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Biomedical subjects

Y Sugie

Publications and source records attributed to Y Sugie.

At least 19 recordsLinked to original sources
PubMed2001

Novel exon 11 skipping mutation in a patient with glycogen storage disease type IIId.

We report the molecular genetic abnormalities of a patient with GSD IIId presenting with progressive myopathy and cardiopathy leading to a fatal outcome. We identified two independent deletions including a 4 bp deletion (117-1120) and a 98 bp deletion (1135-1232) in cDNA. Sequencing of the genomic DNA of the corresponding region revealed a 4 bp deletion in exon 10; however, the other 98 bp deletion corresponding to exon 11, which was deleted in cDNA, was present in genomic DNA. We therefore concluded that skipping of exon 11 occurred in the cDNA of the patient. Intron/exon boundary analysis of the skipped exon 11 revealed no mutation in the consensus splice-site sequence. If normal splicing had occurred, a stop codon would have appeared within exon II due to frameshift mutation. The mechanism of exon skipping observed in our patient is as yet unknown, and it is still not clear whether intraexonal mutation of the preceding exon can influence splice-site selection. It is possible that a unique exon skipping occurred, preventing the appearance of a stop codon in our patient.

Adult↗
PubMed2001

Neurotrophic actions of novel compounds designed from cyclopentenone prostaglandins.

Previously we found that some cyclopentenone prostaglandin derivatives promoted neurite outgrowth from PC12 cells and dorsal root ganglia explants in the presence of nerve growth factor; and so we referred to them as neurite outgrowth-promoting prostaglandins (NEPPs). In this study, NEPPs protected HT22 cells against oxidative glutamate toxicity. NEPP6, one of the most effective promoters of neurite outgrowth in PC12 cells, protected the cells most potently among NEPPs 1--10. Several derivatives, NEPPs 11--19, were newly synthesized based on the chemical structure of NEPP6. NEPP11 had a more potent neuroprotective effect than NEPP6. NEPP11 also prevented the death of cortical neurons induced by various stimuli and reduced ischemic brain damage in mice. Biotinylated compounds of NEPPs were synthesized to investigate their cellular accumulation. NEPP6-biotin protected the cells and emitted potent signals from the cells. In contrast, biotinylated non-neuroprotective derivatives emitted much weaker signals. These results suggest that NEPPs are novel types of neurotrophic compounds characterized by their dual biological activities of promoting neurite outgrowth and preventing neuronal death and that their accumulation in the cells is closely associated with their neuroprotective actions.

Animals↗
PubMed2001

CJ-15,801, a novel antibiotic from a fungus, Seimatosporium sp.

A novel antibiotic, CJ-15,801 (I), was isolated from the fermentation broth of a fungus, Seimatosporium sp. CL28611. The structure was determined to be a pantothenic acid analog having an alpha,beta-unsaturated carboxylic acid moiety by spectroscopic analyses. The compound inhibits the growth of multi-drug resistant (MDR) Staphylococcus aureus strains with MIC ranging from 6.25 to 50 microg/ml.

Anti-Bacterial Agents↗
PubMed2001

A new antibiotic CJ-17,665 from Aspergillus ochraceus.

A new antibiotic, CJ-17,665 (I) was isolated from the fermentation broth of Aspergillus ochraceus, CL41582. It inhibits growth of multi-drug resistant Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, with MICs of 12.5, 12.5 and 25 microg/ml, respectively. The structure contains a diketopiperazine and an indole N-oxide moiety that is unusual in natural products.

Anti-Bacterial Agents↗
PubMed2001

New pyrrolizidinone antibiotics CJ-16,264 and CJ-16,367.

Two new antibiotics, CJ-16,264 (I) and CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457. These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coli with altered permeability (imp). Comparison of an antibacterial profile between the two compounds suggested that the gamma-lactone portion of I is important for the activity.

Anti-Bacterial Agents↗
PubMed2001

[Clinical evaluation of treatment with fluvoxamine, a selective serotonin reuptake inhibitor in children with autistic disorder].

The serotonin system has been implicated in the pathoetiology of autistic disorder. To examine the clinical effects of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) in children with autistic disorder, eighteen patients underwent a cross-over, double-blind trial of fluvoxamine treatment after a written informed consent was obtained from patients' parents. Fluvoxamine treatment resulted in significant improvements in some clinical findings such as eye contact and language use, as tested by behavioral assessment scores consisting of twenty items (p < 0.05). The improvement in language use was also confirmed by parental assessments. Clinical Global Impression Scale was improved in approximately half of the patients. No severe adverse effect was observed during the trial. Thus SSRI treatment in autistic children may be of value.

