Biomedical subjects

A Mazumder

Publications and source records attributed to A Mazumder.

At least 127 records · Page 7Linked to original sources

PubMed1991

Interaction of various cytokines with interleukin 2 in the generation of killer cells from human bone marrow: application in purging of leukemia.

We have shown that incubation of bone marrow (BM) with interleukin 2 (IL-2) generates activated bone marrow cells (ABM) with potent tumoricidal activity in vitro and in vivo. The present study was carried out to define the interaction of other cytokines with IL-2 in generation of ABM. Our data show that interleukin 1 (IL-1), interferon (IFN)- both gamma and alpha, and tumor necrosis factor (TNF-alpha) significantly increased the cytolytic potential of ABM. Interleukin 3, interleukin 4, transforming growth factor-beta and adherent cells were reduced, while granulocyte-macrophage colony-stimulating factor had no influence on the generation of cytolytic activity. IL-1 was enhanced while TNF-alpha depressed the BM progenitor cell activity in vitro. The IL-2-induced purging ability of BM contaminated with leukemic cells was increased by IL-1, TNF-alpha and IFN-gamma. This study shows that biomodulation of BM with combination of cytokines in vitro can be useful in purging a large leukemic burden.

Bone Marrow↗

PubMed1991

The effect of amphotericin B, aztreonam, imipenem and cephalosporins on the bone marrow progenitor cell activity.

The effects of certain antibiotics on the colony forming activity of human bone marrow cells in semisolid methylcellulose medium in vitro and on murine BM cells in spleen colony forming units (cfu-s) in vivo were evaluated. Amikacin, gentamicin, piperacillin, co-trimoxazole and pentamidine had little or no effect on human bone marrow progenitor cell function; amphotericin B, aztreonam, ceftazidime and imipenem caused significant suppression of human colony forming unit-erythroid (cfu-e), burst forming unit-erythroid (bfu-e) and colony forming unit-granulocyte macrophage (cfu-gm) at both peak and trough serum concentrations. At molar equivalent concentrations ceftazidime, cefotaxime and cefoperazone caused significant decreases in human cfu-e, bfu-e and cfu-gm in vitro (P less than 0.01) and murine cfu-s in vivo (P less than 0.05); cefoxitin, cefuroxime, ceftizoxime and ceftriaxone did not suppress human bone marrow progenitor cell activity. Gentamicin, piperacillin and ceftriaxone had no effect on murine cfu-s formation. Further studies to evaluate the effect of these antibiotics on human bone marrow in vivo are suggested.

Amphotericin B↗

PubMed1991

A study on the prevalence of tuberculosis in a rural community of Bangladesh.

The population of two villages of Chagalnaiya Upazila was selected for a study on the prevalence of pulmonary tuberculosis through a two stage screening process. Initial screening was conducted on 3406 persons which is 78% of the total population (3920) of the two villages. The initial screening revealed 182 persons with the history of cough lasting 4 weeks or more, chest pain, continuous fever and haemoptysis. Sputum examinations for Acid Fast Bacilli (AFB) of tuberculosis detected 21 sputum positive cases giving a prevalence rate of 6.2 (per 1000 population) higher than the estimated national average of 5.0 per 1000. Most of the cases were not receiving treatment. Some social and environmental factors of suspected and detected cases were also studied.

Adolescent↗

PubMed1990

Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice.

We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft-versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.

Animals↗

PubMed1990

Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis.

