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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 181 records · Page 10Linked to original sources
PubMed2001

[A case of IgA nephropathy associated with silicosis].

A 51-year-old male who had been working as a building wrecker for 20 years, was admitted to our hospital in June 1999 for proteinuria and hematuria examination. He started this work in 1978. Twelve years later, severe coughing and bloody sputum began and he was diagnosed as having silicosis in 1995. Urinalysis on admission showed proteinuria(294 mg/day), microhematuria(20-30/hpf), RBC cast and granular cast. High serum IgA(770 mg/dl) and high serum interleukin-6(IL-6) (3,280 pg/dl) were found. A renal biopsy showed mild mesangial matrix expansion and mesangial cell proliferation with IgA deposition, which was diagnosed as IgA nephropathy. Chest X-rays showed multiple small nodular lesions on both lung fields indicating silicosis. In Nov. 1999, he resigned from his job as a building wrecker because of increasing coughing and bloody sputum associated with body weight loss. Within 3 months after stopping this work, coughing and bloody sputum disappeared and the abnormal urinalysis findings returned to normal. Serum IgA and serum IL-6 data improved to 462 mg/dl and 2.5 pg/dl, respectively. It is suggested that silicon exposure might be related to the pathogenesis of IgA nephropathy in this patient.

Biomarkers↗
PubMed2001

Ultrastructural study of mouse renal glomeruli under various hemodynamic conditions by an "in vivo cryotechnique".

Three-dimensional ultrastructure of mouse renal glomeruli under various hemodynamic conditions was studied by scanning electron microscopy with an "in vivo cryotechnique" followed by freeze-substitution. These results were also compared with those of conventionally fixed glomeruli at different perfusion pressures. Some kidneys of anesthetized mice were directly frozen in vivo under normal blood flow condition. Others were frozen in the same way after ligation of the lower abdominal aorta or their heart arrest. The frozen specimens were routinely freeze-substituted, freeze-dried and ion-sputtered for SEM. For another conventional fixation method, some kidneys were perfused with glutaraldehyde at pressures of 150 cm or 250 cm water, and other renal cortical tissues were routinely immersion-fixed with glutaraldehyde. In freeze-substituted specimens with the in vivo cryotechnique, interdigitating foot processes of podocytes exhibited smooth surface contours with less shrinkage and their surfaces were arranged more tightly than those seen by the conventional fixation method. In the anesthetized mice, filtration slits between the foot processes were found to be narrow after the heart arrest, but they were wide under the normal blood flow condition. After the aorta ligation, the filtration slits became wider and the foot processes were more elongated. The ultrastructure of capillary loops in functioning renal glomeruli were revealed to be dynamically changing in the living state, depending on various hemodynamic conditions.

Animals↗
PubMed2001

Central tinnitus: a case report.

We report a case of acute-onset unilateral tinnitus in a 25-year-old woman. Analysis of imaging studies indicated that the tinnitus was likely caused by an acute hemorrhage of a small cavernous angioma that was located adjacent to the contralateral primary auditory cortex. This case provides substantial support for the concept that central tinnitus might indeed represent a pathologic activation of neural networks of nonspecific auditory perception.

Adult↗
PubMed2000

Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites.

Brevican is a member of the lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system. The susceptibility of brevican to digestion by matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9, -10, and -13 and membrane type 1 and 3 MMPs) and aggrecanase-1 (ADAMTS4) was examined. MMP-1, -2, -3, -7, -8, -10, and -13 degraded brevican into a few fragments with similar molecular masses, whereas the degradation products of aggrecanase-1 had apparently different sizes. NH(2)-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain. MMP-1, -2, -3, -7, -8, -10, and -13 preferentially attacked the Ala(360)-Phe(361) bond, whereas aggrecanase-1 cleaved the Glu(395)-Ser(396) bond, which are similar to the cleavage sites observed with cartilage proteoglycan (aggrecan) for the MMPs and aggrecanase-1, respectively. These data demonstrate that MMP-1, -2, -3, -7, -8, -10, and -13 and aggrecanase-1 digest brevican in a similar pattern to aggrecan and suggest that they may be responsible for the physiological turnover and pathological degradation of brevican.

