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Biomedical subjects

N Oishi

Publications and source records attributed to N Oishi.

At least 19 recordsLinked to original sources

Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.

Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).

Journal Article↗

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Journal Article↗

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

Journal Article↗

Correlation between erythrocyte aldose reductase level and human diabetic retinopathy.

AIM: To examine the relation between aldose reductase (AR) and the development and progression of diabetic retinopathy by comparing the erythrocyte AR levels with the prevalence of diabetic retinopathy in NIDDM patients. METHODS: A clinic based cross sectional study was used. 611 NIDDM patients and 73 controls were enrolled. Erythrocyte AR levels were determined by ELISA. These AR levels were then correlated with patient age, duration of diabetes, and HbA(1c) levels. AR levels were also correlated with the prevalence of diabetic retinopathy in the entire NIDDM patient group and in three subgroups formed by separating the NIDDM patients by their duration of diabetes. The prevalence of diabetic retinopathy significantly increased with increased erythrocyte AR levels in patients with duration of diabetes of less than 10 years. A similar, but non-significant correlation between the prevalence of retinopathy and increased erythrocyte AR levels was observed in patients with diabetes duration of 10-20 and >/=20 years. RESULTS: The prevalence of diabetic retinopathy increased with increased erythrocyte AR levels in NIDDM patients with a duration of diabetes of less than 10 years. CONCLUSION: It was suggested that the inhibition of AR in patients with early NIDDM might be beneficial in reducing the development of diabetic retinopathy.

Adult↗

Activity-dependent neural tissue oxidation emits intrinsic ultraweak photons.

Living organisms have been known to spontaneously emit ultraweak photons in vivo and in vitro. Origin of the photon emission remains unclear, especially in the nervous system. The spontaneous ultraweak photon emission was detected here from cultured rat cerebellar granule neurons using a photomultiplier tube which was highly sensitive to visible light. The photon emission was facilitated by the membrane depolarization of neurons by a high concentration of K+ and was attenuated by application of tetrodotoxin or removal of extracellular Ca2+, indicating the photon emission depending on the neuronal activity and likely on the cellular metabolism. Furthermore, almost all the photon emission was arrested by 2,4-dinitrophenylhydrazine, indicating that the photon emission would be derived from oxidized molecules. Detection of the spontaneous ultraweak photon emission will realize noninvasive and real-time monitoring of the redox state of neural tissue corresponding to the neuronal activity and metabolism.

Animals↗

Improved direct measurement of leptonic coupling asymmetries with polarized Z bosons.

We present final measurements of the Z boson-lepton coupling asymmetry parameters A(e), A(mu), and A(tau) with the complete sample of polarized Z bosons collected by the SLD detector at the SLAC Linear Collider. From the left-right production and decay polar angle asymmetries in leptonic Z decays we measure A(e) = 0.1544+/-0.0060, A(mu) = 0.142+/-0.015, and A(tau) = 0.136+/-0.015. Combined with our left-right asymmetry measured from hadronic decays, we find A(e) = 0.1516+/-0.0021. Assuming lepton universality, we obtain a combined effective weak mixing angle of sin (2)theta(eff)(W) = 0.230 98+/-0.000 26.

Journal Article↗

First symmetry tests in polarized Z0 decays to bbg.

We have made the first direct symmetry tests in the decays of polarized Z0 bosons into fully identified bbg states, collected in the SLD experiment at SLAC. We searched for evidence of parity violation at the bbg vertex by studying the asymmetries in the b-quark polar- and azimuthal-angle distributions, and for evidence of T-odd, CP-even or CP-odd, final-state interactions by measuring angular correlations between the three-jet plane and the Z0 polarization. We found results consistent with standard model expectations and set 95% C. limits on anomalous contributions.

Journal Article↗

Suppression of oncogenic viral interferon regulatory factor (vIRF) of Kaposi's sarcoma-associated herpesvirus by ribozyme-mediated cleavage.

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8) has been etiologically associated with several malignancies including Kaposi's sarcoma and primary effusion lymphoma. Oncogenic viral interferon regulatory factor (vIRF) encoded by KSHV ORF-K9 is a homologue of cellular interferon regulatory factor (IRF), and has been demonstrated to inhibit type I/II interferon signal transduction and transform NIH3T3 cells through the interactions with IRF-1, IRF-3, and CBP/p300 proteins. To counteract vIRF's pathogenic role, we have developed five ribozymes targeting ORF-K9 mRNA to suppress vIRF expression. The vIRF RNA substrates were cleaved up to 80% in a substrate-specific manner in transcript cleavage assays in vitro. In a transient transfection assay, two of the ribozymes efficiently suppressed the expression of vIRF protein measured by dual-color immunofluorescence assay that simultaneously detects the expression of both vIRF protein and ribozyme. Flow cytometry analysis showed that these ribozymes reduced vIRF expression up to 76%. A mutant ribozyme had no cleavage activity in vitro, but exhibited antisense effect in vivo. These results suggest that the ribozymes may provide a new approach for functional knockout of vIRF gene, and are potential candidates of antiviral therapy for KSHV-related malignancies.

