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Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 703 records · Page 39Linked to original sources

Quality of hearing preservation in acoustic neuroma surgery.

OBJECTIVE: This study aimed to investigate the factors affecting the quality of postoperative hearing in acoustic neuroma. STUDY DESIGN: The study was designed as a retrospective case review. SETTING: The study was performed at the Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan. PATIENTS: The subjects were 94 patients with unilateral acoustic neuroma. INTERVENTION: Hearing preservation surgery was performed in the subjects via the extended cranial fossa approach or the middle cranial fossa approach. MAIN OUTCOME MEASURES: The outcome measures included patient's age and gender, hearing level, speech discrimination score, tumor size, and surgical approach. The relationship between the qualities of preoperative and postoperative hearing and the long-term prognosis of preserved hearing also was investigated. RESULTS: In 94 subjects, there were 47 patients whose hearing was preserved (HP group) and 47 patients whose hearing was not preserved (non-HP group). Overall, hearing preservation rate was 50%. There were no significant differences in age, gender, and tumor size between the two groups. The hearing preservation rate was significantly higher in patients with an intracanalicular tumor than that with a larger tumor. The better the preoperative quality of hearing was, the higher the postoperative one. Although the preserved hearing deteriorated after surgery in 4 patients, no significant hearing deterioration was observed in the other 43 patients. CONCLUSIONS: The results of this study indicated that the diagnosis for acoustic neuroma in the early stage with serviceable hearing is the most important to improve the quality of postoperative hearing.

Adolescent↗

[Results of clinical study with epirubicin hydrochloride injectable solution in hepatoma].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic artery and a three-week drug-free interval followed. Of 15 patients with hepatocellular carcinoma registered in this study, 14 patients were eligible, and they all completed the entire course. The objective was to investigate the safety of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug reactions frequently observed in these 14 eligible cases were leukopenia, neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and tolerable. With these results. Epirubicin-RTU was considered to be a safe pharmaceutical product to inject into the hepatic artery.

Adult↗

Evaluation of glomerular filtration rate by camera-based method in both children and adults.

UNLABELLED: We describe a method to evaluate glomerular filtration rate (GFR) in both children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40 children and 92 adults with various degrees of renal function. The percent renal uptake at 2-2.5 min after tracer arrival in the kidney was determined with background subtraction and correction for soft-tissue attenuation and was correlated by linear regression analysis with GFR measured from two blood samples. A perirenal region of interest was used for background subtraction. Renal depth was computed using the equations determined or validated on the basis of CT measurements, and the attenuation coefficient was set at 0.12. The obtained regression equation was used to predict GFR. Renal function was also assessed by the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939). GFR was successfully predicted using the regression equation in both children and adults. Gates' method severely overestimated GFR in children and provided less accurate values even in adults than our method. CONCLUSION: The method presented here requires neither blood sampling nor additional imaging and allows estimation of GFR in both children and adults.

Adult↗

[Advanced hepatocellular carcinoma: therapeutic results in 110 patients and therapeutic strategy].

The prognoses of 110 patients with advanced hepatocellular carcinoma (HCC) in stages III and IV were studied retrospectively. These patients were treated mainly by transarterial chemoembolization (TAE) or chemoinfusion using Lipiodol. Some of the patients underwent percutaneous ethanol injection therapy (PEIT) or tumor resection following TAE. Hepatic function, tumor stage, vascular involvement, type of tumor invasion, number of tumors and number of treatments affected the prognosis of the patients. The prognosis was better in the Child A group than in Child B and C. In the Child C group, the prognosis was markedly poor, and was least affected by any treatment. The prognoses in the patients with multiple nodular lesions, massive or diffuse lesions, were much poorer than those with a few nodular lesions. Tumor thrombosis in the central portal vein and distant metastasis greatly exacerbated the therapeutic results. Repeat therapy yielded a favorable therapeutic result when hepatic function was tolerable. Surgical intervention and PEIT were an effective therapy in a few patients. In advanced HCC, liver function and tumor extension should be fully evaluated, and it is important to determine the most effective therapeutic modalities to improve the survival of patients.

