[Acute pulmonary cryptococcosis].
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Biomedical subjects
Publications and source records attributed to S Sone.
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Human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy nonsmoking donors exhibited primarily low levels of cytolytic activity against allogeneic tumor target cells. These AM acquired enhanced capacity to kill tumor cells following a 24-hr incubation in vitro with endotoxin [lipopolysaccharide (LPS)]. Maximal tumoricidal activity of LPS-activated AM as measured by lysis of tumor target cells was obtained after incubation with tumor cells for 72 hr. LPS-activated AM lysed allogeneic tumor cell lines of different origins but did not affect normal, nonneoplastic cells. We conclude that LPS induces human AM to become tumoricidal. This method should be useful in studies on therapeutic agents enhancing AM-mediated cytotoxicity in situ.
Homogeneous preparations of human alveolar macrophages (AM) were obtained by bronchoalveolar lavage of the lungs of healthy nonsmokers. These AM exhibited a low level of spontaneous cytolytic activity against allogeneic A375 melanoma cells. Tumoricidal activity of AM could be generated and/or augmented by incubation in vitro with either lipopolysaccharides (LPS) or muramyl dipeptide (MDP). MDP derivatives were encapsulated within multilamellar (MLV) liposomes composed of phosphatidylcholine-phosphatidylserine (PC/PS). Dose-response experiments established that liposome-encapsulated MDP augmented the tumoricidal activity of AM at concentrations about 100 times lower than free MDP in the medium. AM activated by MLV containing MDP destroyed allogeneic tumor cell lines, but did not affect cultures of normal, non-neoplastic cells. An inactive derivative, MDP-L, encapsulated in MLV liposomes did not potentiate the tumoricidal activity of AM. We conclude that human AM respond to MDP in vitro and that liposomes containing MDP are far more efficient than unencapsulated, free MDP for enhancing the tumoricidal activity of human AM.
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The multiple systemic administration of multilamellar liposomes composed of phosphatidylserine and phosphatidylcholine (molar ratio 3:7) that contained water-soluble muramyl dipeptide (MDP) activated alveolar macrophages to become tumoricidal and eradicated established spontaneous pulmonary and lymph node metastases. Spontaneously metastasizing melanoma cells were injected into the footpads of mice. After 4-5 weeks, the tumors were resected by a midfemoral amputation; 3 days later, twice-weekly injections of liposomes were initiated and continued for 4 weeks. In some experiments the mice were killed 2 weeks after the final treatment. Seventy-four percent of animals injected with liposomes containing MDP were free of visible metastases. In a separate life-span experiment, 60% of mice treated with liposome-encapsulated MDP were tumor-free 120 days after the last liposome treatment or 110 days after all control mice treated with free MDP or control liposome preparations had died of disseminated cancer. These data suggest that the systemic administration of liposomes containing MDP, or similar compounds that produce macrophage activation, may provide an additional useful approach to the therapeutic regimens currently used to eradicate cancer metastases.
Treatment of F344 rat alveolar macrophages (AMs) in vitro with cell-free supernatant fluids obtained from concanavalin-A (Con A)-stimulated syngeneic lymphocytes induced extensive fusion. The lymphokine responsible for the fusion of AMs (but not other cells) is here referred to as AM fusion factor (Con-A-MFF). Fusion is dependent on the dose of Con-A-MFF and the population density of AM cultures and occurred 10 hours after Con-A-MFF was added to cultures of normal AMs. Con-A-MFF must interact with AMs for more than 8 hours before full expression of fusion is reached at 24 hours. Using a technique allowing for sequential scanning to transmission electron microscopy analysis of cells, the authors determined the relationship of the morphologic characteristics of the surface and the internal structure of cells fusing to form multinucleate giant cells (MGCs). The process of AM fusion begins with the aggregation of AMs, followed by interdigitation of cell processes. Serial sections of MGCs showed lysosomes associated with remnants of plasma membrane in the cytoplasm. The MGCs contained numerous organelles associated with increased secretory activity of cells.
The purpose of this study was to determine whether the presence of progressively growing pulmonary metastases influences the number and function of alveolar macrophages (AM). Female F344 rats were given i.v. injections of cells from a metastatic variant line of the syngeneic adenocarcinoma MADB-105. At Days 7, 14, 21, and 28 after injection, normal and tumor-bearing animals (3/group) were killed, and their AM were harvested by lavage. The functional integrity of AM was determined by their capacity to phagocytose opsonized erythrocytes and by their ability to respond to a variety of activating agents in vitro. Normal and metastasis-bearing rats were given i.v. injections of Nocardia rubra cell wall skeleton to determine whether the presence of large pulmonary metastases would interfere with AM activation in situ. The data demonstrated that the presence of progressively growing lung metastases led to a slight increase in the number of harvested AM and that these cells from tumor-bearing rats were as phagocytic as AM obtained from normal rats. Also, AM harvested from rats with metastases became tumoricidal against syngeneic tumor target cells in response to activation stimuli in vitro and in vivo. We conclude that, in this tumor system, the presence of progressively growing lung metastases doses not suppress the number or function of AM. The use of agents known to activate AM could, therefore, be of benefit in the therapy of pulmonary metastases.
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Normal radiographic appearances of the thymus and anterior and superior mediastinum based on 34 pneumomediastinograms performed on myasthenia gravis patients are discussed. Knowledge of (1) end-on shadow of major vessels in the mediastinum, (2) topographic relation between major vessels and bilateral lobes of the thymus, (3) variable shape, size, and uneven outline of the normal thymus, and (4) irregularly distributed mediastinal fat, helps make more precise radiographic interpretation in this region.
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