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Biomedical subjects

Y Ogura

Publications and source records attributed to Y Ogura.

At least 19 recordsLinked to original sources
PubMed2004

Infrasternal mediastinoscopic surgery for anterior mediastinal masses.

BACKGROUND: Infrasternal mediastinoscopic surgery is a new alternative to the thoracoscopic approach for patients with anterior mediastinal masses. METHODS: We applied this technique to 18 thymectomies, one thymomectomy, and one cystectomy in a total of 20 patients with anterior mediastinal masses and then assessed the surgical results. RESULTS: Infrasternal mediastinoscopic surgery was accomplished in 18 of the 20 patients (90%). The pathological diagnoses included 13 Masaoka stage I thymomas, one stage II thymoma, two stage III thymomas, one thymic cyst, one pericardial cyst, one thymic granuloma, and one mature teratoma. Two patients with stage III thymoma required conversion to sternotomy, one for invasion into the innominate vein and the other for invasion into the pericardium. There was no surgically related mortality or complications in any patients. CONCLUSION: Infrasternal mediastinoscopic surgery is safe and feasible for stage I thymoma and other benign tumors in the anterior mediastinum.

Adult↗
PubMed2003

Monosegmental living donor liver transplantation.

BACKGROUND: Living donor liver transplant (LDLT) program has been started from 1990 in Japan, and is still major form of liver transplantation because of the scarcity of cadaveric donor organs. In small infants, implantation of left lateral segment grafts can be a problem because of a large-for-size graft. Until November 2002, we performed 867 transplants for 828 patients (561 children and 306 adults), and 14 cases received monosegment grafts from living donors. METHODS: Fifteen patients, median age 211 days, median weights 5.95 kg, received monosegmental LDLT. The indication for using this technique was infants with an estimated graft-to-recipient weight ratio of over 4.0%. RESULTS: Graft and patient survival is 85.7%. There were no differences in donor operation time and blood loss between monosegmentectomy and left lateral segmentectomy. Segment III grafts were indicated in 13 cases. Two vascular complications were observed (one hepatic artery thrombosis and one portal vein thrombosis). CONCLUSIONS: Monosegental living donor liver transplantation is a feasible option with satisfactory graft survival in small babies with liver failure.

Body Weight↗
PubMed2003

Release of non-glycosylated polymeric immunoglobulin receptor protein.

Using a recombinant vaccinia virus containing the T7 RNA polymerase, we have established a system for the transient expression of human polymeric immunoglobulin receptor (pIgR) in baby hamster kidney cells, a baby hamster-derived fibroblastic cell line. This transfection system resulted in the successful expression of pIgR in these cells, and Western blot analysis showed that human pIgR was expressed as two different molecular weight forms of 92 and 107 kDa. Treatment with endoglycosidase H showed that the difference between these two forms was due to the glycosylation status of the protein. In order to examine the functional role of glycosylation, we treated the transfected cells with tunicamycin, which prevents a core glycosylation step in the endoplasmic reticulum. Non-glycosylated pIgR was released into the culture medium of the transfected cells, albeit with extremely low efficiency. Taking these results together, we conclude that the glycosylation of pIgR may play a positive role in the efficient transport or release of free pIgR.

Animals↗
PubMed2003

Suppressive effects of selectin inhibitor SKK-60060 on the leucocyte infiltration during endotoxin induced uveitis.

BACKGROUND: It is well known that selectin is involved in the development of endotoxin induced uveitis (EIU), and has a major role in leucocyte infiltration. Recently, a novel selectin inhibitor (SKK-60060) that can block P and L selectins in vitro has been developed. This study was designed to investigate the anti-inflammatory effects of SKK-60060 on the inflammatory reaction during EIU in rats by studying leucocyte-endothelium interactions. METHODS: EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). SKK-60060 was administered 15 minutes before LPS injection, and its suppressive effects on inflammatory leucocyte behaviour were evaluated in vivo with acridine orange digital fluorography; the diameters of retinal arteries and veins were also measured. After these studies, aqueous humour was collected to evaluate leucocyte infiltration and protein leakage. RESULTS: After LPS injection, rolling leucocytes were observed in major retinal veins, followed by leucocyte infiltration into the vitreous cavity. Following treatment with SKK-60060, leucocyte rolling was significantly inhibited in the retinal veins (p <0.01), and subsequent leucocyte infiltration into the vitreous cavity was also significantly suppressed (p <0.01). Retinal vasodilation was also substantially suppressed in SKK-60060 treated rats (p <0.01). Similarly, leucocyte infiltration and protein leakage into the aqueous humour were reduced significantly by SKK-60060 (p <0.01). CONCLUSIONS: SKK-60060 treatment significantly inhibited the inflammatory reaction induced by LPS. Its inhibitory effects on P and L-selectin resulted in suppression of leucocyte infiltration and the subsequent inflammatory reaction caused by accumulated leucocytes. The current findings suggest that SKK-60060 may be useful in the management of uveitis.