TNF and IFN-gamma are thought to be involved in the immune response to mycobacterial infection because they exhibit antimycobacterial effects in vitro. To investigate the roles of these cytokines in vivo at the site of disease activity in human tuberculosis, we evaluated local cytokine production in patients with tuberculous pleuritis. Both TNF and IFN-gamma were selectively concentrated 5- to 30-fold in pleural fluid, compared to blood of the same patients. Messenger RNA for both cytokines was detected in pleural tissue by in situ hybridization, suggesting that selective cytokine concentration is due to local cytokine production. Two Mycobacterium tuberculosis cell wall components, the protein-peptidoglycan complex and lipoarabinomannan, caused dose-dependent release of TNF by pleural fluid mononuclear cells and may constitute the stimuli for TNF production in the pleural space. In contrast to results obtained for TNF release, the protein-peptidoglycan complex, but not lipoarabinomannan, stimulated IFN-gamma release by pleural fluid mononuclear cells. The clinical manifestations of tuberculous pleuritis, such as fever, exudative pleural effusion, and tissue necrosis, may be due to the effects of elevated local TNF concentrations, produced in response to mycobacterial cell wall components.

Cell Wall↗

PubMed1990

Hemolytic anemia in a cancer patient treated with recombinant interferon-gamma.

Currently, three classes of interferon are used in the treatment of malignancies. Interferon-gamma is the best studied. Bone marrow suppression as well as immune hemolytic anemia have been described. Heretofore, only bone marrow suppression has been attributed to interferon-gamma (IFN gamma). In this report, we describe a woman with lung cancer being treated with IFN gamma in whom acute hemolytic anemia occurred. Immune hemolysis did not appear to be the cause. We concluded that in addition to bone marrow suppression, hemolysis should be considered in a patient receiving IFN gamma in whom an unexplained drop in hematocrit occurs.

Adenocarcinoma↗

PubMed1990

Heterogeneity of cell surface structures involved in cytotoxicity mediated by lymphokine activated killer cells.

Lymphokine activated killer (LAK) cells mediate the lysis of a variety of histologically distinct tumor targets. We investigated the nature and diversity of the structures involved in the recognition phenomenon by evaluating the effects of treating effector and target cells with trypsin and chymotrypsin, enzymes that disrupt surface protein molecules. Chymotrypsin and trypsin treatment of B16 target cells, a murine melanoma cell line, significantly abolished killing by LAK cells. Alternatively, neither of these treatments in P815 cells, a murine mastocytoma cell line, affected killing by LAK cells. Moreover, we found a differential effect of both these enzymes on YAC-1 cells, a murine leukemia cell line, with trypsin having a less inhibitory effect on cytolysis than chymotrypsin. The nature of the LAK cell receptor that presumably plays a role in binding target antigen was also investigated. Treatment of LAK cells with chymotrypsin significantly reduced lysis of the B16 and YAC-1 target cell types. However, trypsin treatment of the effectors only inhibited killing of the B16 tumor cell line. Cytotoxicity exerted against YAC-1 remained unaltered upon trypsinization of LAK cells. These cumulative results indicate heterogeneity of both the receptors on the LAK cells and the surface antigen molecules recognized on these targets. The use of YAC-1 as a target provided us with a tool to compare the LAK with the natural killer (NK) systems. The overall effect of proteolytic enzyme treatment in reducing cell lysis was more pronounced in the NK than in the LAK system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

A novel approach to purging of leukemia by activation of bone marrow with interleukin 2.

The cytotoxic potential of interleukin 2 (IL-2) activated bone marrow (ABM) was compared with that of IL-2 activated peripheral blood lymphocytes (LAK cells) against three hematologic tumor cell lines (K-562, CEM, Daudi) and fresh lymphoid blasts in short-term chromium release assays. ABM was found to be superior to LAK cells against all tumor cells tested. The recovery of bone marrow (BM) cells dropped with passage of time in culture but their clonogenic potential was not impaired (with or without IL-2). BM contaminated with CEM cells and treated with IL-2 showed significant ability to purge itself of the leukemic cells in semisolid agar culture; the purging ability of 3- and 1-day ABM was comparable. IL-2 alone or BM alone had no influence on the growth of CEM cells. This study suggests that BM can be activated with IL-2 in vitro to generate the ability to eliminate contaminating leukemic cells without affecting its progenitor cell function in vitro.

Bone Marrow↗

PubMed1989

Potent graft antitumor effect in natural killer-resistant disseminated tumors by transplantation of interleukin 2-activated syngeneic bone marrow in mice.

