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Yuko Nakamura

Publications and source records attributed to Yuko Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Structural basis of RNA-dependent recruitment of glutamine to the genetic code.

Glutaminyl-transfer RNA (Gln-tRNA(Gln)) in archaea is synthesized in a pretranslational amidation of misacylated Glu-tRNA(Gln) by the heterodimeric Glu-tRNA(Gln) amidotransferase GatDE. Here we report the crystal structure of the Methanothermobacter thermautotrophicus GatDE complexed to tRNA(Gln) at 3.15 angstroms resolution. Biochemical analysis of GatDE and of tRNA(Gln) mutants characterized the catalytic centers for the enzyme's three reactions (glutaminase, kinase, and amidotransferase activity). A 40 angstrom-long channel for ammonia transport connects the active sites in GatD and GatE. tRNA(Gln) recognition by indirect readout based on shape complementarity of the D loop suggests an early anticodon-independent RNA-based mechanism for adding glutamine to the genetic code.

Acylation↗
PubMed2006

Comparative assessment of distribution of blackcurrant anthocyanins in rabbit and rat ocular tissues.

Anthocyanins (ACs) are phenolic compounds that are distributed widely in fruits and vegetables. Although consumption of these compounds has been shown to improve visual function, the distribution of ACs in ocular tissue has not been examined in detail. The aim of this study was therefore to evaluate the ocular distribution of blackcurrant anthocyanins (BCAs) in rats and rabbits after oral, intravenous (i.v.) and intraperitoneal (i.p.) administration. Identification and quantification of ACs were carried out using high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) and high-performance liquid chromatography (HPLC) with UV-visible detection, respectively. BCAs were identified in the plasma and whole eye after oral and i.p. administration in rats. No other peaks were detected in either plasma or ocular tissues after administration when the absorbance of the eluate was monitored at 520 nm. This finding indicates that intact forms of ACs were present in rats after administration of BCA. In rats given i.p. administration, the concentration of total ACs in the whole eye and some ocular tissues was higher than that measured in plasma. These results suggested that ACs detected in the ocular tissues were not due to residual blood. Following i.v. administration in rabbits, four ACs were identified in the plasma and several ocular tissues including the aqueous humor, cornea, sclera, choroid, ciliary body, iris and retina. A small amount of ACs was also detected in the vitreous and lens. In conclusion, this study demonstrated that BCAs were absorbed and distributed in ocular tissues as intact forms. Our data show clearly that intact forms of BCAs pass thorough the blood-aqueous barrier and blood-retinal barrier in both rats and rabbits.

Administration, Oral↗
PubMed2006

Role of free radicals and metal ions in direct current-induced cytotoxicity.

The purpose of this study was to investigate the mechanism of direct current (DC)-induced cytotoxicity. To test the working hypothesis that electrolysis products are responsible for the DC-induced cytotoxicity, the cytotoxic effects between the direct and indirect DC treatment against human polymorphonuclear cells (PMNs) was compared. The indirect DC treatment (treatment with the culture medium exposed to DC) was comparable in cytotoxicity to the direct DC treatment, suggesting that electrolysis products have an important role in DC-induced cytotoxicity. Metal ions released from different electrodes into the culture medium were quantified by the inductively coupled plasma-mass spectroscopy. Higher concentrations of Ag, Zn, and Ni and chromium were released from Ag, Zn, and stainless steel (St) electrodes, respectively, whereas much lower concentrations of Ni and Ti were released from Ni-Ti electrode. Further, electron spin resonance spectroscopy with spin-trapping agent showed that the direct current with the following metal electrodes generated alkoxyl radical (St and Ni-Ti electrodes), hydrogen radical (Ag and Au electrodes), and both carbon and alkoxyl radicals (Zn electrode), respectively. These results suggest that free radicals and metal ions released from electrodes contribute to the cytotoxicity of DC treatment used for iontophoresis.

Culture Media↗
PubMed2006

Distribution of PrP(Sc) in cattle with bovine spongiform encephalopathy slaughtered at abattoirs in Japan.

