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Biomedical subjects

I Yoshida

Publications and source records attributed to I Yoshida.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors.

Squalene synthase (SQS; EC 2.5.1.21) plays an important role in the cholesterol biosynthetic pathway. We discovered ER-28448, 5-(N-[2-butenyl-3-(2-methoxyphenyl)]-N-methylamino)-1, 1-penthylidenebis(phosphonic acid) trisodium salt, as a potent and selective inhibitor of SQS. ER-28448 inhibited SQS in rat liver microsome with an IC(50) value of 3.6 nm. We also prepared ER-27856, the tripivaloyloxymethyl ester prodrug of ER-28448. Although less active than ER-28448 in a liver microsome assay, ER-27856 more potently inhibited cholesterol biosynthesis in rat hepatocytes; and ER-27856 orally inhibited de novo cholesterol biosynthesis in Sprague-Dawley rats, with an ED(50) value of 1.6 mg/kg. In HepG2 cells, ER-27856 upregulated low density lipoprotein receptor activity to 2.1 times that of control. A time-course study indicated that the inhibitory effect of ER-27856 on cholesterol biosynthesis in rats continued for up to 8 h. In a study of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMGRIs), atorvastatin actively suppressed cholesterol biosynthesis for 8 h, whereas the effect of pravastatin and simvastatin diminished at 4 and 8 h, respectively. In rhesus monkeys, 4 days of oral administration of ER-27856 lowered plasma total cholesterol (TCHO) more potently than did these HMGRIs. Whereas atorvastatin significantly elevated plasma alanine aminotransferase, a marker of hepatotoxicity, to 3.7 times at 100 mg/kg, ER-27856 increased the level only 1.4 times at 10 mg/kg, at which doses the hypocholesterolemic effect was equivalent. During 28 days of administration, ER-27856 reduced TCHO and non-high density lipoprotein (non-HDL) cholesterol by 72 and 95%, respectively. These results demonstrate that ER-27856 had more potent hypocholesterolemic activity and less hepatotoxic effect than HMGRIs. ER-27856 may contribute to the treatment of hypercholesterolemic patients.

Alanine Transaminase↗
PubMed2000

Re-use of left internal thoracic artery for redo operation after MIDCAB.

We report a case of recycling of left internal thoracic artery (LITA) in situ in reoperation of coronary artery bypass grafting. A 41-year-old male, who has poor-controlled hypercholesterolemia, was bypassed LITA to the left anterior descending artery (LAD) in minimally invasive direct coronary artery bypass (MIDCAB) manner at the other hospital. Four months later, he felt short of breath on effort. Coronary angiogram showed stenoses of the left main trunk and anastomosis site of the LITA. At redo operation, we skeletonised the LITA and reused it in situ to the LAD. Using the skeletonised method for re-harvesting LITA made the graft reach a more distal portion without tension. He is doing well at 18 months after surgery. In selected patients, recycling of the used arterial grafts can reserve other arterial grafts for redo operations in the future.

Adult↗
PubMed2000

[Surgical treatment of bronchial carcinoid: report of seven cases].

Seven patients with pulmonary carcinoid including three with typical carcinoid and four with atypical carcinoid were reported. There were 3 males and 4 females, with an age range of 37 to 80 years. All patients with typical carcinoid had pathological stage I. Of the patients with atypical carcinoid, one patient had stage I, two stage IIIA and one stage IIIB. All but two patients underwent lobectomy and mediastinal lymph node dissection. Bronchoplastic operation or right pneumonectomy were performed in the two patients. All but one patient underwent absolute or relative curative operation. Only one patient died on the 4th postoperative day. One patient with atypical carcinoid died of cancer recurrence 4 years after surgery. One patient died of breast cancer. One patient underwent surgery for metachronous multiple lung cancer, and he is doing well without recurrence. In conclusion, a limited operation is thought to be acceptable only in patients with typical carcinoid in a peripheral lesion without lymph node metastasis. Lobectomy and mediastinal lymph node dissection is necessary for the atypical carcinoid case.

