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A Kasuya

Publications and source records attributed to A Kasuya.

At least 19 recordsLinked to original sources
PubMed2005

The cell death machinery controlled by Bax and Bcl-XL is evolutionarily conserved in Ciona intestinalis.

Bax and Bcl-XL are key regulators of apoptosis in mammals. Here we report the functional characterization of two Bcl-2 homologues, ciBax and ciBcl-XL, in a basal invertebrate-chordate ascidian Ciona intestinalis. CiBax is a Ciona homologue of the BH1-3 pro-apoptotic protein Bax, whereas ciBcl-XL is a Bcl-XL-like anti-apoptotic protein. Molecular modeling analysis showed that ciBax and ciBcl-XL share both sequence and structural similarities to human Bax and Bcl-XL, respectively. Like their human counterparts, ciBax could form a homodimer or oligomers as well as heterodimerize with ciBcl-XL, and overexpression of ciBax caused apoptosis that could be attenuated by ciBcl-XL. Mutagenesis studies showed that the BH3 domain of ciBax is critical for its cell death-inducing function and also for its interaction with ciBcl-XL. In Ciona embryos, ectopic expression of ciBax but not its BH3 deletion mutant resulted in cell dissociation and apoptosis after late gastrula stage of embryonic development. Moreover, not only wild type ciBcl-XL but also a mutant ciBcl-XL(F101V), which is unable to interact with ciBax, could block cell dissociation and developmental deficit in Ciona embryos induced by overexpression of ciBax. Taken together, these findings suggest that functional homologues of both the BH1-3 death effector Bax and the pro-survival Bcl-XL exist in sea squirt Ciona intestinalis, and they control the cell death machinery independent of their heterodimerization.

Animals↗
PubMed2001

Thermal effect in unoccupied molecular orbitals of C60 molecules adsorbed on a Si(001)-(2 x 1) surface studied by NEXAFS.

We report here the temperature-dependent unoccupied molecular orbitals (MO's) of C60 molecules adsorbed on a Si(001)-(2 x 1) surface measured using near edge x-ray absorption fine structure (NEXAFS). At 300 K, the NEXAFS spectrum reveals that the interaction between a 1.0 monolayer (ML) C60 film and a Si(001) surface is mainly the van der Waals force. After annealing the samples at 500 K, we observe an increment in the full-width at half-maximum of unoccupied MO's, which indicates the change of the interaction. Moreover, the lowest unoccupied molecular orbital (LUMO) shifts to the higher photon energy side and the intensity of the LUMO+1 relative to that of the LUMO+3 decreases in the NEXAFS spectrum. These results suggest that the strong interaction induced at 500 K has a covalent character, to which the LUMO+1 contributes.

Journal Article↗
PubMed2001

Interaction between peroxisome proliferator-activated receptor gamma and its agonists: docking study of oximes having 5-benzyl-2,4-thiazolidinedione.

The molecular modelling of oximes having 5-benzyl-2,4-thiazolidinedione moieties, agonists of the peroxisome proliferator-activated receptor gamma (PPAR gamma), was performed with respect to their structures complexed with the ligand binding domain of PPAR gamma. For each ligand molecule, the 5-benzyl-2,4-thiazolidinedione head group was used as an anchor and the conformation of the rest of the molecule was searched for the most energetically favorable interaction with the receptor by systematic conformation search and manual modelling. Although both tail-up and tail-down configurations, which have been observed in the crystal structure of eicosapentaenoic acid when complexed with PPAR delta, appeared among the lowest energy structures for most of the compounds, potent agonists were found to adopt a configuration similar to that of rosiglitazone when bound to PPAR gamma, according to the crystal structure. The structure-activity relationships were analyzed based on the receptor-ligand interaction. The alkyl group and the aromatic ring of the tail group of the ligands had hydrophobic interactions with the receptor, and these interactions were found to be essential for the strong activity.

