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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 199 records · Page 11Linked to original sources
PubMed2000

Growth inhibitory effects of ATP and its derivatives on human fibroblasts immortalized with 60Co-gamma rays.

In our previous study (Katayama B et al, Int J Mol Med 2: 603-606, 1998), cell growth inhibition caused by ATP added to cultures was found to be greater in immortalized human fibroblasts than in the normal human fibroblasts. Since it has been reported that ATP affects cells via P2-purinergic receptors, growth inhibitory effects of ATP and its derivatives on immortalized human fibroblasts were investigated in the present study in order to learn what type of receptors are involved in ATP cytotoxicity. The ATP derivatives used in this study were: ATP, ADP, beta, gamma-methyleneadenosine 5'-triphosphate (MeATP), 2' & 3'-o-(4-benzoylbenzoyl) adenosine, triethylammonium salt (BzATP), adenosine 5'-o-(3-thiotriphosphate) (ATPgammaS), 2-methylthioadenosine 5'-triphosphate (2-MeSATP) and UTP. The extent of cytotoxicity induced by these drugs was found to be in the order of: ATP=ADP>ATPgammaS>MeATP=BzATP. On the other hand, neither 2-MeSATP nor UTP showed any cytotoxicity. These findings indicate that ATP may exert the cell growth inhibition by certain kinds of signal transduction via P2x or P2y purinergic receptors which affect intrinsic channels/pores of cell membrane and/or G protein activation. As a result, intracellular elevation in the concentrations of ions such as calcium and potassium, membrane depolarization, loss of endogenous ions/metabolites, and activation of inositol phospholipid-specific phospholipase C may occur. Actually, a dihydropyridine calcium channel blocker, nifedipine, and an ATP-sensitive K+-channel blocker, glybenclamide, reduced the growth inhibitory effects of ATP on the cells to some extent. The growth inhibition caused by ATP was not due to apoptosis or induction of a cyclin/CDK kinase inhibitor, P21.

Adenosine Triphosphate↗
PubMed2000

Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats.

Portal vein branch embolization is often performed before hepatectomy to prevent postoperative liver failure. It is, however, still not clear how the embolized lobe shrinks and the non-embolized lobe proliferates in counterbalance. We investigated the expression of positive and negative regulators of hepatocyte growth to clarify the mechanisms of liver growth and atrophy in a rat portal vein ligation (PVL) model compared with partial hepatectomy (PH). A significant increase in DNA synthesis within the non-ligated lobe reached a peak at 36 h, a delay of 12 h as compared with PH, while no increase occurred in the ligated lobe. Expression of hepatocyte growth factor mRNA remarkably increased in the non-ligated growing lobe between 6 and 24 h, but was only slightly elevated in the ligated shrinking lobe. Contrarily, negative regulators of hepatocyte proliferation, such as TGF-beta1 and IL-1beta, were strongly expressed in the ligated shrinking lobe. Thus, the changes of portal venous flow and/or pressure caused by PVL may contribute to induction of different kinds of growth factors between the ischemic and non-ischemic lobes; these factors possibly regulate liver regeneration and atrophy after PVL.

Animals↗
PubMed2000

[Simple evaluation of CT findings in the paranasal sinuses for chronic sinusitis].

The CT scores and scoring for improvement based on them, which we proposed previously, is a simple and highly reproducible method of evaluation of sinus units before and after an operation for chronic sinusitis. We compared this evaluation method with the results of quantitative assay and showed its advantages and disadvantages. The subjects were 258 sinuses in patients who underwent endonasal sinus surgery (ESS) in the department of otolaryngology, Kyoto Prefectural University of Medicine Hospital from April 1996 to April 1997. The subjects were evaluated according to the following 4 grades negligible shadow in the paranasal sinus CT scored 0, less than 50% shadow scored 1, more than 50% of shadow scored 2, and mostly filled with shadow scored 3. Furthermore, the preoperative and postoperative CT scores were compared and the rate of improvement was rated in the following 3 grades: score 0 for unchanged or aggravated subjects, score 1 for subjects showing improved CT score by 1 grade, and score 2 for those showing improved CT score by 2 grades or a postoperative CT score of 0. Quantitative image analysis was input into a personal computer and the ratio occupied by the shadow was calculated, as the shadow ratio. While some discrepancies were seen in parts in the comparison of the quantitative image analysis and CT scores as the former captures minute shadows, a positive correlation was obtained overall. Attention is needed to accurately evaluate small paranasal sinuses such as the frontal sinus, and small amounts of shadow, which are areas where errors may occur. A satisfactory correlation was obtained between the score for the improvement rate and the difference in the shadow ratios before and after surgery. The CT scores and the scores for the improvement rate showed no difference from the results of other evaluation methods reported in the past, and evaluation of similar precision was possible. It was thought that this simple evaluation method of CT findings in the paranasal sinuses, which we examined in the present study, was quite useful as a simple stage-classification method that could be utilized in everyday practice considering its facility, reproducibility and satisfactory precision.