Adult↗
PubMed2000

[Reye's syndrome].

A nationwide survey on Reye's syndrome(RS) was described. And problems between RS and influenza virus such as etiology, pathophysiology, differential diagnosis and epidemiology were reviewed. So-called aspirin issue on RS was re-evaluated according to recent advance of RS research. Finally future aspect of Reye's syndrome was also discussed.

Child, Preschool↗
PubMed1999

Structure and localization of the mouse prolyl oligopeptidase gene.

We have cloned and characterized the genomic structure of the mouse gene for prolyl oligopeptidase that is mapped to chromosome 10B2-B3. The gene is about 92 kilobases in size and contains 15 exons. All exon-intron junction sequences conform to the GT/AG rule. Comparison with the presumed domain structures of the mouse prolyl oligopeptidase indicates that the propeller domain of the enzyme is encoded by exons 3-10, whereas the catalytic domain is encoded by exons 1-3 and 10-15. The catalytic triad residues are encoded by two exons (Ser(554) on exon 13 and His(680) and Asp(642) on exon 15). The 5'-flanking region of the mouse prolyl oligopeptidase gene has structural features found in housekeeping gene promoters, including a GC-rich segment and an absence of TATA and CAAT boxes. A primer extension assay showed the presence of multiple sites for the initiation of transcription. Transient transfection analysis demonstrated that the 5'-flanking region of the gene can direct efficient expression in COS1 cells. Deletion studies revealed that the downstream 125-base pair sequence of the region is required for promoter activity in the cells.

Animals↗
PubMed1999

Enhanced GRK5 expression in the hearts of cardiomyopathic hamsters, J2N-k.

GTP binding protein-coupled receptor kinase 5 (GRK5) cDNA was cloned from the hearts of Syrian hamsters. The hamster GRK5 cDNA contained 1770 nucleotides encoding 590 amino acids, and the nucleotide sequence had 89.6% homology to the human homologue. An inbred cardiomyopathic hamster strain, J2N-k, was used to investigate the alteration of GRK5 mRNA expression in the setting of congestive heart failure. M-mode echocardiography revealed significant dilatation of the left ventricle and a decrease of left ventricular contractility in 20-week-old J2N-k hamsters compared with age-matched control hamsters, J2N-n. Semi-quantitative RT-PCR showed that GRK5 mRNA expression in the hearts of J2N-k was significantly higher than in those of J2N-n (J2N-k 60.3 +/- 13.3, J2N-n 25.8 +/- 17.2 arbitrary units, p < 0.005, n = 6 in each group). These results suggest that an enhanced GRK5 expression might play a role in the reduced responsiveness to catecholamines in failing hearts via beta-adrenergic receptor phosphorylation.

Aging↗
PubMed1999

Pilot study of gas chromatographic-mass spectrometric screening of newborn urine for inborn errors of metabolism after treatment with urease.

Gas chromatographic-mass spectrometric (GC-MS) techniques for urinary organic acid profiling have been applied to high-risk screening for a wide range of diseases, mainly for inborn errors of metabolism (IEM), rather than to low-risk screening or mass screening. Using a simplified procedure with urease-pretreatment and the GC-MS technique, which allows simultaneous determination of organic acids, amino acids, sugars and sugar acids, we performed a pilot study of the application of this procedure to neonatal urine screening for 22 IEM. Out of 16,246 newborns screened, 11 cases of metabolic disorders were chemically diagnosed: two each of methylmalonic aciduria and glyceroluria, four of cystinuria, and one each of Hartnup disease, citrullinemia and alpha-aminoadipic aciduria/alpha-ketoadipic aciduria. The incidence of IEM was thus one per 1477, which was higher than the one per 3000 obtained in the USA in a study targeting amino acids and acylcarnitines in newborn blood spots by tandem mass spectrometry. Also, 227 cases were found to have transient metabolic abnormalities: 108 cases with neonatal tyrosinuria, 99 cases with neonatal galactosuria, and 20 cases with other transient metabolic disorders. Two hundred and thirty-eight cases out of 16,246 neonates (approximately 1/68) were thus diagnosed using this procedure as having either persistent or transient metabolic abnormalities.

