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Biomedical subjects

A Miyazaki

Publications and source records attributed to A Miyazaki.

At least 19 recordsLinked to original sources
PubMed2004

Case report: fatal ventricular tachycardia exacerbated by fever in a child.

Primary ventricular tachycardia (VT) is rare in children. We report a child with VT exacerbated by fever which was ultimately fatal. His first episode occurred at 5 months old and recurred with fever, occasionally causing syncope. Episodes were difficult to control with antiarrhythmic agents during fever but remitted with antipyretics. He was admitted to hospital 23 times because of VT and died suddenly with fever when he was 17 years old. At autopsy, severe fatty replacement of the bundle of His and interstitial fibrosis of the sinus node was found.

Adolescent↗
PubMed2003

First case of a single heterozygote of an abnormal hemoglobin, Hb Stanmore, [beta111(G13)Val-->Ala].

We describe a hemoglobin beta-chain mutant detected incidentally in an unusual profile of glycated hemoglobin (HbA1c) measured by ion-exchange HPLC. Analysis of intact globin by electrospray ionization mass spectrometry (ESI-MS) and peptide analysis by on-line HPLC-ESI-MS-MS revealed the substitution, [beta111(G13)Val-->Ala], which was confirmed by DNA analysis. This was the second case of Hb Stanmore. As the first case combined beta(0)-thalassemia, and the family study in that case showed no case of Hb Stanmore without combined thalassemia, the case presented here is the first case of single heterozygote, and the first Japanese case. Hb Stanmore is isoelectrophoretically silent with only mild clinical symptoms, although stability by isopropanol test was positive.

Adult↗
PubMed2001

Extensive investigations on oxidized amino acid residues in H(2)O(2)-treated Cu,Zn-SOd protein with LC-ESI-Q-TOF-MS, MS/MS for the determination of the copper-binding site.

The ESI (electrospray ionization)-Q-TOF (tandem quadrupole/orthogonal-acceleration time-of-flight) mass spectrometer combined with the nano-HPLC (high performance liquid chromatography) system was utilized to pinpoint the Cu-binding site in Cu,Zn-SOD (superoxide dismutase) protein. Cu,Zn-SOD was treated with hydrogen peroxide, intended to specifically oxidize histidine residues coordinated to the copper ion as a mass spectrometric probe. The oxidized Cu,Zn-SOD was then fragmented with the successive treatment of endoproteinase Asp-N and DTT (dithiothreitol). Separation of the peptide mixture with the nano-HPLC and the on-line ESI-Q-TOF MS analysis revealed that only two peptide fragments were oxidized to a significant extent. Further analyses of oxidized peptide fragments with LC-ESI-Q-TOF-MS/MS disclosed that three out of four Cu-coordinated histidine residues were specifically oxidized by action of a redox-active copper ion and hydrogen peroxide, demonstrating the copper-catalyzed oxidation of amino acid ligands could be a versatile tool for the mass spectrometric determination of the copper-binding site. In addition, proline and valine residues in the proximity of the Cu ion were found to be oxidized upon H(2)O(2) treatment.

Amino Acid Sequence↗
PubMed2001

Identification of a novel human ankyrin-repeated protein homologous to CARP.

We cloned a novel ankyrin repeat protein, Arpp, by immunoscreening a cDNA library constructed from a human esophageal carcinoma cell line, TE1, with an antibody directed to a hypothetical protein encoded by antisense p53 mRNA. Arpp protein is composed of 333 amino acids and contains four ankyrin-like repeat motifs in the middle portion of the protein, a PEST-like sequence and a lysine-rich sequence similar to a nuclear localization signal in the N-terminal region, and a proline-rich region containing consensus phosphorylation sites in the C-terminal region. Protein sequence analysis revealed that Arpp is homologous (52.7% identity) to Carp which is shown to be involved in the regulation of the transcription of the cardiac ventricular myosin light chain 2 gene. Arpp mRNA was found to be expressed in normal skeletal and cardiac muscle. Interestingly, Arpp expression was detectable in bilateral ventricles, but undetectable in bilateral atria and large vessels, suggesting that Arpp may play a specific function in cardiac ventricles as well as skeletal muscles.

Ankyrin Repeat↗
PubMed2001

Influence of ventricular morphology on aerobic exercise capacity in patients after the Fontan operation.