Adult↗
PubMed2000

[A case of saccular aneurysm of the coronary artery post PTCA].

We experienced a 48-year-old man who was diagnosed as having a saccular aneurym of the coronary artery by CAG after an otherwise uneventful percutaneous transluminal coronary angioplasty (PTCA). At the time of operation, the aneurysm, measured 15 mm, and arose from the 3rd segment of the right coronary artery. Aneurysmal formation after successful PTCA is not rare and is related to the overinflating balloon. It is necessary to evaluate the coronary artery after PTCA by IVUS. There were no symptoms after the operation and he was discharged at 21th postoperative day.

Angioplasty, Balloon, Coronary↗
PubMed2000

[Hepatectomy (parenchyma-preserving) for hilar cholangiocarcinoma].

The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy as surgical treatment for hilar cholangiocarcinoma. Ninety-three resected patients with hilar cholangiocarcinoma were included in this study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66); the parenchyma-preserving hepatectomy (PPH) group (n = 14); and the local resection (LR) group(n = 13). The EXH group underwent hepatectomy more extensive than hemihepatectomy, the PPH group underwent hepatectomy less extensive than hemihepatectomy; and the LR group underwent extrahepatic bile duct resection without hepatic resection. Surgical curability of the PPH and EXH groups was better than that of the LR group. Surgical morbidity was higher in the EXH group(48%) than in the LR group (8%) and the PPH group(14%) (p < 0.01 and p < 0.05, respectively). The survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR (29% vs 8% at 5 years, respectively, p < 0.05). However, no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analysis showed that significant prognostic factors for survival were resected margins, lymph node status, and vascular resection. In conclusion, PPH may be beneficial in highly selected patients based on cancer extent and high-risk patients with liver dysfunction and advanced age.

Analysis of Variance↗
PubMed2000

Substituted 3-phenylsulfonylquinazoline-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.

A series of 3-phenylsulfonylquinazoline-2,4-dione derivatives have been synthesized and evaluated for their ability to inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The phenyl moiety of quinazoline participates in a hydrophobic interaction where an optimum size is required. In this moiety, 7-chloroquinazoline is the best moiety for inhibiting chymase, chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrophobic electron-withdrawing groups at the 4-position potentiated the activity. Anthranil moiety also enhanced the activity. Pyridylmethyl and N-pyridylacetamide at the 1-position gave an IC50 in the order of 10(-8)M. Molecular modeling studies on the interaction of 7-chloro-3-(4-chlorophenylsulfonyl) quinazoline-2,4(1H, 3H)-dione (4) with the active site of human heart chymase suggested that the phenyl moiety of quinazoline interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, the moiety at the 1-position locates in the S2-S3 subsites and the 4-carbonyl and 3-sulfonyl group interact with the oxyanion hole and the His57 side-chain of chymase, respectively.

Chymases↗
PubMed2000

[Renin gene].

Explore the source record for details and available documents.

Animals↗
PubMed2000

Effect of operator variability on dentin bond strength of two-step bonding systems.