Autistic Disorder↗
PubMed2001

[Rett syndrome].

Explore the source record for details and available documents.

Female↗
PubMed2000

Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes.

Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon receptor from adenylate cyclase activation in rat liver membranes (1). We have examined the effects of skyrin on cells transfected with the human glucagon receptor and on isolated rat and human hepatocytes. The skyrin used was isolated from Talaromyces wortmanni American Type Culture Collection 10517. In rat hepatocytes, skyrin (30 micromol/l) inhibited glucagon-stimulated cAMP production (53%) and glucose output (IC50 56 micromol/l). There was no detectable effect on epinephrine or glucagon-like peptide 1 (GLP-1) stimulation of these parameters, which demonstrates skyrin's selective activity. Skyrin was also evaluated in primary cultures of human hepatocytes. Unlike cell lines, which are largely unresponsive to glucagon, primary human hepatocytes exhibited glucagon-dependent cAMP production for 14 days in culture (EC50 10 nmol/l). Skyrin (10 micromol/l) markedly reduced glucagon-stimulated cAMP production (55%) and glycogenolysis (27%) in human hepatocytes. The inhibition of glucagon stimulation was a specific property displayed by skyrin and oxyskyrin but not shared by other bisanthroquinones. Skyrin is the first small molecular weight nonpeptidic agent demonstrated to interfere with the coupling of glucagon to adenylate cyclase independent of binding to the glucagon receptor. The data presented in this study indicate that functional uncoupling of the human glucagon receptor from cAMP production results in metabolic effects that could reduce hepatocyte glucose production and hence alleviate diabetic hyperglycemia.

Animals↗
PubMed1999

Assessment of mucosal immune response in genitourinary tract using urine.

A novel method to assess mucosal immune response in the genitourinary mucosa after immunization with a mucosal vaccine has been developed. In this method, secretory IgA antibody is measured by a highly sensitive enzyme immunoassay (immune-complex transfer enzyme immunoassay) using urine as a specimen. The urinary IgA antibody response could be detected by the immune-complex transfer enzyme immunoassay. In contrast, a conventional enzyme immunoassay (enzyme-linked immunosorbent assay (ELISA)) could not detect this response because of its low sensitivity. Because urine samples can be collected easily and nontraumatically, not only from experimental animals but also from humans, both males and females, the present method may be applicable for assessing the protective efficacy of candidates for mucosal vaccines against sexually transmitted microorganisms, such as human immunodeficiency virus. Furthermore, the usefulness of this method for novel mucosal vaccine formulae was shown for a model in which vaccine antigen and Bordetella pertussis adjuvant were adsorbed onto CaCO, and enclosed in enteric coated capsules.

Adjuvants, Immunologic↗
PubMed1998

Development of a highly sensitive and specific two-site enzyme immunoassay for parathyroid hormone (1-34): application to pharmacokinetic study on intranasal parathyroid hormone (1-34) in human.

A highly sensitive and specific two-site enzyme immunoassay for parathyroid hormone (1-34) (PTH(1-34)) and its usability for the pharmacokinetic study are described. Plasma samples were incubated simultaneously with 2,4-dinitrophenylated anti-PTH(1-34) IgG and anti-PTH(1-34) Fab'-beta-D-galactosidase conjugate. The immune complex formed of the three components was trapped onto (anti-2,4-dinitrophenyl group) IgG-coated polystyrene balls. beta-D-Galactosidase activity bound to the polystyrene balls was assayed by fluorometry. The practical detection limit of PTH(1-34) was 50 fg (12 amol)/0.05 ml of sample and 1 pg/ml as the concentration and practically no interference occurred by PTH(1-84) and PTH-related protein (1-34) up to 300 pg/ml and 10 ng/ml, respectively. The application of this method has enabled us to directly estimate the bioavailability of PTH(1-34) dosed intranasally at the prescribed level (0.090 mg). The pharmacokinetic parameters of the intranasal PTH(1-34) (n = 4) thus estimated were as follows: the area under the plasma concentration-time curve (AUC) = 20,500+/-15,900(SD) pg.min/ml; the mean residence time (MRT) = 194+/-16.3(SD) min; and the maximal concentration (Cmax) = 98+/-51 (SD) pg/ml with the maximal time (Tmax) = 35.0+/-12.2(SD) min.

Adult↗
PubMed1998

Determination of the bioavailability of intranasal elcatonin in humans: development of a sandwich transfer enzyme immunoassay for elcatonin.

