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V K Ghanta

Publications and source records attributed to V K Ghanta.

At least 73 records · Page 4Linked to original sources
PubMed1982

Inhibitory effect of L-homoarginine on murine osteosarcoma cell proliferation.

An organ-specific alkaline phosphatase inhibitor, L-homoarginine, at 44.5 mM concentration inhibited [3H]thymidine uptake by C3H/He mouse osteosarcoma (OS) cells, while L-arginine, L-phenylalanine, and glycine had little effect on the uptake. This inhibitory effect of L-homoarginine persisted even after the cells were washed free of the amino acid with fresh media. L-Homoarginine did not affect [3H]thymidine uptake by mouse myeloma MOPC 104E cells. In long-term culture, 22.3 mM L-homoarginine inhibited proliferation of OS cells. L-Arginine at the same concentration inhibited the proliferation to a lesser extent. On the other hand, L-phenylalanine and glycine did not affect in vitro proliferation of OS cells. When the same number of viable OS cells was inoculated s.c. after culturing the 24 hr with 44.5 mM L-homoarginine or L-arginine, the tumor growth in mice given injections of L-homoarginine (but not L-arginine)-treated cells was delayed markedly. Electron microscopic studies indicated that the inhibiting effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, biochemical assay for acid phosphatase of cell homogenates demonstrated a 2-fold increase of activity in L-homoarginine-treated cells when compared to controls and L-arginine-treated cells. Thus, L-homoarginine inhibits proliferation and alkaline phosphatase activity of mouse OS cells and appears to increase acid phosphatase activity in synthesis of lysosomal granules.

Alkaline Phosphatase↗
PubMed1982

Immunosuppressive effect of mouse serum lipoproteins. II. In vivo studies.

Normal mouse serum lipoproteins suppress a number of immunologic functions, such as mitogen stimulation, primary immune response, and allograft rejection in vivo. The effects of one class of lipoproteins, high density lipoprotein (HDL), were investigated after i.v. administration. Maximum suppression of spleen and peripheral blood lymphocyte (PBL) mitogen stimulation occurred when HDL was administered up to 8 hr before testing. Spleen cells remained suppressed 48 hr after injection, while PBL regained most of their activities. Injection of HDL 24 hr after sheep red blood cell (SRBC) immunization was as effective as giving HDL 8 hr before SRBC in suppressing primary immune response to SRBC. Induction of T cell allograft immunity was also suppressed by the injection of HDL.

Animals↗
PubMed1981

Immunosuppressive effect of mouse serum lipoproteins. I. In vitro studies.

Three classes of lipoproteins, very low, low, and high density, were isolated from normal mouse sera and characterized with respect to electrophoretic mobility, content, and composition. All 3 classes of mouse serum lipoproteins migrated into the alpha region at different rates and were composed of more phospholipid and less triglyceride and cholesterol than lipoproteins from man. High density lipoprotein (HDL) was the major lipoprotein, carrying 70% of the serum cholesterol and phospholipid and 85% of the total lipoprotein. Whole mouse serum and all classes of mouse serum lipoproteins inhibited lymphocyte proliferation stimulated by mitogens. No strain specificity was observed. HDL contributed about 73% of the total inhibitory activity. The effect of apoprotein and the lipid portion of very low, low, and high density lipoproteins were also studied.

Animals↗
PubMed1981

Effect of immune response to sheep red blood cells on plasmacytoma MOPC 104 E.

BALB/c mice were given 1 x 10(6) MOPC 104E plasmacytoma cells i.v. to disseminate the neoplasm to various organs. Twenty-five days after implantation and at a time when the neoplastic B-cell clone was in the exponential growth phase, the mice were given i.p. injections of a mixture of antigens containing sheep red blood cells and levan. Each mouse was monitored simultaneously for immunoglobulin M (IgM) anti-dextran myeloma protein produced by the plasmacytoma and anti-sheep red blood cell hemolysin. The increase and decrease of these markers permit assessment of the expansion of the abnormal B-cell clone during the rise and fall of a normal B-cell clone in response to a specific antigen. The model was used to determine (a) the extent of the suppression of myeloma protein, (b) how long inhibition can be maintained, and (c) how soon it occurs after antigen is administered. The results showed that, as the IgM antibody response to sheep red blood cells begins to peak, it exerts a transient suppressive effect on either the MOPC 104E growth or on the cellular release of MOPC 104E IgM. The suppressive effect was noticeable 4 days after antigen administration for only 24 hr. These results indicated that plasmacytoma cells in vivo can recognize signals for either suppression of growth or release of the idiotypic MOPC 104E IgM and were not inconsistent with the view that myeloma may be the result of a defect in B-cell regulation.

