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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 343 records · Page 19Linked to original sources
PubMed1997

Histological diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc epitope.

This study evaluates whether immunohistochemical staining using antibody TKH-2 is presented as a sensitive method for the histological diagnosis of amniotic fluid embolism (AFE). TKH-2 is the sensitive antibody clearly directed to sialyl Tn, NeuAc alpha 2-6GalNAc and reacts with meconium- and amniotic fluid-derived mucin-type glycoprotein. Formalin-fixed, paraffin-embedded maternal lung tissue sections were obtained from four cases of patients showing AFE, and four women uninvolved with AFE served as control. Specimens were stained using the streptavidin-biotin-immunoperoxidase method. The results of immunostaining were compared with those of hematoxylin-eosin (H&E) or a conventional Alcian blue stain. Remarkable positive TKH-2 stainings were observed easily within the pulmonary vasculature in patients with AFE syndrome. AFE can be easily missed on H&E sections. Compared with TKH-2 staining, Alcian blue staining also may be insufficient to show intravascular mucin in the maternal lung sections. TKH-2 immunostaining is the sensitive method to detect meconium- and amniotic fluid-derived mucin in the lung sections of patients with AFE syndrome.

Adult↗
PubMed1997

Antibiotic delivery system using bioactive bone cement consisting of Bis-GMA/TEGDMA resin and bioactive glass ceramics.

A novel drug delivery system containing cephalexin (CEX) as a model drug using a new bioactive bone cement consisting of 15% bisphenol-alpha-glycidyl methacrylate (Bis-GMA), 15% triethylene-glycol dimethacrylate (TEGDMA) resin and 70% apatite- and wollastonite-containing glass-ceramic (A-W GC) powder was investigated. A-W GC powder containing CEX powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin, and furthermore its compressive strength was expected to be higher than that of polymethylmethacrylate cement. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. The drug release rate increased with increasing amount of CEX in the mixture. All of the drug release profiles followed the Higuchi equation at the initial stage, but not at later stages. As hydroxyapatite was precipitated out on the cement surface, the drug release rate decreased. These results suggest that the CEX release rate from bioactive bone cement could be controlled by varying the amount of drug in the cement system.

Biomechanical Phenomena↗
PubMed1997

Effect of sodium bicarbonate amount on in vitro indomethacin release from self-setting carbonated-apatite cement.

PURPOSE: In the present study, to develop a drug delivery system with higher bioactivity in hard tissues by using the self-setting bioactive carbonate apatite cement, we have investigated the effects of sodium bicarbonate content on the in vitro drug release from a self-setting bioactive carbonate apatite cement containing indomethacin (IMC). METHODS: The cement powder systems constituted an equimolar mixture of tetracalcium phosphate (Ca4(PO4)2O) and dicalcium phosphate dihydrate (CaHPO4.2H2O), hydroxyapatite (HAP, Ca10(PO4)6(OH)2) seed crystals and sodium bicarbonate. Two types of 2% IMC loaded-cements were prepared as follows, one containing 0% HAP seed crystal and 0-10% sodium bicarbonate, and the other containing 40% HAP seed crystal and 0-10% sodium bicarbonate. The drug release profiles from 2% IMC loaded-cements were measured in simulated body fluid at pH 7.25 and 37.0 degrees C. RESULTS: The drug release profiles from the cement matrix systems with or without seed crystals were estimated using a moment analysis computer program. The mean drug release time (MDT) and the time required for 50% drug release of the cement containing 0 and 40% seed crystal decreased with an increase of sodium bicarbonate. Furthermore, after the drug release the total pore volume of the cement matrix, as measured by mercury porosimetry, increased with an increase of sodium bicarbonate. CONCLUSIONS: MDT and T50's were a function of adding the amount of sodium bicarbonate. The results of the relationship between the micropore distribution, total volume of pores after drug release and drug release supported the hypothesis that the variation in drug release from the cements resulting from the addition of sodium bicarbonate was mainly due to an increase in the diffusion of the drug in the micropores of the cement by dissolution or erosion of the cement matrix.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth but do not disturb lamin farnesylation and localization in human tumour cells.