Adult↗

[Appropriate laboratory use of microbiological testing for quality control and nosocomial infection control].

Useful information from clinical microbiological tests is required for clinical diagnosis and treatment of infectious disease, whereas concern about the quality of information is still low. To provide reliable information in clinical microbiological testing, it is necessary to control the quality of clinical specimens, because of its random character. Through effective use of laboratory testing database, it will be possible to shift away our vague management of pre-analytic phase of quality control so far to its established system based on objective evaluation. During the past 4 years, after the introduction of microbiological tests and information system in our hospital, the characteristics of sputum have become worse contrary to our expectations. This suggests that quality control needs successive improvements, even in service departments such as clinical laboratories. Application of laboratory testing database to nosocomial infection control is considered to be a performance of post-analytic phase of quality control from the viewpoint of effective use of laboratory data. We presented in this paper our practical application of the database to the short-term and long-term control of nosocomial infection.

Clinical Laboratory Information Systems↗

Impaired parallel fiber-->Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit.

The glutamate receptor delta2 subunit (GluRdelta2) is specifically expressed in cerebellar Purkinje cells (PCs) from early developmental stages and is selectively localized at dendritic spines forming synapses with parallel fibers (PFs). Targeted disruption of the GluRdelta2 gene leads to a significant reduction of PF-->PC synapses. To address its role in the synaptogenesis, the morphology and electrophysiology of PF-->PC synapses were comparatively examined in developing GluRdelta2 mutant and wild-type cerebella. PCs in GluRdelta2 mutant mice were normally produced, migrated, and formed spines, as did those in wild-type mice. At the end of the first postnatal week, 74-78% of PC spines in both mice formed immature synapses, which were characterized by small synaptic contact, few synaptic vesicles, and incomplete surrounding by astroglial processes, eliciting little electrophysiological response. During the second and third postnatal weeks when spines and terminals are actively generated, the percentage of PC spines forming synapses attained 98-99% in wild type but remained as low as 55-60% in mutants, and the rest were unattached to any nerve terminals. As a result, the number of PF synapses per single-mutant PCs was reduced to nearly a half-level of wild-type PCs. Parallelly, PF stimulation less effectively elicited EPSCs in mutant PCs than in wild-type PCs during and after the second postnatal week. These results suggest that the GluRdelta2 is involved in the stabilization and strengthening of synaptic connectivity between PFs and PCs, leading to the association of all PC spines with PF terminals to form functionally mature synapses.

Animals↗

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq.

Mice lacking the alpha-subunit of the heterotrimeric guanine nucleotide binding protein Gq (Galphaq) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of the cerebellum is not overtly disturbed, and excitatory synaptic transmission from parallel fibers to cerebellar Purkinje cells (PCs) and from climbing fibers (CFs) to PCs is functional. However, about 40% of adult Galphaq mutant PCs remain multiply innervated by CFs because of a defect in regression of supernumerary CFs in the third postnatal week. Evidence is provided suggesting that Galphaq is part of a signaling pathway that is involved in the elimination of multiple CF innervation during this period.

Age Factors↗

Structural coupling between the oxygen-evolving Mn cluster and a tyrosine residue in photosystem II as revealed by Fourier transform infrared spectroscopy.

