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Articles by H. Suzuki
Total Records ( 6 ) for H. Suzuki
  K. Tanaka , Y. Tani , J. Asai , F. Nemoto , Y. Kusano , H. Suzuki , Y. Hayashi , K. Asahi , M. Nakayama , T. Miyata and T. Watanabe
  Aims  Skin autofluorescence, a non-invasive measure of the accumulation for advanced glycation end products, has been reported to be a useful marker for diabetic vascular risks in the Caucasian population. The aim of this study was to evaluate associations between skin autofluorescence and vascular complications in non-Caucasian patients with Type 2 diabetes.

Methods  Subjects in this cross-sectional study comprised 130 Japanese patients with Type 2 diabetes. Skin advanced glycation end products were assessed by skin autofluorescence using an autofluorescence reader. Association between skin autofluorescence and severity of vascular complications was evaluated.

Results  Of the 130 patients, 60 (46.2%) had microvascular complications such as diabetic retinopathy, neuropathy and nephropathy, 10 (7.7%) had macrovascular complications and 63 (48.5%) had micro- and/or macrovascular complications. Skin autofluorescence increased with severity of vascular complications. Independent determinants of skin autofluorescence were age (β = 0.24, < 0.01), mean HbA1c in previous year (β = 0.17, = 0.03), microvascular complications (β = 0.44, < 0.01) and macrovascular complications (β = 0.27, P < 0.01). Multiple logistic regression analysis revealed that diabetes duration (odds ratio 1.15, < 0.01), systolic blood pressure (odds ratio 1.04, P = 0.01), skin autofluorescence (odds ratio 3.62, P = 0.01) and serum albumin (odds ratio 0.84, P < 0.01) were independent factors for the presence of vascular complications in these patients.

Conclusions  Skin autofluorescence had independent effects on vascular complications in Japanese patients with Type 2 diabetes. This indicates that skin advanced glycation end products are a surrogate marker for vascular risk and a non-invasive autofluorescence reader may be a useful tool to detect high-risk cases in non-Caucasian patients with diabetes.

  M Kozawa , M Honma and H. Suzuki
 

Although primary human hepatocytes are commonly used for induction studies, the evaluation method is associated with several problems. More recently, a reporter gene assay has been suggested to be an alternative, although the contribution of only transfected nuclear receptors can be evaluated. The aim of the present study was to establish a method by which the extent of in vivo CYP3A4 induction in humans can be quantitatively predicted based on in vitro results with a reporter gene assay. From previous reports, we calculated in vivo induction ratios (Rin vivo) caused by prototypical inducers based on the alterations in the hepatic intrinsic clearance of probe drugs. Next, we derived equations by which these Rin vivo values can be predicted from the results of a reporter gene assay. To use the data obtained from a reporter gene assay, rifampicin was used as a reference drug. The correction coefficient (CC), which is used to quantitatively correlate the activity of inducers between in vitro and in vivo situations, was calculated by comparing the predicted data with the observed Rin vivo values for rifampicin. With the calculated CC value, good correlations were found between the predicted and observed Rin vivo values for other inducers such as phenobarbital, phenytoin, and omeprazole. Taken together, with the equations derived in the present study, we have been able to predict the extent of in vivo induction of human CYP3A4 by inducers in a time-dependent and quantitative manner from in vitro data.

  M Kozawa , M Honma and H. Suzuki
 

Although primary human hepatocytes are commonly used for induction studies, the evaluation method is associated with several problems. More recently, a reporter gene assay has been suggested to be an alternative, although the contribution of only transfected nuclear receptors can be evaluated. The aim of the present study was to establish a method by which the extent of in vivo CYP3A4 induction in humans can be quantitatively predicted based on in vitro results with a reporter gene assay. From previous reports, we calculated in vivo induction ratios (Rin vivo) caused by prototypical inducers based on the alterations in the hepatic intrinsic clearance of probe drugs. Next, we derived equations by which these Rin vivo values can be predicted from the results of a reporter gene assay. To use the data obtained from a reporter gene assay, rifampicin was used as a reference drug. The correction coefficient (CC), which is used to quantitatively correlate the activity of inducers between in vitro and in vivo situations, was calculated by comparing the predicted data with the observed Rin vivo values for rifampicin. With the calculated CC value, good correlations were found between the predicted and observed Rin vivo values for other inducers such as phenobarbital, phenytoin, and omeprazole. Taken together, with the equations derived in the present study, we have been able to predict the extent of in vivo induction of human CYP3A4 by inducers in a time-dependent and quantitative manner from in vitro data.