OBJECTIVES: This study investigated the influences of ventricular morphology, hemodynamics and clinical findings on exercise capacity in patients after the Fontan operation. BACKGROUND: Determinants of exercise capacity after the Fontan operation remain unclear. METHODS: Peak oxygen uptake (PVo2) was determined in 105 patients by exercise test and compared to hemodynamics and clinical findings. Patients were divided into three groups based on ventricular morphology: those with a right ventricle (group RV), a biventricle (group BV) and a left ventricle (group LV). RESULTS: Ten patients with atrioventricular valve regurgitation (AVVR) or hypoxia exhibited a low PVo2. After excluding these patients, although PVo2 did not correlate with hemodynamics, except ventricular ejection fraction (p < 0.02), it correlated with age at the Fontan operation and exercise test (p < 0.002). The PVo2 was higher in group LV (63+/-9%) than in groups RV (55+/-9%) and BV (55+/-12%) (p < 0.01), while an inverse correlation between PVo2 and age at operation was demonstrated only in group RV (p < 0.05). Groups RV or BV and age at exercise test were associated with a lower PVo2, whereas group LV was an independent predictor of a higher PVo2 (p < 0.01). During 4.2 years of follow-up, a decrease in peak heart rate was related to a decrease in PVo2 (p < 0.05). The PVo2 decreased in group RV (p < 0.01). CONCLUSIONS: In addition to AVVR, hypoxia, and heart rate response, ventricular morphology is related to exercise capacity. Early Fontan operation may be beneficial in terms of exercise capacity, especially in the group RV patients.

Adolescent↗
PubMed2001

Transcriptional activation of the thyroglobulin promoter directing suicide gene expression by thyroid transcription factor-1 in thyroid cancer cells.

Gene therapy with thyroglobulin (TG) promoter and a prodrug/suicide gene combination may prove useful as a treatment for thyroid carcinoma. However, most poorly differentiated and anaplastic thyroid carcinomas have lost the ability to express the TG gene expression accompanied by loss of transcription factors [thyroid transcription factor-1 (TTF-1), TTF-2, or Pax-8] interacting with the TG promoter. In anticipation of developing transcriptionally targeted gene therapy of TG-nonproducing thyroid carcinomas, we investigated the effect of TTF-1 gene transfer on TG promoter activity and the cytotoxic effect obtained by the TG promoter-driven HSV-TK gene along with ganciclovir in thyroid carcinoma and nonthyroidal cells. Using a chimeric construct containing the 5'-flanking region of the rat TG gene between -826 and +39 bp and the luciferase gene, TG promoter activity was detected in a normal rat thyroid cell line (FRTL-5), but not in a dedifferentiated line of thyroid cells (FRT) expressing Pax-8 but not TTF-1, TTF-2, or TG [TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)], or in a human papillary thyroid carcinoma cell line [BHP15-3; TTF-1(-)/TTF-2(-)/Pax-8(-)/TG(-)], a human pulmonary cell line [H441; TTF-1(+)/TTF-2(-)/Pax-8(-)/TG(-)], or a dog kidney epithelial cell line [MDCK; TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. Cotransfection of the TTF-1 expression vector stimulated TG promoter activity in FRT and BHP15-3 dedifferentiated thyroid cells, but not in H441 pulmonary cells. Only weak activation was observed in MDCK kidney cells. We then constructed recombinant adenovirus vectors, AdTTF-1 and ADTGTK: AdTTF-1 contained cytomegalovirus promoter and rat TTF-1 cDNA; AdTGTK carried the TG promoter-driven HSV-TK gene. Infection with AdTGTK and combined with GCV treatment induced a cytotoxic effect in FRTL-5 cells but not in dedifferentiated thyroid or nonthyroid cells. Cotransduction of AdTTF-1 and AdTGTK permitted 90% cytotoxicity for BHP15-3 and >95% cytotoxicity for FRT, as well as for BHP7-13 and BHP18-21v thyroid cancer cell lines [both/TTF1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. In contrast, little cytotoxicity was seen for H441 and MDCK cell lines even with 300 microg/ml of ganciclovir. These results suggest that cotransduction of a TG promoter-controlled suicide gene and the TTF-1 gene by adenoviral vectors confers transcriptionally targeted gene-mediated cytotoxicity in poorly differentiated thyroid carcinoma cells unable to express the TG gene.

Adenoviridae↗
PubMed2001

The role of galectin-3 in endocytosis of advanced glycation end products and modified low density lipoproteins.

Galectin-3, a member of beta-galactoside-binding lectin family, is suggested to be an AGE-receptor. To examine this possibility, we prepared CHO cells overexpressing human galectin-3 (galectin-3-CHO cells). Galectin-3-CHO cells showed a specific and saturable binding to (125)I-AGE-BSA with Kd of 3.1 microg/ml. (125)I-AGE-BSA was endocytosed by galectin-3-CHO cells and underwent lysosomal degradation. The endocytosis of (125)I-AGE-BSA was inhibited not only by unlabeled AGE-BSA but also by acetylated LDL and oxidized LDL, ligands for the scavenger receptor family. Furthermore, (125)I-oxidized LDL and (125)I-acetylated LDL were actively endocytosed by galectin-3-CHO cells and the incubation with acetyl-LDL led to intracellular accumulation of cholesteryl esters, indicating the role of galectin-3 in endocytosis of AGE-proteins and modified LDLs. Since galectin-3 was localized and up-regulated in foam cells at human atherosclerotic lesions, the present results suggest that galectin-3 plays an important role in formation of atherosclerotic lesions in vivo, by modulating endocytic uptake of AGE-proteins and modified LDLs.

