000 R irradiated EL-4 cells 10 days before sacrifice and tested for the presence of cytotoxic T-lymphocytes (CTL). The results show that weight and hematocrit were similar among the groups. Treatment with FTS significantly elevated the number of PBL. Spleen stimulation in mice treated with 1 microgram TP5 was depressed to mitogen concanavalin A (ConA) and lipopolysaccharide (LPS) stimulation. The phytohemagglutinin (PHA) response was not different among the treatment groups. The PBL mitogen response to ConA and LPS was generally increased over saline control in the hormone treated groups but was not statistically significant. The PHA response was only slightly elevated. No CTL was generated in nude mice in any of the groups. However, there was a statistically significant general depression of NK activity in all of the hormone treated animals compared with saline. The results indicate that the basic differentiation defect of the T-cells of nude mice cannot be restored to full functional activity by short-term treatment.

Aging↗
PubMed1991

Survey of thymic hormone effects on physical and immunological parameters in C57BL/6NNia mice of different ages.

Immunosenescence occurs with aging, which is seen in decline in response to mitogens PHA, ConA, decline in cell-mediated immunity, increase in anemia, and increase in autoimmune antibodies to erythrocytes and DNA. These studies compared FTS, TP5, TM4, and TF5 in C57BL/6NNia mice. Mice aged 4, 26, 52, 78 and 104 wk were treated with various hormones 5x/wk for 3 wk and monitored for hormonal effects on weight; hematocrit; peripheral blood, spleen, and thymic cell numbers; spleen and peripheral blood cell mitogen responses to PHA, ConA, LPS; IgM hemolysin autoantibody; and cell-mediated cytotoxicity to P815 allogenic cells. Hormone treatments altered mitogen responses, enhanced IgM hemolysin autoantibody production, and modulated cell-mediated immune responses. The effects were not consistent for every hormone. There was a tendency for enhancement in younger mice and suppression in older animals. Treatment with FTS showed the greatest changes in either enhancing or suppressing the different parameters measured. The hormonal effects appeared to be age specific in that certain activities were altered for certain age groups but not in others. Hormone treatment did not restore any immune parameters in old mice to the level of young animals. In general, the different hormones did not consistently produce the same effects in C57BL/6NNia mice of different age groups. Even though all animals received from National Institutes on Aging (NIA) animal models program were held under strictly controlled conditions, intrinsic variations between cohorts of different ages are difficult to control. Cohorts of aging animals tested at different times might be intrinsically different. This inherent variability in the cohorts could affect the range of activity, specificity and reproducibility of hormone effects in vivo. Most importantly, it should be emphasized that cross-sectional data identifies age differences rather than age changes. There is no assurance that age changes in any individual or in all subpopulations follow this pattern. In our studies only healthy animals were used. Old, sick, or tumor-bearing animals were culled out prior to being sent to us. Therefore, the 78- and 104-wk-old mice represent selected healthy cohorts. The age changes that take place can be answered only from repeated measurements made in the same individual over time.

Aging↗
PubMed1991

Role of immune cells in the Pavlovian conditioning of specific resistance to cancer.

It has been demonstrated that significant protection against YC8 lymphoma can be induced in mice preimmunized with normal DBA/2 spleen cells. The DBA/2 spleen cells used as alloantigens share minor histocompatibility determinants with the YC8 tumor. We have used this model to investigate the nature of the immunity conferred by treatment with the alloantigen and infer that the conditioned resistance observed was maintained by the same effector mechanism. The results demonstrated that repeated immunization of tumor bearing mice with the alloantigen had some beneficial effect as shown by the slower rate of growth of the tumor, and an increase in median survival time over controls. The observations showed however that once tumor was present in vivo, the use of potent tumor specific vaccine can help in increasing survival but can no longer produce high incidence of regressions and cures. Conditioning can potentiate the effects of this treatment by increasing survival and cure.

