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Biomedical subjects

Y Kawase

Publications and source records attributed to Y Kawase.

At least 19 recordsLinked to original sources
PubMed2006

Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres.

Gelatin hydrogel microspheres (GHMs) have been reported as novel non-viral vectors for gene or protein delivery (GHM therapy). However, the components of an effective catheter-based delivery strategy for GHM therapy are unknown. We evaluated the effectiveness of three catheter-based strategies for cardiac GHM therapy: (1) antegrade injection (AI) via coronary arteries; (2) retrograde injection (RI) via coronary veins; and (3) direct myocardial injection (DI) via the coronary sinus. AI distributed microspheres homogeneously throughout the target area with 73+/-11% retention. RI scattered microspheres non-homogenously with 22+/-8% retention. DI distributed microspheres in the needle-advanced area with 47+/-14% retention. However, despite high efficiency, AI did not show biological effects of inducing angiogenesis from basic fibroblast growth factor bound to GHMs. Furthermore, focal micro-infarctions, owing to micro-embolism of aggregated GHMs into small coronary arterioles, were detected in the AI group. Conversely, only RI and DI groups displayed increased coronary flow reserve. DI groups also demonstrated increased capillary density. These results suggest that RI and DI are effective for cardiac GHM therapy, while AI appears inappropriate owing to the risk of focal infarctions.

Animals↗
PubMed2005

Aerobic composting of waste activated sludge: kinetic analysis for microbiological reaction and oxygen consumption.

In order to examine the optimal design and operating parameters, kinetics for microbiological reaction and oxygen consumption in composting of waste activated sludge were quantitatively examined. A series of experiments was conducted to discuss the optimal operating parameters for aerobic composting of waste activated sludge obtained from Kawagoe City Wastewater Treatment Plant (Saitama, Japan) using 4 and 20 L laboratory scale bioreactors. Aeration rate, compositions of compost mixture and height of compost pile were investigated as main design and operating parameters. The optimal aerobic composting of waste activated sludge was found at the aeration rate of 2.0 L/min/kg (initial composting mixture dry weight). A compost pile up to 0.5 m could be operated effectively. A simple model for composting of waste activated sludge in a composting reactor was developed by assuming that a solid phase of compost mixture is well mixed and the kinetics for microbiological reaction is represented by a Monod-type equation. The model predictions could fit the experimental data for decomposition of waste activated sludge with an average deviation of 2.14%. Oxygen consumption during composting was also examined using a simplified model in which the oxygen consumption was represented by a Monod-type equation and the axial distribution of oxygen concentration in the composting pile was described by a plug-flow model. The predictions could satisfactorily simulate the experiment results for the average maximum oxygen consumption rate during aerobic composting with an average deviation of 7.4%.

Aerobiosis↗
PubMed2003

Acute renal failure due to adenovirus-associated obstructive uropathy and necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient.

Management of post-transplant complications caused by severe adenoviral infection remains a major therapeutic challenge. A 17-year-old male who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia developed complete anuria following hemorrhagic cystitis 34 days after the transplant procedure. The computed tomogram scan revealed bilateral hydronephrosis, indicating acute renal failure because of obstructive uropathy. The emergency procedure of percutaneous nephrostomy caused massive bleeding in the left kidney, which eventually required a nephrectomy. Adenovirus-positive severe necrotizing tubulointerstitial nephritis was the histopathological diagnosis. Post-transplant acute renal failure because of hydronephrosis, which could be complicated by adenovirus-induced renal parenchymal disease, is of great concern and may cause significant problems with interventional treatment.

Acute Kidney Injury↗
PubMed2001

Potent and selective ET-A antagonists. 2. Discovery and evaluation of potent and water soluble N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.

In the preceding article,(1) we outlined the discovery and structure-activity relationship of a potent and selective ET(A) receptor antagonist 1 and its related compounds. Metabolites of 1 having potent selective ET(A) receptor antagonist activity were identified. This study suggested the metabolic pathways of 1 were considerably affected by species. Consequently, structural modification of 1 intended to improve the complexity of the metabolic pathway, and water solubility was performed. The subsequent introduction of a hydroxyl group into the tert-butyl moiety of 1 led to the discovery of our new clinical candidate, 6b, which showed a higher water solubility, a uniform metabolic pathway among species, and very high affinity and selectivity for the human ET(A) receptor (K(i) for ET(A) receptor: 0.015 +/- 0.004 nM; for ET(B) receptor: 41 +/- 21 nM).

Animals↗
PubMed2001

Potent and selective ET-A antagonists. 1. Syntheses and structure-activity relationships of N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.