The flash-induced Fourier transform infrared (FTIR) difference spectrum of the oxygen-evolving Mn cluster upon S1-to-S2 transition (S2/S1 spectrum) was measured using photosystem II (PS II) core complexes of Synechocystis 6803 in which tyrosine residues were specifically labeled with 13C at the ring-4 position. The double-difference spectrum between the unlabeled and labeled S2/S1 spectra showed that the bands at 1254 and 1521 cm-1 downshifted by 25 and 15 cm-1, respectively, upon ring-4-13C-Tyr labeling. This observation indicates that there is a tyrosine residue coupled to the Mn cluster, and the vibrational modes of this tyrosine are affected upon S2 formation. From a comparison of the above band positions and isotopic shifts in the S2/S1 spectrum with those of the FTIR spectra of tyrosine in aqueous solution at pH 0.6 (Tyr-OH) and pH 13.4 (Tyr-O-) and of the YD./YD FTIR difference spectrum, the 1254 and 1521 cm-1 bands were assigned to the CO stretching and ring CC stretching modes of tyrosine, respectively, and this tyrosine was suggested to be protonated in PS II. The observation that the effect of the S2 formation on the tyrosine bands appeared as a decrease in intensity with little frequency change could not be explained by a simple electrostatic effect by Mn oxidation, suggesting that the Mn cluster and a tyrosine are linked via chemical and/or hydrogen bonds and the structural changes of the Mn cluster are transmitted to the tyrosine through these bonds. On the basis of previous EPR studies that showed close proximity of YZ to the Mn cluster, YZ was proposed as the most probable candidate for the above tyrosine. This is the first demonstration of the structural coupling between YZ and the Mn cluster in an intact oxygen-evolving complex. This structural coupling may facilitate electron transfer from the Mn cluster to YZ. Our observation also provides an experimental support in favor of the proton or hydrogen atom abstraction model for the YZ function.

Bacterial Proteins↗

Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord.

The glutamate transporter GLAST is localized on the cell membrane of mature astrocytes and is also expressed in the ventricular zone of developing brains. To characterize and follow the GLAST-expressing cells during development, we examined the mouse spinal cord by in situ hybridization and immunohistochemistry. At embryonic day (E) 11 and E13, cells expressing GLAST mRNA were present only in the ventricular zone, where GLAST immunoreactivity was associated with most of the cell bodies of neuroepithelial cells. In addition, GLAST immunoreactivity was detected in radial processes running through the mantle and marginal zones. From this characteristic cytology, GLAST-expressing cells at early stages were judged to be radial glia cells. At E15, cells expressing GLAST mRNA first appeared in the mantle zone, and GLAST-immunopositive punctate or reticular protrusions were formed along the radial processes. From E18 to postnatal day (P) 7, GLAST mRNA or its immunoreactivity gradually decreased from the ventricular zone and disappeared from radial processes, whereas cells with GLAST mRNA spread all over the mantle zone and GLAST-immunopositive punctate/reticular protrusions predominated in the neuropils. At P7, GLAST-expressing cells were immunopositive for glial fibrillary acidic protein, an intermediate filament specific to astrocytes. Therefore, the glutamate transporter GLAST is expressed from radial glia through astrocytes during spinal cord development. Furthermore, the distinct changes in the cell position and morphology suggest that both the migration and transformation of radial glia cells begin in the spinal cord between E13 and E15, when the active stage of neuronal migration is over.

ATP-Binding Cassette Transporters↗

Estimates of the cost-effectiveness of a single course of interferon-alpha 2b in patients with histologically mild chronic hepatitis C.