ADAM Proteins↗
PubMed2000

X-Ray anomalous scattering study of a charge-ordered state in NaV2O5

Charge ordering of V4+ and V5+ in NaV2O5 has been studied by an x-ray diffraction technique using anomalous scattering near a vanadium K-absorption edge to critically enhance a contrast between the two ions. A dramatic energy dependence of the superlattice intensities is observed below T(C) = 35 K. The charge ordering pattern is the fully charged zigzag-type ladder with the unit cell 2ax2bx4c, but not the chain-type originally proposed for the spin-Peierls state. Charge disproportionation suggested in our model as the average valence V(4.5+/-delta(c)/2) is observed below T(C), showing continuous variation of delta(c) as a function of temperature.

Journal Article↗
PubMed2000

Diurnal rhythms of retinal phospholipid synthetic enzymes are retained but their activities are decreased in rats under alpha-linolenic acid deficiency.

Rats fed a safflower oil (alpha-linolenic acid (ALNA)-deficient) diet over the course of two generations had significantly decreased docosahexaenoic acid (22:6n-3) and increased docosapentaenoic acid (22:5n-6) contents in the major retinal phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) when compared with those fed a perilla oil (ALNA-sufficient) diet, but the compositions of phosphatidylinositol acyl chains were relatively unaffected. The contents of individual phospholipids in the retina were essentially the same for the two dietary groups. The activities of the rate-limiting enzymes in the de novo synthesis of PC and PE, CTP:phosphocholine cytidylyltransferase (CT), and CTP:phosphoethanolamine cytidylyltransferase (ET), respectively, were measured in the retinas excised at 5:00, 9:00, 13:00, and 17:00 h from rats adapted to a 24-h cycle with lights on from 7:00 to 19:00 h. Both enzymes exhibited significant diurnal rhythms with the lowest activities at 5:00 h and gradually increasing activities following exposure of the rats to light; the maximum activities were at 13:00 h for CT and 17:00 h for ET. The diurnal rhythms were not significantly affected by the above-mentioned diets. However, both enzyme activities at each collection time point were significantly lower in the safflower oil group than in the perilla oil group. These results suggest that retinal phospholipid turnover associated with shedding, phagocytosis, and resynthesis of the rod outer segments is limited by ALNA deficiency.

Animals↗
PubMed2000

Phosphorylation by cyclin-dependent protein kinase 5 of the regulatory subunit of retinal cGMP phosphodiesterase. II. Its role in the turnoff of phosphodiesterase in vivo.

Retinal cGMP phosphodiesterase (PDE) is regulated by Pgamma, the regulatory subunit of PDE, and GTP/Talpha, the GTP-bound alpha subunit of transducin. In the accompanying paper (Matsuura, I., Bondarenko, V. A., Maeda, T., Kachi, S., Yamazaki, M., Usukura, J., Hayashi, F., and Yamazaki, A. (2000) J. Biol. Chem. 275, 32950-32957), we have shown that all known Pgammas contain a specific phosphorylation motif for cyclin-dependent protein kinase 5 (Cdk5) and that the unknown kinase is Cdk5 complexed with its activator. Here, using frog rod photoreceptor outer segments (ROS) isolated by a new method, we show that Cdk5 is involved in light-dependent Pgamma phosphorylation in vivo. Under dark conditions only negligible amounts of Pgamma were phosphorylated. However, under illumination that bleached less than 0.3% of the rhodopsin, approximately 4% of the total Pgamma was phosphorylated in less than 10 s. Pgamma dephosphorylation occurred in less than 1 s after the light was turned off. Analysis of the phosphorylated amino acid, inhibition of Pgamma phosphorylation by Cdk inhibitors in vivo and in vitro, and two-dimensional peptide map analysis of Pgamma phosphorylated in vivo and in vitro indicate that Cdk5 phosphorylates a Pgamma threonine in the same manner in vivo and in vitro. These observations, together with immunological data showing the presence of Cdk5 in ROS, suggest that Cdk5 is involved in light-dependent Pgamma phosphorylation in ROS and that the phosphorylation is significant and reversible. In an homogenate of frog ROS, PDE activated by light/guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was inhibited by Pgamma alone, but not by Pgamma complexed with GDP/Talpha or GTPgammaS/Talpha. Under these conditions, Pgamma phosphorylated by Cdk5 inhibited the light/GTPgammaS-activated PDE even in the presence of GTPgammaS/Talpha. These observations suggest that phosphorylated Pgamma interacts with and inhibits light/GTPgammaS-activated PDE, but does not interact with GTPgammaS/Talpha in the homogenate. Together, our results strongly suggest that after activation of PDE by light/GTP, Pgamma is phosphorylated by Cdk5 and the phosphorylated Pgamma inhibits GTP/Talpha-activated PDE, even in the presence of GTP/Talpha in ROS.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Serum interleukin-18 levels are elevated in schizophrenia.