Modifications to the ET(A/B) mixed type compounds 1 (Ro. 46-2005) and 2 (bosentan) were performed. Introduction of a pyrimidine group into 1 resulted in a dramatic increase in affinity for the ET(A) receptor, and the subsequent optimization of substituents on the pyrimidine ring led us to the discovery of N-(6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-5-(4-methylphenyl)-4-pyrimidinyl)-4-tert-butylbenzenesulfonamide (7k), which showed an extremely high affinity for the human cloned ET(A) receptor (K(i) = 0.0042 +/- 0.0038 nM) and an ET(A/B) receptor selectivity up to 29 000 (K(i) = 130 +/- 50 nM for the human cloned ET(B) receptor). The compound was designed on the hypothesis that the hydrogen atom of the hydroxyl group in 1 and 2 played a role not as a proton donor but as an acceptor in the possible hydrogen bonding with Tyr129. Since the incorporation of a pyrimidinyl group into the hydroxyethoxy side chain of the nonselective antagonist (1) dramatically enhanced both the ET(A) receptor affinity and selectivity, and since similar results were obtained from the benzene analogues, we put forward the hypothesis that a "pyrimidine binding pocket" might exist in the ET(A) receptor.

Animals↗
PubMed2001

Cutting edge: IL-18-transgenic mice: in vivo evidence of a broad role for IL-18 in modulating immune function.

IL-18 has been shown to be a strong cofactor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8+CD44high T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4, and IFN-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4, IL-5, and IL-13 than control wild-type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.

Adjuvants, Immunologic↗
PubMed2001

Disruption of imprinted expression of U2afbp-rs/U2af1-rs1 gene in mouse parthenogenetic fetuses.

The present study shows that the U2afbp-rs gene, a paternally expressed imprinted gene, is activated and expressed in a biallelic manner from maternal alleles in parthenogenetic mouse fetuses on day 9.5 of gestation. The mean expression was detected to be 88% (31-134%) of that in control biparental fetuses, using real-time quantitative reverse transcription and polymerase chain reaction. This disrupted expression of the gene was associated with changes in the chromatin structure but not with the methylation pattern in the regulation region. The present results show that parental specific expression of imprinted genes is not always maintained in uniparental embryos. This suggests that both parental genomes are necessary to establish parental specific expression of the U2afbp-rs gene.

Animals↗
PubMed2001

Comparison of intracytoplasmic sperm injection for inbred and hybrid mice.

We compared the results of intracytoplasmic sperm injection (ICSI) that leads to full term development of hybrid (B6C3F1 and B6D2F1) and inbred (C57BL/6) mouse embryos. Although fertilization and pre-implantation development of C57BL/6 eggs were similar to those of F1 hybrid eggs, post-implantation development of the embryos from C57BL/6 females was significantly poorer than those of the eggs from hybrid females. Reciprocal crosses of C57BL/6 and B6C3F1 gametes revealed that the low rate of post-implantation development of C57BL/6 embryos was due to oocyte factor(s), rather than the sperm factor.

Animals↗
PubMed2001

Axial length and refractive error in X-linked retinoschisis.

PURPOSE: To examine the relationship between axial length and refractive error in patients with X-linked retinoschisis. DESIGN: To determine whether the hypermetropia frequently found in patients with X-linked retinoschisis is axial hypermetropia. METHODS: The axial length and refractive error were measured in 29 right eyes of 29 patients. The patients were divided into two groups: a juvenile group with ages <13 years (12 eyes) and an adult group with ages > or =13 years (17 eyes). The axial length of the right eye of 30 adult men without eye diseases whose refractive error ranged from +/- 1.0 diopter served as controls. RESULTS: In the adult patient group, the refractive error was significantly more hypermetropic and the axial length was significantly shorter than was the normal adult group (P <.001). CONCLUSION: These results strongly suggest that the hypermetropia in patients with X-linked retinoschisis is axial hypermetropia.

Adolescent↗
PubMed2001

Dynamic process of apoptosis in adult rat cardiomyocytes analyzed using 48-hour videomicroscopy and electron microscopy: beating and rate are associated with the apoptotic process.