Recently, many inhibitors of farnesyl protein transferase (FPTase) have been identified. Some of them interrupt cell growth in addition to Ras and nuclear lamin processing of Ras-transformed cells. We have tested the effect of the FPTase inhibitors manumycin, an analogue of farnesyl diphosphate, and KT7595, a gliotoxin derivative, on Ras farnesylation, DNA synthesis and the anchorage-dependent and -independent growth of human colon carcinoma (LoVo), hepatoma (Mahlavu and PLC/PRF/5) and gastric carcinoma (KATO III). Both drugs severely inhibited DNA synthesis, cellular proliferation and Ras farnesylation in LoVo and moderately reduced them in Mahlavu and PLC/PRF/5 but not in KATO III. Complete sequencing of ras genes, however, revealed that LoVo and KATO III have activated Ki-ras and activated N-ras, respectively, whereas Mahlavu and PLC/PRF/5 have no activated ras. We next checked whether the inhibition of the cellular proliferation is due to the blocking of nuclear lamin function. Neither drug disturbed lamin farnesylation and localization, as demonstrated using metabolic labelling, immunoblotting and indirect immunofluorescence. These results indicate that manumycin and KT7595 can inhibit Ras farnesylation and cell growth without disturbing the farnesylation and localization of the lamins on human tumour cell lines.

Alkyl and Aryl Transferases↗
PubMed1997

Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos.

BACKGROUND: Vertebrates have numerous lateral asymmetries in the position of their organs, but the molecular basis for the determination of left-right (L-R) asymmetries remains largely unknown. TGFbeta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination. RESULTS: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome. These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos. However, the major expression domains of the two genes are different: lefty-1 expression is predominantly confied to the left side of ventral neural tube, whereas lefty-2 is strongly expressed in the lateral plate mesoderm on the left side. In embryos homozygous for the iv and inv mutation, which cause situs inversus, the expression sites of both genes are affected, either reversed or bilaterally, indicating that lefty-1 and lefty-2 are downstream of iv and inv. Although Lefty-1 and Lefty-2 prepro-proteins are not readily processed in cultured cells, BMP2-Lefty chimeric proteins can be processed to a secreted form. We have examined the activities of Lefty-1 and Lefty-2 in Xenopus embryos. In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction. The direct neuralizing activities of Lefty-1 and Lefty-2 thus seem remarkably similar to those of BMP antagonists such as noggin and chordin, suggesting that the action of Lefty-1 and Lefty-2 may be to locally antagonize BMP (bone morphogenic protein)-mediated signals in tissues positioned on the left side of the mouse embryos. CONCLUSION: There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a L-R asymmetric fashion and are downstream of iv and inv. Lefty-1 and Lefty-2 possess direct neuralizing activity in Xenopus embryos, resembling the activities of BMP antagonists.

Amino Acid Sequence↗
PubMed1997

Mdes, a mouse homolog of the Drosophila degenerative spermatocyte gene is expressed during mouse spermatogenesis.

A new mouse gene Mdes has been identified, which has a significant sequence homology with a Drosophila gene degenerative spermatocyte (des) that is required for the initiation of meiosis in spermatogenesis. The expression pattern of the Mdes transcript during mouse spermatogenesis is similar to that of the des transcript curing Drosophila spermatogenesis. Based on these results, it is proposed that the products of Mdes and des have a phylogenetically conserved role in vertebrate and invertebrate spermatogenesis.

Amino Acid Sequence↗
PubMed1997

Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis.

Liver fibrosis/cirrhosis is characterized by hyper-accumulation of fibrous tissue components and is commonly observed in later or terminal states of chronic hepatic diseases. In ongoing work, we found that the administration of human recombinant hepatocyte growth factor (hrHGF) suppressed the onset of liver fibrosis/cirrhosis in several distinct models and accelerated the recovery from liver fibrosis/cirrhosis in rats. Repeated administration of porcine serum for 10 weeks to rats induced liver fibrosis without any accompanying hepatocellular injuries; in addition, the intravenous (i.v.) administration of hepatocyte growth factor (HGF) to these rats suppressed increases in fibrous components and hydroxyproline contents in the liver, thus preventing the onset of liver fibrosis. Repeated administration of dimethylnitrosamine (DMN) for four weeks induced liver cirrhosis, as characterized by the hyper-accumulation of fibrous components, infiltration of mononuclear leukocytes, and hepatic dysfunction. When HGF was injected daily for four weeks along with DMN-treatment, the onset of DMN-induced hepatic fibrosis/cirrhosis was suppressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver were decreased. When HGF was injected for two weeks following four weeks of DMN-treatment, HGF accelerated the recovery from liver cirrhosis and prevented death due to hepatic dysfunction. Likewise, HGF-injection suppressed the onset of liver fibrosis, when liver fibrosis had been induced by long-term treatment with carbon tetrachloride (CCl4). Thus, the administration of HGF holds great promise for treating subjects with liver fibrosis/cirrhosis as a result of chronic hepatic injury.