Animals↗
PubMed1991

In vivo enhancement of NK cell activity with met-enkephalin and glycyl-glutamine: their possible role in the conditioned response.

These studies investigated the effect of met-enkephalin, glycyl-glutamine, and naltrexone on NK cell activity in vivo and in vitro. It was found that both met-enkephalin (which shares the amino-terminal end of beta-endorphin) and glycyl-glutamine (which reflects the carboxyl-terminal end of beta-endorphin) can enhance the NK cell activity of mice prestimulated with a low dose (1 microgram/mouse) of poly I:C. Naltrexone had no effect. In vivo prestimulation of the mice with 1 microgram poly I:C was necessary as mice which were not pretreated with poly I:C did not show enhanced NK cell activity when treated with either met-enkephalin or glycyl-glutamine. In vitro studies however indicate that the drugs when cultured together with the NK cells from mice preactivated with poly I:C did not have a direct stimulatory effect on the NK cells. These studies imply that while beta-endorphin released from the pituitary could be involved in enhancement of activated NK cells in vivo other indirect peripheral pathways might be involved. The results suggest beta-endorphin probably reacts with other accessory type cells which in turn release the mediators which are required for the stimulation of NK cells in vivo.

Animals↗
PubMed1991

A behavioral augmentation of natural immunity: odor specificity supports a Pavlovian conditioning model.

BALB/c mice were conditioned by pairing an odor to an injection of poly-inosinic:poly-cytidylic acid (poly I:C), a strong inducer of natural killer (NK) cell activity as the unconditioned stimulus (US). When later reexposed to the odor conditioning stimulus (CS), these mice showed a conditioned augmentation of the NK cell response to a suboptimal dose of 1 microgram poly I:C. The two stimuli used in these studies were camphor (Ca) and citronella oil (Cr) odors, two chemically-related but distinct odor stimuli. The conditioned mice demonstrated the ability to discriminate between Ca and Cr, such that the conditioned response (CR) was only elicited by the odor CS used in the formation of the conditioned association. Exposure of conditioned mice to the non-associated odor stimulus on the test day did not elicit a change in the NK cell response to the suboptimal dose of poly I:C when compared to mice in the US group that had been given the US on day 0 without pairing to either odor stimulus. This specificity of the CR for the odor CS and not the unassociated odor stimulus supports the interpretation that the elevation of NK cell activity in this paradigm is due to Pavlovian conditioning and therefore dependent on central nervous system (CNS) associative processes.

Animals↗
PubMed1990

Conditioning: a new approach to immunotherapy.

It has been demonstrated by Parmiani et al. (Int. J. Cancer, 29: 323-332, 1982) that a significant protective effect can be obtained against the transplanted syngeneic YC8 lymphoma by prior immunization of BALB/c mice with normal allogeneic DBA/2 spleen cells. Using this well established tumor model, we investigated a novel approach, conditioning of specific immunotherapeutic activity. For this purpose, we used the odor of camphor as the conditioning stimulus and allogeneic DBA/2 spleen cells as unconditioning stimulus. We associated the conditioning and unconditioning stimuli two, three, and four times. Following this the conditioned animals were reexposed to the odor of camphor only. In each case, we observed a delay in tumor growth and in some instances the conditioned group performed better than the immunotherapy control group. These results indicate that a limited number of treatments with the antigen is better than the continuous treatment in maintaining the immunity and the homeostasis of the system.

Animals↗
PubMed1990

Host response to myeloma: effect of syngeneic spleen cells on the growth and function of MOPC 104E myeloma in vitro.