Dynamic process of apoptosis has not been elucidated in adult rat cardiomyocytes. Soluble Fas ligand (0.1 microg/ml) in the presence of actinomycin D (0.05 microg/ml) induced apoptosis in cultured adult rat cardiomyocytes, as documented by activated caspase-3, DNA fragmentation, and apoptotic ultrastructure. In the present model, we observed 60 adult cardiomyocytes with a normal rod shape under a real-time videomicroscope continuously for 48 hours. Seventeen cells (28%) were unchanged and 7 cells (12%) showed oncosis (so-called necrosis) in which no beating was evident. In the remaining 36 cells (apoptosis, 60%), a slow beating (17 +/- 3/min) was initiated 16 +/- 1 hours later. Approximately 1 hour later, the rod cells showed long-axial shortening as bone- or club-like, or square-shaped, accompanied with faster beating rates (35 +/- 7/min). In 29 cells (type A1 and A2), marked shrinkage occurred; the cellular shape became almost completely round with a smooth surface and the beating ceased 3.0 +/- 0.4 hours later. Then, smooth budding appeared 0.6 +/- 0.2 hours later. Apoptotic bodies were found in 8 cells 10 +/- 4 hours later (type A1, 13%) but not in 21 cells (type A2, 35%). In the other 7 cells (type A3, 12%), the cell surface became rough 8 +/- 3 hours later and the beating ceased. Maximal beating rate was greatest in type A1 (72 +/- 26/min) and greater in type A2 (29 +/- 5/min) than in type A3 (10 +/- 2/min). Electron microscopy confirmed apoptotic ultrastructure even in the cardiomyocytes with bone-, club-like, or square shapes, suggesting that type A3 as well as A1 and A2 is also under apoptotic process. A caspase inhibitor, zVAD.fmk, blocked beating, apoptotic morphology, and DNA fragmentation, indicating these depended on caspase activation. In the caspase-dependent apoptotic process of cultured adult cardiomyocytes, beating and the following deformity of the cellular edges were the initial signs and the rate of beating was related with the subsequent three different processes of apoptosis.

Animals↗
PubMed2001

Expression of neural cell adhesion molecule in pancreatic cancer.

Neural cell adhesion molecule (NCAM) has been found to be a significant factor for survival in various solid tumors. In the present study, we examined the expression of NCAM in exocrine tumors of the pancreas by immunohistochemistry, using two monoclonal antibodies against NCAM and polysialic acid (MAB735). Expression of NCAM was seen mainly in the cytoplasm of the following cells: regenerating duct cells among neoplastic tissue, hyperplastic islet cells, intrapancreatic nerves and ganglia, as well as tumor cells. There was no reactivity with MAB735. We found a significant correlation between intense NCAM expression (i.e., expression in more than 50% of all tumor cell mass) and survival rates in tubular adenocarcinoma, particularly moderately differentiated tumors (p < 0.05). There was no statistically significant relation between NCAM reactivity and tumor stage or any of the clinicopathologic parameters described by the Japan Pancreas Society (p > 0.05). We conclude that the expression of NCAM in tubular adenocarcinoma of the pancreas, particularly in moderately differentiated tumors, has a significant impact on the overall patient survival.

Adult↗
PubMed2001

Apoptosis, rather than oncosis, is the predominant mode of spontaneous death of isolated adult rat cardiac myocytes in culture.

A number of isolated adult cardiomyocytes dies within a few days of culture and the mode of death has recently been suggested to be apoptosis, based on its association with the appearance of DNA fragmentation. However, morphological evidence is still lacking and precise analysis, including quantification, has not been performed. Adult rat ventricular cardiomyocytes isolated by enzymatic dissociation were incubated for 7 days in a serum-free medium (the rapid attachment model) and after various incubation periods, both attached and floating cells were counted and classified based on combined criteria of morphology and membrane permeability (dye exclusion): type 1, rod cells with intact membranes; type 2, non-rod cells with intact membranes; and type 3, non-rod cells with ruptured membranes. The number of both rod-shaped and dye-excluding cells decreased with the incubation period. After 7 days culture, the number of residual cells decreased to 12% of the initial value. Electron microscopy identified type 1 cells as viable, type 2 cells as viable or apoptotic, and type 3 as undergoing oncosis (primary necrosis) or secondary post-apoptotic necrosis. Ultrastructural morphometry revealed that oncotic cell death occurred predominantly during the early phase of culture whereas the more abundant apoptotic cell death occurred throughout the culture period. In conclusion, although both apoptotic and oncotic death occur in the natural course of adult rat cardiomyocytes in short-term culture, apoptosis is more predominant. Because of the high incidence of spontaneous cell death predominantly via apoptosis, this information is important for the interpretation of studies using this cell type in culture.

Animals↗
PubMed2001

Application of the piezo-micromanipulator for injection of embryonic stem cells into mouse blastocysts.

Microinjection of embryonic stem (ES) cells into mouse blastocysts is one of the most important techniques for production of knockout or transgenic mice. However, skillful manipulation techniques and tremendous effort are required for this method. To overcome this difficulty, we applied a piezo-micromanipulator (PMM), which has been used for intracytoplasmic sperm injection in mice and production of cloned mice, for the injection of ES cells into blastocysts. When ES cells were injected by using a conventional method, 91% of the blastocysts were manipulated successfully. Using the PMM significantly (P < 0.01) increased the success rate of ES injection to 97%. The number of embryos manipulated in an hour increased from 9.7 embryos with the conventional method to 27.0 embryos with the PMM method. The injected ES cells did not show any detrimental effects due to a pulse from the PMM. After embryo transfer of the manipulated blastocysts, 39% of the newborns were chimeric mice with the conventional method, whereas 42% of the neonates were chimeric after the PMM method. These results indicate that microinjection of the ES cells into blastocysts is more efficient by the PMM method than the conventional method.

Animals↗