Animals↗

[Species differences in the in vitro metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl].

In vitro Metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl (CB138) was studied using liver microsomes from rats, hamsters and guinea pigs. Guinea pig liver microsomes formed four metabolites named as M-1, M-2, M-3 and M-4 and these metabolites were all increased to about 4-5 fold of untreated microsomes by pretreatment of phenobarbital. Liver microsomes of rats and hamsters showed much less activity to metabolize CB138 than those of guinea pigs. Only phenobarbital-treated microsomes produced very small amounts of M-3 in rats and M-1, M-2 and M-3 in hamsters, but untreated and MC-treated microsomes did not. When mass spectra of the methylated derivatives of M-1, M-2, M-3 and M-4 were measured in GC/MS, the former two possess the molecular ion of 354 and the latter two had the molecular ion of 388. In addition, the mass fragmentation pattern indicated that M-1, M-2, M-3 and M-4 are 2-OH-4,5,2',3',4'-pentachlorobiphenyl, 5-OH-2,4,2',3',4'-pentachlorobiphenyl, 3-OH-CB138 and 2-OH-3,4,5,2',3',4'-hexachlorobiphenyl, respectively. Of four metabolites, the chemical structures of M-3 and M-4 were supported by the synthesized authentic compounds. From these results, it is suggested that the metabolism of CB138 in guinea pig liver proceeds mainly via 2,3-epoxide as an intermediate and a PB-inducible P450, CYP2B18, is the most important isozyme in CB138 metabolism.

Animals↗

Novel Dictyostelium unconventional myosin, MyoM, has a putative RhoGEF domain.

We have cloned a novel unconventional myosin gene myoM in Dictyostelium. Phylogenetic analysis of the motor domain indicated that MyoM does not belong to any known subclass of the myosin superfamily. Following the motor domain, two calmodulin-binding IQ motifs, a putative coiled-coil region, and a Pro, Ser and Thr-rich domain, lies a combination of dbl homology and pleckstrin homology domains. These are conserved in Rho GDP/GTP exchange factors (RhoGEFs). We have identified for the first time the RhoGEF domain in the myosin sequences. The growth and terminal developmental phenotype of Dictyostelium cells were not affected by the myoM(-) mutation. Green fluorescent protein-tagged MyoM, however, accumulated at crown-shaped projections and membranes of phase lucent vesicles in growing cells, suggesting its possible roles in macropinocytosis.

Amino Acid Sequence↗

Elasticity of mutant myosin subfragment-1 arranged on a functional silver surface.

Elasticity of a two-dimensionally arranged myosin subfragment-1 (S1) was measured by using a surface forces apparatus. To prepare a two-dimensionally arranged S1-monolayer on a functionalized silver surface, we used genetically engineered Dictyostelium S1 molecules. A highly reactive cysteine residue was fused to the COOH-terminus using the recombinant DNA method. On the other hand, the maleimide groups was self-assembled onto a silver surface. Then the mutant S1 molecules were chemically bound to the functionalized silver surface at its COOH-terminus. This arrangement technique was necessary in order to create a stable S1-monolayer by chemical bond formation onto the silver surface. The occupied area of the single S1 on the silver surface was about 110 nm(2). In the interaction between the S1-monolayer and mica surfaces in aqueous solution, a long-range attractive force was observed. The elastic constants (stiffness and Young's modulus) of myosin S1 were evaluated from force-distance profiles in aqueous solution, using the Hertz theory. We found that the stiffness (or spring constant) and Young's modulus of S1 in the absence of nucleotide are 4.4 +/- 1.0 pN/nm and 0.71 +/- 0.16 GPa, respectively.

Aluminum Silicates↗

[Comparative study on metabolism of three tetrachlorobiphenyls with animal liver microsomes].