The current study is a continuation of our previous work showing that bone marrow activated in interleukin 2 has antitumor and antiviral activity in vitro. The antitumor efficacy of IL-2-activated bone marrow cells in vivo was assessed here. Our results indicated that bone marrow cells activated in IL-2 for 3 days (ABM) have antitumor activity in vivo and cause significant tumor regression in mice being treated with ABM and concurrent i.p. administration of IL-2. In mice also bearing larger tumor burdens, those receiving ABM and i.p. IL-2 showed the most significant tumor regression. The ABM seem to be more potent than conventional IL-2-activated spleen lymphokine-activated killer cells. In studies done using lower dosages of IL-2 or log lower number of cells, the ABM caused more significant tumor regression than lymphokine-activated killer cells. We also assessed the antitumor efficacy of short term (1 day) IL-2-activated bone marrow, the short term-activated bone marrow being preferred in bone marrow, transplantation because of the minimum amount of cells lost due to its shorter incubation period. We also showed that short term-activated bone marrow caused tumor regression similar to ABM and could reconstitute lethally irradiated mice similar to fresh bone marrow. Therefore, the biomodulation of bone marrow cells could be used as an active therapeutic tool in autologous bone marrow transplantation, producing graft versus tumor effects without any graft versus host effect.

Animals↗

PubMed1989

Generation and characterization of IL-2-activated bone marrow cells as a potent graft vs tumor effector in transplantation.

The potential of bone marrow transplantation as an immunotherapeutic modality, using biomodulation of the marrow cells has been ignored in autologous transplantation. Furthermore, many common cancers such as lung, colon, prostate, and pancreas are resistant to even transplant doses of conventional agents and hence require novel approaches such as biomodulation. This study shows that we can generate cytotoxic killer cells similar to lymphokine-activated killer cells capable of lysing NK-resistant tumor cells in vitro if we incubate human or murine bone marrow in IL-2. This was accomplished without affecting the ability of the bone marrow to fully reconstitute mice similar to that of fresh nonactivated bone marrow. Studies evaluating the IL-2 activated human bone marrow in vitro also indicated that these activated bone marrow have similar CFU to that of fresh human marrow. Furthermore, in murine in vivo studies, the activated bone marrow (ABM) caused significant tumor regression in tumor-bearing mice. Also, these ABM cells had similar or higher tumoricidal activity and longer kinetics than spleen lymphokine-activated killer cells in vitro. Also, the ABM had purging ability in vitro. Therefore this IL-2 ABM could be used as an active therapeutic tool and not just as a passive rescue element in the autologous bone marrow transplantation setting.

Animals↗

PubMed1989

Synergistic antitumor effects of interleukin 2 and the monoclonal Lym-1 against human Burkitt lymphoma cells in vitro and in vivo.

Interleukin 2 (IL-2) regulates immune responses by inducing proliferation and differentiation of T-cells into cytotoxic cells, inducing lymphokine activated killer activity and enhancing antibody dependent cellular cytotoxicity (ADCC). Lym-1, a monoclonal antibody, recognizes a membrane antigen present on the surface of B-lymphoma cells and can be used for ADCC. We therefore used Raji (human Burkitt lymphoma) cells to study the efficacy of combination therapy with IL-2, lymphokine activated killer activity, and Lym-1. In vitro ADCC assays using Lym-1 showed that preincubation of peripheral blood lymphocytes with IL-2 had a synergistic antitumor effect. The maximum synergism was achieved when peripheral blood lymphocytes were incubated with IL-2 for 3 days as compared to 1 or 2 days, with the optimal concentration of IL-2 being 1000 units/ml. This effect was specific for Lym-1 as demonstrated by experiments using an irrelevant (antimelanoma) monoclonal antibody or an irrelevant target cell (A375). The ADCC was blocked by an anti-Fe receptor antibody (3G8). In vivo experiments performed by growing Raji tumors in nude mice also demonstrated the increase in ADCC and the synergism between IL-2 and Lym-1 in terms of decreased tumor size and growth. The mechanism of this synergy is probably from activation of cells mediating ADCC. This raises the possibility that treatment of patients with low doses of IL-2 in combination with Lym-1 may enhance immune responses and thereby antitumor activity.

