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Biomedical subjects

Yoko Sugawara

Publications and source records attributed to Yoko Sugawara.

4 recordsLinked to original sources

Roxithromycin promotes lymphocyte apoptosis in Dermatophagoides-sensitive asthma patients.

A new macrolide, roxithromycin, may be an effective treatment for asthma. Lymphocyte apoptosis is impaired in patients with asthma, while spontaneous apoptosis increases during remission, and such changes may be involved in the onset and remission of mite-sensitive asthma. Lymphocyte apoptosis was evaluated by incubating cells from patients with asthma in the presence of roxithromycin. Low concentrations of roxithromycin (1-500 ng/ml) augmented the early, but not late, phase of apoptosis in Dermatophagoides farinae-stimulated peripheral blood mononuclear (PBM) cells, while high concentrations of roxithromycin (1 microg/ml; 6 microg/ml is the maximum serum level) augmented both the early and late phases of apoptosis. In both unstimulated and phytohemagglutinin-stimulated cells, roxithromycin did not significantly affect the induction of apoptosis. In cells from normal subjects, roxithromycin did not affect the induction of apoptosis. Other antibiotics, including cefazolin and ampicillin, did not cause significant induction of apoptosis. Fas ligand, but not Fas receptor, expression on D. farinae-stimulated cells was up-regulated after stimulation with 1 microg/ml roxithromycin, while Bcl-2 expression on both unstimulated and D. farinae-stimulated cells showed a decrease after the same treatment. Roxithromycin can induce apoptosis of D. farinae-activated lymphocytes in patients with D. farinae-sensitive asthma. Induction of the Fas/Fas ligand system and reduced Bcl-2 expression were involved in the promotion of apoptosis by roxithromycin treatment.

Adolescent↗

X-ray crystallographic characterization and phasing of a fucose-specific lectin from Aleuria aurantia.

A fucose-specific lectin from Aleuria aurantia was crystallized in its native form and was also cocrystallized with HgCl(2). Crystallization was performed using the sitting-drop vapour-diffusion method with ammonium sulfate as a precipitant. Both the Hg-free native crystals and the Hg cocrystals belong to the hexagonal space group P6(5)22. The unit-cell parameters for the Hg-free form are a = 84.0, c = 250.1 A and for the Hg cocrystals are a = 83.9, c = 254.3 A. Both forms of the crystals diffract X-rays to 2.3 A resolution and are suitable for high-resolution crystal structure determination. Initial phasing was successfully performed by the MAD method using the Hg cocrystals and the electron density obtained was good enough for model building.

Ascomycota↗

Algorithm for normal mode analysis with general internal coordinates.

A technique for performing normal vibrational analysis for biological macromolecules using general internal coordinates is proposed. The technique is based on the conventional algorithm for calculating the second derivatives of potential and kinetic energies using intramolecular dihedral angles, intermolecular translation, and rotation as variables [Braun, W. et al., J Phys Soc Jpn 1984, 53, 3269]. We extend the algorithm to include more general internal coordinates, bond stretching, angle bending, and so forth, without assuming two-body interactions. The essential point is the separation of the variables for potential functions and vibrational analysis. With our technique, we can arbitrarily choose any combination of internal coordinates as variables, free from the functional form of potential energy. We can analyze complex systems such as a multiple molecular system including solvents or a transition state of chemical reactions. In addition, mixed use of the potentials of molecular mechanics and quantum chemistry is possible.

Journal Article↗

Induction of peripheral mononuclear cell apoptosis in asthmatic patients in remission.

Apoptosis regulates inflammatory cell survival in allergic inflammation, and decreased apoptosis contributes to the chronicity of inflammation. To investigate the mechanisms of onset and remission of mite-sensitive childhood asthma, we evaluated peripheral blood mononuclear cell apoptosis in patients with asthma and in remission. There was a similar percentage of hypodiploid cells in unstimulated mononuclear cell cultures from patients with active asthma (29.5+/-5.0%) and normal individuals (25.9+/-4.9%). In contrast, the percentage increased in patients in remission (44.5+/-3.2%). In Dermatophagoides farinae (Df) antigen-stimulated mononuclear cell, the stimulation index was lower in patients with active asthma (0.95+/-0.06%) than in normal individuals (1.31+/-0.16%). In contrast to active patients, the proportion of hypodiploid cells stimulated with Df in patients with remission was equivalent to that of normal controls. After phytohemaglutinin (PHA) stimulation, the percentage of hypodiploid cells in patients with active asthma (35.1+/-3.2%) was also lower than in normal individuals (48.5+/-4.3%) or patients in remission (49.5+/-5.7%). Apoptosis occurred predominantly in CD8+, but not CD4+, cells in patients in remission. Interleukin IL-2 inhibited apoptosis in Df-activated cells in normal individuals, whereas IL-2 did not inhibit apoptosis in cells from patients in remission as well as with active asthma. The expression of Fas receptors on resting mononuclear cells was similar in the three groups. However, Fas receptor expression in Df-stimulated mononuclear cells was greater in patients with active asthma than in healthy individuals. In patients with remission that was equivalent to healthy controls. The PHA increased Fas expression to a similar degree in the three groups. With regard to Fas ligand, the expression was lower in unstimulated cultured mononuclear cells from patients than in normal individuals. In patients in remission that was comparable to normal individuals. The Df stimulation upregulated the Fas ligand in patients with active asthma, and downregulated it in patients in remission. In conclusion, apoptosis in Df-stimulated mononuclear cells is impaired in patients with active asthma, while spontaneous apoptosis of CD8+ cells in vivo is augmented in patients in remission, and may be involved in the onset and remission of mite-sensitive asthma.

Adolescent↗