Three 80- to 95-month-old Holstein dairy cattle infected naturally with the agent of bovine spongiform encephalopathy (BSE) and slaughtered at abattoirs in Japan were examined for the distribution of disease-specific and protease-resistant prion protein (PrP(Sc)) by immunohistochemistry (IHC) and Western blot (WB) analyses. The cattle showed no clinical signs or symptoms relevant to BSE but were screened as positive by enzyme-linked immunosorbent assay, a rapid test for BSE. This positive result was confirmed by IHC or WB in a specimen of the medulla oblongata. Histopathologically, these cattle showed no vacuolation in tissue sections from the central nervous system except for the medulla oblongata. Both IHC and WB analyses revealed PrP(Sc) accumulation in the brain, spinal cord, satellite and ganglionic cells of the dorsal root ganglia, and the myenteric plexus of the distal ileum. In addition, small amounts of PrP(Sc) were detected in the peripheral nerves of 2 cattle by WB. No PrP(Sc) was demonstrated by either method in the Peyer's patches of the distal ileum; lymphoid tissues including the palatine tonsils, lymph nodes, and spleen; or other tissues. The distribution of PrP(Sc) accumulation in the preclinical stage was different between naturally infected cattle and cattle inoculated experimentally with the BSE agent.

Abattoirs↗
PubMed2005

Myocilin gene expression in the trabecular meshwork of rats in a steroid-induced ocular hypertension model.

PURPOSE: To investigate the expression pattern of myocilin in the trabecular meshwork of normal and dexamethasone-induced ocular hypertensive rat eyes. MATERIALS AND METHODS: An ocular hypertension model was generated by application of topical dexamethasone to rat eyes 4 times daily for 1, 2, and 4 weeks. Age-matched untreated eyes served as controls. The intraocular pressure (IOP) was monitored by electronic Tono-pen under anesthesia. The protein and mRNA levels of myocilin in the trabecular meshwork and endothelial lining of Schlemm's canal were investigated by immunohistochemistry and in situ hybridization, respectively. For semiquantitative evaluation, areas with positive staining were analyzed by a computer-assisted image-processing system with NIH software. RESULTS: The IOP in rat eyes was elevated after 2 weeks of topical dexamethasone treatment. Despite the IOP elevation, the protein and mRNA levels of myocilin in the trabecular meshwork and around Schlemm's canal in the steroid-treated eyes were not different from those of controls. CONCLUSION: No discernible changes in myocilin expression in the chamber angle indicate that myocilin may not be directly linked to ocular hypertension, at least not in rat eyes after relatively short-term steroid application.

Animals↗
PubMed2005

Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients.

To compare the efficacy, adverse effects, and patient compliance of latanoprost monotherapy with unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of chronic primary angle-closure glaucoma (CACG), 36 Japanese patients with CACG following laser iridotomy (LPI) were treated for 12 weeks with instillation of latanoprost alone or with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. After 12 weeks of treatment, latanoprost reduced intraocular pressure (IOP) from 22.2 +/- 2.0 mmHg to 14.8 +/- 1.9 mmHg (33% reduction); timolol maleate and dorzolamide hydrochloride also reduced IOP from 22.5 +/- 2.2 mmHg to 17.1 +/- 2.7 mmHg (24% reduction). Latanoprost monotherapy significantly lowered IOP compared with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. Furthermore, a systemic adverse effect of bradycardia was not observed in the latanoprost monotherapy group. Concerning compliance, no significant difference was observed between the two groups. Thus, latanoprost monotherapy is more effective than unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of CACG following relief of pupillary block in Japanese patients.

Aged↗
PubMed2005

Cytotoxicity of direct current with antibacterial agents against host cells in vitro.

The purpose of this study was to investigate the cytotoxicity of iontophoresis treatment using direct current (DC) with or without antibacterial agents. The following antibacterial agents were used: diamine silver fluoride (AgF); sodium fluoride (NaF); and iodine zinc iodide (JJZ). The cytotoxic activity of DC with or without antibacterial agents against human polymorphonuclear cells (PMNs) was evaluated by the 3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. It was noted that DC (2 mA) killed PMNs in a time-dependent manner and the cytotoxicity was enhanced when DC was combined with antibacterial agents. The toxic effect of antibacterial agents was in the order: AgF>JJZ>NaF. The death of PMNs by DC was evaluated by flow cytometry using annexin V-FITC/propidium iodide staining. DC appeared to induce necrosis rather than apoptosis of PMNs. These results suggest that iontophoresis treatment using DC and antibacterial agents may induce necrotic cytotoxicity in host cells around periapical lesions.

Analysis of Variance↗
PubMed2005

Infection route-independent accumulation of splenic abnormal prion protein.

