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Biomedical subjects

Y Keisari

Publications and source records attributed to Y Keisari.

At least 55 records · Page 3Linked to original sources
PubMed1989

Defective leukocyte fungicidal activity in end-organ resistance to 1,25-dihydroxyvitamin D.

Recent studies have shown 1,25(OH)2D3 receptor-mediated modulation of leukocyte proliferation, differentiation, and function. We examined the phagocytosis and killing of microorganisms by neutrophils and monocytes from five patients of three families with hereditary resistance to 1,25(OH)2D3. Phagocytosis of microorganisms by patients' neutrophils and monocytes was normal. However, defective neutrophil killing activity toward Candida albicans (30-40% of controls) was found in all patients. The killing of Staphylococcus aureus was normal. The neutrophil chemiluminescence, nitroblue tetrazolium (NBT) dye reduction, and the generation of superoxide ions and hydrogen peroxide by neutrophils and monocytes after induction by either soluble stimuli or zymozan particles, did not differ from those in controls. The neutrophil myeloperoxidase activity was also normal. Monocytes obtained from two patients of different families before long-term calcium infusion therapy and after they became normocalcemic, demonstrated a similar impaired fungicidal activity toward Saccharomyces cerevisiae, indicating that hypocalcemia itself was not the cause of the killing defect. However, the addition of the Ca+2 ionophore A23187 (1 microM) to the test medium restored the monocyte fungicidal activity to normal. As patients' neutrophil cytosolic free calcium concentration was similar to that in controls, it is suggested that 1,25-(OH)2D3 exerts its effect on leukocyte function by a putative receptor-mediated regulation of subcellular calcium localization which may be important for fungicidal activity.

Calcitriol↗
PubMed1987

Differential stimulation of mononuclear phagocyte IL 1 production and oxidative burst by tumor-promoting and non-tumor-promoting agents.

Adherent bone marrow, spleen and peritoneal mouse macrophages, as well as human peripheral blood monocytes were exposed in vitro to the phorbol ester derivatives 12-O-tetradecanoyl-phorbol-13-acetate (TPA), phorbol 13-monoacetate (PA), phorbol 12-myristate (PM), phorbol 12,13-diacetate (PDA), phorbol 12,13 dibutyrate (PDBu), TPA-20 aldehyde (TPA-AL), phorbol 12-retinoate 13-acetate (PRA), 4-alpha TPA (alpha-TPA) and to mezerein (MEZ) and aplysiatoxin (APL). The triggered macrophages/monocytes were tested for the production of an IL 1-like activity by the thymocyte proliferation assay and for H2O2 generation in a quantitative method which is based on the H2O2-mediated and horseradish peroxidase-dependent oxidation of phenol red. The results showed that strong first stage and second stage tumor promoters such as TPA, PDBu, PRA, MEZ and APL are also strong stimulators of IL 1 and H2O2 generation, whereas weak tumor promoters exhibited a low, if any, effect at all. The afore-described findings lend support to the idea that chronic inflammatory phagocytes might play a role in the tumor promoting process by furnishing both carcinogenic and growth factors at the site of tumor origin.

Animals↗
PubMed1987

On the interactions between macrophages and developmental stages of Schistosoma mansoni: the cytotoxic mechanisms involved in macrophage-mediated killing of schistosomula in vitro.

In an in vitro cytotoxicity assay, mouse adherent peritoneal exudate macrophages (APEM), harvested 8-10 weeks post Schistosoma mansoni infection caused sizable (greater than 90%) specific killing of schistosomula. This cidal effect was not diminished by the addition of scavengers of oxidative burst products to the cytotoxicity assay, albeit macrophages from schistosome-infected mice produced more H2O2 than did macrophages from non-infected mice. Of inhibitors of lysosomal enzyme function and release added to the cytotoxicity assay, trypan blue (1 mg/ml) fully abolished the schistosomulicidal effect; hydrocortisone (100 micrograms/ml) was partly effective, and gold salts (1 mg/ml) were ineffective. A cidal effect was not apparent in the absence of L-arginine nor in the presence of excess (greater than 400 micrograms/ml) L-arginine, L-lysine or L-ornithine. Arginase (5 U/ml) totally abrogated the schistosomulicidal effect. The findings suggest that a macrophage protein of a lysosomal origin, dependent on arginine for its reaction and/or production, may be involved in the in vitro killing of schistosomula by macrophages from S. mansoni-infected mice.