Interleukin-18 (IL-18) is a recently discovered proinflammatory cytokine which plays a pivotal role in T helper 1 (Th1) responses. IL-18 is produced by macrophage-like cells, and inappropriate IL-18 production has been known to be involved in immunological disturbances. Schizophrenia is a common disease whose pathogenesis is still unclear; however, an activation of the inflammatory response system, including the Th1 cytokine response, may be related to the pathophysiology of schizophrenia. We measured the serum IL-18 levels of 66 schizophrenics and age- and sex-matched control subjects by using an ELISA assay. We found significantly increased serum IL-18 levels in the schizophrenic patients (P=0.0002). This finding supports the hypothesis that immune activation is involved in the pathophysiology of schizophrenia.

Adult↗
PubMed2000

Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein.

Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2'-dGTP (8-oxo-dGTP) to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine (8-oxo-G) into nascent DNA. Bacterial and mammalian homologs of MutT protein share the phosphohydrolase module (MutT: Gly37-->Gly59). By saturation mutagenesis of conserved residues in the MutT module, four of the 10 conserved residues (Gly37, Gly38, Glu53 and Glu57) were revealed to be essential to suppress spontaneous A:T-->C:G transversion mutation in a mutT(-) mutator strain. For the other six residues (Lys39, Glu44, Thr45, Arg52, Glu56 and Gly59), many positive mutants which can suppress the spontaneous mutation were obtained; however, all of the positive mutants for Glu44 and Arg52 either partially or inefficiently suppressed the mutation, indicating that these two residues are also important for MutT function. Several positive mutants for Lys39, Thr45, Glu56 and Gly59 efficiently decreased the elevated spontaneous mutation rate, as seen with the wild-type, hence, these four residues are non-essential for MutT function. As Lys38 and Glu55 in human MTH1, corresponding to the non-essential residues Lys39 and Glu56 in MutT, could not be replaced by any other residue without loss of function, different structural features between the two modules of MTH1 and MutT proteins are evident.

Amino Acid Sequence↗
PubMed2000

Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer.

Inactivation of p53, which represents the most prevalent genetic alteration in lung cancer, has been shown to play a crucial role in the acquisition of genomic instability. We examined 44 lung cancer specimens to search for mutations in the CHK1 and CHK2 genes, which have been suggested to play roles in regulating p53 after DNA damage. We found that the CHK2 gene was somatically mutated in lung cancer in vivo, although at a low frequency, and that a previously undescribed shorter isoform of CHK1 was expressed preferentially in small cell lung cancer in a tumor-predominant manner. Additional studies are warranted to investigate the functional significance of these changes as well as the potential involvement of other components in this important pathway to maintain genomic stability.

Amino Acid Sequence↗
PubMed2000

Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast.

To investigate the alterations of genetic instabilities in carcinogenesis of the breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast. These studies were performed by means of examining microsatellite-length polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159, and D17S855) from microdissected paraffin sections. Allelic loss or imbalance, considered a loss of heterozygosity (LOH), tended to be more frequently seen in IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS was lower than that in comedo type DCIS. Furthermore, the frequency of microsatellite instability (MSI) at only one locus in DCIS (28%) was statistically higher than that in IDC (6%) (P<0.001), while there was no difference between the frequency of MSI at multiple loci in DCIS (6%) and that in IDC (3%). Together, these observations indicate that chromosomal losses of 16q may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur high-grade DCIS, and that MSI occurring at only one locus is not yet clear and MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.

Adult↗
PubMed2000

Anomaly of 155Gd and 157Gd isotope effects in ligand exchange reactions observed by ion exchange chromatography

The isotope effects of gadolinium in Gd-EDTA ligand exchange system were studied by means of ion exchange chromatography. The separation coefficients of gadolinium isotopes, epsilon, and the local enrichment factors, beta, were calculated from the observed isotopic ratios at the front and rear boundaries of the gadolinium adsorption band. Clear mass independent anomalies were observed in the isotope effects of 155Gd and 157Gd. The relation between the isotope effects of gadolinium isotopes, studied by the three-isotope plot and the separation coefficient methods, and the mass of gadolinium isotopes was found to be related to the change in the mean square radius of the nuclear charge distribution parameter, (r2), of these isotopes, which suggests that the nucleus shape and size highly affect the gadolinium isotope effects in chemical exchange reactions.