Animals↗
PubMed1981

Assessment of myeloma maintenance regimen of prednisone. Adriamycin, imuran, and vincristine in a murine plasmacytoma model.

A current southeastern cancer study group protocol for the treatment of multiple myeloma involves induction with BCNU, cyclophosphamide, and prednisone (BCP) and maintenance with either melphalan and prednisone (MP), prednisone, Adriamycin, imuran, and vincristine (PAIV), or delayed treatment of relapsed cases following induction. These combinations of drugs are used as induction regimens to establish their chemotherapeutic effects and hematological toxicity in the murine MOPC 104E plasmacytoma model. The three combinations of drugs produce rapid, reliable, and reproducible tumor regressions. However, MP is the only combination which consistently gives long-term disease-free survivors. This particular regimen has least toxicity and is considered to be most effective. BCP produces complete remission with no relapses; however, long-term survivors are not observed with this combination due to early deaths because of drug toxicity. Most of the mice on the PAIV regimen die due to drug toxicity. This combination is considered least effective. With the different drug regimens, toxic events and regressions are noted to occur at different time periods, indicating that perhaps tumor cells in different stages are being destroyed. Toxic events as measured by hematocrit and body weight changes always precede regression by several days. This disparity between rapid drug effects on the host and a delayed effect on the tumor remains unexplained but may possibly be used to advantage in designing future trials.

Animals↗
PubMed1980

Surgical adjuvant chemotherapy of metastatic murine osteosarcoma.

A C3H murine osteosarcoma was used to investigate the effects of surgical adjuvant chemotherapy and to establish the relationship between primary tumor size and the number of metastatic lung tumor foci. The transplanted primary tumor was allowed to grow for 28 or 33 days and the lungs were monitored for microscopic colonies. Animals whose tumors were left in situ had 6-124 and 32-338 colonies in the lungs at 28 and 33 days, respectively. When the primary tumor was excised on day 10 post implantation, metastatic tumor colonies on day 33 were reduced to 0-24 colonies. The results indicated that the longer the primary tumor was left in the host the greater was the number of tumor cells which seeded to the lungs. Early surgical (day 10) removal of the tumor gave better survival than late (day 20) surgical removal of the tumor. When cyclophosphamide chemotherapy was used with surgery, better survival (80%) was seen. Cyclophosphamide alone did not improve survival over that seen for tumor-bearing controls. Late surgery with adjuvant chemotherapy increased survival time.

Amputation, Surgical↗
PubMed1980

Maintenance of MOPC 104E myeloma in plateau phase.

MOPC 104E myeloma cells are brought under host regulation after treatment with cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea, or cis-dichlorodiammineplatinum(II). The first indication of this phenomenon is the plateau level of immunoglobulin M(lambda) [IgM(lambda)]. The myeloma recurs more frequently in animals with high plateau levels of IgM(lambda) even when remission is maintained for greater than 200 days. The growth rate of the recurring tumor is altered when compared with the original tumor in the same individual. Different drugs and dosages produce stable myeloma of different sizes. Treatment with cyclophosphamide (10 to 200 mg/kg), or 1,3-bis(2-chloroethyl)-1-nitrosourea (25 mg/kg) gives stable myeloma that produces low plateau levels of IgM(lambda). This myeloma does not show late recurrence. Combination of 1,3-bis(2-chloroethyl)-1-nitrosourea, cyclophosphamide, and cis-dichlorodiammineplatinum(II) in low doses or cis-dichlorodiammineplatinum(II) alone gives a stable myeloma clone(s) which produces IgM(lambda) which plateaus at higher levels, and the myeloma clone recurs relatively late in the life of the animal. These results show that treatment does not lead to the elimination of the dominant myeloma clone. Clonal dominance is, however, broken when the proliferative potential is interrupted by drug treatment. The resulting long stable phase supports the view that the proliferation, the expression of the plasma cell maturation sequences, and the secretion of IgM(lambda) are under normal host regulation. Aging presumably causes a loss of regulatory control permitting clonal expansion and recurrence of the myeloma in animals with high plateau levels of the IgM(lambda). The MOPC 104E myeloma model demonstrates for the first time a conversion of the malignant form to the indolent form as seen for humans.

Animals↗
PubMed1980

Characterization of an auto-rosette inhibitory fraction in mouse serum.