The accumulation kinetics of the abnormal form of prion protein (PrP(Sc)) in spleens and brains of scrapie (Obihiro-1)-infected mice at various times after intracerebral (i.c.), intraperitoneal (i.p.), or oral inoculation were studied. PrP(Sc) was first detected by Western blotting with anti-prion protein antibodies on days 70 and 116 after i.c. (3 microg) in spleens and brains, respectively. Although the amount of cerebral PrP(Sc) gradually increased to the maximum level on day 152 after i.c. inoculation, splenic PrP(Sc) established the maximum level on day 116 after i.c. inoculation then registered slight decreases up to day 152 with further incubation. The detectable levels of cerebral PrP(Sc) by Western blotting were established on day 231 or 259, whereas those of splenic PrP(Sc) were detected on day 94 or 93, after i.p. and oral infection, respectively. The splenic PrP(Sc) decreased slightly thereafter. These results indicate that splenic PrP(Sc) increased before cerebral PrP(Sc) established a detectable level in a manner independent of the inoculation route.

Animals↗
PubMed2004

Assessment of chamber angle pigmentation during longterm latanoprost treatment for open-angle glaucoma.

PURPOSE: This study aimed to determine whether the longterm use of latanoprost is associated with an increase in trabecular pigmentation, especially in subjects in whom iris pigmentation has increased. METHODS: We enrolled 50 subjects for whom treatment was to start for ocular hypertension, primary open-angle glaucoma or normal tension glaucoma. All subjects received latanoprost 0.005% daily. Trabecular pigmentation was documented using gonioscopic photography of the inferior quadrant at baseline, every 3 months for the first year and every 6 months for the second and third years. Three glaucoma specialists evaluated the series of gonioscopic photographs for each eye of each subject in a masked fashion. The intraocular pressure (IOP) was also recorded at each visit. RESULTS: A total of 41 subjects (79 eyes) completed 3 years of follow-up, and none showed any increase in the grade of trabecular pigmentation, including 10 subjects (20 eyes) in whom the iridial pigment increased. CONCLUSION: Although latanoprost increased iridial pigmentation in some subjects, we found no evidence of an increase in trabecular pigmentation over the 3 years of follow-up.

Antihypertensive Agents↗
PubMed2004

Analysis of information submitted by clinical trial sponsors regarding the safety of investigational drugs.

During performance of clinical trials in medical institutions, information regarding the safety of investigational drugs is submitted by trial sponsors according to guidelines for good clinical practice. In the present study, reports of clinical trials conducted at the University of Tokyo Hospital were examined, focusing on the safety information provided to the Institutional Review Board (IRB). Two hundred two reports (52 protocols) of safety information were submitted to the IRB by clinical trial sponsors between April 2000 and March 2001, of which 185 contained a total of 3021 cases of adverse events. Of those, 194 reports were judged by clinical investigators/physicians not to be associated with any significant problems and the trials were continued. For 157 of those 194 reports, it was considered unnecessary to inform the test subjects of the report contents, including the adverse events. The decision of whether or not the test subjects should be informed of such contents tended to depend on the causal relationship between the adverse events and drug intake, as well as the predictability of the adverse events. For 8 of those 194 reports, the IRB recommended that the clinical investigators/ physicians provide information to the test subjects and/or submit detailed information on the status of these subjects to the IRB. From these results, we suggest that establishment of a system to unify and evaluate drug safety information is necessary to provide safe and efficient clinical trials.

Clinical Trials as Topic↗
PubMed2004

[Myeloperoxidase].

Explore the source record for details and available documents.

Acute Disease↗
PubMed2003

Impairment of superoxide dismutase activation by N-terminally truncated prion protein (PrP) in PrP-deficient neuronal cell line.

Previous studies have reported a neuroprotective role for cellular prion protein (PrP(C)) against apoptosis induced by serum deprivation in an immortalized prion protein gene (Prnp)-deficient neuronal cell line, but the mechanisms remain unclear. In this study, to investigate the mechanisms by which PrP(C) prevents apoptosis, the authors compared apoptosis of Prnp(-/-) cells with that of Prnp(-/-) cells expressing the wild-type PrP(C) or PrP(C) lacking N-terminal octapeptide repeat region under serum-free conditions. Re-introduction of Prnp rescued cells from apoptosis, upregulated superoxide dismutase (SOD) activity, enhanced superoxide anion elimination, and inhibited caspase-3/9 activation. On the other hand, N-terminally truncated PrP(C) enhanced apoptosis accompanied by potentiation of superoxide production and caspase-3/9 activation due to inhibition of SOD. These results suggest that PrP(C) protects Prnp(-/-) cells from apoptosis via superoxide- and caspase-3/9-dependent pathways by upregulating SOD activity. Furthermore, the octapeptide repeat region of PrP(C) plays an essential role in regulating apoptosis and SOD activity.

Amyloid↗
PubMed2003

Stimulatory effect of cyanidin 3-glycosides on the regeneration of rhodopsin.