A sandwich transfer enzyme immunoassay for elcatonin (ECT) and its usability for the pharmacokinetic study are described. The anti-salmon calcitonin (SCT) antibody was used for the present assay. The assay procedure consisted of the reaction of ECT with 2,4-dinitrophenylbiotinyl anti-SCT IgG and anti-SCT Fab'-beta-D-galactosidase conjugate, trapping onto (anti-2,4-dinitrophenyl bovine serum albumin) IgG-coated polystyrene balls, eluting with epsilonN-2,4-dinitrophenyl-L-lysine and transferring to streptavidin-coated polystyrene balls and fluorometric detection of beta-D-galactosidase activity. The practical detection limit of ECT was 0.15 pg (44 amol)/50 microl of sample and 3 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of ECT dosed intranasaly at a therapeutic level (100 IU, 17 microg) for its anti-osteoporotic effect as compared to an intramuscular dose (40 IU, 6.7 microg). The pharmacokinetic parameters of the intranasal ECT (n = 6) thus estimated were as follows: the area underthe serum concentration-time curve (AUC) = 2,570 +/- 1,650 (SD) pg x min/ml, and the maximal concentration (Cmax) = 60 +/- 25 (SD) pg/ml with the maximal time (Tmax) = 17.5 +/- 6.9 (SD) min, when the AUC for the intramuscular ECT (n = 9) = 9,460 +/- 5,870 (SD) pg x min/ml and the Cmax = 165 +/- 79 (SD) pg/ml with the Tmax = 16.1 +/- 4.2 (SD) min.

Administration, Intranasal↗
PubMed1997

A sandwich transfer enzyme immunoassay for salmon calcitonin: determination of the bioavailability of intranasal salmon calcitonin in human.

A sandwich transfer enzyme immunoassay for salmon calcitonin (SCT) and its usability for the pharmacokinetic study are described. The assay procedure consisted of the reaction of SCT with 2,4-dinitrophenyl biotinyl anti-SCT IgG and anti-SCT Fab'-beta-galactosidase conjugate, trapping onto (anti-2,4-dinitrophenyl bovine serum albumin) IgG-coated polystyrene balls, eluting with epsilon N-2,4-dinitrophenyl-L-lysine and transferring to streptavidin-coated polystyrene balls and fluorometric detection of beta-D-galactosidase activity. The practical detection limit of SCT was 0.05 pg (15 amol)/50 microliters of sample and 1 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of SCT dosed intranasally at the therapeutic level (160 IU, 31 micrograms) for its anti-osteoporotic effect as compared to an intramuscular dose (10 IU, 1.9 micrograms). The pharmacokinetic parameters of the intranasal SCT (n = 6) thus estimated were as follows: the area under the blood concentration-time curve (AUC) 9400 +/- 5400 (SD) pg.h/ml, and the mean residence time (MRT) = 42 +/- 14 (SD) min, when the AUC for the intramuscular SCT (n = 3) = 5600 +/- 2000 (SD) pg.h/ml and the MRT = 39 +/- 19 (SD) min.

2,4-Dinitrophenol↗
PubMed1997

CJ-12,954 and its congeners, new anti-Helicobacter pylori compounds produced by Phanerochaete velutina: fermentation, isolation, structural elucidation and biological activities.

Seven new phthalide compounds with anti-Helicobacter pylori activities were isolated from the basidiomycete Phanerochaete velutina CL6387. The two most potent phthalide compounds, CJ-12,954 and CJ-13,014, have MICs of 5 ng/ml. The structure-activity relationship shows that the presence of a spiroketal part in addition to the phthalide part, greatly enhances the activity. The phthalide compounds appear to be specific for H. pylori, since they did not show antibacterial activities when tested against a panel of other microorganisms.

Anti-Bacterial Agents↗
PubMed1996

[Nine cases of debrancher deficiency (glycogen storage disease type III) presenting muscle weakness--study on clinicobiochemical analysis].

In nine patients aged 3 to 45 years with glycogen storage disease type III (GSD III) presenting muscle weakness, the clinical manifestations and biochemical subtype-classifications based on organ specificity or enzymatic varieties of debrancher enzyme were analyzed. All the patients developed muscle weakness since childhood. Five patients who showed muscle weakness beginning from childhood became apparently progressive during adult life. Cardiac involvements were noticed in six patients. Eight patients were diagnosed as having type IIIa and one type IIId. Our results suggest that progressive muscle weakness and cardiac symptoms are not rare in GSD III patients, especially in the patients with enzyme deficiency in muscle tissue as well as liver. Hence we recommend to measure debrancher activity in muscle tissue in order to predict the clinical prognosis of the patients with GSD III.

1,4-alpha-Glucan Branching Enzyme↗