Normal mouse sera inhibited auto-erythrocyte rosette formation by mouse thymus cells. Serum inhibitory factor was associated with high density lipoprotein (HDL) isolated from mouse sera with sequential flotation ultra-centrifugation techniques. Other portions of normal mouse sera, i.e., very low density lipoprotein (VLDL), low density lipoprotein (LDL), lipoprotein-free serum, and delipidated HDL had little or no inhibitory activity. A 20-fold purification with 68% recovery of total serum activity was obtained by this isolation procedure. HDL from the serum of BALB/c, C57BL/6, C3H, and NZB/BIN mice inhibited BALB/c auto-rosettes. Inhibition was observed when lymphocytes were preincubated with HDL and then washed before assaying, but there was no inhibition when erythrocytes were pretreated.

Animals↗
PubMed1980

A murine plasmacytoma model for screening active drugs for human myeloma.

The basic problem of current animal models is the inability to select and rate the relative effectiveness of new drugs of myeloma of man. As a first step in broaching this problem, results of clinical drug trial studies were used for predicting activity of the drugs in the MOPC 104E plasmacytoma model. Comparison of the model with human myeloma and six additional murine plasmacytomas for drug response indicates close correlation between the reported results in man and the expected results in the animal models. The MOPC 104E model was versatile because drug effects could be rapidly measured in vivo in individual animals. The effect of the drug on the rate of growth, the rate of regression, the doubling time, the number of tumor cells killed, and the tumor and drug toxicities on the host could be continuously measured. These measurements were used to select active drugs and to rate the relative activity of the different drugs for myeloma.

Animals↗
PubMed1979

Age related changes in auto-erythrocyte rosettes in the C57BL/6J and NZB/BINJ mice.

The changes in the auto-erythrocyte rosetting thymic and splenic lymphocytes and the induction of autoimmunity was followed with age in C57BL/6J and NZB/BINJ mice. The auto-erythrocyte rosetting cells (auto-RFC) showed shifts in their pattern in both thymus and spleen in C57BL/6J and NZB/BINJ mice. Both strains had approximately the same percentage (approximately 3%) of thymic auto-RFC at 1 month of age. In C57BL/6J mice the rosette population increased to 6.6% by 2 months, declined after 3 months and subsequently increased gradually with age. In contrast, the NZB/BINJ thymic auto-rosettes peaked at 4 months and gradually declined thereafter. Both the NZB/BINJ and C57BL/6J strains were tested for the presence of anti-erythrocyte antibodies by the direct Coombs' agglutination test. The results showed that at 6 and 10 months 50% and 90% of the NZB/BINJ mice were positive for antibodies, respectively, and the thymic and splenic auto-RFC dramatically decreased in numbers. In the C57BL/6J mice during this same period, very low incidence of auto-antibodies was detected by the Coombs' test and auto-RFC increased in numbers.

Aging↗
PubMed1979

Sequential appearance of auto-erythrocyte antibody immunoglobulin classes with age.

The autoimmune, short-lived, NZB/BINJ mice were followed for the changes taking place in the number of thymic and splenic nucleated cells from day 1 up to 12 mo of age. The long-lived C57BL/6J mice were monitored in parallel with the NZB mice to see whether similar changes were reflected. Both strains of mice were investigated for the sequential appearance of anti-erythrocyte autoantibody classes by the direct Coombs' agglutination test. IgG1 was the first class of antibody detected on the erythrocytes and was followed by IgG3, IgG2 and IgA, simultaneously. IgM was the last antibody to react with erythrocytes. The C57BL strain had a very small number of mice with low levels of IgG1 antibody on erythrocytes throughout the study.

Aging↗
PubMed1979

A methodological approach to the prediction of anticancer drug effect in humans.

Tumor cells from animals and humans were treated with drugs under tissue culture conditions. Tumor cells from the sensitive L1210 model were studied first. A dose-response curve was derived between drug exposure and subsequent cytotoxicity in L1210. The concentration of drug and duration of exposure were factors critical to the subsequent development of in vitro cytotoxicity. The in vitro dosage which effected 50% leukemic cell death in L1210 cells correlated with reported in vivo drug levels. Other tumor models and human neoplastic cells were studied at this dosage level. A good correlation was noted in these studies between the in vivo responsiveness and the in vitro chemotherapy results in both animals and humans. It was suggested by these results that it may be possible to predict cancericidal drug activity for individual neoplasms by assaying the tumor cells in vitro for drug sensitivity.

Animals↗
PubMed1978

Age dependent reaction of mouse thymus cells with autologous and syngeneic erythrocytes.