Animals↗
PubMed2001

Scavenger receptor class B type I-mediated reverse cholesterol transport is inhibited by advanced glycation end products.

Cellular interactions of advanced glycation end products (AGE) are mediated by AGE receptors. We demonstrated previously that class A scavenger receptor types I and II (SR-A) and CD36, a member of class B scavenger receptor family, serve as the AGE receptors. In this study, we investigated whether scavenger receptor class B type I (SR-BI), another receptor belonging to class B scavenger receptor family, was also an AGE receptor. We used Chinese hamster ovary (CHO) cells overexpressed hamster SR-BI (CHO-SR-BI cells). (125)I-AGE-bovine serum albumin (AGE-BSA) was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by CHO-SR-BI cells. (125)I-AGE-BSA exhibited saturable binding to CHO-SR-BI cells (K(d) = 8.3 microg/ml). Endocytic uptake of (125)I-AGE-BSA by CHO-SR-BI cells was completely inhibited by oxidized low density lipoprotein (LDL) and acetylated LDL, whereas LDL exerted only a weak inhibitory effect (<20%). Cross-competition experiments showed that AGE-BSA had no effect on HDL binding to these cells and vice versa. Interestingly, however, SR-BI-mediated selective uptake of HDL-CE was completely inhibited by AGE-BSA in a dose-dependent manner (IC(50) <10 microg/ml). Furthermore, AGE-BSA partially inhibited (by <30%) the selective uptake of HDL-CE in human hepatocarcinoma HepG2 cells (IC(50) <30 microg/ml). In addition, [(3)H]cholesterol efflux from CHO-SR-BI cells to HDL was significantly inhibited by AGE-BSA in a dose-dependent manner (IC(50) <30 microg/ml). Our results indicate that AGE proteins, as ligands for SR-BI, effectively inhibit both SR-BI-mediated selective uptake of HDL-CE and cholesterol efflux from peripheral cells to HDL, suggesting that AGE proteins might modulate SR-BI-mediated cholesterol metabolism in vivo.

Animals↗
PubMed2001

Levels of tissue inhibitor of metalloproteinases-1 and matrix metalloproteinases-1 and -8 in gingival crevicular fluid following treatment with enamel matrix derivative (EMDOGAIN).

The mechanism of enamel matrix derivative (EM D) action on the periodontal wound healing process is not well understood. However, earlier in vitro studies from our laboratory demonstrated that EMD stimulated the proliferation of both periodontal ligament and gingival fibroblast cells. Therefore, the purpose of this study was to further evaluate the effect of EMD on the early wound healing process by assessing the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in gingival crevicular fluid (GCF). Sixteen patients, each of whom had one or two pairs of infrabony defects located contralaterally in the same arch, were included in this clinical trial. Thirty-six infrabony defects were randomly assigned treatment with flap surgery plus EMD or flap surgery plus placebo. At baseline and at 2, 4 and 12 week follow-up evaluation visits, GCF was sampled with paper strips. After determination of GCF volume, TIMP-1, MMP-1 and MMP-8 GCF levels were measured by an enzyme-linked immunosorbent assay. Intragroup analysis: At week 2 following surgery, when compared to baseline all parameters in each study group, except MMP-1, significantly increased (p<0.05). There were no significant differences between 4 or 12 weeks and baseline in either study group. Intergroup analysis: At 4 weeks after surgery, GCF volume and TIMP-1 levels showed a significant decrease (p<0.05) in the EMD group, when compared to the placebo group. MMP-1 levels at weeks 2, 4 and 12, and MMP-8 levels at weeks 4 and 12 were significantly lower (p < 0.05) in the EMD group compared to the placebo group. EMD compared to placebo treated sites demonstrated a more rapid return to baseline levels of TIMP-1, MMP-1 and MMP-8. These findings suggest that treatment with flap surgery and EMD, compared to flap surgery with placebo, accelerated healing at an earlier stage of wound healing following surgery.

Alveolar Bone Loss↗
PubMed2001

Determination of butyl-, phenyl-, octyl- and tributylmonomethyltin compounds in a marine environment (Bay of Bengal, India) using gas chromatography-inductively coupled plasma mass spectrometry.