Alanine Transaminase↗
PubMed1997

Identification of the Syrian hamster cardiomyopathy gene.

The BIO14.6 hamster is a widely used model for autosomal recessive cardiomyopathy. These animals die prematurely from progressive myocardial necrosis and heart failure. The primary genetic defect leading to the cardiomyopathy is still unknown. Recently, a genetic linkage map localized the cardiomyopathy locus on hamster chromosome 9qa2.1-b1, excluding several candidate genes. We now demonstrate that the cardiomyopathy results from a mutation in the delta-sarcoglycan gene that maps to the disease locus. This mutation was completely coincident with the disease in backcross and F2 pedigrees. This constitutes the first animal model identified for human sarcoglycan disorders.

Amino Acid Sequence↗
PubMed1997

A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus.

PACE4 is a processing protease which processes the precursor protein to the mature protein. Currently, four PACE4 isoforms have been reported [Tsuji, A. et al. (1994) Biochem. Biophys. Res. Commun. 200, 943 950]. In this study, we have cloned cDNA encoding a novel isoform, PACE4E, by screening the human brain cerebellum cDNA library and reverse transcriptase polymerase chain reaction analysis of total RNA from human hepatoma HepG2 cells. The PACE4E cDNA encoded an amino acid sequence of 975 residues. The sequence from the amino terminus to Arg900 of PACE4E was identical to the corresponding sequence of PACE4A, but the carboxy terminal sequence (75 residues) was unique and contained a hydrophobic cluster (Leu952-Gly968). PACE4E cDNA was transiently transfected in COS-1 cells, and the expressed proteins were a 112-kDa precursor form and a 105-kDa mature form. They were secreted into the culture medium, but their secretion was retarded compared with that of PACE4A. The expression of a mutant of PACE4E truncated up to the hydrophobic cluster from the carboxy terminus resulted in a remarkable increase in secretion level, suggesting that PACE4E tends to be retained intracellularly due to interaction with the membrane through the hydrophobic cluster. On the contrary, the transient expression experiment of PACE4C showed that only 68-kDa protein (precursor form) was detected in the cell and not secreted into the medium. In addition, coexpression experiment revealed that PACE4E was able to process the precursor form of von Willebrand factor to the mature form, but PACE4C did not process it.

Amino Acid Sequence↗
PubMed1997

Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease.

PACE4 (paired basic amino acid cleaving enzyme) is a member of a family of the mammalian kexin-like proprotein convertases containing a subtilisin-like catalytic domain. Previously we reported seven isoform mRNAs of PACE4 that vary in size and 3'-coding sequence [A. Tsuji et al. (1994) Biochem. Biophys. Res. Commun. 200, 943-950; K. Mori et al. (1997) J. Biochem. 121, 941-948]. To determine the origin of these isoforms, the entire human PACE4 gene has been isolated as a set of overlapping genomic DNA fragments, and analyzed by restriction enzyme digestion and nucleotide sequence determination. The human PACE4 gene spans at least 250 kb and is distributed over 25 exons that range in size from 39 to 1,422 base pairs. Human PACE4 gene is the largest kexin-like proprotein convertase gene reported to date. The most striking feature of its genomic structure is the size of the introns and the number of exons, although the general organization of signal peptide, propeptide, and catalytic domains, which are conserved in this family, is very similar to that reported for other kexin-like protease genes. The structural analysis of PACE4 genomic DNA indicates that multiple PACE4 transcripts are produced as a consequence of alternative RNA splicing events, including exon skipping, and differences in the usage of the inner 5'-splicing donor and polyadenylation sites. A major transcriptional start site was detected 314 bp upstream from the ATG translational start site by primer extension analysis. Sequence analysis of the 5'-flanking region revealed that PACE4 gene lacks TATA and CCAAT boxes in the proximal upstream region of the start site, although potential binding sites for several transcription factors including SP1, AP1, AP2, PEA3, Ets-1, GHF (growth hormone factor)-1, CREB (cyclic AMP response element binding protein), and basic helix-loop-helix proteins, were present. An unusual sequence of six tandem repeats of a nonadecamer (GGCCTGGGGGTTCACCTGC) containing an E box is found in the 5'-flanking region. These results suggest that PACE4 is not a constitutive gene product and its expression is regulated by various transcription factors.