Gas Chromatography-Mass Spectrometry↗
PubMed1999

An IKLLI-containing peptide derived from the laminin alpha1 chain mediating heparin-binding, cell adhesion, neurite outgrowth and proliferation, represents a binding site for integrin alpha3beta1 and heparan sulphate proteoglycan.

We synthesized and characterized several peptides containing the IKLLI sequence in the alpha1 chain of laminin-1. The IKLLI-containing peptides, such as LA4 (CSRNLSEIKLLISRARK), LA5 (EIKLLIS) and LA5L (SEIKLLIS), were found to mediate heparin binding and cell adhesion, while also promoting neurite outgrowth in PC12 cells. Furthermore, peptides LA4 and LA5 also mediated proliferation. However, a scrambled peptide, LA5S (ILEKSLI), did not show any of these activities. Anti-LA4 antibodies inhibited laminin- and LA5-mediated cell adhesion and neurite outgrowth, and anti-(integrin alpha3) and anti-(integrin beta1) antibodies inhibited LA5-mediated cell adhesion and neurite outgrowth. Heparin and heparan sulphate inhibited LA5-mediated heparin binding and PC12 cell adhesion in a dose- dependent manner. The IC50 for inhibition of heparin binding and cell adhesion was observed with 9 microM and 8 microM heparin/heparan sulphate respectively. Furthermore, heparan sulphate proteoglycan also inhibited LA5-mediated PC12 cell adhesion with an IC50 of 100 micrograms/ml. However, chondroitin sulphate (dermatan sulphate) did not inhibit cell adhesion. These data suggest that an IKLLI-containing peptide derived from the laminin alpha1 chain may be an active site of laminin and that its cell adhesion may thus interact with both integrin alpha3beta1 and cell- surface heparan sulphate proteoglycan.

Amino Acid Sequence↗
PubMed1999

Laminin inhibits both Abeta40 and Abeta42 fibril formation but does not affect Abeta40 or Abeta42-induced cytotoxicity in PC12 cells.

Laminin has recently been reported to inhibit both Abeta40 and Abeta42 fibril formation in vitro. Laminin was thus suggested to be an effective therapeutic agent for Alzheimer's disease. However, some recent reports have shown that Abeta fibril formation may not necessarily be linked to the development of Abeta neurotoxicity. In the present study, we thus investigated whether or not laminin affects Abeta40 and Abeta42-induced neurotoxicity. The findings of the present study by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye reduction test showed laminin not to have an inhibitory effect on Abeta40 or Abeta42-induced cytotoxicity in PC12 cells while Abeta fibril formation was inhibited under the conditions used in the present study. The findings of the present study therefore do not support the hypothesis that Abeta fibril formation is absolutely required for the development of Abeta cytotoxicity.

Amyloid beta-Peptides↗
PubMed1999

Effect of CpG methylation on expression of the mouse imprinted gene Mest.

We previously reported isolation of the mouse gene, Mest (mesoderm-specific transcripts), which is mapped to the proximal part of chromosome 6 and predominantly expressed in the mesoderm and its derivatives during development. Peg1, a paternally expressed gene isolated by a systematic screening of imprinted genes, was recently demonstrated to be identical to Mest. We and others have shown that the human homolog (MEST) of Mest is also imprinted so as to be expressed from the paternal copy and maps to 7q32. To study transcriptional regulation of Mest/Peg1, we examined the effect of DNA methylation on its expression. In the embryonal carcinoma (EC) cell line, MC12, from which Mest was originally isolated, the 5'-region harboring presumptive promoter of the gene was undermethylated. On the other hand, C4XX, a subclone of MC12 which had lost expression of Mest, was characterized by extremely high levels of methylation in the 5'-region, demethylation of which resulted in activation of Mest. Furthermore, a methylated reporter construct with the luciferase gene under the control of the putative promoter region of Mest was not competent to produce luciferase activity in MC12 cells. These results suggest a suppressive role for DNA methylation in Mest expression. However, neither methylated nor unmethylated reporter constructs showed luciferase activity in a primary culture from the adult kidney, in which Mest is down-regulated despite apparent unmethylation of the paternal allele. Taken together, the data suggest that there are probably two modes of regulation for the Mest gene; one being a methylation-dependent mechanism that regulates imprinted expression of Mest during development, and the other being a methylation-independent mechanism that is involved in down-regulation of Mest in adult tissues.