Animals↗
PubMed1987

Experience with bacillus Calmette-Guérin in patients with superficial bladder tumors. Value of monocyte activation in intravesical bacillus Calmette-Guérin therapy.

Twenty-four patients with transitional cell carcinoma of the bladder, who had failed thiotepa therapy, were subjected to immunotherapy with intravesical bacillus Calmette-Guérin (BCG) by a modification of the Morales protocol. The results show a marked decline in the number of recurrent tumors following BCG immunotherapy. From a cumulative recurrence of 1 in 8.3 months, recurrences declined to 1 in 82 months. In parallel with the clinical follow-up, the level of the in vivo activation of peripheral blood monocytes of the treated patients, as a result of immunostimulation with BCG, was monitored by the quantitation of oxidative burst products released by the cells. The oxidative burst capacity of peripheral blood monocytes were found to undergo an increase of 80-140% in 5 of 10 patients tested. The patients with a high level of activation of peripheral blood monocytes did not have tumor recurrence while 3 of the 5 patients who did not show an increase in the oxidative burst had recurrent tumors. The possibilities for utilizing the oxidative burst test as an early indicator for distinction between patients who will respond to BCG immunotherapy and nonresponders is discussed.

Adult↗
PubMed1986

Increased oxidative burst potential exhibited by macrophages during graft-versus-host reactions in mice.

Graft versus host reactions (GVHR) in mice are accompanied by macrophage activation. Since macrophage oxidative burst (OB) was found to increase in activated macrophages (MPs), we examined the OB of peritoneal and spleen MPs from mice during GVHR. Parental spleen lymphocytes, were injected i.p. into F1 hybrids (BALB/cXC57Bl/6) and at different intervals following injection we monitored the number of peritoneal exudate cells (PEC), spleen enlargement, and the OB of both peritoneal and spleen adherent MPs. Macrophage OB was assessed by measuring O-2 and H2O2 production, following stimulation with the phorbol ester TPA. The spleen-to-body weight ratio increased by 40-70% in mice with GVHR during the period of 6-20 days post-injection and decreased to almost normal levels after 27 days. In such mice with GVHR the number of PEC returned to normal (approximately equal to 6 X 10(6) cells/animal) after 20 days compared with 5 days in control mice (injected with F1 spleen cells). Adherent peritoneal MPs from control mice and mice with GVHR exhibited increased OB activity 3 days following treatment. However, in the control mice the OB response returned to normal within 6 days, while in the experimental mice it showed a slight decrease after 6 days, increased again within 9-17 days, and finally decreased 20-27 days after treatment. Adherent spleen MPs from mice with GVHR generated a high response 6 days posttreatment, which gradually returned to the basal level after 17 days. These findings suggest that during GVHR in mice, macrophage OB was potentiated, giving rise to cytotoxic products such as O2- and H2O2, which may contribute to tissue damage during GVHR.

Animals↗
PubMed1986

The interactions between macrophages and developmental stages of Schistosoma mansoni: effect of macrophage function modulators on the viability of S. mansoni in vivo and in vitro.

ICR mice infected with Schistosoma mansoni developed sizable concomitant immunity to a challenge infection 10 weeks, but not 7 weeks, following the primary infection. At 7 weeks, postprimary-infection mice exhibited increased resistance to reinfection when treated with BCG or MDP. BCG even rendered noninfected mice resistant to infection. Macrophage function inhibitors such as silica and trypan blue did not abolish the concomitant immunity state, but they increased the worm burden due to a single infection, whether given before or after the infection. The onset of concomitant immunity in infected mice was paralleled by the appearance in their peritoneal exudate of schistosomulicidal-adherent macrophages. Such cells were evident at 9 but not 7 weeks of infection. The in vivo injection of MDP accelerated their appearance in infected mice, while silica, trypan blue, and carrageenan abolished it. The findings suggest that highly activated schistosomulicidal macrophages develop in infected mice, and might participate in the destruction of the invading parasite.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Stimulation of human monocyte oxidative burst and related cytotoxicity by tumor-promoting and non-tumor-promoting diterpene esters, indole alkaloids and polyacetate-type agents.