BACKGROUND: Chronic hepatitis C is a major cause of illness and death in the United States. Interferon-alpha 2b can induce clinical, biochemical, and virologic remission in some patients with chronic hepatitis C, but the long-term cost-effectiveness of this treatment, particularly in patients with histologically mild disease, is unknown. OBJECTIVE: To estimate the cost-effectiveness of interferon-alpha 2b in mild chronic hepatitis C. DESIGN: Meta-analysis of five prospective trials and cost-effectiveness analysis. Projection of the clinical and economic outcomes expected from loss of hepatitis C virus was done by using a Markov simulation. The potential effect of uncertainty in the model assumptions was tested by using sensitivity analyses. DATA SOURCES: Search of the MEDLINE database, opinions of expert panels, hospital cost data, and adjusted physician charges. PATIENTS: Hypothetical cohorts with histologically mild chronic hepatitis C. INTERVENTION: The model assumed a single 6-month course of recombinant interferon-alpha 2b. MEASUREMENTS: Life expectancy, quality-adjusted life expectancy, costs, and marginal cost-effectiveness ratios from a managed care perspective. RESULTS: In 27% of patients with mild chronic hepatitis C treated with interferon-alpha 2b for 6 months, serum alanine aminotransferase levels permanently returned to normal and viral status remained negative. The model estimated that interferon-alpha 2b treatment in this population should increase life expectancy by 3.1 years if given at 20 years of age, by 1.5 years at 35 years of age, and by 22 days at 70 years of age; discounted marginal cost-effectiveness ratios are $500, $1900, and $62,000 per year of life gained, respectively. Varying the long-term response rates and progression rates for mild and moderate chronic hepatitis to near zero in sensitivity analyses substantially affected the results: Ratios ranged from $31,000 for a 20-year-old patient to $640,000 for a 70-year-old patient. CONCLUSIONS: On the basis of estimations in this mathematical model of the natural history of chronic hepatitis C, treating mild chronic hepatitis with interferon-alpha 2b should prolong life expectancy at a reasonable marginal cost per year of life gained, particularly in younger patients.

Alanine Transaminase↗

Fourier transform infrared study on the primary donor P798 of Heliobacterium modesticaldum: cysteine S-H coupled to P798 and molecular interactions of carbonyl groups.

Light-induced Fourier transform infrared (FTIR) difference spectra of the primary donor P798 upon its cation formation (P798(+)/P789) were measured using the membranes and purified RC complex of Heliobacterium modesticaldum. A differential signal at 2550/2560 cm-1 was observed in the difference spectra and assigned to the S-H stretching mode of cysteine by an isotopic shift to 1854/1861 cm-1 upon deuteration. The observed frequencies indicate that this S-H forms a strong hydrogen bond and that the bond is further strengthened upon P798(+) formation. Polarized FTIR difference spectra showed that this S-H group is oriented at <40 degrees with respect to the membrane normal. It was proposed that the cysteine S-H is coupled to P798 through a hydrogen-bond network or by direct hydrogen bonding to either a P798 carbonyl or a ligand histidine. In the carbonyl stretching region, differential signals were observed at 1741/1737, 1725/1718, 1702/1693, and 1687/1666 cm-1. In a dry membrane film, the signal at 1687/1666 cm-1 was mostly lost and hence was assigned to the amide I bands arising from the protein conformational change, which was suppressed upon dehydration of the membranes. The 1702/1693 cm-1 signal was assigned to the 13(1)-keto C&dbd;O of P798, which was free from hydrogen bonding and had a nearly parallel orientation to the membrane plane. The upshift by 9 cm-1 upon P798 oxidation, which is much smaller than upshifts of monomeric (bacterio)chlorophylls [(B)Chls] in organic solution, indicates that the positive charge on P798(+) is significantly delocalized in a BChlg dimer. The signals at 1741/1737 and 1725/1718 cm-1 were assigned to a free and a hydrogen-bonded ester C=O group, respectively. The dichroism measurement showed that the C=O of 1741/1737 cm-1 was oriented nearly parallel to the membrane plane while that of 1725/1718 cm-1 was considerably tilted by <31 degrees to the membrane normal. It was proposed that one of the two ester signals arose from the 13(2)-carbomethoxy C=O of P798 while the other arose either from the 17(2)-ester C=O of P798 or from an ester C&dbd;O of adjacent BChlg or 8(1)-OH-Chla that was electrostatically influenced by oxidation of P798.

Amino Acids, Dicarboxylic↗

Separation of oligo/polymers of 5-N-acetylneuraminic acid, 5-N-glycolylneuraminic acid, and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid by high-performance anion-exchange chromatography with pulsed amperometric detector.