PURPOSE: To examine the influence of operator variability on adhesion to dentin of recently developed two-step bonding systems. MATERIALS AND METHODS: A self-etching primer system, Fluoro Bond/Lite-Fil II A (FB) and a one-bottle adhesive system, Single Bond/Z100 (SB) were employed. Three groups, each consisting of 15 operators, were selected from the dentists at the university (Group 1), undergraduate students (Group 2), and general practitioners (Group 3). Labial surfaces of extracted bovine teeth were ground on wet 600-grit SiC paper and then washed and dried with oil-free compressed air. These surfaces were treated according to each adhesive system's instructions and the restorative resins were condensed into a Teflon mold (2 mm height, 4 mm internal diameter) and then light-cured. The finished specimens were stored in 37 degrees C distilled water for 1 hr. These specimens were tested in a shear mode at a cross-head speed of 1.0 mm/min. The mean and standard deviation were subjected to two-way ANOVA (P < 0.05). RESULTS: Significant differences in bond strength of the two adhesives were found within each operator group. A wider variation in bond strength was seen for SB compared to FB for the three different groups. Mean bond strengths for the faculty group were statistically greater than those of the other two groups, which did not differ significantly. Even though the specimen preparation was done under in vitro conditions, the large coefficients of variation indicate it may be difficult to create suitable surface conditions for optimal bonding.

Adhesiveness↗
PubMed1999

Physicochemical Properties of 2-Vinylpyridine Telomers Possessing Multihydrocarbon Chains in Aqueous Solution and at the Silica/Aqueous Solution Interface.

Physicochemical properties of multialkylated surfactants of partially quaternized 2-vinylpyridine telomers having multihydrocarbon side chains (nRm-2VPQ: n, number of chains; m, alkyl chain length) in aqueous solutions were investigated. The critical micelle concentration (cmc) and surface tension at the cmc were 13 µmol dm(-3) and 52 mNm(-1) for 2.1R(8)-2VPQ, 7.1 µmol dm(-3) and 37 mNm(-1) for 2.5R(12)-2VPQ, and 4.7 µmol dm(-3) and 40.0 mNm(-1) for 3.4R(12)-2VPQ, respectively. The aggregation numbers at the cmc determined by the light scattering method were 4 +/- 1 for 2.1R(8)-2VPQ, 45 +/- 10 for 2.5R(12)-2VPQ, and 11 +/- 1 for 3.4R(12)-2VPQ. Thus, the number of chains and the alkyl chain length of the telomers affected the micellar properties in aqueous solutions. At the interface of the silica/aqueous solution, the adsorbed amounts of the telomers increased sharply at their low concentrations and reached a plateau by forming a monolayer and a subsequent bilayer. Silica suspensions also showed a dispersion-flocculation-redispersion sequence with the telomer concentration, where the maximum sedimentation rate was influenced by the number of chains and the alkyl chain length of the telomers. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Manumycin A, inhibitor of ras farnesyltransferase, inhibits proliferation and migration of rat vascular smooth muscle cells.

Restenosis after angioplasty is thought to be caused by proliferation and migration of vascular smooth muscle cells (VSMCs), and it is a most serious problem in medical treatment. A low dose (50 ng/ml) of manumycin A, an inhibitor of p21(ras) (ras) farnesylation, significantly inhibited proliferation of rat VSMCs stimulated by the platelet-derived growth factor (PDGF). The mitoinhibitory effect of manumycin A was dose- and time-dependent but was independent of cell density. Western blot analysis showed that manumycin A reduced the amount of functional ras localized at the cytoplasmic membrane and inhibited the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK). Manumycin A also inhibited VSMC migration and disorganized alpha actin fibers, as shown by immnofluorecence staining. These results indicate that the interruption of the ras/MAPK signal transduction pathway and the disorganization of alpha actin fibers are the main cause of manumycin A inhibition of VSMC proliferation and migration induced by PDGF.

Alkyl and Aryl Transferases↗
PubMed1999

Massive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan, associated with consumption of white radish sprouts.

In July 1996, an outbreak of Escherichia coli O157:H7 infection occurred among schoolchildren in Sakai City, Osaka, Japan. This outbreak developed in 13 North-East District and 34 Middle-South District elementary schools in the city. All children hospitalized on July 17-19 had presented on July 8 (North-East District) and July 9 (Middle-South District). School lunches served on July 1 and 8 in the North-East District and on July 1, 4, 8, and 9 in the Middle-South District were proposed by a food consumption study to be associated with infection. White radish sprouts from a single farm were the only uncooked food common to the most highly implicated meals on the involved days in two school districts (sweet and sour chicken with lettuce on July 8 in the North-East District and chilled Japanese noodles on July 9 in the Middle-South District). Two incidents of E. coli O157:H7 in neighboring areas were also related to white radish sprouts from the farm. The pulse-field gel electrophoresis patterns of isolates from patients in these two districts and the neighboring areas were identical. Thus, it was concluded that the cause of the outbreak was the white radish sprouts shipped on July 7-9 from one particular farm.