In vitro metabolism of 3,5,3',4'-, 3,5,3',5'- and 2,4,3',4'-tetrachlorobiphenyls (TCBs) was studied using liver microsomes from rats, guinea pigs and hamsters. 3,5,3',4'-TCB was metabolized to 4-hydroxy-3,5,3',4'-TCB with liver microsomes of 3-methyl-cholanthrene (MC)- and 3,4,5,3',4'-pentachlorobiphenyl (PenCB)-treated rats but not of phenobarbital (PB)-treated ones. This result suggests that a MC-inducible cytochrome P450 isoform, probably CYP1A1, is more important in the in vitro metabolism of 3,5,3',4'-TCB in rat liver and that the isoform attacks the 3,5-dichloro-substituted phenyl ring more predominantly than 3,4-dichloro-substituted one. In 3,5,3',5'-TCB metabolism, liver microsomes from MC- and 3,4,5,3',4'-PenCB-treated hamsters formed 4-hydroxy-3,5,3',5'-TCB to a similar extent to rats reported previously. Guinea pig liver microsomes formed no metabolite. In 2,4,3',4'-TCB metabolism, PB accelerated 3-, 5- and 4-hydroxylations in guinea pigs and also 3- and 5-hydroxylations in hamsters, suggesting the involvement of a PB-inducible P450 isoform, presumably P450GP-1 and P450HPB-1, respectively. On the other hands, MC- and 3,4,5,3',4'-PenCB-treatment resulted in the marked increase of 4-hydroxylation in hamsters, but in the suppression of 4-hydroxylation in guinea pigs. From these results, it is suggested that the hydroxylation of coplanar TCBs such as 3,5,3',4'- and 3,5,3',5'-TCB is catalyzed by a MC-inducible P450 in rats and hamsters, whereas non-coplanar TCBs such as 2,4,3',4'-TCB which possesses both PB- and MC-like inducing ability of liver enzymes are metabolized by one or more kinds of P450 isoform induced by PB and MC.

Animals↗

Soluble thrombomodulin and antibodies to bovine glomerular endothelial cells in patients with Henoch-Schönlein purpura.

AIM: To evaluate the clinical significance of soluble thrombomodulin and antiendothelial cell antibodies (AECA) in children with Henoch-Schönlein purpura. METHODS: Binding of serum AECA to bovine glomerular endothelial cells was evaluated by enzyme linked immunosorbent assay, cytotoxicity against glomerular endothelial cells by spectrophotometric assay, and soluble thrombomodulin concentrations by sandwich enzyme immunoassay. RESULTS: IgA AECA were detected in seven of 15 patients with Henoch-Schönlein purpura and nephritis, but were not detected in patients without nephritis or in controls. Patients with Henoch-Schönlein nephritis had raised titres of IgA AECA and serum thrombomodulin; severe proteinuria and renal histological changes were associated with raised titres of IgA AECA and raised serum thrombomodulin. No subjects had complement dependent cytotoxicity against glomerular endothelial cells. CONCLUSIONS: High titres of IgA AECA and raised serum thrombomodulin may be clinically useful markers of renal involvement in patients with Henoch-Schönlein purpura.

Adolescent↗

Dynamic electron microscopy of ATP-induced myosin head movement in living muscle thick filaments.

Although muscle contraction is known to result from movement of the myosin heads on the thick filaments while attached to the thin filaments, the myosin head movement coupled with ATP hydrolysis still remains to be investigated. Using a gas environmental (hydration) chamber, in which biological specimens can be kept in wet state, we succeeded in recording images of living muscle thick filaments with gold position markers attached to the myosin heads. The position of individual myosin heads did not change appreciably with time in the absence of ATP, indicating stability of the myosin head mean position. On application of ATP, the position of individual myosin heads was found to move by approximately 20 nm along the filament axis, whereas no appreciable movement of the filaments was detected. The ATP-induced myosin head movement was not observed in filaments in which ATPase activity of the myosin heads was eliminated. Application of ADP produced no appreciable myosin head movement. These results show that the ATP-induced myosin head movement takes place in the absence of the thin filaments. Because ATP reacts rapidly with the myosin head (M) to form the complex (M. ADP.Pi) with an average lifetime of >10 s, the observed myosin head movement may be mostly associated with reaction, M + ATP --> M.ADP. Pi. This work will open a new research field to study dynamic structural changes of individual biomolecules, which are kept in a living state in an electron microscope.

Actin Cytoskeleton↗

Antibodies to endothelial cells in Kawasaki disease lyse endothelial cells without cytokine pretreatment.

Kawasaki disease (KD) is characterized by diffuse vasculitis and marked immune activation. To confirm the presence of antiendothelial cell antibodies (AECA) and cytotoxicity of AECA, we investigated the presence of AECA using ELISA and cytotoxicity of AECA in KD. Sera from patients with acute KD were assessed for binding to human umbilical vein endothelial cells (HUVEC) using a cell-based ELISA, and for cytotoxicity against HUVEC as indicated by the conversion of a tetrazolium salt (MTT) into a coloured product. IgM AECA were detected in 8/19 KD sera, IgG AECA were detected in 5/19 KD sera. Significant differences in both AECA titres existed between patients and febrile and afebrile controls. Six out of 19 patients showed complement-dependent cytotoxicity against HUVEC. Cytotoxicity was significantly enhanced by pretreating HUVEC with tumour necrosis factor (TNF), and reduced by incubation with gammaglobulin. Serum titres of IgM AECA in the KD patients were positively correlated with cytotoxicity. Findings suggest that IgM AECA mediates complement-dependent cytotoxicity against endothelial cells in patients with KD, and gammaglobulin may reduce complement-dependent cytotoxicity of AECA against endothelial cells.

Antibody-Dependent Cell Cytotoxicity↗