The effect of coculturing nonadherent and plastic adherent cells from the spleen with MOPC 104E KI81 for short (24 h) and long term (7 days) was investigated. In both culture systems, the effect of the spleen cells on the secretion of IgM by plaque-forming cells assay and growth of the plasmacytoma by cell counts and flow cytometry was measured. In these studies, a low effector:target (E:T) ratio which did not produce cytotoxicity to MOPC 104E cells was used. We observed that while nonadherent spleen cells from normal or MOPC 104E-primed mice inhibited secretion of IgM by the MOPC 104E cells, they stimulated the proliferation of MOPC 104E cells two times faster than MOPC 104E cells cultured alone. Plastic adherent cells from the spleens of normal mice or MOPC 104E-primed mice also inhibited secretion of IgM by the tumor cells as measured by plaque formation, and stimulated proliferation of MOPC 104E in 24 h coculture. Plastic adherent cells from normal nonprimed mice initially stimulated the myeloma to grow, but by 24 h, a large fraction of the population was in the G1 or possibly resting state. The effect of nonadherent and plastic adherent cells on the stem cell activity of MOPC 104E was also tested in 7-day colony-forming assays. Nonadherent cells had no effect on colony-forming units or plaque formation. Plastic adherent cells from normal spleen cells inhibited plaque formation by 68% but had no effect on colony formation. However, plastic adherent cells from spleens of mice primed in vivo with MOPC 104E tumor cells suppressed plaque formation by 98% and also reduced colony formation. The results showed that inhibition by macrophages of IgM production by MOPC 104E cells is independent of cell proliferation. The adherent macrophages from both normal and in vivo-primed spleen cells were Mac.1 positive after 7 days of coculture with MOPC 104E cells. However, the density of Mac.1 was greater on primed macrophages.

Animals↗
PubMed1990

Characterization of 5B12.1, a monoclonal antibody specific for IL-6.

A monoclonal antibody (MAb) specific for interleukin-6 (IL-6) was generated by fusing SP2/0 cells with spleen cells from a mouse immunized with rat spleen cell derived plasmacytoma growth factor (rat PCT-GF). This MAb inhibited the growth of an IL-6-sensitive murine plasmacytoma clone, MD90, in the presence of the immunogen, rat PCT-GF. More interesting, however, this MAb demonstrated species cross-reactivity by neutralizing murine (recombinant and P388D1 cell line-derived) and human (recombinant) IL-6. IL-6 neutralization activity was also established in other IL-6 bioassays, such as the proliferation of spleen cells, plasmacytoma T1165, and a B-cell hybridoma 7TD1. IL-6 neutralization was overcome partially by increasing the concentration of PCT-GF. The MAb had no effect on PCT-GF-independent plasmacytoma KI81 proliferation. Plastic petri dish-bound MAb removed rmIL-6 activity. These results suggest that this MAb specifically binds IL-6 and neutralizes bioactivity of various PCT-GF, rmIL-6, and rhIL-6.

Animals↗
PubMed1989

Naltrexone blocks the expression of the conditioned elevation of natural killer cell activity in BALB/c mice.

An elevation of natural killer (NK) cell activity was conditioned by the association of a camphor odor conditioning stimulus (CS) with an injection of 20 micrograms polyinosinic:poly-cytidylic acid (poly I:C), the unconditioned stimulus (US). Poly I:C elicits the production and secretion of interferon (IFN), which induces an increase in NK cell activity. Reexposure to the CS occurred on Days 3 and 5 after the association trial on Day 0. Immediately following the CS exposure on Day 5, 1 microgram poly I:C was administered to all animals. This procedure resulted in an increased NK cell activity in the conditioned (CND), but not the nonconditioned (NC), mice. In this study we have shown that the expression of the conditioned response was blocked by an injection of naltrexone (NTX) at 10 mg/kg ip when given immediately prior to the two test CS odor exposures. Peripheral treatment (ip) with a quaternary form of naltrexone (QNTX), which is a less potent opiate antagonist, at the same dose and at the same time relative to the CS odor reexposure did not block the conditioned response. The formation of the conditioned association did not appear to be disrupted by NTX at the 10 mg/kg dose when given immediately prior to the trial odor exposure on Day 0. No modulation of NK cell activity was observed in any of the control groups treated with naltrexone or the quaternary analog. Because of the inability of the QNTX to block the conditioned response, we hypothesize that the opiate receptors involved in the conditioned response and blocked by NTX were within the central nervous system (CNS). Whether this response is peripherally or centrally mediated, we have shown that opiate receptors represent part of the mechanism which mediates the conditioned augmentation of NK cell activity.