Organotin compounds (butyl-, phenyl-, octyl- and tributylmonomethyltin) and inorganic tin were quantified in sea-water and sediments from two harbours and several locations on the southeast coast of India using highly sensitive and selective gas chromatography-inductively coupled plasma mass spectrometry (GC-ICP-MS), adopting new extraction and analytical techniques with extremely low detection limits (water, 0.019-0.85 pg l(-1); sediment, 0.23-0.48 ng g(-1)). The concentrations of monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) in sea-water from Tuticorin harbour varied from 0.64 to 4.97, 3.0 to 26.8 and 0.3 to 30.4 ng Sn l(-1), respectively. MBT, DBT and TBT in sediments from harbour areas ranged from 1.6 to 393, 1.3 to 394 and ND (not detected) to 1280 ng Sn g(-1) (dry weight), respectively. Natural methylation in both harbours was established by quantifying tributylmonomethyltin (TBMMT) residues (sea-water, ND-0.19 ng Sn l(-1); sediment, ND-765 ng Sn g(-1) dry weight). In sea-water, octyltins were also determined as monooctyltin (MOT) > dioctyltin (DOT) > trioctyltin (TOT). Butyltin contamination in commercial harbours is evident, but other coastal waters are not contaminated with organotin residues. The high concentration of inorganic tin in estuarine sediment indicates an elevated rate of debutylation in the estuarine environment. Both methylation and debutylation of TBT in Chennai harbour were greater than in Tuticorin harbour. A significant correlation (r2 = 0.75) between total butyltin and organic carbon contents in sediment was found. To our knowledge, this is the first report on the distribution of butyltins and methylated butyltin in sea-water and sediment and octyltins in sea-water in the Indian marine environment.

Carbon↗
PubMed2001

Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and -2.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme that produces cholesteryl esters in various tissues. In mammals, two ACAT genes (ACAT1 and ACAT2) have been identified. Together, these two enzymes are involved in storing cholesteryl esters as lipid droplets, in macrophage foam-cell formation, in absorbing dietary cholesterol, and in supplying cholesteryl esters as part of the core lipid for lipoprotein synthesis and assembly. The key difference in tissue distribution of ACAT1 and ACAT2 between humans, mice and monkeys is that, in adult human liver (including hepatocytes and bile duct cells), the major enzyme is ACAT1, rather than ACAT2. There is compelling evidence implicating a role for ACAT1 in macrophage foam-cell formation, and for ACAT2 in intestinal cholesterol absorption. However, further studies at the biochemical and cell biological levels are needed in order to clarify the functional roles of ACAT1 and ACAT2 in the VLDL or chylomicron synthesis/assembly process.

Animals↗
PubMed2001

Lupus anticoagulant in myasthenia gravis associated with IgM gammopathy.

The plasma of a patient with myasthenia gravis had strong lupus anticoagulant activity and his IgM paraprotein displayed non-specific inhibition to coagulation factors IX, XI, XII, prekallikrein, and high molecular weight kininogen. He was placed on prednisolone, which resulted in improvement in his myasthenic symptoms, but the prolongation of APTT and macroglobulinemia remained. Double filtration plasmapheresis successfully decreased the serum IgM level from 1,190 mg/dl to 375 mg/dl and APTT improved from 58 s to 38 s. Myasthenia gravis is frequently associated with other autoimmune diseases, but the association with lupus anticoagulant and IgM gammopathy is rare.

Humans↗
PubMed2001

Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D(3) or 9-cis-retinoic acid in undifferentiated THP-1 cells.

We have previously shown that acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) protein content increases significantly during the human monocyte-macrophage differentiation process. To gain further insight, we used undifferentiated human monocytic THP-1 cells as a model system with which to examine whether ACAT-1 mRNA and protein content can be increased by treating cells with 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] or with 9-cis-retinoic acid (9-cis-RA), two agents known to upregulate the expression of various genes during the monocyte-macrophage differentiation process. Immunoblot analysis with anti-human ACAT-1 antibodies revealed that ACAT-1 protein was increased by 2.6-fold, using 1,25-(OH)(2)D(3) at a physiological concentration (100 pM). ACAT-1 protein was also increased when using 9-cis-RA, but only at relatively high concentrations (0.1;-1 microM). Northern blot analysis revealed that among the four ACAT-1 mRNA transcripts (2.8, 3.6, 4.2, and 7.0 kb) examined, only the 2.8- and 3.6-kb transcripts were selectively increased. On the basis of enzyme assays in vitro, ACAT activity was increased 3.0-fold by using 100 nM 1,25-(OH)(2)D(3), and 1.8-fold by using 1 microM 9-cis-RA. Together, our results suggest that 1,25-(OH)(3) participates in ACAT-1 gene expression during the monocyte-macrophage differentiation process.

Alitretinoin↗