Alternative Splicing↗
PubMed1997

Mouse Mef2b gene: unique member of MEF2 gene family.

The myocyte enhancer factor 2 (MEF2) gene family, which belongs to the MADS [MCM1, agamous, deficiens, serum response factor (SRF)] superfamily, is thought to play an important role in differentiation of myocytes, including cardiomyocytes. To better understand the mouse Mef2 gene family, the mouse Mef2b gene, which was found to be expressed in undifferentiated embryonal cells, was characterized. The Mef2b gene was found to be more than 30 kb in length, consisting of 11 exons. Eight exons correspond to coding regions and the remaining 3 exons for the 5' part are alternatively used. Two internal exons are subject to alternative splicing, resulting in production of four subtypes of mouse MEF2B peptides. Fluorescence in situ hybridization (FISH) and inter-specific backcross analysis identified the Mef2b gene locus. Mef2b gene was expressed in heart or skeletal muscle of early mouse embryo, but not in those of adult mouse. Functionally, mouse MEF2B did not exhibit DNA binding with the MEF2 consensus element in vitro, but did cause transcriptional activation of the MEF2 element, although it was less effective than human MEF2B. Based on these results, mouse MEF2B seems to have a unique character, distinct from other MEF2 family members.

Amino Acid Sequence↗
PubMed1997

Topographic comparison of subneural apparatuses at neuromuscular junctions in normal and dystrophic (mdx) mice: a scanning electron microscope study.

The differences in the morphodifferentiation of subneural apparatuses (SNAs) at neuromuscular junctions (NMJs) in the extensor digitorum longus muscle of normal and dystrophic (mdx) mice were examined by scanning electron microscopy. In normal mice, primitive shallow cup-like synaptic troughs present at birth had developed to anastomosing grooves containing both pit-like and slit-like junctional folds (JFs) during the 2nd postnatal week. At the 35th day, the SNAs had developed to almost the adult forms, consisting of labyrinthine synaptic grooves with exclusively slit-like JFs. In the mdx mice, the SNAs showed transformation similar to those in the normal mice until the 35th postnatal day. After this period, SNAs with a number of cup-like depressions occurred and increased in number. These morphological changes seemed to be found on regenerating muscle fibers after necrosis, probably indicating the remodelling of their NMJs.

Animals↗
PubMed1997

Prosthetic replacement of the hip in dogs using bioactive bone cement.

Total hip arthroplasties were performed in dogs using bioactive bone cement consisting of silane treated CaO-MgO-SiO2-P2O5-CaF2 glass powder as the filling particles and bisphenol-a-glycidyl methacrylate based resin as the organic matrix, and the outcomes were compared with the results of polymethylmethacrylate bone cement. The mechanical properties of the bioactive bone cement were stronger than the mechanical properties of polymethylmethacrylate bone cement. The bonding strength of the bioactive bone cement to bone in dogs' femora increased with time, reaching 4.7 MPa at 6 months, whereas that of polymethylmethacrylate bone cement did not increase, remaining at 1.0 MPa. Results of histologic examination showed direct bonding between the bioactive bone cement and bone, and the bony trabeculae around the cement mantle grew with time. However, in polymethylmethacrylate bone cement, an intervening soft tissue layer was evident at the bone cement interface. Direct bonding of the bioactive bone cement at the interface through an apatite layer of 30 microm in thickness was shown through observation with the scanning electron microscopy. Using this bioactive bone cement in clinical settings may help alleviate serious problems associated with cemented total hip arthroplasty, such as aseptic loosening of the implant and mechanical failure of the bone cement.

