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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 541 records · Page 30Linked to original sources
PubMed1994

A novel member, PC7, of the mammalian kexin-like protease family: homology to PACE4A, its brain-specific expression and identification of isoforms.

By polymerase chain reaction (PCR) with primers corresponding to the sequences of catalytic domain conserved among the mammalian kexin-like protease family, a cDNA fragment encoding a novel member of the family was obtained from rat pituitary. A cDNA for the novel protease was obtained from three overlapping clones isolated from a rat pituitary cDNA library using the PCR product as a screening probe. The protein, designated as PC7, encoded by this cDNA contained a putative activation site with the sequence RXKR, subtilisin-like catalytic domain and a homo B region which are typical of mammalian kexin-like proteases, and short cysteine-rich region at the carboxyl-terminal end. It exhibited surprising sequence similarity to PACE4A. The PC7 transcript was expressed at high levels in the brain. However it was undetectable in the liver, kidney, heart, and spleen. The presence of PC7 isoforms (PC7A and PC7B) was also shown.

Amino Acid Sequence↗
PubMed1994

Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase.

The effects of wortmannin (WT), an inhibitor of phosphatidylinositol (PI) 3-kinase, on differentiation of PC12 cells were analyzed. WT inhibited PI 3-kinase activity of PC12 cells at a concentration of 10(-7) M in vivo and in vitro. Transient inhibition of PI 3-kinase activity at the time of nerve growth factor stimulation had no effect on activation of the ras protein or neurite formation by the cells. However, continuous inhibition of PI 3-kinase blocked differentiation at the step just before neurite formation. When WT was applied to cells growing neurites, elongation of the neurites was stopped at that step. These results suggest that PI 3-kinase may be involved in neurite elongation.

Androstadienes↗
PubMed1994

The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.

We identified the rat homolog to the human Wilson disease (WD) gene as the gene responsible for hepatitis (hts) in the Long Evans Cinnamon (LEC) rat. A genetic study using fifty-three backcross progenies showed that the rat WD gene detected by Southern blotting using the human WD gene as a probe was tightly linked to the hts phenotype of the LEC rat with no recombination. LEC is a transcriptionally deficient mutant because no transcript of the rat WD gene could be found in the LEC rat by Northern blotting. This rat WD gene was mapped to 16q12.23-12.3 by fluorescence in situ hybridization and mouse x rat somatic cell hybrid analysis.

Animals↗
PubMed1994

Molecular cloning of a novel receptor tyrosine kinase gene, STK, derived from enriched hematopoietic stem cells.

To identify the novel receptor tyrosine kinases (RTKs) critical to the proliferation of hematopoietic stem cells, we performed polymerase chain reaction-based cloning from highly purified murine hematopoietic stem cells. Lineage marker-negative, c-KIT-positive, and Ly6A/E- or Sca-1-positive (Lin-c-KIT+Sca-1+) cells were sorted by a fluorescence-activated cell sorter. Two sets of degenerate oligonucleotide primers were directed to the conserved sequences of the catalytic domain, and were used to amplify cDNAs that encode protein tyrosine kinases (PTKs). One hundred cDNA clones were sequenced and 8 RTKs were identified, as well as 12 non-RTKs and 2 serine/threonine kinases. Sixteen cDNAs were identical to the known kinase genes (PKC beta, JAK-1, JAK-2, TYK-2, HCK, FGR, FYN, BLK, c-FES, FER, c-ABL, c-KIT, FLK-1, FLK-2, IGF1R, and ECK). Six novel cDNA sequences (stk series) were identified. However, three of them turned out to be BPK, RYK, and TEK. The remaining three showed high homology to S6 kinase II, JAK-2, and v-SEA/c-MET, respectively. Characterization of full-length cDNA sequence of the v-SEA/cMET-related gene showed that this was a novel RTK gene and we named this gene STK (stem cell-derived tyrosine kinase). We identified two distinct forms of STK cDNA; the short one encoded a putative truncated protein that lacked most of the extracellular domain. STK was expressed at various stages of hematopoietic cells, including stem cells, but we could not detect any apparent expression in other adult tissues. The expression of the truncated form of mRNA was more predominant than that of the complete form. STK was assigned by fluorescent in situ hybridization to the R-positive F1 band of chromosome 9, the same region to which hepatic growth factor-like protein has been assigned. Characterization of these PTKs, including STK, will be helpful to elucidate the molecular mechanism of the growth regulation of hematopoietic stem cells.