The age dependent events influencing the rosette forming capacity of Balb/c thymus and spleen cells against autologous or syngeneic erythrocytes were examined. A large number of autologous and syngeneic rosette forming cells (RFC) were observed in normal Balb/c mice in vitro. RFC were significantly greater in the thymus than in the spleen. The rosette forming T-cells (T-RFC) have the following characteristics: newborn Balb/c thymus has T-cells which react syngeneic erythrocytes from older donors. The T-RFC showed broad cross-reactivity with erythrocytes from other mouse strains but low reactivity with human or sheep erythrocytes. The auto and syngeneic T-RFC could be enhanced by non-specific serum proteins (FCS or BSA) or EDTA but was effectively inhibited by normal mouse serum. T-RFC resided in the cortisone sensitive population. The data indicate that the development of autologous and syngeneic rosette formation of thymus cells is dependent on the age of the erythrocyte donor. The age dependent change on the erythrocyte surface occurred relatively early in the life of the animal. The results also imply that certain subpopulations of thymus lymphocytes are capable of recognizing possible surface antigenic changes of the erythrocytes.

Aging↗
PubMed1978

Tumor immunology of experimental osteosarcoma.

A spontaneous AP positive C3H murine OS was used to determine the effects of various treatment modalities. AP served as a useful circulating biomarker of the in vivo tumor growth. In animals whose tumor was amputated, the elevation of the marker indicated the presence of pulmonary metastases. It was used to establish the time of recurrence after a partially effective chemotherapy or combination modality. In this model, when the neoplasm was surgically excised at 10 days posttransplantation, 70--80% of the mice showed presence of lung metastases. Specific immunotherapy with irradiated tumor cells did not alter the course of the disease. Passively transferred immune allogeneic cells to tumor bearing mice at an effector to target cell ratio of 1:1 in vivo were ineffective. The murine OS model is extremely useful to plan and institute different combinations of treatment modalities and optimize the conditions for an effective treatment in a relatively short time.

Alkaline Phosphatase↗
PubMed1977

Autoimmune disease antigens.

The first step towards understanding the cellular interaction which results in autoimmune disease is to determine what triggers the recognition between a specific autoimmune antigen determinant and the cellular receptor. In this review, we have focused on the antigen inducing experimental allergic encephalitis (EAE) because the antigen has been characterized and a relatively large body of information on its biological activities has been accumulated. Clearly, a specific allergic encephalitis-producing determinant is present and is represented on a relatively small portion of the molecule. The determinant induces a wide variety of biological reactivities, some of which are classed as cellular mediated. An attempt is made to dissect activities such as blast transformation (BT), migration inhibitory factor (MIF), in vivo delayed type hypersensitivity reaction (DTH) and EAE and to relate them to the structural requirements which the determinants possess. The complexities which arise indicate that subpopulations of cells with different receptor activities may respond selectively and that recognition of the receptor is produced by an EAE determinant consisting of three amino acids in a specific linear sequence. Furthermore, under experimental circumstances the EAE activity can be dissociated from the other activities (BT, MIF, DTH), indicating that while these tests are used generally to follow various human autoimmune disease activities, they may represent the reaction of a broad spectrum of cells.

Amino Acid Sequence↗
PubMed1977

An experimental approach to relate a tumor-associated enzyme marker to tumor cell numbers.

Alkaline phosphatase was monitored in 17 mice with s.c.-implanted tumors to relate the total circulating alkaline phosphatase to the total number of tumor cells in each mouse. There was a semilogarithmic relationship between the alkaline phosphatase units and the number of tumor cells. A time-independent standard plot of alkaline phosphatase and the number of tumor cells was used to estimate the size of disseminated and localized tumors. In animals treated with cyclophosphamide, the alkaline phosphatase marker was used to monitor the regression and recurrence of the neoplasm in vivo.

Alkaline Phosphatase↗
PubMed1977

cis-dichlorodiammineplatinum(II) chemotherapy in experimental murine myeloma MOPC 104E.

Data are presented indicating marked antineoplastic activity for cis-dichlorodiammineplatinum(II) in MOPC 104E myeloma. One-eighteenth of the dose that produced 100% cures can be combined with noncurative, low doses of cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea to produce antineoplastic activity of the same degree as that produced by much higher dose regimens which regularly produce cures. Since, in the past, results of therapeutic trials in plasma cell tumors in humans have paralleled results in this animal model, clinical trials of cis-dichlorodiammineplatinum in multiple myeloma appear warranted.

Animals↗