Animals↗
PubMed1999

Identification of a heparin binding site and the biological activities of the laminin alpha1 chain carboxy-terminal globular domain.

The carboxy-terminal globular domain (G-domain) of the laminin alpha1 chain has been shown to promote heparin binding, cell adhesion, and neurite outgrowth. In this study, we defined the potential sequences originating from the G-domain of laminin alpha1 chain which possess these functional activities. A series of peptides were synthesized from the G-domain, termed LG peptides (LG-1 to LG-6) and were tested for their various biological activities. In the direct [3H] heparin binding assays, LG-6 (residues 2,335-2,348: KDFLSIELVRGRVK) mediated high levels of [3H]heparin binding, and this peptide also directly promoted cell adhesion and spreading, including B16F10, M2, HT1080, and PC12 cells. The peptide LG-6 also promoted the neurite outgrowth of PC12 cells, mouse granule cells, and chick telencephalic cells. An anti-peptide LG-6 antibody inhibited laminin-1 and peptide LG-6-mediated cell adhesion and neurite outgrowth. Furthermore, an anti-integrin alpha2 antibody also inhibited the cell adhesion activity. These results suggest that peptide LG-6 plays a functional role as a heparin binding site in the G-domain of the laminin alpha1 chain, and this sequence was thus concluded to play a crucial role in regulating cell adhesion and spreading and neurite out-growth which is related to integrin alpha2.

Amino Acid Sequence↗
PubMed1999

Diastolic potentials in verapamil-sensitive ventricular tachycardia: true potentials or bystanders of the reentry circuits?

BACKGROUND: Diastolic potentials (DP) are reported to be recorded in intracardiac electrograms during verapamil-sensitive ventricular tachycardia (VT) in which QRS complexes show complete right bundle branch block with a superior axis. The purpose of this study was to ascertain whether the DP recorded in the endocardial mapping during VT reflects the activation of the VT circuit. METHODS AND RESULTS: The study group consisted of 16 men and 2 women. The earliest activation site (EA site) was determined and the DP was recorded in the endocardial mapping during VT. We evaluated the response of the cycle length of VT, the interval between the ventricular activation and the DP (V-DP), and the interval between the DP and the ventricular activation (DP-V) to intravenous verapamil. Radiofrequency current was delivered to the EA site, the site where the DP was recorded, and the site where the DP and the Purkinje fiber potential of the left bundle branch (LB) were simultaneously recorded. In 15 patients, the DP was recorded in the wide posterior fascicle region of the LB. After verapamil, the cycle length of VT, the V-DP, and the DP-V were prolonged from 365 +/- 53 to 490 +/- 65, 315 +/- 30 to 368 +/- 30, and 50 +/- 27 to 123 +/- 36 ms, respectively, in 6 patients. The LB was recorded in all patients and the DP was recorded preceding the LB in 12 patients. VT was successfully ablated at the site where the DP and the LB were simultaneously recorded in all these patients. Ablation at the other sites failed. CONCLUSIONS: Radiofrequency ablation at the site where the DP was simultaneously recorded preceding the LB completely abolished the verapamil-sensitive VT. The DP recorded with the LB simultaneously might reflect the slow conduction zone activity of the reentry circuit located within the Purkinje fiber network.

Adolescent↗
PubMed1999

Synthesis and anti-influenza virus activity of novel pyrimidine derivatives.