Child↗
PubMed1999

The relationship of DNA ploidy to chromosomal instability in primary human colorectal cancers.

The aim of this investigation was to corroborate the relationship between DNA ploidy and chromosomal variation in surgically removed colorectal cancers. For 101 specimens from 21 advanced colorectal cancers, the numerical variations in chromosomes 7, 17, and 18 among cells were measured by fluorescence in situ hybridization using DNA probes specific for centromere of each chromosome, and DNA ploidy was determined by laser scanning cytometry or flow cytometry. DNA diploidy (DNA index = 1.0) was linked with minor variation in copy number of chromosomes 7, 17 and 18, whereas DNA aneuploidy (DNA index > or = 1.2) was found exclusively in tumors with large variations in centromere copy number for all chromosomes. There was a significant difference in the degree of intercellular variations in chromosome copy number between diploid and aneuploid clones for all chromosomes examined (P < 0.001). In near-diploid clones (1.0 < DNA index < 1.2), the numerical variation of chromosome 18 was significantly different from that in diploid clones (P < 0.002), but it was not different from that in aneuploid clones. These observations support the hypothesis that chromosomal instability is associated with DNA aneuploidy in colorectal cancers. Additionally, they suggest that near-diploid tumors are also unstable at a lower level than classic aneuploid tumors and that all chromosomes are not affected equally in near-diploid cases.

Adult↗
PubMed1999

Enhanced activity of cyclin A-associated kinase in immortalized human fibroblasts.

Deregulation of cell cycle regulatory mechanisms leads to disruption of normal control of cell growth and may be associated with neoplastic transformation. To determine whether immortalized human cells have alterations in their cell cycle regulatory mechanisms, we analyzed cell cycle regulatory proteins in 2 immortalized human fibroblast cell lines, KMST-6 and OUMS-24/P6X, established by repeated irradiation with (60)Co gamma rays alone or mutant p53 gene transfection plus X-ray irradiation, respectively. Both the immortalized cell lines had markedly enhanced activity of cyclin A-associated kinase as compared with their normal counterparts. The high activity of cyclin A-associated kinase was well correlated with the increased expression of cyclin A mRNA and its protein. In addition, the immortalized cell lines showed significantly reduced amounts of p21(Cip1/Waf1/Sdi1), a potent inhibitor of cyclin dependent kinases. Furthermore, among the pRb family of proteins, p107 and p130, were hyperphosphorylated in both the immortalized cell lines, suggesting possible participation in upregulation of cyclin A associated kinase activity. These changes represent some important characteristics of immortalized cells.

Blood Proteins↗
PubMed1999

Chymase-dependent angiotensin II formation in human vascular tissue.

BACKGROUND: Some reports have suggested that, in vitro, human heart chymase in homogenates contributes little to angiotensin (Ang) II formation in the presence of natural protease inhibitors such as alpha-antitrypsin. We studied whether chymase bound to heparin, resembling an in vivo form, could contribute to Ang II formation in the presence of natural protease inhibitors. METHODS AND RESULTS: The Ang II formation was increased time-dependently after incubation in an extract (1 mg of protein/mL) of human vascular tissues containing Ang I. The concentration of Ang II in the extract after incubation for 30 minutes was 1.67+/-0.06 nmol/mL, and we regarded this quantity of Ang II as 100%. The Ang II formation was inhibited 10%, 95%, and 96% by 1 micromol/L lisinopril, 100 micromol/L chymostatin, and 0.1 g/L alpha-antitrypsin, respectively. The extract was applied to a heparin affinity column. After the column was washed with PBS, the eluted PBS contained a weak Ang II-forming activity, which was completely inhibited by lisinopril. The eluted PBS, to which >0.8 mol/L NaCl had been added, showed a strong Ang II-forming activity which was inhibited by chymostatin and alpha-antitrypsin. After the application of the extract, the column was washed with PBS and then an Ang I solution in PBS was applied to the column. The Ang II formation in the PBS eluted from the incubated column was increased time-dependently. The concentration of Ang II in the PBS (1 mL) eluted from the column after incubation for 30 minutes was 2.56+/-0.28 nmol/mL, and we regarded this quantity of Ang II as 100%. To study the effects of inhibitors, the extract (1 mg of protein/mL) was applied to a heparin affinity column (1 mL) which was preequilibrated with PBS (3 mL); 100 micromol/L chymostatin or 0.1 g/L alpha-antitrypsin in PBS (1 mL) was then applied to the column. After the column was washed with PBS (3 mL), Ang I solution (1 mg/mL) in PBS was applied to the column, and the column was incubated for 30 minutes. The Ang II formation in the PBS eluted from the column was suppressed up to 5% by application of chymostatin, although this was not affected by application of alpha-antitrypsin. CONCLUSIONS: These findings suggest that human chymase bound to heparin plays a functional role in Ang II formation in the presence of natural protease inhibitors such as alpha-antitrypsin.