Animals↗
PubMed1989

Immunoregulation of murine plasmacytoma. I. Generation of anomalous killer cells in vitro by cocultivation with MOPC 104E.

Murine plasmacytoma MOPC 104E-K181 is a tissue culture cell line of MOPC 104E derived from BALB/c mice. MOPC 104E-K181 implanted subcutaneously in syngeneic normal mice regresses spontaneously after an initial growth of about 10 mm. Mice that regressed tumors or mice immunized intraperitoneally with mitomycin C-treated MOPC 104E-K181 myeloma could reject subsequent challenge of viable K181 myeloma cells. In contrast to euthymic mice, T-cell-deficient athymic nude mice developed subcutaneous tumors after challenge and died from progressive tumor growth, suggesting the critical role of T cells in tumor regression. In vitro induction of cytotoxic cells was used to define the immunologic mechanism by which the host can suppress tumor growth. Spleen cells from immune mice did not show cytolytic activity in 51Cr release cytotoxicity assay, but showed inhibitory action of tumor proliferation in vitro at an effector cell to target cell ratio of 500:1 in a [3H]thymidine incorporation assay. To determine if cytotoxicity could be induced against MOPC 104E-K181 cells, in vitro sensitizing cultures were studied. We have demonstrated that normal BALB/c spleen cells became cytotoxic against MOPC 104E-K181 cells after 5 days cultivation with mitomycin C-treated stimulator cells at an optimal responder to stimulator cell ratio of 5:1. Treatment of anti-Thy-1.2 serum plus complement abolished cytotoxic activity of effector cells. Cytotoxic cells lysed not only MOPC 104E-K181 cells used for stimulation but also H-2k osteosarcoma cells. It was concluded that Thy-1.2-positive cytotoxic cells with nonspecific anomalous reactivity could be induced in murine plasmacytoma-stimulating cultures.

Animals↗
PubMed1989

Immunoregulation of murine plasmacytoma. II. Target selectivity of anomalous killer cells and role of immune T cells for the induction.

Requirements for the induction of anomalous killer (AK) cells to syngeneic MOPC 104E-KI81 plasmacytoma, and their pattern of reaction were investigated. The AK cells are Thy-1.2 positive and were induced by cocultivation of normal BALB/c spleen cells for 5 days in vitro with mitomycin C-treated MOPC 104E-KI81 cells in RPMI 1640 medium supplemented with fetal calf serum and 2-mercaptoethanol. The pattern of reactivity was investigated by direct cytotoxicity and indirect cold target inhibition assays using a panel of target cells. The results from cold target inhibition show that anomalous killer cells react with various tumor targets in the same preferential order as the results shown in direct cytotoxicity assay, and indicates that the AK cell population may be detecting the same determinants expressed to different degrees on panels of target cells. Kinetic study showed that peak cytotoxic responses were observed on day 5 and day 4, for primary and secondary sensitizing cultures, respectively. Cytotoxicity was not generated when nude mouse spleen cells were used as responder cells, suggesting the essential role of T cells in the induction. Nylon wool-column-purified splenic T cells from mice primed in vivo with intraperitoneal injection of MMC-treated stimulator cells, but not from normal mice, were able to generate AK cells in vitro. These results indicate that generation of AK cells with NK-cell-like reactivity needs inductive factors provided by the immune reaction between sensitized T cells and stimulatory MOPC 104E-KI81 cells.

Animals↗
PubMed1989

In vitro and in vivo growth control of transformed lymphoid cells expressing plasma membrane galactosyltransferase.