Efficient synthetic routes of 2-amino-4-(omega-hydroxyalkylamino)pyrimidine derivatives were investigated in relation to the anti-influenza virus activity of these compounds. The derivatives in which cyclobutyl and cyclopentyl groups were introduced to the beta-position of the aminoalkyl group (especially the cyclobutyl group substituted by a phenylalkyl group at the 3'-position) resulted in improved antiviral potency: i.e. an average 50% effective concentration for inhibition of plaque formation (EC50, microM) of 0.1-0.01 microM for both types A and B influenza virus. The antiviral efficacies were in the order of amino group > hydroxyiminomethyl group > halogen substitution at the 5-position, and chlorine or methoxy group > hydrogen at the 6-position of the pyrimidine ring. The antiviral indices of these compounds were 2-6 with respect to the 50% inhibitory concentration for cell proliferation (IC50, microM) for growing cells, but > 500 to > 10(4) with respect to the IC50 for stationary cells, indicating that these compounds may be efficacious for the topical treatment of influenza virus infection.

Animals↗
PubMed1999

Elimination of CO2 in patients with carbonic anhydrase II deficiency, with studies of respiratory function at rest.

We evaluated the elimination of CO2 in three Japanese adults with carbonic anhydrase II (CA II) deficiency, as compared with that in 10 healthy volunteers. The patients had no signs of respiratory distress. Heart rate, body temperature, ventilation volume, respiratory rate and (a-ET) PCO2 were found to be higher and PaCO2 tended to be higher in the patients than those in the volunteers, while forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), tidal volume, end-tidal PCO2 (PETCO2), pH and HCO3- in arterial blood were lower in the patients. All three patients had non-anion-gap metabolic acidosis, due to renal losses of bicarbonate, but with virtually no compensatory reduction in PaCO2. However, the high VE and PaO2 suggested that respiratory compensation for this metabolic acidosis was occurring, the elimination of CO2 was possibly facilitated by the presence of other carbonic anhydrase isoenzymes in the pulmonary capillaries. Thus, CA II deficiency causes mild to moderate impairments in CO2 elimination.

Adolescent↗
PubMed1999

Maxillary protraction and chincap appliance treatment effects and long-term changes in skeletal class III patients.

The purpose of this study was to investigate the orthopedic effects of combined maxillary protraction appliance (MPA) and chincap therapy on growing Japanese girls and the posttreatment changes after growth is complete. To estimate the actual effects of treatment and posttreatment changes, we used a series of templates that had been constructed from semilongitudinal data of Japanese girls with normal occlusion. During treatment, forward movement of the maxilla with counterclockwise rotation, and backward and downward movement of the mandible with clockwise rotation and growth retardation were observed. The forward movement of the maxilla persisted until growth was complete. During the posttreatment period, the mandible maintained its improved position but showed excessive growth, which could be a rebound change. These results indicate that combined MPA and chincap treatment is effective for correcting skeletal Class III malocclusion.

Adolescent↗
PubMed1999

Thoracoscopic resection of intrathoracic vagus neurofibroma.

A thoracoscopic resection of mediastinal neurofibroma originating from the intrathoracic vagus nerve was successfully performed in an 18-year-old female. This report reviews the clinical and morphological features of intrathoracic vagus neurofibroma. Often neurofibroma has multiple lesions and/or multinodular shape. Thoracoscopic resection is a useful treatment for patients with intrathoracic neurofibroma, although careful observation is necessary when performing a radical resection.

Adolescent↗
PubMed1999

Carbon dioxide insufflation aids video-assisted thoracic surgery in a young child.

A 3-year-old girl with pectus excavatum successfully underwent exploration using video-assisted thoracic surgery. A complete pericardial defect was identified. The lung was kept totally collapsed during the procedure using low-flow (1 L/min), low-pressure (7 mmHg) carbon dioxide insufflation. This technique is expected to be a safe adjunct to thoracoscopic procedures in infants and small children.

Carbon Dioxide↗