Amino Acid Sequence↗
PubMed1994

Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.

PACE4 has been identified as a second human subtilisin-like protease by Keifer et al. [DNA and Cell Biology (1991) 10, 757-769]. In this study, we isolated two novel cDNAs coding for PACE4 isoforms (PACE4C and PACE4D) from a human placenta cDNA library. The deduced PACE4C protein sequence (652 amino acids) lacks the cysteine-rich region located at the carboxy terminus of PACE4. The DNA sequence of the 3'-untranslated region (1 kb) of PACE4C is not homologous to the PACE4 sequence. The protein (497 amino acids) encoded by PACE4D cDNA lacks a signal peptide, a propeptide and the cysteine-rich region. These isoform cDNAs were also isolated from rat pituitary cDNA library.

Amino Acid Sequence↗
PubMed1994

Subtypes of endothelin ETA and ETB receptors mediating venous smooth muscle contraction.

In rabbit saphenous vein, endothelin (ET)-1 and ET-3 induced sustained contractions whereas the selective agonists of the ETB receptor, sarafotoxin S6c (STXc) and IRL 1620, induced transient contractions. In the presence of an ETA antagonist, BQ-123, contractions induced by ET-1, STXc and IRL 1620 did not change whereas ET-3 induced only transient contraction. The ETB antagonists, RES-701-1 and IRL 1038, only weakly antagonized the effects of these stimulants. In the muscle pretreated with STXc, neither STXc nor IRL 1620 was effective whereas ET-3 induced sustained contraction at higher concentrations than ET-1. In the muscle pretreated with STXc, BQ-123 weakly antagonized the effect of ET-1 and abolished the effect of ET-3. These results suggest that there are two types of ET receptors; less tachyphylactic and isopeptide-selective ETA receptor, and tachyphylactic and isopeptide-nonselective ETB receptor. The ETA receptors may be further classified as a BQ-123-sensitive ETA1 and a BQ-123-insensitive ETA2 subtypes. The ETB receptors may also be subclassified as the ETB1 and ETB2 subtypes based on the sensitivity to the ETB antagonists.

Animals↗
PubMed1994

Identification of targeting proteinase for rat alpha 1-macroglobulin in vivo. Mast-cell tryptase is a major component of the alpha 1-macroglobulin-proteinase complex endocytosed into rat liver lysosomes.

The alpha 1-macroglobulin-proteinase complex endocytosed into rat liver lysosomes was purified by a series of column chromatographic steps on concanavalin A-Sepharose, Sephacryl S-300, DEAE-cellulose and TSK gel DEAE-5PW columns. The complex contained no detectable alpha 2-macroglobulin. Studies on the substrate specificity indicated that the complex had tryptase-like activities towards various synthetic substrates, but no elastase, chymotrypsin, cathepsin-B and cathepsin-L activities. The proteinase activity was completely inhibited by di-isopropyl fluorophosphate, leupeptin and antipain, indicating that the proteinase bound to alpha 1-macroglobulin is a serine proteinase. Two protein bands (62 and 59 kDa) of the complex were labelled with [3H]diisopropyl fluorophosphate and both bands cross-reacted with anti-(mast-cell tryptase)antibody. These results suggest that mast-cell tryptase is a major targeting proteinase for alpha 1-macroglobulin in vivo. The main alpha-macroglobulin-proteinase complex in the adjuvant-treated rats was also the alpha 1-macroglobulin-tryptase complex, even though the plasma level of alpha 2-macroglobulin was elevated.

Amino Acid Sequence↗
PubMed1994

Chromosome mapping of the human (RECA) and mouse (Reca) homologs of the yeast RAD51 and Escherichia coli recA genes to human (15q15.1) and mouse (2F1) chromosomes by direct R-banding fluorescence in situ hybridization.