The level of beta 1-4 galactosyltransferase activity was examined in a number of spontaneously, chemically, or virally transformed murine tumor cell lines. Increased levels of enzyme activity were observed for the murine myeloma cell line K181 and in vivo MOPC 104E. The Maloney Sarcoma Virus (MSV) transformed T-cell lymphoma, YC-8, also demonstrated elevated levels of enzyme activity when compared to a second independently MSV transformed T stem-cell lymphoma, LSTRA. Cell surface immunofluorescence was also detected in YC-8 with a monoclonal antibody for galactosyltransferase. The introduction of galactosyltransferase specific substrates, both in vivo and in vitro, led to the retardation of growth in the cell lines K181, MOPC 104E, and YC-8, but not in the cell line LSTRA; this suggests the selective growth control of transformed cells demonstrating elevated levels of galactosyltransferase.

Animals↗
PubMed1989

Regression of MOPC 104E plasmacytoma with monoclonal anti-idiotype antibodies.

We investigated the therapeutic effectiveness of monoclonal anti-idiotype (anti-M104E5) antibodies. Our in vitro studies show monoclonal anti-idiotype-specific antibody SJL18-1 showed a selective inhibitory property for MOPC 104E cells over two cross-reactive idiotype antibodies N-20-2 (IgM, IdX-M104E, and J558) and CD3-2 (IgG1, IdX-M104E, and J558). Based on these observations, we further examined their biological activities in vivo. Mice given 2 x 10(4) MOPC cells s.c. were treated with various doses of the antibodies i.v. on days 0, 7, 14, 21, and 28 after tumor transplantation. In the group treated with 100 micrograms of N-20-2 antibody, the antibody treatment prevented the growth of MOPC 104E in some of the mice. Treatment of tumor-bearing mice with SJL18-1 antibody (10 to 1,000 micrograms/mouse) did not provide any survival benefit. On the other hand, in mice treated with 50 micrograms of CD3-2 antibody, four of ten mice had regression of their palpable tumors. It is important to note that the least effective antibody (CD3-2) in vitro was the most effective in vivo, and the most effective antibody (SJL18-1) in vitro did not show any survival benefit. Preliminary data indicate that the most likely mechanism of in vivo regulation of MOPC 104E myeloma is by cytostatic lymphocytes.

Animals↗
PubMed1988

Conditioned augmentation of natural killer cell activity. Independence from nociceptive effects and dependence on interferon-beta.

Injection of mice with 20 micrograms polyinosinic: polycytidylic acid (Poly I:C) after exposure to camphor odor results in a conditioned augmentation of natural killer cell (NK) activity. In this study, we show that the conditioned response is not the result of nociceptive stimulation and that interferon-beta (IFN), but not IFN-alpha can replace Poly I:C as the unconditioned stimulus (US). Two conditioned stimuli (CS) were used with equivalent results. A combination CS consisting of a novel taste (saccharin) and a 125 mg/kg injection of LiCl that induces gastric upset was paired with a Poly I:C or IFN-beta (1 X 10(4) IU) injection. This resulted in an augmentation of NK activity when the conditioned animals were reexposed to the saccharin-LiCl CS. In addition, an identical conditioned response was elicited when a camphor odor CS was paired with either of these US. To test whether the conditioned response might be an artifact not detected by our controls, a mock conditioning experiment was performed, which assessed the differential effect of multiple exposures to the saccharin-LiCl CS without a CS/US pairing. The mock conditioned group was significantly suppressed relative to saline treated controls, whereas the mock nonconditioned group and the mock conditioned group that was not reexposed to the CS after conditioning did not show significant suppression. This indicates that the augmentation observed in the conditioned group after CS/US pairing was not the result of exposure to the CS itself. Small doses of Poly I:C (5 micrograms or 2.5 micrograms) given on days 3 and 5 (or on day 5 only) to boost NK activity had the effect of increasing the magnitude of the conditioned response measured on day 6. In addition, an identical conditioned response was observed when the interval between the CS/US pairing and the later CS exposures was changed, which places the test for the conditioned response either on day 6 (CS given on days 3 and 5) or day 10 (CS given on days 7 and 9). These results show that the observed conditioned enhancement of NK activity in conditioned animals is not caused by any nociceptive properties of the CS itself and is dependent on the IFN-beta produced after Poly I:C injection in the conditioned paradigm.