Flow modulation effect on N incorporation into GaAs(1-x)Nx films during chemical beam epitaxy growth
  H. Suzuki , K. Nishimura , K. Saito , Y. Ohshita , N. Kojima and M. Yamaguchi
 

The change in the surface concentration of N ([N]s) on a GaAs surface under N and As source injections is investigated using the N atomic layer doping (N-ALD) technique, and the key factor determining [N]s is discussed. The As and N precursors source gases are trisdimethylaminoarsenic (TDMAAs, [N(CH3)2]3As) and monomethylhydrazine (MMHy, N2H3CH3), respectively. N-ALD layers are prepared by using two gas injection sequences (A: MMHy injection and B: MMHy and TDMAAs injections). [N]s increases with decreasing growth temperature in both sequences. [N]s in sequence A is higher than that of sequence B. In sequence B, Δ[N]st is proportional to exp(–tN), where t and τN are the gas injection time and the residence time of N, respectively. It is observed that the number of vacant sites, [V]s,N, remaining constant during gas injections. In sequence A, Δ[N]st cannot be fitted by a single exponential function, indicating that [V]s,N is not constant. From these results, we suggest that the vacant sites at the surface are created not only by N desorption but also by As desorption. It has been found that As desorption is enhanced by MMHy injection. As desorption reaction has been confirmed by in situ auger electron spectroscopy measurements. These results indicate that [N]s is determined by the competitive absorption between N and As, [V]s,N, and τN.

  N Kurosawa , T Hirata and H. Suzuki
 

The amino-acid sequence of a putative tryptophan monooxygenase (PTMO) from Ralstonia solanacearum is homologous with that of proenzyme (proPAO) of l-Phe oxidase (deaminating and decarboxylating) (PAO) from Pseudomonas sp. P-501 in their overall sequences. PTMO was expressed in E. coli and purified, but had no catalytic activity to oxidize l-Phe. By treating PTMO with various proteases, the Pronase-treated PTMO (PTMOp) showed a relatively high activity to oxidize l-Phe, l-Trp, l-Tyr and l-Met. Studies on the stoichiometry of the reaction showed that l-Phe and l-Tyr were mostly oxygenated, that l-Met was mostly oxidized, and both oxygenation and oxidation of l-Trp was observed. Initial velocity patterns were a ping-pong type with l-Phe and l-Tyr, and a sequential type with l-Trp and l-Met as substrate. The spectrum of enzymes with sufficient amounts of these substrates to reduce the enzyme showed a long wavelength species (purple complex) with l-Phe, but not with l-Tyr, l-Trp and l-Met. These results lead to the conclusion that PTMO and PTMOp belong to proPAO and PAO, respectively.

  T Moriguchi , K Ida , T Hikima , G Ueno , M Yamamoto and H. Suzuki
 

We characterized the crystal structures of heterotetrameric sarcosine oxidase (SO) from Corynebacterium sp. U-96 complexed with methylthioacetate (MTA), pyrrole 2-carboxylate (PCA) and sulphite, and of sarcosine-reduced SO. SO comprises -, β-, - and -subunits; FAD and FMN cofactors; and a large internal cavity. MTA and PCA are sandwiched between the re-face of the FAD isoalloxazine ring and the β-subunit C-terminal residues. Reduction of flavin cofactors shifts the β-subunit Ala1 towards the -subunit Met55, forming a surface cavity at the oxygen-channel vestibule and rendering the β-subunit C-terminal residues mobile. We identified three channels connecting the cavity and the enzyme surface. Two of them exist in the inter-subunit space between and β-subunits, and the substrate sarcosine seems to enter the active site through either of these channels and reaches the re-side of the FAD isoalloxazine ring by traversing the mobile β-subunit C-terminal residues. The third channel goes through the -subunit and has a folinic acid-binding site, where the iminium intermediate is converted to Gly and either formaldehyde or, 5,10-methylenetetrahydrofolate. Oxygen molecules are probably located on the surface cavity and diffuse to the FMN isoalloxazine ring; the H2O2 formed exits via the oxygen channel.

 
 
 
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