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K Arahata

Publications and source records attributed to K Arahata.

155 records · Page 9Linked to original sources
PubMed1987

Isolation of a Ca-dependent erythrolytic protein (perforin) from cytotoxic T-lymphocytes.

A Ca-dependent erythrolytic protein (perforin) was isolated from a cytotoxic T-cell line (CTLL2). Cellular extracts were fractionated on DEAE-cellulose and hydrophobic Phenyl-Sepharose columns. Lytic activity was tightly bound to the hydrophobic column and was eluted with 50% ethyleneglycol. The erythrolytic activity was dependent on the concentration of Ca2+ ions, and heparin accelerated the lysis of erythrocytes by perforin 10-fold, with a half maximal concentration of 12 ng/ml. The activity was strongly inhibited by micromolar concentrations of heavy metal ions, such as Zn2+ and Fe2+, and glycylarginine-methylcoumarinamide (Gly-Arg-MCA) in the presence of 100 ng/ml heparin.

Animals↗
PubMed1986

Monoclonal antibody analysis of mononuclear cells in myopathies. III: Immunoelectron microscopy aspects of cell-mediated muscle fiber injury.

We have previously obtained light microscopical immunocytochemical evidence for cell-mediated muscle fiber injury and destruction in polymyositis and inclusion body myositis. To evaluate further interactions of the different cell phenotypes with each other and with the muscle fibers, the T8, T4, and Leu 7 markers in 7 cases of polymyositis and in 9 cases of inclusion body myositis were localized by immunoelectron microscopy. In the early stages of the cell-mediated process, T8+ cells and macrophages are apposed against, and/or send spikelike processes into, nonnecrotic muscle fibers. Leu-7+ cells penetrate fibers infrequently, and T4+ cells do not penetrate muscle fibers. Subsequently, an increasing number of T8+ cells and macrophages traverse the basal lamina; focally replace, displace, or compress the fiber; and spikes from these cells honeycomb the adjacent muscle fiber regions. The macrophages contain only few heterophagic vacuoles and therefore act in a cytotoxic rather than a phagocytic capacity. The integrity of the muscle fiber surface membrane facing the invading cells is maintained, but the possibility also exists that the membrane is damaged and rapidly repaired, or that the damage cannot be detected by electron microscopy. Nearby fiber regions often show either degenerative or regenerative changes. Ultimately, segments of the entire muscle fiber are replaced by the invading cells.

Antibodies, Monoclonal↗
PubMed1986

Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies.

Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer (K) and natural killer (NK) cells, and the Ia antigen were used to analyze mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle. The analysis, which was quantitative, was performed according to diagnosis and site of accumulation. Cells at perivascular, perimysial, and endomysial sites of accumulation, and cells focally surrounding and invading nonnecrotic muscle fibers, were analyzed separately. Individual antigens were localized in 2-micron serial sections, or multiple antigens were demonstrated in a given section by sequential paired immunofluorescence. The latter approach allowed the identification of the cell phenotypes in which functional properties are defined by multiple markers, e.g., T8+ and T4+ cells that are either activated or not activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK cells of varying maturity and killing capability. The interactions of inflammatory cells of various types with each other and the muscle fiber were further investigated by immunoelectron microscopy. In SD, the findings provide evidence for a cell-mediated immune effector response against a connective tissue and/or vascular element. In DM, the effector response appears to be predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or without accompanying macrophages. Because T-cell-mediated injury is antigen- and major histocompatibility complex-restricted, clones of T cells must have been sensitized previously to a muscle fiber-associated surface antigen. The identity of the putative antigen(s) remains an important, unsolved question.

Adolescent↗
PubMed1984

Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells.

In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cells, T cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were used for cell typing. Macrophages were identified by the acid phosphatase reaction. Few extravascular mononuclear cells occurred in normal muscle. In all inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages was present. Mature K/NK cells were rare in all diseases. In dermatomyositis, polymyositis, and inclusion body myositis, there was a positive gradient for T cells, T8+ cells, and activated T cells and a negative gradient for B cells and T4+ cells between perivascular and endomysial sites. In scleroderma the predominant perimysial exudate consisted mostly of T cells and macrophages. The percentage of B cells at all sites, and the T4+/T cell ratio in the endomysium, were significantly higher in dermatomyositis than in the other diseases. In polymyositis and inclusion body myositis, the endomysial exudate contained a large number of T cells, T8+ cells, and activated T cells but only sparse B cells. T cells accompanied by macrophages focally surrounded and invaded nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers in Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma were similarly affected. We infer that (1) T-B, T-T, and T-macrophage cooperativities are likely to exist in muscle in different myopathies; (2) T cell-mediated fiber injury plays a role in polymyositis and inclusion body myositis; (3) T cell-mediated fiber injury can also occur in inherited diseases, such as Duchenne dystrophy; and (4) a local humoral response may occur in muscle in dermatomyositis and possibly in polymyositis and inclusion body myositis.

Adolescent↗
PubMed1984

Monoclonal antibody analysis of mononuclear cells in myopathies. II: Phenotypes of autoinvasive cells in polymyositis and inclusion body myositis.

In 6 cases of polymyositis and 6 of inclusion body myositis, phenotypes of mononuclear cells focally surrounding and invading muscle fibers were analyzed. By localizing the T8, T4, and Ia markers with direct immunofluorescence and acid phosphatase enzyme cytochemically in the same sections, five different phenotypes were simultaneously identified in a given section: T8+ and T4+ cells that were either activated (Ia+) or not activated (Ia-), and acid phosphatase--reactive and Ia+ macrophages. This approach permitted the separate and quantitative assessment of the distributions of the different phenotypes among the invading versus the surrounding cells. In both polymyositis and inclusion body myositis, the invading cells were selectively enriched in the T8+ phenotype. One-third of all invading cells and one-half of the invading T8+ cells were activated. T4+ cells were more abundant among the surrounding than the invading cells, and only a small proportion of the T4+ cells were activated. These findings are especially significant in view of the cytotoxic capability of the T8+ cells and because histocompatibility factors permit T8+ but not T4+ cells to recognize an antigen on muscle fibers. Macrophages accounted for 21 to 31% of the cells invading or surrounding nonnecrotic fibers. For purposes of comparison, we also analyzed mononuclear cells in necrotic fibers: 80% of these cells were macrophages, and only 20% were T cells. The findings indicate that in polymyositis and inclusion body myositis, nonnecrotic muscle fibers are injured by autoinvasive T8+ cells that act in concert with macrophages. Further, the findings strongly imply previous sensitization of clones of T cells to muscle fiber-associated surface antigen(s).

Adolescent↗
PubMedDate not supplied

A carrier of Duchenne muscular dystrophy with dilated cardiomyopathy but no skeletal muscle symptom.

A 29-year-old female developed dilated cardiomyopathy at 20 years of age but with no muscle symptoms. Her 2-year-old son with Duchenne muscular dystrophy (DMD)_had no demonstrable deletion in the dystrophin gene, but all fibers except for 5% 'revertant' fibers in a muscle biopsy specimen had no dystrophin. Both skeletal and cardiac muscle biopsy specimens from the mother showed a mosaic distribution of dystrophin-positive and -negative fibers, and so she was diagnosed as being a manifesting carrier of DMD. We conclude that, when one encounters a female patient with idiopathic cardiomyopathy with a high serum creatine kinase level, the suspicion of her being a manifesting DMD carrier should be ruled out.

Adult↗