A sensitive and efficient method to analyze oligo/ poly-sialic acids containing alpha2-8-linked 5-N-acetylneuraminic acid (Neu5Ac), 5-N-glycolylneuraminic acid (Neu5Gc), and deaminated neuraminic acid (KDN) using high-performance anion-exchange chromatography (HPAEC) with a pulsed amperometric detector (PAD-2) has been developed. Using a CarboPac PA-100 column and sodium nitrate as the pushing agent, polymers in colominic acid with degree of polymerization (DP) up to 80 were separated in 68 min. A similar DP-based resolution was also obtained on a CarboPac PA-1 column. The elution ladders of the Neu5Ac, Neu5Gc, and KDN series were sufficiently different to be used as diagnostic indices. This technique was applied to identification of the sialic acid components in a polysialoglycoprotein (PSGP) sample as well as monitoring the oligo/poly-KDN-containing fractions during the purification of KDN-containing glycoprotein (KDN-gp). The maximum DPs of oligo-Neu5Gc and oligo-KDN that can be detected in PSGP and KDN-gp hydrolysates were 11 and 8, respectively. The high sensitivity of this method was demonstrated by the quantification of Neu5Ac oligomers. Distributions of the monomer and oligo/polymers in the acid and enzymatic hydrolysates of colominic acid and PSGP under different conditions were also studied.

Anion Exchange Resins↗

Anti-Helicobacter pylori agents. 1. 2-(Alkylguanidino)-4-furylthiazoles and related compounds.

A series of 2-(alkylguanidino)-4-[5-(acetamidomethyl)furan-2-yl]thiazoles and related compounds were synthesized and evaluated for antimicrobial activity against Helicobacter pylori, inhibitory effect on gastric acid secretion, and histamine H2-receptor antagonist activity. Introduction of alkyl substituents on the guanidino moiety resulted in a significant increase in antimicrobial activity, which was associated with the alkyl chain length. Of the compounds obtained, the n-hexylguanidino derivative 13 demonstrated a 250-fold improvement in activity (MIC = 0.11 micrograms/mL) over the unsubstituted guanidino derivative 7. Alkyl-substituted guanidino derivatives also displayed gastric antisecretion and H2-antagonist activities. However, a simple correlation between the alkyl chain length and the activities was not found in these assays. Replacement of the guanidine with other bioisosteric groups (thiourea, urea, or (dimethylamino)methyl) resulted in loss of all activities tested. Thus the guanidino moiety was found to be essential for activity in this series of compounds.

Animals↗

Extra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses.

We used silver-enhanced immunogold electron microscopy to reveal synaptic localization of the glutamate transporter EAAT4 in mouse cerebellar Purkinje cells (PCs). Gold-silver particles representing the EAAT4 were densely localized on extra-junctional membrane, but not on junctional membrane of PC spines in contact with parallel fiber or climbing fiber terminals. No particle accumulations were observed at inhibitory synapses formed on cell body and dendritic shafts of PCs. Therefore, the EAAT4 is selectively targeted to the extra-junctional site of excitatory PC synapses. The finding suggests that the EAAT4 transports glutamate or its related amino acids from outside the synaptic cleft, which would facilitate glutamate diffusion from the synaptic cleft to the extrasynaptic space and restrict glutamate spillover to adjacent synapses.

Amino Acid Transport System X-AG↗

Analysis of the psbU gene encoding the 12-kDa extrinsic protein of photosystem II and studies on its role by deletion mutagenesis in Synechocystis sp. PCC 6803.