Human peripheral blood monocytes were cultured and exposed to plant diterpenes, indole alkaloids and polyacetates with various degrees of tumor-promoting activity. The effect of the above-mentioned encounter on monocyte function was examined, as expressed by H2O2 production and lysis of dog erythrocytes by the cells, and the inhibition of 3H-PDBu binding to the monocytes by the various test agents. The most effective reagents in both activation of monocyte function and inhibition of 3H-PDBu binding were 12-0-tetradecanoyl-phorbol 13-acetate (TPA), phorbol 12, 13 dibutyrate, teleocidin, and aplysiatoxin which are known to be strong tumor promoters. Strong stimulation of monocyte function was also exerted by the weak tumor promoters, phorbol 12-retinoate 13-acetate, mezerein and debromoaplysiatoxin. Non-tumor-promoting phorbol diterpenes such as phorbol 12, 13-diacetate, phorbol 12-myristate, phorbol 13-acetate and 4-alpha TPA were 1,000 times less effective than TPA in monocyte stimulation and inhibition of 3H-PDBu binding. These results indicate that stimulation of human monocyte H2O2 production and related cytotoxicity might discriminate effectively between tumor-promoting and non-tumor-promoting reagents.

Binding, Competitive↗
PubMed1985

The synergistic tumoricidal activity of anticancer drugs and oxidative burst-triggered macrophages.

The anticancer drugs adriamycin (ADR) and actinomycin D (AMD) were tested for their effect on the oxidative burst (OB) of mouse peritoneal macrophages (MPM) and on the killing of tumor cells by OB-stimulated MPM. The oxidative burst of MPM determined by hydrogen peroxide (H2O2) production was severely impaired by ADR (10 micrograms/ml) and AMD (40 micrograms/ml) after a 1 h treatment and by lower concentrations of the drugs following a 24 h treatment. The toxicity of the drugs against MPM was comparable to their effect on EL4 cells. Pretreatment of EL4 and TLX-9 tumor cells with sublethal amounts of ADR for 4 h rendered the cells sensitive to the cytotoxic effect of OB-stimulated MPM which were otherwise unable to kill these cells. It seems that anticancer drugs and OB-stimulated macrophages can cooperate in the destruction of tumor cells in vitro.

Animals↗
PubMed1985

Macrophage oxidative burst (OB) and related cytotoxicity--II. Differential sensitivity of erythrocytes from various animals to OB dependent lysis.

Red blood cells (RBCs) from various animals, when exposed to oxidative burst (OB)-stimulated mouse macrophages, showed differences in sensitivity to OB dependent lysis. The increasing order of sensitivity was: mouse, hamster, rabbit, guinea pig, sheep and human RBCs. The degree of OB dependent hemolysis did not correlate with either the capacity of the various cells to degrade H2O2 or their osmotic fragility. The relative sensitivity of the various RBCs to OB products generated by macrophages concurred with their sensitivity to H2O2 generated by an enzymatic system. The differential sensitivity may be correlated with the sphingomyelin content of the cells.

Animals↗
PubMed1985

Development of resistance to MOPC-315 plasmacytoma after intralesional and intraperitoneal melphalan therapy of tumor-bearing BALB/c mice. II. Enhancement of in vitro cell-mediated cytotoxicity by combined chemotherapy-immunotherapy.

As previously reported, tumor-bearing BALB/c mice can be cured by split-course melphalan therapy, with 40-60% of the treated animals developing resistance to subsequent challenge with viable MOPC-315. The present study deals with the identification of effector-cytotoxic cells that may be developed as a result of chemotherapy-induced tumor regression and their possible potentiation by active, specific immunization with melphalan- and glutaraldehyde-treated MOPC-315 plasmacytoma cells. The cytotoxic potential of spleen-derived lymphocytes in treated animals could be demonstrated only after in vitro sensitization against mitomycin-treated MOPC-315 cells. Lymphocyte-mediated cytotoxicity, as measured against syngeneic 51Cr-labeled MOPC-315, could be detected in melphalan-cured animals and was significantly enhanced by active immunization as compared to the cytotoxicity seen in normal and tumor-bearing mice. With the use of M109 syngeneic, unrelated tumor cells as control targets in the assay, no cytotoxicity was detected. Macrophage cytotoxicity was not significantly enhanced in any of the treatment groups described, with these assays performed 6-8 weeks following treatment and cure. When in vitro killing of MOPC-315 targets was tested with the use of peritoneal macrophages harvested shortly following cure of ascitic tumor by ip injected melphalan, the cytotoxic response was significantly enhanced. In conclusion, following chemotherapy-mediated cure of established MOPC-315 tumors, splenic lymphocytes exhibited enhanced antitumor cytotoxicity, which was further augmented by active immunization. Macrophage activation, as measured by direct cytotoxicity against MOPC-315 targets, was found to occur locally and early following the event of melphalan-induced tumor regression.

