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Biomedical subjects

Kotaro Suzuki

Publications and source records attributed to Kotaro Suzuki.

26 records · Page 2Linked to original sources

Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation.

Interleukin-25 (IL-25) is a recently described T helper 2 (T(H)2) cell-derived cytokine that belongs to the IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T-cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cells were stimulated by immunoglobulin E cross-linking, IL-25 mRNA was induced within 30 minutes in a calcineurin-dependent manner, and the levels of IL-25 mRNA were comparable with those of activated T(H)2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting. These results suggest that mast cells may enhance T(H)2-type immune response by producing IL-25.

Animals↗

Lineage-specific negative regulation of STAT-mediated signaling by proteolytic processing.

Accumulating evidence suggests that STAT-mediated signaling plays critical roles in cell differentiation and/or cell expansion and that in turn, STAT-mediated signaling is regulated strictly by many mechanisms. In murine mast cells, when Stat6 is activated by IL-4 and translocated to the nucleus, Stat6 is cleaved by a nucleus-associated protease (namely Stat6-protease). Similarly, the activated Stat5 is cleaved by a protease (Stat5-protease) in the nucleus of myeloid progenitors. These STAT proteases cleave the corresponding STAT proteins at the carboxyl-terminus and the resultant STAT proteins function as dominant negative molecules. Functionally, Stat6-protease protects mast cells from Stat6-dependent growth inhibition while Stat5-protease maintains the immature state of myeloid progenitors. In addition, it has been shown that the activated Stat3 is cleaved in mature neutrophils. These findings indicate that the proteolytic processing of STAT proteins by the nucleus-associated protease functions as a lineage-specific negative-regulator of STAT-mediated signaling.

Animals↗

Relation between serum 3-deoxyglucosone and development of diabetic microangiopathy.

OBJECTIVE: 3-Deoxyglucosone (3-DG), a highly reactive intermediate of the glycation reaction, has been suggested to contribute to the development of diabetes complications. To verify this hypothesis, we assessed the relation between serum 3-DG concentrations and the severity of diabetic microangiopathy in diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a high-performance liquid chromatography assay to determine the serum 3-DG concentrations of 110 diabetic patients with different degrees of severity of diabetic microangiopathy and 57 age-matched control subjects. RESULTS: The fasting serum 3-DG level in diabetic patients was significantly (P < 0.001) higher than that in control subjects (353 +/- 110 vs. 199 +/- 53 nmol/l). The 3-DG levels were significantly (P < 0.001) elevated even in the diabetic patients showing normoalbuminuria (n = 62, 322 +/- 79 nmol/l) compared with control subjects. The 3-DG levels were further elevated in the patients with microalbuminuria (n = 30, 383 +/- 146 nmol/l) and overt proteinuria (n = 18, 410 +/- 100 nmol/l) (P = 0.027 and P < 0.001 vs. normoalbuminuria group, respectively). This phenomenon was basically reproduced in a category of retinopathy. Furthermore, the diabetic patients with low nerve conduction velocity showed a tendency to display higher 3-DG levels. CONCLUSIONS: The present results show that the fasting serum 3-DG level is elevated in diabetic patients and that the patients with relatively higher 3-DG levels were prone to suffer from more severe complications, indicating a possible association of 3-DG with diabetic microangiopathy.

Adult↗

Semen cryopreservation for patients with malignant or non-malignant disease: our experience for 10 years.

PURPOSE: We report our experience in 10 years of sperm cryopreservation to reveal the present state of the cryopreservation project. MATERIALS AND METHODS: 42 germ cell tumor, 110 non-germ cell tumor and 2 non-malignant disease patients who visited our clinic for semen cryopreservation were retrospectively analyzed. RESULTS: Only 7 (20%) out of 35 unilateral testicular tumor patients who had received no chemotherapy met the WHO criteria for sperm concentration and motility. However, there were no patients with azoospermia. Three testicular tumor patients with previous chemotherapy and 4 retroperitoneal germ cell tumor patients had poor sperm concentrations and motilities. Twenty (52%) out of 38 non-germ cell tumor patients without previous chemotherapy met the WHO criteria. In contrast, only 9 patients (13%) met the WHO criteria among 72 patients with previous chemotherapy. Twenty-nine patients (40%) with chemotherapy were azoospermia. Totally, 74 (96%) of 77 tumor patients' semen without chemotherapy and 34 (45%) of 75 with chemotherapy were cryopreserved. Sperm from a patient with testicular torsion were cryopreserved. CONCLUSION: Most cancer patients without previous chemotherapy, regardless of underlying disease, had abundant motile sperm. However, half of the patients who had received chemotherapy did not have suitable sperm for freezing. It is important to inform young cancer patients of the cryopreservation project immediately after the diagnosis is made.