Adjuvants, Immunologic↗
PubMed1988

Augmentation of natural immunity and regulation of tumor growth by conditioning.

We have reported the effect of classical (Pavlovian) conditioning of natural immunity on survival of tumor-bearing mice. In the first study, we have observed that mice conditioned, transplanted with tumor, and re-exposed to conditioned stimulus (camphor odor) had an increase in median survival (day 43, as compared to days 34, 38, and 37 of various control groups). Two of these conditioned mice lived more than 120 days and showed early tumor growth, but were free of disease at day 97. We report the observations of a repeat study. Two groups of conditioned mice were used for these studies. One group was re-exposed to the conditioning stimulus following transplantation with tumor (CND) and the second group was not re-exposed to odor of camphor (CNDo). Statistically significant delay in growth of MOPC 104E in the CND group was observed when compared with the CNDo group. The survival data supports the observations of tumor IgM values. In an independent study, we investigated the possible mechanisms of MOPC 104E regulation in vitro. Plastic adherent spleen cells (macrophage cells) from mice primed in vivo with MOPC 104E tumor cells suppressed tumor IgM production by MOPC cells by 98% and also reduced colony formation by MOPC cells. The possible mechanism(s) of regulation of tumor growth in conditioned mice might be mediated by plastic adherent activated macrophages.

Animals↗
PubMed1988

Host response to myeloma: I. Induction of cytotoxic and suppressor T cells by in vivo immunization with MOPC 104E plasmacytoma.

Spleen cells from BALB/c mice immunized with mitomycin C-treated MOPC 104E plasmacytoma cells demonstrated negligible cytotoxic activity (less than 10% specific cytotoxic activity) in the 51Cr release assay. These cells exhibited increased cytotoxic activity when they were secondarily sensitized in vitro with mitomycin C-treated MOPC 104E cells. Spleen cells from normal mice showed tumor-specific cytotoxic activity when cocultured with mitomycin C-treated tumor cells at the optimal responder to stimulator ratio of 25:1. The level of cytotoxic activity obtained by in vivo primed and secondarily in vitro sensitized spleen cells did not exceed the level of activity obtained by in vitro primary sensitized cells. Significant suppression of the cytotoxic activity of in vitro primary sensitized cells was observed when cocultured with in vivo primed spleen cells during primary sensitization in vitro at a responder to suppressor cell ratio of 1:1. Suppressor cells of in vivo primed mice were removed by treatment with anti-Thy 1.2 and complement. These results suggest that spleen cells from in vivo primed mice consisted of at least two subpopulations of cells, a cytotoxic (prekiller) and suppressor T cells. Attempts to induce cytotoxic cells in vivo might have failed because of the appearance of suppressor T cells.

Animals↗
PubMed1987

Conditioned enhancement of natural killer cell activity, but not interferon, with camphor or saccharin-LiCl conditioned stimulus.

Pavlovian conditioning of the natural killer (NK) cell response has been demonstrated by pairing camphor with polyinosinic:polycytidylic acid (poly I:C) in nine association trials. The NK cell response could be conditioned also by using combined saccharin and lithium chloride (LiCl) as the conditioned stimulus. The camphor and saccharin-LiCl paradigms were tested to determine if the conditioned NK cell activity was the result of conditioning of the interferon response. Interferon levels were measured at 6 hr and NK cell activity at 24 hr after application of the conditioned stimulus. The interferon levels measured in separate experiments were not uniformly elevated in conditioned animals compared with controls.

Animals↗