Animals↗
PubMed1984

Macrophage oxidative burst and related cytotoxicity. I. Differential activation by tumor-promoting and non-tumor-promoting phorbol esters.

Mouse peritoneal macrophages elicit an oxidative burst (OB) response upon stimulation with the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA). In this study we compare the OB-stimulating capacity of phorbol ester derivatives, structurally related to TPA, which differ in their tumor-promoting activity. Non-tumor-promoting derivatives such as phorbol 13-acetate, phorbol 12-myristate, TPA-20-aldehyde and 4-O-methyl TPA were tested. These reagents stimulate macrophages to generate OB products such as O-2 and H2O2, yet the amounts required for stimulation are 1,000 times higher than the amounts of TPA required to elicit a comparable response. It has also been observed that, in the same order of magnitude, the above-mentioned derivatives are less efficient than TPA in rendering macrophages cytolytic toward erythrocytes. Another strong tumor promoter tested, teleocidin, has been found to be as potent as TPA in the activation of macrophage OB and in related activities.

Animals↗
PubMed1984

Oxidative burst-dependent tumoricidal and tumorostatic activities of paraffin oil-elicited mouse macrophages.

Mouse peritoneal macrophages (MPM) from C57BL/6J, BALB/c, A strains, and (BALB/ cfemale X C57BL/ 6Jmale )F1 offspring were treated with the oxidative burst (OB)-stimulant 12-O-tetradecanoylphorbol 13-acetate, and their in vitro tumoricidal, tumorostatic , and OB activities were examined. Paraffin oil-elicited, but not thioglycollate (TG)-elicited, MPM exhibited cytotoxicity only toward Yac-1 cells and cytostatic activity toward Yac-1, EL 4, RBL-5, and RLmale 1 lymphoma cells. This activity was in correlation with the reduced capacity of TG-elicited cells to generate OB products. The toxic effect of such activated MPM was partially inhibited by catalase, superoxide dismutase, cytochrome c, and vitamin E (alpha-tocopherol) and was augmented by horseradish peroxidase and the catalase inhibitor aminotriazole (3-amino-1H-1,2,4-triazole), thus indicating the involvement of oxygen-derived toxic reagents, mainly hydrogen peroxide, in the MPM-mediated damage inflicted on the tumor cells. EL 4 cells incubated with nonstimulated MPM exhibited enhanced growth both in vitro and in vivo, whereas OB-stimulated MPM inhibited the growth of such cells in the same experimental systems.

Animals↗
PubMed1983

The oxidative burst and related phenomena in mouse macrophages elicited by different sterile inflammatory stimuli.

Mouse peritoneal macrophages (MPM) elicited by paraffin oil (PO) or thioglycollate (TG) were compared in their capacity to generate oxidative burst (OB) products such as superoxide ion (O2-) and hydrogen peroxide (H2O2) and lyse target erythrocytes. Strong OB stimulants such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA), opsonized zymosan; and wheat-germ agglutinin (WGA) were found to stimulate O2 and H2O2 production by both PO- and TG-elicited MPM. PO-elicited MPM exhibited a vigorous OB response compared to TG-elicited MPM and showed a higher degree of self iodination in the presence of 125I. Macrophage-mediated cytolysis of 51Cr-labeled red blood cells, following OB stimulation, was revealed by PO-elicited MPM triggered by TPA, opsonized zymosan, WGA, and Concanavalin A. TG-elicited MPM failed to respond to TPA and opsonized zymosan. In the presence of horseradish peroxidase, both PO- and TG-elicited MPM exhibited augmented cytocidal activities upon stimulation with TPA, whereas catalase abrogated the capacity of TPA-stimulated MPM to lyse red blood cells, which may suggest the involvement of H2O2 in the lytic process.

Animals↗