Journal Article↗
PubMed2000

Observation of a spin-flip M1 transition in 7(lambda)Li.

Using a large-acceptance germanium detector array (Hyperball), we have observed a spin-flip M1 gamma transition between the ground-state spin doublet of (7)(Lambda)Li (3/2(+)-->1/2(+)). The observed energy of 691.7+/-0.6(stat)+/-1.0(syst) keV provides crucial information on the strength of the spin-spin interaction between a Lambda and a nucleon. This is the first observation of well-identified hypernuclear gamma transitions using germanium detectors.

Journal Article↗
PubMed2000

Dietary n-3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus.

Dietary deprivation of alpha-linolenic acid (n-3) through two generations has been shown to lower performance in an operant-type brightness-discrimination learning test in rats. Here, we examined a possible correlation between nerve growth factor (NGF) content and n-3 fatty acid status in the brain. Female rats were fed a semipurified diet supplemented with safflower oil (n-3 fatty acid-deficient) and their offsprings were fed a diet supplemented with either 3% safflower oil (Saf group) or a mixture of 2.4% safflower oil plus 0.6% ethyl eicosapentaenoate (Saf+EPA group) after weaning. The brain docosahexaenoic acid (22:6n-3, DHA) content in the Saf group was less than half of that in the Per group fed a diet supplemented with 3% perilla oil (n-3 fatty acid-sufficient) throughout the duration of the experiment. The DHA level of the Saf+EPA group was restored to the level of the Per group. However, the NGF contents in the hippocampus of the Saf and Saf+EPA groups were half that of the Per group. In the piriform cortex, the NGF content tended to be higher in the Saf and Saf+EPA groups than in the Per group. These results indicate that dietary n-3 fatty acid deficiency and restoration affect NGF levels differently among different brain regions.

Animals↗
PubMed2000

Immunolocalization of dystrobrevin in the astrocytic endfeet and endothelial cells in the rat cerebellum.

Dystrobrevin is a newly discovered dystrophin-associated protein that is classified as alpha- and beta-dystrobrevin. Previous studies reported that dystrophin, utrophin, syntrophin and beta-dystroglycan were expressed in the cerebellum. In the present study, we examined cellular and subcellular localization of dystrobrevin in the adult rat cerebellum immunohistochemically. Confocal microscopy showed that dystrobrevin was expressed around blood vessels and under the pia mater as dystrophin, utrophin and beta-dystroglycan were. Immunoelectron microscopy demonstrated that dystrobrevin was localized not only in the astrocytic endfeet around blood vessels and under the pia mater, but also in endothelial cells. Considering the fact that dystrobrevin possesses multiple phosphotyrosine kinase residues, these data suggest that dystrobrevin plays a role in blood-brain barrier functions as a component of the dystrophin complex.

Animals↗
PubMed2000

Eosinophil-specific regulation of gp91(phox) gene expression by transcription factors GATA-1 and GATA-2.

The glycoprotein gp91(phox) is an essential component of the phagocyte NADPH oxidase and is expressed in eosinophils, neutrophils, monocytes, and B-lymphocytes. We previously suggested an eosinophil-specific mechanism of gp91(phox) gene expression. To elucidate the mechanism, we performed functional assays on deletion mutants of the gp91(phox) promoter in various types of gp91(phox)-expressing cells. A 10-base pair (bp) region from bp -105 to -96 of the promoter activated transcription of the gene in eosinophilic cells, but not in neutrophilic, monocytic, or B-lymphocytic cells. A 2-bp mutation introduced into the GATA site spanning bp -101 to -96 (-98GATA site) of the fragment abolished its activity. Gel shift assays using a GATA competitor and specific antibodies demonstrated that both GATA-1 and GATA-2 specifically bound to the -98GATA site with similar affinities. Individual transfection of GATA-1 and GATA-2 into Jurkat cells, which have neither endogenous GATA-1 nor GATA-2, activated the -105/+12 construct in a -98GATA site-dependent manner. Combined transfection of GATA-1 and GATA-2 activated the promoter less than transfection of GATA-1 alone. These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.

Base Sequence↗