We mapped the human (RECA) and mouse (Reca) homologs of the yeast RAD51 and Escherichia coli recA genes to human and mouse chromosomes by direct R-banding fluorescence in situ hybridization. This gene was assigned to human chromosome 15q15.1 and to mouse chromosome 2F1, respectively. This is the first report on the precise localization of this gene to human and mouse chromosomes. This gene was mapped to a region on human chromosome 15q15.1 and mouse 2F1 that is believed to be a conserved syntenic group.

Animals↗
PubMed1994

Cardiovascular and renal functional effects of an antagonist of the guanylyl cyclase-linked ANF receptor.

A selective antagonist for the cGMP-linked ANF receptor was used to assess inhibition of cardiovascular and renal actions of atrial natriuretic factor (ANF). Two groups of anesthetized rats were injected with antagonist or vehicle, respectively, prior to an infusion of ANF. A third group received neither antagonist injection nor ANF infusion and served as a time control. Compared to ANF infusion alone, prior antagonist administration was associated with significant reduction of both the hypotension and hemoconcentration following peptide infusion, although significant residual effects were still present. Glomerular filtration rates during ANF infusion were significantly lower in the antagonist group. The increases in urinary salt and water excretion were also partially blocked by the antagonist. Microcatheterization studies showed significant partial reversal of ANF-induced inhibition of sodium chloride and water reabsorption in the medullary collecting duct. We conclude that the antagonist is an effective specific blocker of the cardiovascular, renal hemodynamic, and tubular effects of ANF, providing a useful new tool to elucidate the regulatory roles of this peptide hormone system.

Animals↗
PubMed1994

Interleukin-6 in transcatheter arterial embolization for patients with hepatocellular carcinoma. Effects of serine protease inhibitor.

BACKGROUND: Modulation of serum levels of circulating cytokines and inflammatory responses with a serine protease inhibitor was studied in 34 patients with hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS: The 34 patients were randomly divided into two groups: 17 patients received 500 mg gabexate mesilate, a serine protease inhibitor, intravenously twice a day for 5 days after TAE, and the remaining 17 patients did not receive the drug. RESULTS: In the patients not given the drug, circulating interleukin-6 (IL-6) markedly increased 1 day after TAE, reached a peak (approximately 8 times the pretreatment value) after 4 days, and remained elevated 7 days after TAE. In comparison, in the patients given the drug, circulating IL-6 was at a significantly lower level at 4 and 7 days after TAE (P < 0.05, respectively). Both groups did not show significant change in circulating interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) during the week after TAE. The drug also showed a tendency to keep patient temperature below 38 degrees C, and the elevation of serum C-reactive protein (CRP) concentration to less than 1 mg/dl after TAE (P < 0.05, respectively). CONCLUSIONS: The serum level of circulating IL-6 can be modulated by serine protease inhibitor, and this may contribute to suppressing inflammatory responses, such as fever and acute-phase protein synthesis, in the liver after TAE.

Aged↗
PubMed1994

Scanning electron microscopic observations of the vascular structure of vertebral end-plates in rabbits.

We used scanning electron microscopy to examine the microcirculation in the vertebral end-plates of rabbits. The arteriola arborizes and swells at the end-plate and then coils to make a microvessel loop. This loop is the structure we refer to as a vascular bud. We suggest that these loop structures of the capillaries play a major role in the nutrition of the intervertebral discs.

Animals↗
PubMed1994

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 3. Physicochemical properties and drug-release rate of bovine insulin and bovine albumin.

A novel drug-deliver device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using bovine insulin and bovine albumin as model polypeptide drugs. Equimolar mixtures of the calcium phosphate powders containing bovine insulin and bovine albumin were transformed into a hydroxyapatite cement after being mixed with a dilute phosphoric acid solution. X-ray diffraction and FT-IR spectra results suggested that the raw materials transformed into lower crystallinity of hydroxyapatite as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for more than 3 weeks. Release from the drug-loaded cements followed the Higuchi model equation.

Bone Cements↗
PubMed1994

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 4. Effects of the mixing solution volume on the drug-release rate of heterogeneous aspirin-loaded cement.

