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Biomedical subjects

S Yamano

Publications and source records attributed to S Yamano.

At least 127 records · Page 7Linked to original sources

Determination of urinary metabolites of thiamine propyl disulfide in humans.

Gas chromatographic procedure for the quantitative determination of methyl propyl sulfone (MPS), 2-hydroxypropyl methyl sulfone (2HPMS) and 3-hydroxypropyl methyl sulfone (3HPMS) in urine was developed. By using this procedure, the urinary excretion of MPS, 2HPMS and 3HPMS after oral dose of thiamine propyl disulfide (TPD) was investigated in healthy adults, in order to assess their ability of drug disposition including metabolism. Among these metabolites, 2HPMS was predominant and the other two were minor. 2HPMS was excreted most in the 24--36 h urine and the time course of excretion of this metabolite was almost the same among these subjects. In 4th day urine, a significant amount of 2HPMS was still excreted. On the contrary, the time course of excretion of MPS varied among subjects and also at different occasions in the same subjects. 3HPMS was excreted most in the 0--12 or 12--24 h urine and more rapidly excreted than 2HPMS. Two-fold interindividual differences in the amount of 2HPMS in the 0--48 h urine occurred and intraindividual difference was also observed. Inter- and intraindividual differences in the amount of MPS in 0--48 h urine were much larger than that in 2HPMS. In 3HPMS, these differences were slightly less than in 2HPMS. Sex difference in the excretion of MPS and 2HPMS was not observed.

Adult↗

[Relationship between circulating androgens and ovarian hyperstimulation syndrome in anovulatory patients treated with hMG-hCG].

In order to evaluate relationship between circulating androgens levels and development of ovarian hyperstimulation syndrome (OHS) in anovulatory patients treated sequentially with hMG and hCG, serum concentrations of androstenedione (A), testosterone (T) as well as estradiol (Ed) were measured serially in a total of 17 anovulatory patients including 9 who did not develop OHS and 8 who developed mild or moderate OHS. Increase of Ed levels during the period of hMG treatment varied remarkably in individual patients with OHS ranging from 7.2 to 190.1 times as much the pretreatment value. On the other hand, increase of A levels during the hMG treatment was recorded in the range from 2.0 to 3.2 times as much the pretreatment value in 4 patients with mild OHS, and from 1.5 to 5.9 in 4 patients with moderate OHS. However, the ratio of A increase remained within 1.4 times in patients without OHS. A transient increase of circulating T was observed in 2 days after commencement of hCG treatment, ranging between 1.4 and 3.2 times in patients without OHS, between 1.8 and 2.4 times in patients with mild OHS and between 3.8 and 6.8 times in patients with moderate OHS. It is concluded that serial measurements of A and T during the course of hMG and hCG treatments respectively appear to be an additional index other than Ed to predict development of OHS.

Androgens↗

Protection from experimental endotoxemia by a recombinant adeno-associated virus encoding interleukin 10.

BACKGROUND: Interleukin 10 (IL-10) is a homodimeric cytokine that shows considerable clinical promise. Adeno-associated virus (AAV) vectors appear increasingly useful for in vivo gene-transfer applications. METHODS: A recombinant AAV type 2 vector encoding human IL-10 (rAAVhIL10) was constructed by using an adenoviral-free, three-plasmid co-transfection. Cytokine production was measured by using an enzyme-linked immunosorbent assay. Endotoxic shock was induced by lipopolysaccharide (LPS) injection. RESULTS: As media from rAAVhIL10-infected COS cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout (KO) mice challenged with Brucella abortus, it was clear that vector-derived hIL-10 was biologically active in vitro. Intravenous or intramuscular administration of relatively modest levels of rAAVhIL10 (10(10) genomes) to IL-10 KO mice resulted in hIL-10 secretion into the bloodstream, which, at 8 weeks, gave median serum levels of 0.9 and 0.45 pg/ml, respectively. Acute endotoxic shock led to a 33% mortality rate, and severe morbidity, in control IL-10 KO mice, whereas no mortality and little morbidity were seen in IL-10 KO mice given rAAVhIL10 7 weeks earlier. CONCLUSIONS: The findings demonstrate that a modest dose of rAAVhIL10 administered in vivo provides long-term protection against LPS-induced endotoxic shock in a murine model. Thus, this vector may be useful for clinical applications requiring sustained IL-10 expression, for example in the treatment of several autoimmune diseases.

Animals↗

Specific cytotoxicity of antibody to YAL-198, a sperm antigen peptide, to murine zygote.