Adult↗
PubMed1999

Lack of effect of carbohydrate depletion on some properties of human mast cell chymase.

Human chymase from vascular tissues was purified to homogeneity by heparin affinity and gel filtration chromatography. Treatment of human chymase with endoglycosidase F resulted in cleavage of the carbohydrate moiety yielding a deglycosylation product that did not lose its catalytic activity. This enzymatic deglycosylation product was enough to explore possibilities that N-glycan might modify some properties of human chymase. Substrate specificity, optimum pH and the elution profile from the heparin affinity gel were not affected by the deglycosylation. Only a slight but significant difference was observed in the Km value for conversion of angiotensin I to angiotensin II. Other kinetic constants such as kcat were not influenced. The kinetics of conversion of big endothelin-1 to endothelin-1(1-31) were not significantly affected. The deglycosylated human chymase was more susceptible to deactivation under alkaline pH and thermal stress. Even at physiological temperature and pH, the activity of glycosylated human chymase was more stable. From these results, it appears that the N-glycan of human chymase contributes to the stability of this enzyme but not to its functional properties.

Carbohydrates↗
PubMed1999

Tranilast suppresses vascular chymase expression and neointima formation in balloon-injured dog carotid artery.

BACKGROUND: Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell-stabilizing antiallergic agent. We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II-forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. METHODS AND RESULTS: Either tranilast (50 mg/kg BID) or vehicle was orally administered to beagles for 2 weeks before and 4 weeks after balloon injury. Four weeks after the injury, remarkable neointima was formed in the carotid arteries of vehicle-treated dogs. Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. Angiotensin-converting enzyme (ACE) activity was slightly increased in the injured arteries, whereas ACE mRNA levels were not. Tranilast treatment completely prevented the increase in chymaselike activity, reduced the chymase mRNA levels by 43%, and decreased the carotid intima/media ratio by 63%. In vehicle-treated injured arteries, mast cell count in the adventitia showed a great increase, which was completely prevented by the tranilast treatment. Vascular ACE activity and mRNA levels were unaffected by tranilast. CONCLUSIONS: Tranilast suppressed chymase gene expression, which was specifically activated in the injured arteries, and prevented neointima formation. Suppression of the chymase-dependent ANG II-forming pathway may contribute to the beneficial effects of tranilast.

Animals↗
PubMed1999

Identification and characterization of nuclear pore subcomplexes in mitotic extract of human somatic cells.

In higher eukaryotic cells, it is generally thought that nuclear pore complex disassembles at the beginning of mitosis and reassembles at the end. Using a monoclonal antibody that recognizes nuclear pore antigens, we found that, at mitosis of mammalian somatic Hela cells, the nuclear pore complex disassembles into at least three subcomplexes, termed subcomplexes A, B and C (molecular mass; 2 MDa<, approximately 660 kDa, and approximately 440 kDa, respectively). The direct partial amino acid sequencing of the components of these subcomplexes indicates that the A subcomplex contains CAN/Nup214/p250 and p62 and the B subcomplex also contains p62, indicating that p62 is contained in two different subcomplexes. Subcomplex C was shown to consist of Nup98 and human RAE1, a human homolog of yeast Rae1p/Gle2p. Since Nup98 and Rae1p/Gle2p have been reported to be involved in mRNA export, this suggests that some of the mitotic subcomplex may be formed by functionally related proteins.

Amino Acid Sequence↗