Animals↗

PubMed1989

The potential usefulness of interleukin-2 activated bone marrow cells as an active therapeutic tool against cytomegalovirus infection in a bone marrow transplantation setting.

Bone marrow transplantation (BMT) has been used in recent years for the treatment of immunodeficiency diseases, aplastic anemia, and leukemia. However, there are a number of serious problems and limitations associated with autologous or allogeneic BMT. One of these is an increase in opportunistic infections, of which cytomegalovirus (CMV) infection is one of the most important. Cytomegalovirus has been associated with more frequent deaths than any other single agent, with no reproducibly successful or therapy currently available. Recently usage of interleukin-2 or immunomodulation has been suggested as a powerful modality to combat infectious disease. In this study we showed that bone marrow activated in interleukin-2 for 2 days has the ability to lyse spleen cells infected for 3 days with murine CMV (acute infection model) or salivary gland cells infected for 7 days (chronic infection model), while nonactivated bone marrow or natural killer (NK) cells showed no such lysis. The majority of activated cells involved in lysis were antiasialo GM1-, Thy-1+/-, indicating a population of cells other than the natural killer-cell population involved.

Animals↗

PubMed1988

Successful therapy of natural killer-resistant pulmonary metastases by the synergism of gamma-interferon with tumor necrosis factor and interleukin-2 in mice.

The problem associated with lymphokine (gamma-interferon, interleukin-2, and tumor necrosis factor) therapy in cancer is that high toxic doses of these lymphokines must be administered for any significant antitumor results. Therefore this study was undertaken to investigate the antitumor efficacy of these lymphokines in a disseminated pulmonary metastasis when used in combination with each other at dosages well below the toxic level. The role of the immune system of the host, sequencing of lymphokines, and histopathological aspects of lymphokine therapy were also investigated.

Animals↗

PubMed1988

Therapy of disseminated NK-resistant tumor by the synergistic effects of recombinant interleukin-2 and tumor necrosis factor.

Tumor necrosis factor and interleukin-2 each in recombinant form have antitumor activity against established tumors if used in high enough dosages. The problem associated with such high dosages is the high degree of toxicity and expense encountered. Therefore, this study was undertaken to look at the antitumor efficacy of these two lymphokines when used together at dosages well below the toxic levels. Our results using recombinant human interleukin-2 (IL-2) and recombinant human tumor necrosis factor (TNF) against established methylcholanthrene-induced fibrosarcoma (MCA sarcoma) pulmonary metastases showed that TNF and IL-2 therapy at low nontoxic dosages alone did not produce significant tumor regression, but when combined at the same dosage synergize producing significant antitumor effects in mice induced with MCA sarcoma. This was also evident from histopathological examination of the lungs where the maximum tumor reduction along with the maximum lymphocytic infiltration into tumor was seen when TNF and IL-2 were combined. In this tumor regression, inherent immunity of the treated mice was needed, since in those mice in which we induced immunosuppression by using radiation, tumor regression was not seen when TNF and IL-2 therapy was combined in the doses efficacious in immunocompetent mice. Tumor regression is also dependent on the sequence of administration of IL-2 and TNF, since when IL-2 was administered before TNF, the tumor regression was more significant than when TNF was administered before IL-2 or when both were administered simultaneously to mice with established pulmonary tumors. Therefore the synergistic effect of IL-2 and TNF could be used as an efficacious but inexpensive and nontoxic alternative to therapy with lymphokine activated killer (LAK) cells + IL-2.

Animals↗

PubMed1987

Lysosome rich cells contain the lytic activity of lymphokine-activated killer cell populations.