Animals↗
PubMed2003

Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis.

BACKGROUND AND AIMS: Genetic variation in NOD2 has been associated with susceptibility to Crohn's disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls. PATIENTS AND METHODS: Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method. RESULTS: Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls. CONCLUSIONS: These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.

Adolescent↗
PubMed2002

Detection of cardiomyocyte apoptosis in forensic autopsy cases.

The purpose of the present study was to determine reliable parameters for the detection of apoptotic cells for use as a diagnostic marker during the early stage of acute myocardial infarction (AMI) in forensic autopsy cases. Myocardial tissues taken from forensic autopsy cases were examined by immunohistochemical and molecular-biological methods using the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labelling (TUNEL) and the DNA laddering methods. In cases of AMI with a time period between 2 h from onset to death and 20 h post-mortem time, the nuclei of cardiomyocytes were stained positive with the TUNEL method and DNA fragmentation of myocardial cells was detected by agarose gel electrophoresis. Similar findings were obtained in cases of carbon monoxide (CO) intoxication. However, no apoptotic cells were found in other cases such as methamphetamine (MAP) intoxication, tetrodotoxin intoxication, alcohol intoxication, asphyxia, head injury, heart injury or myocarditis. These findings suggested that it would be possible to apply TUNEL-positive cells as a diagnostic marker during the early stages of AMI.

Adult↗
PubMed2001

Expression of glia maturation factor during retinal development in the rat.

Glia maturation factor plays important roles in the development and growth of glia and neurons. We investigated the expression and localization of Glia maturation factor-beta (GMFB) and Glia maturation factor-gamma (GMFG) in the rat retina. By northern blot analysis, both GMFB and GMFG mRNAs were detected in retina as early as embryonic day (E) 18 and persisted until adult. The expression of GMFB mRNA was always much greater than that of GMFG mRNA. In situ hybridization showed that the GMFB mRNA signal was positive in the retina from E14 till adult. Immunostaining revealed that GMFB protein was present in the inner layer of retina at E14 and P1, and in Müller cells in adult. GMFG immunoreactivity was observed only in the inner limiting membrane from E14 to P1 rat retina, and was not detected in the adult retina. These results show that GMFs are synthesized and localized mainly in Müller cells in the rat retina, and suggest that they may contribute to the development and growth of glia and neurons.

Animals↗
PubMed2001

Drug targeting to choroidal neovascularization.

Subfoveal choroidal neovascularization (CNV) causes significant visual loss, especially in patients with age-related macular degeneration (AMD). Several pharmaceutical treatments that use anti-angiogenic agents have been tried to inhibit the activity of CNV experimentally and clinically. In general, however, systemically administered drugs may reach not only targeted tissues but also other tissues, resulting in unwanted side effects. Also, to maintain therapeutic levels of the drugs in targeted tissues, frequent administration for an extended period of time is required. To solve these problems, drug delivery systems targeted to the CNV are being developed. Anatomic characteristics of CNV tissues resemble those of tumor vasculature, exhibiting enhanced permeability and retention effect. Drug targeting to CNV may be feasible in the same manner as it is to tumors. In this review, we describe two approaches of drug targeting to CNV: passive targeting and active targeting.

Animals↗
PubMed2001

Biodegradable scleral plugs for vitreoretinal drug delivery.

Intraocular controlled drug release is one way to facilitate drug efficacy and decrease side effects that occur with systemic administration. Vitreoretinal drug delivery with the biodegradable scleral plug has been investigated. The scleral plug, which is made of biodegradable polymers and drugs, can be implanted at the pars plana using a simple procedure, and it gradually releases effective doses of drugs with polymer biodegradation for several months. The release profiles of the drugs were dependent on the kind of polymers used, their molecular weights, and the amount of drug in the plug. The plugs are effective for treating vitreoretinal diseases such as proliferative vitreoretinopathy. The implantation site was replaced with connective tissue. Electroretinography and histologic studies revealed little retinal toxicity. This implantable scleral plug was supposed to be advantageous for diseases such as cytomegalovirus retinitis that respond to repeated intravitreal injections and for vitreoretinal disorders that require vitrectomy.