Anthocyanins have been suggested to improve visual functions. This study examined the effect of four anthocyanins in black currant fruits on the regeneration of rhodopsin using frog rod outer segment (ROS) membranes. Cyanidin 3-glycosides, glucoside and rutinoside, stimulated the regeneration, but the corresponding delphinidins showed no significant effect. The formation of a regeneration intermediate was suggested to be accelerated by cyanidin 3-rutinoside. Their effects on the cGMP-phosphodiesterase activity in the ROS membranes were also investigated but found to be negligible. It was concluded that the major effect of anthocyanins in rod photoreceptors is on the regeneration of rhodopsin.

Animals↗
PubMed2003

Perforating pilomatricoma in a process of total elimination.

Perforating pilomatricoma is a rare clinical variant of pilomatricoma. We report a case of pilomatricoma with ulceration indicating total elimination. The lesion consisted mainly of laminating shadow cells surrounded by invaginating epidermis. We believe that this case can be considered within the category of perforating pilomatricoma.

Aged↗
PubMed2003

Transfection of prion protein gene suppresses coxsackievirus B3 replication in prion protein gene-deficient cells.

The susceptibility of prion protein gene (Prnp)-null cells to coxsackievirus B3 (CVB3) was investigated. Primary cultures of murine Prnp(-/-) brain cells were more sensitive to CVBs than corresponding cells from wild-type mice. The viral susceptibility of a Prnp-null cell line (HpL3-4) derived from the murine hippocampus was compared with that of two established cell lines (HeLa and HEp-2) that are widely employed for CVB3 studies. After infection with CVB3, HpL3-4 cells showed a very rapid and complete cytopathic effect (CPE). CPE developed earlier and viruses replicated at higher titres in HpL3-4 cells compared with HeLa and HEp-2 cells. Under a semi-solid medium, plaques developed rapidly in CVB3-infected HpL3-4 cells. To confirm the effect of Prnp on virus infection, a Prnp(-/-) cell line and a Prnp-transfected neuronal cell line were analysed. The replication and release of infectious particles of CVB3 in Prnp(-/-) cells were significantly more effective than those of the Prnp-transfected cell line. Levels of type I interferon (IFN) after CVB3 infection were higher in the Prnp-transfected cell line than in Prnp(-/-) cells, whereas apoptotic cells were more obvious in the Prnp(-/-) cells than in those of the Prnp-transfected cell line. These findings suggest that the absence of Prnp retards the induction of CVB3-induced IFNs, resulting in an enhanced CVB3 production and apoptotic cell death. Furthermore, our data indicate that the HpL3-4 cell line may provide a novel and sensitive system for isolation of CVB3 from clinical specimens.

Animals↗
PubMed2003

Anti-cariogenic properties of a water-soluble extract from cacao.

The addition of a water-soluble extract from cacao-extracted powder (CEPWS) to a cariogenic model food, a white chocolate-like diet that contains 35% sucrose, significantly reduced caries scores in SPF rats infected with Streptococcus sobrinus 6715, compared to control rats fed a white chocolate-like diet. CEPWS markedly inhibited water-insoluble glucan (WIG) synthesis through crude glucosyltransferases (GTFs) from Streptococcus sobrinus B13N in vitro. GTF-inhibitor(s) in CEPWS was prepared through three-step fractionation, and was termed CEPWS-BT, which is a high molecular weight (>10 kDa) heat-stable matrix of sugar, protein, and polyphenol. When the inhibitory effect of CEPWS-BT on glucan synthesis was examined using the purified GTF-I, GTF-T, and GTF-U enzymes from S. sobrinus B13N, significant reduction in GTF-I and GTF-T activity as a result of adding CEPWS-BT at low concentrations was observed. These results suggest that the addition of CEPWS to cariogenic food could be useful in controlling dental caries.

Animals↗
PubMed2003

[Acute lymphoblastic leukemia with invasive fungal infection causing complete atrioventricular block].

A 62-year-old female was diagnosed as having acute lymphocytic leukemia in October 2001. She achieved complete remission after induction therapy with L-asparaginase, doxorubicin, vincristine and prednisolone. However, an invasive fungal infection developed in the lung, followed by a sudden complete atrioventricular block. Her heart rate was brought back to normal by the administration of isoproterenol. In spite of anti-fungal therapies, the patient finally succumbed to pneumonia in January 2002. Autopsy revealed an invasion of fungi into the lung, mitral valves and atrioventricular node. We need to pay attention to such a cardiac complication when an immunocompromised host suffers from an invasive fungal infection.

Female↗