ABSTRACT
A 20-year-old man presented with microcytic hypochromic anemia (hemoglobin: 9.3 g/dl, MCV: 82.0 fl, MCHC: 29.5 g/dl) and dimorphism RBCs in circulating blood (RDW: 26.8%). Ringed sideroblasts accounted for 29.5% of bone marrow erythroblasts. Iron overload was also observed. Because the patient had a clear family history of anemia, he was given a diagnosis of X-linked sideroblastic anemia. The activity of delta-aminolevulinic acid synthase (ALAS) in bone marrow erythroblasts was low. However, we did not detect mutation of the gene for ALAS. The patient has responded well to a treatment regimen consisting of oral vitamin B6, Fe-chelation therapy, and phlebotomy.
Subject(s)
Anemia, Sideroblastic/genetics , Genetic Linkage , X Chromosome , Adult , Humans , Male , PedigreeABSTRACT
Murine B16-F10 melanoma was treated with local microwave hyperthermia, local injection of murine recombinant interferon-beta (rIFN-beta) or a combination of both in order to investigate the augmentation of anti-proliferative effects with this combination treatment. Concerning the local modulation of immunological reactions of the host, local hyperthermia at 43 degrees C for 15 min on murine melanoma caused remarkable infiltration of natural killer cells and local injection of rIFN-beta led to considerable infiltration of T cells. When these two modalities were combined, the infiltration of NK cells completely disappeared and, instead, remarkable augmentation of T cell infiltration occurred. Synergistic suppressive effects on melanoma growth with occasional scar formation were seen with this combined modality. These results indicate that local hyperthermia with a combination of rIFN-beta modulates local immune reactions of the host, and probably this immune reaction is partly involved in the course of the suppression of tumor growth.
Subject(s)
Hyperthermia, Induced , Interferon-beta/therapeutic use , Melanoma, Experimental/pathology , Melanoma, Experimental/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Animals , Cell Division/physiology , Cell Movement , Combined Modality Therapy , Interferon-beta/pharmacology , Mice , Mice, Inbred C57BL , Microwaves , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , T-Lymphocytes/pathology , T-Lymphocytes/physiology , Tumor Cells, CulturedABSTRACT
Fidler's B16-F10 melanoma was locally treated either with recombinant interleukin-2 (rIL-2) or microwaval hyperthermia, and immunological responses of the host to the melanoma after each treatment were investigated by immunofluorescent staining of the tissue. It was found that the local injection of rIL-2 either into the base of the tumor or into the upper part of the tumor directly caused infiltration of mainly NK cells and macrophages in the interstitials and/or in the tumor nests. T cells were also observed but the extent of infiltration was less in both treatments. Local microwaval hyperthermia of melanoma at 42 degrees C for 30 min or at 43 degrees C for 15 min also caused infiltration of NK cells and macrophages. Positive staining of the melanoma tissue with anti-ICAM-1 antibody after hyperthermia was seen in the interstitials adjacent to melanoma nests containing necrotic melanoma cells caused by hyperthermia. Based on the results, the rationality of combination of hyperthermia with local injection of rIL-2 will be discussed.
Subject(s)
Hyperthermia, Induced , Immunocompetence , Immunologic Factors/therapeutic use , Interleukin-2/therapeutic use , Killer Cells, Natural/pathology , Macrophages/pathology , Melanoma, Experimental/therapy , Microwaves , Skin Neoplasms/therapy , Animals , Cell Adhesion Molecules/analysis , Female , Inflammation , Intercellular Adhesion Molecule-1 , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Necrosis , Neoplasm Proteins/analysis , Recombinant Proteins/therapeutic use , Skin Neoplasms/immunology , Skin Neoplasms/pathologyABSTRACT
TNF stimulated superoxide (O2-) release directly in human granulocytes in a dose-dependent manner (1 to 1000 U/ml), although its potency was weak. TNF-induced O2- release was inhibited by cAMP agonists or ionomycin, and was not accompanied with an increase in cytoplasmic free Ca2+ [( Ca2+]i) and membrane potential changes (depolarization). These findings indicate that neither Ca2+ mobilization nor membrane depolarization is required for TNF-receptor-mediated cell activation. The pretreatment of human granulocytes with TNF enhanced O2- release and membrane depolarization in parallel stimulated by the receptor-mediated Ca2+-mobilizing agonists (FMLP, Con A, and wheat germ agglutinin) or the Ca2+ ionophore ionomycin, but not by PMA, a direct activator of protein kinase C. The optimal effect was obtained by pretreatment of cells with 100 U/ml TNF for 5 to 10 min at 37 degrees C, although the magnitude of enhancement varied according to the agonists used as subsequent stimuli. TNF did not affect an increase in [Ca2+]i stimulated by the Ca2+-mobilizing agonists, except Con A. Con A-induced increase in [Ca2+]i was enhanced by TNF in a dose-dependent manner. These diverse effects of TNF could be partly explained by the exclusive potentiation by TNF of the metabolic events triggered by an increase in [Ca2+]i.