The gene encoding the 12-kDa extrinsic protein of photosystem II from Synechocystis sp. PCC 6803 was cloned based on N-terminal sequence of the mature protein. This gene, named psbU, encodes a polypeptide of 131 residues, the first 36 residues of which were absent in the mature protein and thus served as a transit peptide required for its transport into the thylakoid lumen. A psbU gene deletion mutant grew photoautotrophically in normal BG11 medium at almost the same rate as that of the wild type strain. This mutant, however, grew apparently slower than the wild type did upon depletion of Ca2+ or Cl- from the growth medium. Photosystem II oxygen evolution decreased to 81% in the mutant as compared with that in the wild type, and the thermoluminescence B- and Q-bands shifted to higher temperatures accompanied by an increase in the Q-band intensity. These results indicate that the 12-kDa protein is not essential for oxygen evolution but may play a role in optimizing the ion (Ca2+ and Cl-) environment and maintaining a functional structure of the cyanobacterial oxygen-evolving complex. In addition, a double deletion mutant lacking cytochrome c-550 and the 12-kDa protein grew photoautotrophically with a phenotype identical to that of the single deletion mutant of cytochrome c-550. This supports our previous biochemical results that the 12-kDa protein cannot bind to photosystem II in the absence of cytochrome c-550 (Shen, J.-R., and Inoue, Y. (1993) Biochemistry 32, 1825-1832).

Amino Acid Sequence↗

Movements of truncated kinesin fragments with a short or an artificial flexible neck.

To investigate the role of the neck domain of kinesin, we used optical trapping nanometry to perform high-resolution measurements of the movements and forces produced by recombinant kinesin fragments in which the neck domains were shortened or replaced by an artificial random coil. Truncated kinesin fragments (K351) that contain a motor domain consisting of approximately 340 aa and a short neck domain consisting of approximately 11 aa showed fast movement (800 nm/s) and 8-nm steps. Such behavior was similar to that of recombinant fragments containing the full-length neck domain (K411) and to that of native kinesin. Kinesin fragments lacking the short neck domain (K340), however, showed very slow movement (<50 nm/s), as previously reported. Joining an artificial 11-aa sequence that was expected to form a flexible random chain to the motor domain (K340-chain) produced normal fast ( approximately 700 nm/s) and stepwise movement. The results suggest that the neck domain does not act as a rigid lever arm to magnify the structural change at the catalytic domain as has been believed for myosin, but it does act as a flexible joint to guarantee the mobility of the motor domain.

Animals↗

Site-specific de-N-glycosylation of diglycosylated ovalbumin in hen oviduct by endogenous peptide: N-glycanase as a quality control system for newly synthesized proteins.

Hen ovalbumin (OVA) is known to exist as a singly N-glycosylated form with a glycan chain on Asn-292 in egg white. Previous studies showed that di-N-glycosylated form of OVA [Di-OVA; CHO-Asn-292/CHO-Asn-311 (CHO, N-glycan chain)], which has two N-glycan chains on Asn-292 and Asn-311, was expressed only transiently in hen oviduct. Di-OVA was not found in egg white, suggesting that this form cannot be secreted normally and may possibly be converted to mono-N-glycosylated OVA (CHO-Asn-292/Asp-311) by the action of peptide:N-glycanase (PNGase) during synthesis and secretion. In this study, we have identified the putative PNGase activity in the homogenate of hen oviduct, purified 1,000-fold, and designated as PNGase HO. We examined the reactivity of Di-OVA to PNGase HO and found that this enzyme site-specifically cleaved off the glycan chain at Asn-311 to convert Di-OVA into the mono-N-glycosylated form (CHO-Asn-292/Asp-311). In contrast, this enzyme was found not to act on the mono-N-glycosylated OVA (CHO-Asn-292/Asn-311) found in egg white when it was tested as a substrate. The present findings support our view that de-N-glycosylation catalyzed by PNGase may be involved in quality control of newly synthesized proteins by converting its diglycosylated form into the mono-N-glycosylated form that can be secreted. However, the alternative possibility that de-N-glycosylation may trigger cytosolic degradation of the aberrantly glycosylated glycoprotein cannot be ruled out.

Amidohydrolases↗