Animals↗
PubMed2001

Flow cytometry: an improved method for the selection of highly productive gene-amplified CHO cells using flow cytometry.

In previous work, we clarified the relationship between the productivity and stability of gene-amplified cells and the location of the amplified gene. The location of the amplified gene enabled us to classify resistant cells into two types. One type of resistant cell group, in which the amplified genes were observed near the telomeric region, was named the "telomere type." The other type of cell group, in which the amplified genes were observed in other chromosomal regions, was named the "other type." The phenotypes of these two types of cells are very different. In this experiment, using a fluorescein isothiocyanate-labeled methotrexate (F-MTX) reagent with flow cytometry, we were easily able to distinguish between highly productive cells and the other types of cells. The level of fluorescence differed according to the difference in resistance to MTX. Based on this new finding, highly productive gene-amplified cells could be isolated from heterogeneous gene-amplified cell pools more easily than by the method of limiting-dilution assay. The limiting-dilution method requires several months to obtain highly productive gene-amplified cells, while our flow-cytometry-based method of selection requires only a few weeks.

Animals↗
PubMed2001

Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7.

Most mutations after DNA damage in yeast Saccharomyces cerevisiae are induced by error-prone translesion DNA synthesis employing scRev1 and DNA polymerase zeta that consists of scRev3 and scRev7 proteins. Recently, the human REV1 (hREV1) and REV3 (hREV3) genes were identified, and their products were revealed to be involved in UV-induced mutagenesis, as observed for their yeast counterparts. Human REV7 (hREV7) was also cloned, and its product was found to interact with hREV3, but the biological function of hREV7 remained unknown. We report here the analyses of precise interactions in the human REV proteins. The interaction between hREV1 and hREV7 was identified by the yeast two-hybrid library screening using a bait of hREV7, which was confirmed by in vitro and in vivo binding assays. The homodimerization of hREV7 was also detected in the two-hybrid analysis. In addition, the precise domains for interaction between hREV7 and hREV1 or hREV3 and for hREV7 homodimerization were determined. Although hREV7 interacts with both hREV1 and hREV3, a stable complex formation of the three proteins was undetectable in vitro. These findings suggest the possibility that hREV7 might play an important role in regulating the enzymatic activities of hREV1 and hREV3 for mutagenesis in response to DNA damage.

Carrier Proteins↗
PubMed2001

Apoptosis and allograft rejection in the absence of CD8+ T cells.

BACKGROUND: The requirement for cytotoxic T lymphocytes during allograft rejection is controversial. We previously demonstrated that CD8+ T cells are not necessary for allograft rejection or for the induction of apoptosis in rat small intestinal transplantation. In this study, we examined the mechanisms of apoptosis and rejection after liver transplantation in the absence of CD8+ T cells. METHODS: Either Lewis or dark agouti rat liver grafts were transplanted into Lewis recipients to create syngeneic and allogeneic combinations. CD8+ T cells were depleted in an additional allogeneic group by treatment with OX-8 mAb on day -1 and day 1 after liver transplant. RESULTS: Apoptosis and rejection were observed in both the CD8+ T cell-depleted allogeneic and allogeneic grafts by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and radiolabeled-annexin V in vivo imaging. Granzyme B and FasL were expressed in all allogeneic transplants, including those depleted of CD8+ T cells, indicating that a mononuclear cell other than a CD8+ T cell can be the source of these molecules during allograft rejection. Activation of the caspase cascade was detected in all rejecting allografts. Caspases 3, 8, and 9 were activated at similar significantly elevated levels in both allogeneic and CD8+ T cell-depleted liver grafts. CONCLUSION: These data indicate that in the absence of CD8+ T cells an alternative pathway, associated with granzyme B and FasL expression and activation of the caspase cascade, can mediate apoptosis and graft rejection.

Animals↗
PubMed2001

A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-kappaB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.

Adult↗
PubMed2001

A point mutation in nucleoside diphosphate kinase results in a deficient light response for perithecial polarity in Neurospora crassa.