Acetabulum↗
PubMed1997

Intestinal anaerobic bacteria hydrolyse sorivudine, producing the high blood concentration of 5-(E)-(2-bromovinyl)uracil that increases the level and toxicity of 5-fluorouracil.

Sorivudine, 1-beta-D-arabinofuranosyl-5-(E)-(2-bromovinyl)uracil, is a potent antiviral agent against varicella-zoster virus and herpes simplex virus type 1. However, sorivudine should not be used in combination with anticancer drugs such as 5-fluorouracil (5-FU) because (E)-5-(2-bromovinyl)uracil (BVU), a metabolite of sorivudine, inhibits the degradation of 5-FU, resulting in its accumulation in the blood and marked enhancement of the toxicity of 5-FU. Since phosphorolytic enzymes generate BVU from sorivudine, we investigated the distribution of the enzyme activity in rats. High activity was found in the cecal and large intestinal contents, while very low or no detectable activity in the liver, kidney, stomach, cecum, large intestine, and the stomach and small intestinal contents. These results suggest that intestinal microflora play an important role in BVU production. Therefore, we measured the phosphorylase activity in cell-free extracts from 23 aerobes, 16 anaerobes and a fungus. Bacteroides species B. vulgatus, B. thetaiotaomicron, B. fragilis, B. uniformis and B. eggerthii, dominant members of intestinal microflora, had high activity to convert sorivudine to BVU. To elucidate the contribution of intestinal microflora to BVU production in vivo, we administered sorivudine to rats treated with several antibiotics and measured the BVU concentration in the serum of rats. When sorivudine was given to rats treated with ampicillin or a mixture of bacitracin, neomycin and streptomycin, which decreased the numbers of viable aerobes and anaerobes, only a small amount of BVU was found in the serum. BVU concentration in the serum of rats treated with metronidazole to decrease the number of intestinal anaerobes was also very low. In contrast, BVU concentration in the serum of rats treated with kanamycin, which was used to decrease the number of aerobes selectively, was higher than that of non-treated rats. These results also suggest that BVU is produced by intestinal anaerobic bacteria especially Bacteroides species in vivo.

Animals↗
PubMed1997

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats.

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.

Animals↗
PubMed1997

Three cases of pyogenic sacro-iliitis, and factors in the relapse of the disease.

Pyogenic sacro-iliitis (PS) is a rare disease in childhood. Three cases of PS are reported that were difficult to diagnose. Scintigraphy and magnetic resonance imaging (MRI) were useful for diagnosis. One patient suffered from an episode of relapse. Seventeen other cases of PS were reviewed in the literature to investigate the incidence of abnormal imaging findings and various factors in disease relapse. It was found that the incidence of abnormal findings by scintigraphy was significantly higher than that by computed tomography (P = 0.0057). The duration of intravenous antibiotic administration of the relapse group (14.7 +/- 4.7 days) was significantly shorter than that of the non-relapse group (24.3 +/- 10.7 days; P = 0.0376). The statistical analysis suggested that intravenous antibiotic administration is necessary at least for 20 days to prevent a relapse of PS.

Adolescent↗
PubMed1997

Spontaneous rupture of the liver in an uncomplicated pregnancy.

Spontaneous liver rupture has been reported during pregnancy secondary to severe pregnancy-induced hypertension, eclampsia or syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP). Here we report a case diagnosed using CO2 intra-arterial digital subtraction angiography in an uncomplicated pregnancy. A 33-year-old Chinese woman at 39 weeks' gestation underwent a second caesarean delivery. Her pregnancy course had been uneventful. In the immediate postpartum period, she developed clinical signs of hepatic infarction or hematoma. After a blood transfusion and the use of vasoactive agents, her hemodynamic condition became stable. A hepatic angiography was performed before an emergent laparotomy. CO2 intra-arterial digital subtraction angiography revealed a small extravasation that was not found by the conventional method using an ionized medium. This disease should be considered when there occur pain in the upper part of the abdomen and signs of hemorrhagic shock, even in the case of an uncomplicated pregnancy.

Adult↗