Little is known regarding the effectors of lymphokine-activated killer activity. Lysosomotropic agents such as quinacrine can be used to positively sort for lysosome rich cells in natural killer (NK) cell populations. We therefore decided to use this agent to sort lymphokine-activated killer (LAK) cells to characterize their lysosomal content. We found that the positively sorted population contained all the LAK activity, i.e., lysis of NK-resistant tumor cells (B16 melanoma cell line), with the negatively sorted cells having no killing activity. Therefore separation of interleukin-2-incubated cells for LAK activity could be accomplished using sorting after quinacrine staining. The treatment of positively sorted LAK cell populations with L-leucine methyl ester, a lysosomotropic dye which inhibits killing by lysosome rich cells, caused abrogation of killing of the B16 tumor by the treated populations. Single cell conjugate assays were also done on these sorted cells, with positively sorted cells forming the highest and negatively sorted cells the lowest percent of conjugates. Our data therefore indicates the important role of lysosome rich cells in the LAK cell population in the murine system.

Animals↗

PubMed1986

Activation of tumoricidal properties in peripheral blood monocytes of patients with colorectal carcinoma.

The purpose of these studies was to determine whether blood monocytes of patients with different stages of colorectal carcinoma could be activated by various immunomodulators to become tumor cytolytic. Monocytes obtained from 12 colorectal carcinoma patients and 8 normal donors were incubated in vitro with free or liposome-encapsulated agents. The cytotoxic properties of the monocytes were determined subsequent to interaction with radioactively labeled allogeneic colon carcinoma cells, melanoma cells, glioblastoma cells, and allogeneic nontumorigenic skin cells. Blood monocytes from normal donors and all colorectal carcinoma patients were activated in vitro to become tumoricidal by immunomodulators in free form or entrapped within liposomes; i.e., the monocytes recognized and lysed tumorigenic cells but not nontumorigenic cells. The tumoricidal activity of monocytes was observed in blood monocytes obtained from patients even after multiple doses of radiotherapy and chemotherapy, and that fact suggests that the in vivo activation of macrophages may be feasible.

Adult↗

PubMed1985

Regulation of tubulin by triiodothyronine in hypothyroid rat brain.

The effect of T3 (triiodothyronine) on the induction of tubulin in hypothyroid developing rat brain has been examined using organ cultures of brains from late fetal, neonatal and postnatal rats. The neonatal brain displayed maximum sensitivity to T3. Hypothyroidism resulted in a 26% decline in the level of tubulin in the neonatal brain as opposed to a 5-15% decline in the fetal or postnatal brain. Exposure of the hypothyroid neonatal brain to T3 for 2 h in culture led to a 61% rise in the level of tubulin in contrast to a 41% increase seen in the case of normal brain. Total protein synthesis was not significantly affected. The preferential decline of tubulin in the neonatal hypothyroid brain, its enhanced sensitivity to T3 compared to normal brain, and the coincidence of the period of sensitivity to that of brain maturation indicate that the regulation of the level of tubulin by T3 in the developing brain is a natural ontogenic phenomenon.

Aging↗

PubMed1985

Lymphokine-activated killer cells: in vitro and in vivo studies.

The unavailability in humans of the specifically sensitized syngeneic cells that have proven efficacy in mouse tumor models has led us to adopt alternative approaches for the generation of cells reactive with fresh human tumor. We have demonstrated that incubation in lectins, alloantigens, or interleukin 2 for only 3 days can generate cells highly lytic for fresh NK-resistant primary and metastatic tumor but not normal cells. The effector cells are OKT3+, OKT8+, and the precursors appear to be distinct from NK and T cells. In murine models, the adoptive transfer of these activated cells leads to a marked reduction in established lung metastases and prolongation of the survival time, especially when combined with infusions of interleukin 2. We have performed a phase I clinical trial using infusion of large numbers of lectin-activated cells. No major toxicity was found, and circulating activated cells with evidence of migration to tumor were achieved. No major clinical responses occurred in these patients with very large tumor burdens. Clinical trials using the combined administration of interleukin 2-activated cells and recombinant interleukin 2 are in progress.

Animals↗