In Neurospora crassa, the phosphorylation of nucleoside diphosphate kinase (NDK)-1 is rapidly enhanced after blue light irradiation. We have investigated the function of NDK-1 in the blue light signal transduction pathway. A mutant called psp (phosphorylation of small protein) shows undetectable phosphorylation of NDK-1 and is defective in light-responsive regulation of perithecial polarity. Sequencing analysis of ndk-1 cDNA by reverse transcription-polymerase chain reaction revealed that proline 72 of ndk-1 was replaced with histidine in psp. The mutation ndk-1(P72H) resulted in accumulation of normal levels of mRNA and of about 25% of NDK-1(P72H) protein compared with that of wild type as determined by Western blot analysis. The ectopic expression of cDNA and introduction of genomic DNA of wild type ndk-1 in psp (ndk-1(P72H)) suppressed the reduction in accumulation and phosphorylation of NDK-1 and the light-insensitive phenotype. These findings demonstrated that the phenotype of psp was caused by the ndk-1(P72H) mutation. Biochemical analysis using recombinant NDK-1 and NDK-1(P72H) indicated that the P72H substitution in NDK-1 was responsible for the decrease in phosphotransfer activities, 5% of autophosphorylation activity, and 2% of V(max) for protein kinase activity phosphorylating myelin basic protein, compared with those of wild type NDK-1, respectively.

Amino Acid Substitution↗
PubMed2001

Tyrosine kinase inhibition of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms.

Redundant mechanisms mediate colon cancer angiogenesis. Targeting multiple angiogenic factors simultaneously may improve survival of mice with colon cancer metastases. BALB/c mice underwent splenic injection with CT-26 colon cancer cells to generate liver metastases and received administration of either vehicle alone or a tyrosine kinase inhibitor for vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor receptors (SU6668). Mice were sacrificed when they became moribund as determined by a blinded observer. In a parallel experiment, groups of mice were sacrificed at earlier time points to better define the kinetics of the effect of SU6668 on angiogenic parameters over time. SU6668 increased median survival by 58% (P < 0.001) and led to a progressive increase in tumor cell and endothelial cell apoptosis that increased over time. In addition, pericyte vessel coverage and tumor vascularity were significantly decreased in mice treated with SU6668. Based on current knowledge of endothelial cell survival, these data suggest that SU6668 may prevent tumor endothelial cell survival directly (vascular endothelial growth factor) and indirectly (pericyte coverage) by affecting endothelial cell survival mechanisms.

Angiogenesis Inhibitors↗
PubMed2001

Suppression of lens stalk cell apoptosis by hyaluronic acid leads to faulty separation of the lens vesicle.

How the lens vesicle separates normally from the surface ectoderm has not been adequately explained. Apoptosis is an important mechanism that induces tissue development and morphogenesis by physiological cell death during normal development, and hyaluronic acid has been shown to regulate the apoptotic process in various tissues. To elucidate the normal and abnormal processes of lens vesicle separation, we investigated the distribution of apoptotic cells and hyaluronic acid in normal and abnormal lens vesicle development. The offspring from pregnant C57BL/6NJcl mice were removed by laparotomy on days 9, 10, 11, 12, 13, 14, 15, 16 or 18 of gestation. Tissue blocks of the eyes were fixed in 4% paraformaldehyde solution and embedded in paraffin wax. Serial sections of the eye were cut, and sections containing normal lens tissues and spontaneously occurring faulty separation of the lens vesicle were chosen for subsequent procedures. These sections were stained either with TUNEL method for detection of apoptosis or with biotinylated hyaluronic acid binding protein (HABP) for hyaluronic acid. Then TUNEL-positive and HABP-positive reactions in the lens tissues were examined by light microscopy. In normal eye development, the lens stalk connecting the surface ectoderm with the lens vesicle was observed from day 11 through day 12 of gestation, and the lens stalk completely disappeared on day 13 of gestation in this strain. In normally regressive lens stalk, several TUNEL-positive cells were identified, and no positive staining for HABP was seen. However, in spontaneously occurring persistent lens stalk tissues on days 14, 15, 16 and 18 of gestation, no TUNEL-positive cells were detectable, and evident HABP-positive reactions were seen. In eyes on day 12 of gestation with possibly presumed faulty separation of the lens vesicle, no TUNEL-positive cells were detectable and evident HABP-positive reactions were seen in the lens stalk areas. The results indicated that cell death by apoptosis is anatomically closely associated with, appears to be essential for normal regression of the lens stalk, and its failure to occur leads to faulty separation of the lens vesicle. In addition, excessive hyaluronic acid in the lens stalk area may be a possible cause of the lack of apoptosis, inducing its faulty separation.

Animals↗