Adolescent↗

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells.

Interleukin 21 (IL-21) has recently been identified as a multifunctional cytokine that induces the proliferation of T cells and B cells and differentiation of natural killer cells. To determine whether IL-21 regulates IL-4-mediated immune responses, we examined the effect of IL-21 on antigen-specific IgE production in mice. We also examined the effect of IL-21 on IL-4-induced IgE production from B cells and antigen-induced T-helper 2 (T(h)2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production on immunization. IL-21 did not affect T(h)2 cell differentiation or IL-4 production from CD4(+) T cells but directly inhibited IL-4-induced IgE production from B cells at single-cell levels. Moreover, IL-21 inhibited IL-4-induced germ line C(epsilon) transcription in B cells without the inhibition of signal transducer and activator of transcription 6 (Stat6) activation. Taken together, these results indicate that IL-21 down-regulates IgE production from IL-4-stimulated B cells through the inhibition of germ line C(epsilon) transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.

Animals↗

Proteolytic processing of Stat6 signaling in mast cells as a negative regulatory mechanism.

Accumulating evidence has shown the importance of Stat6-mediated signaling in allergic diseases. In this study, we show a novel regulatory mechanism of Stat6-mediated signaling in mast cells. When Stat6 is activated by interleukin (IL)-4 and translocated to the nucleus, Stat6 is cleaved by a nucleus-associated protease in mast cells. The cleaved 65-kD Stat6 lacks the COOH-terminal transactivation domain and functions as a dominant-negative molecule to Stat6-mediated transcription. The retrovirus-mediated expression of cleavage-resistant Stat6 mutants prolongs the nuclear accumulation of Stat6 upon IL-4 stimulation and enhances IL-4-induced gene expression and growth inhibition in mast cells. These results indicate that the proteolytic processing of Stat6 functions as a lineage-specific negative regulator of Stat6-dependent signaling in mast cells, and thus suggest that it may account for the limited role of Stat6 in IL-4 signaling in mast cells.

Animals↗

Successful pregnancy with intrauterine insemination using vasal sperm retrieved by electric stimulation.

OBJECTIVE: To determine the feasibility of electric stimulation applied to the epididymis or vas deferens to retrieve vasal sperm. DESIGN: Two case reports. SETTING: Assisted reproduction practice in a hospital. PATIENT(S): Two patients with retrograde ejaculation and severe asthenozoospermia. INTERVENTION(S): Pulse electric simulation was applied to the epididymis or vas deferens to retrieve sperm via a tube cannulated into the vas deferens. After diluting with culture medium, retrieved sperm were used for IUI. MAIN OUTCOME MEASURE(S): The volume of retrieved vasal fluid and motility parameters of the sperm, the achievement of pregnancy, and outcome of pregnancy. RESULT(S): In patient 1, the volumes of vasal fluids and numbers of sperm were 10-40 microL and 31.4-75.9 x 10(6), respectively, during two cycles. Sperm motility was 88.4%--93.2%. His wife became pregnant and was delivered of a healthy infant by IUI during the second cycle. In patient 2, 0.6 x 10(6) sperm with a motility of 70% were retrieved and used for IUI. However, his wife did not become pregnant. CONCLUSION(S): Electric vasal sperm retrieval is a feasible method for collecting sperm from the vas deferens in selected patients with male factor infertility.

Adult↗

[The effect of high concentration of sodium and potassium ion on motility of human sperm preserved in electrolyte-free solution].

PURPOSE: To assess the effect of high concentration of sodium and potassium ion on the motilities of human sperm following the preservation in electrolyte-free solution. PATIENT: Semen samples were obtained from patients attending our infertility clinic. The motilities of their sperm were more than 40%. METHOD: Ejaculated sperm were washed by using the electrolyte-free Percoll gradient and then preserved in electrolyte-free solution at 4 degrees C for a week. The preserved sperm was incubated and analyzed after the addition of electrolyte solutions under acid or alkaline condition. The sperm were continuously preserved for a day at room temperature and analyzed. RESULT: The sperm was by the addition of 35-135 mM Na+ or 5-135 mM K+ in acid solutions. Under the alkaline conditions, sperm were reactivated without Na+ or K+. However, the addition of 135 mM Na+ or K+ significantly decreased in sperm motilities. The some sperm in the solution containing low concentration of Na+ or K+ ions maintained their motilities for a day at room temperature. However, all sperm lost their motilities in the 135 mM Na+ or K+ solutions. CONCLUSION: The high concentration of Na+ or K+ ions had detrimental effects on motilities of sperm following the preservation in electrolyte-free solution.

Humans↗