Active immunization with the peptide segments rSMP-230 and YAL-198, corresponding to the hydrophilic extracellular domain of two human sperm antigens (rSMP-B and YWK-II, respectively), reduced fertility in female rats by different mechanisms. The anti-rSMP-230 antibody interferes with human and murine fertilization, and the anti-YAL-198 antibody blocks the development of mouse embryos. The authors examined in vitro at which stage the antibodies to rSMP-230 and YAL-198 were cytotoxic to murine embryos up to morula/blastocyst stage. Anti-rSMP-230 antibody was not cytotoxic to any stages. On the other hand, the anti-YAL-198 antibody arrested the growth of embryos at the 2-cell stage but not at more advanced developmental stages. When the anti-YAL-198 antibody was used, spotty staining was observed only on the surfaces of embryos that had arrested at the 2-cell stage. Unstained embryos, however, continued to develop normally. In contrast, the anti-rSMP-230 antibody stained murine sperm but failed to stain murine ova and embryos. The present results suggest that the human sperm components rSMP-B and YWK-II play important roles in sperm-egg interaction and early development of the embryo, respectively.

Animals↗

Progesterone accelerates the onset of capacitation in mouse sperm via T-type calcium channels.

This study was undertaken to evaluate whether progesterone induces capacitation of mouse spermatozoa. When sperm were evaluated by chlortetracycline staining, addition of progesterone significantly increased the proportion of spermatozoa exhibiting the B pattern at 60 minutes of incubation, compared with that before incubation (23 +/- 6.2% vs. 13 +/- 2.9%, p < 0.01) and that in hTF medium without progesterone (23 +/- 6.2% vs. 13 +/- 4.2%, p < 0.01). If the redistribution of proteins in sperm plasma membrane such as protein binding calcium ion were defined as capacitation, it could be said that progesterone promoted capacitation of mouse sperm. This progesterone-induced capacitation was prevented by depletion of extracellular calcium ion and addition of NiCl2, a T-type calcium channel blocker, although thapsigargin, an inhibitor of Ca2+-ATPase, did not increase the number of capacitated sperm (B pattern; progesterone vs. progesterone + depletion of calcium ion, 18 +/- 3.5% vs. 8 +/- 2.5%, p < 0.05, progesterone vs. progesterone + NiCl2, 20 +/- 3.8% vs. 6 +/- 5.2%, p < 01). Furthermore, genistein, a protein tyrosine phosphorylation inhibitor, inhibited progesterone-induced capacitation (B pattern; progesterone vs. progesterone + genistein, 20 +/- 3.8% vs. 11 +/- 2.4%, p < 01). In conclusion, progesterone induces capacitation in mouse sperm and this capacitation may be associated with calcium influx and tyrosine phosphorylation.

Animals↗

Sperm-immobilizing antibodies block capacitation in human spermatozoa.

Sperm-immobilizing antibodies block human fertilization by interfering with the acrosome reaction (AR). To clarify the mechanism of blockage of AR by sperm-immobilizing antibodies, the authors examined their effects on the increase of intracellular free Ca2+ concentration induced by follicular fluids (Ca2+ influx) in spermatozoa and on their capacitation. Sperm-immobilizing antibodies did not suppress Ca2+ influx induced by follicular fluid, but they inhibited capacitation of human spermatozoa. Namely delta%AR (%AR after addition of an AR inducer--%AR before treatment) induced by progesterone was significantly (p < .0001) lower when spermatozoa were incubated in human tubal fluid medium cotaining antibody-positive serum (1.2%), compared to that when incubated in control medium (19.2%). Furthermore, the proportion of both spermatozoa that became capacitated and ones that had become capacitated decreased significantly (p < .0001) after 2, 4, and 6 h of incubation in medium containing antisperm antibody-positive serum, compared to those of spermatozoa incubated in control medium. In conclusion, sperm-immobilizing antibodies may be closely related to their blockage of capacitation.

Acrosome Reaction↗

Concentration of granulocyte elastase in seminal plasma is not associated with sperm motility.

Although elastase could affect sperm motility in vitro, secretory leukocytes protease inhibitor (SLPI) prevents sperm from being attacked by elastase. The authors investigated the correlations of elastase level with sperm motility and SLPI level in vivo. Semen samples (n = 116) were collected and centrifuged after semen analysis. Elastase and SLPI levels were determined by an enzyme immunosorbent assay. Samples were classified by elastase levels into low (<250 ng/mL), moderate (250-1,000 ng/mL), and high elastase groups (> or =1,000 ng/mL). Elastase levels (range, 2.8-23,974.4 ng/mL) were not associated with sperm motility. The median SLPI level in the high elastase group was 15,900 ng/mL (range, 2.860-46,900 ng/mL). However, there was no significant correlation between elastase and SLPI levels in seminal plasma. Since SLPI forms a 1:1 complex with elastase, these results suggest that seminal plasma has a sufficient amount of SLPI to protect spermatozoa from elastase.

Enzyme Inhibitors↗