The effect of the mixing solution volume was investigated on the in vitro drug-release rate of a novel drug-delivery device based on a self-setting bioactive calcium phosphate cement containing aspirin as a model drug. Equimolar mixtures of metastable calcium phosphate powders containing various proportions (3-40 w/w %) of seed hydroxyapatite crystals transformed into hydroxyapatite after being mixed with dilute phosphoric acid. The drug release from cement pellets in vitro into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C by the rotating disk method continued for more than 1 week. The drug-release rate from the cement increased with increasing volumes of mixing solution. The relationship between the liquid/powder ratio and the porosity of the cement was a straight line, indicating that the cement porosity depended on the amount of the mixing solution, but was independent of the amount of seed crystals. Drug release from the cement followed the modified Fick's law, with the rate increasing with the amount of mixing solution, since the porosity depended on the amount. The tortuosity of the cements was estimated from the modified Fick's equation, and the relationships between the drug release rate and the tortuosity of the pore in the drug-loaded cement in the plots were nonlinear. The results suggested that the drug-release rates from the cement were controlled by the drug diffusion in the pores.

Aspirin↗
PubMed1994

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 2. Physicochemical properties and drug release rate of the cement-containing indomethacin.

A novel drug delivery device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro with indomethacin as a model drug. Equimolar mixtures of the calcium phosphate powders containing 2 and 5% of indomethacin were transformed into a hydroxyapatite after being mixed with a dilute phosphoric acid solution. X-ray diffraction and differential scanning calorimetry results suggested that indomethacin transformed into an amorphous form in the pores of the cement matrix as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for > 3 weeks. Release from 2 and 5% drug-loaded cements followed the Higuchi model equation. The drug release profiles of 5% drug-loaded cements with different thicknesses (0.5, 1.0, and 1.5 g) overlapped up to 90% drug release, indicating that the drug concentration gradient in the pore was independent of the thickness of the cement as expected from the model equation.

Adsorption↗
PubMed1994

Effect of cogrinding time on the release of pentoxifylline from waxy matrix tablets.

The release of pentoxifylline from matrix tablets containing palmitic or behenic acids, as waxes, and prepared via cogrinding was investigated. X-ray powder diffraction analysis of the ground drug-wax indicated that particle size could be reduced by grinding without polymorphic transformation. After the coground mixed powder was compressed at 1000 kg/cm2, the drug-release rate from the tablet was evaluated in pH 6.8 buffer at 37 degrees C. The drug-release profiles could be fitted to the Cobby model. The release rate decreased with an increased grinding time and increased significantly with an increased proportion of the drug. The drug-release rate constant from the matrix was calculated using the Cobby equation and the drug-release profiles. Scanning electron microphotographs of the coground product after dissolution tests suggested that mechanochemical energy had been used to cover the drug particles.

Chemistry, Pharmaceutical↗
PubMed1994

A novel skeletal drug delivery system using a self-setting calcium phosphate cement. 5. Drug release behavior from a heterogeneous drug-loaded cement containing an anticancer drug.

A novel drug delivery device based on a self-setting bioactive calcium phosphate cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using the anticancer agent 6-mercaptopurine (6-MP) as a model compound. X-ray diffraction results suggest that equimolar mixtures of the calcium phosphate salts were transformed into hydroxyapatite after being mixed with a dilute phosphoric acid solution, even in the presence of various amounts of 6-MP powder. The inclusion of 6-MP in the reaction mixture resulted in the formation of a homogeneous drug-containing cement. Alternatively, the drug was loaded after cement formation to produce a heterogeneous drug-containing pellet. In vitro drug release from both the homogeneous and heterogeneous drug-loaded cement pellets into simulated body fluid (pH 7.25, 37.0 degrees C) was measured using the rotating-disk method. Release from the homogeneous 5% drug-loaded cements did not obey the Higuchi equation. The release rate from the heterogeneous drug-loaded cements of different thicknesses (1, 2, and 3 mm) was a function of thickness, indicating that release kinetics could be controlled by the design of the cement formulation.

Antineoplastic Agents↗