Hypoglycemic Agents↗
PubMed2001

A method for characterizing carbon nanotubes.

High-resolution transmission electron microscopy and electron energy-loss spectroscopy of a multi-walled carbon nanotube (MWCNT) at elevated temperatures were studied. Although the observation was carried out at 200 kV, the crystal structures of the MWCNT were observed without introducing defects. In addition, contamination on the MWCNT, such as nanobubbles, was removed during the observation at 600 degrees C. In this paper, we report the observation conditions and experimental results. The experimental results obtained both at 600 degrees C and at room temperature were compared.

Letter↗
PubMed2001

A method for assessing the side chain orientations of histidine, asparagine, and glutamine as well as the protonation forms of histidine in protein structures.

In protein X-ray crystallography, it is sometimes impossible to distinguish N and O in amide side chains and N and C in His side chains, resulting in the 'flipped' conformations in these side chains. We have developed a simple, but effective, approach to assess the side chain orientations of His. Asn, and Gln as well as the protonation forms of His in protein structures. This method finds the most favorable side chain orientation and His form by calculating the van der Waals interaction and hydrogen bonding energies around each residue in question. This evaluation is repeated until consistent results are obtained. Our approach was applied to four proteins and in overall approximately 25% of His, Asn, and Gln were evaluated as 'flipped' and 63% of the imidazole rings were suggested to have a polar hydrogen atom only on N epsilon2. In the individual cases, it was found that our results were comparable to or even better than those obtained by a traditional method. The present approach is therefore quite useful to construct initial protein structures for the molecular modeling studies.

Aldehyde Reductase↗
PubMed2000

Origin of anomalous lattice expansion in oxide nanoparticles

Anomalous lattice expansions have been measured for the first time in monodisperse CeO2-x nanoparticles and in BaTiO3 single nanoparticles by electron diffraction. X-ray photoelectron spectroscopy studies on CeO2-x nanoparticles and ab initio computer simulation on BaTiO3 clusters show that the origin of expansion is the decrease of electrostatic force caused by valence reduction of Ce ions and the increase in ionicity of Ti ions, respectively. The lattice constant change of oxide (ionic) nanoparticles with the increase in ionicity would depend on the structure of the particles. Hence, first-principles calculations of large ionic clusters are indispensable.

Journal Article↗
PubMed2000

Conformational analysis of 2-[2-(3-methoxyphenyl) ethyl]phenoxyalkylamines with high 5-HT2 receptor binding affinity.

A conformational analysis of three groups of 2-[2-(3-methoxyphenyl)ethyl]phenoxyalkylamines with high 5-HT2 receptor binding affinity has been performed using the systematic search. Two groups of compounds with different lengths of alkyl chains connecting the amine nitrogen and the central oxygen showed a one order difference in their 5-HT2 receptor binding affinity. The computational analysis of these compounds confirmed the differences in the N--O distances between the two groups, quantitatively. A probable active conformation was proposed based on a superimposition of the stable conformations over a rigid molecule, mianserin. Two hydroxy derivatives in the third group showed a significant difference in their binding affinity depending on the stereochemistry of the hydroxy group. The difference in the energetically favorable order of the stable conformations reasonably explained the relationship between the stereochemistry and the binding activity. A molecular dynamics-based conformational search was also carried out to compare it with the systematic search.

Alkanes↗
PubMed1999

Intrarenal angiotensin converting enzyme inhibition in spontaneously hypertensive rats.

We examined the hypotensive effect of enalapril in relation to the local renin-angiotensin system of the kidney in spontaneously hypertensive rats (SHR). Oral administration of enalapril for 7 days decreased mean arterial blood pressure and renal tissue angiotensin II concentration without affecting plasma angiotensin II concentration in SHR. The enalapril treatment did not affect maximum binding of angiotensin II to renal tubules and glomeruli in SHR. In normotensive Wistar-Kyoto rats, no significant changes in mean arterial blood pressure, renal and plasma angiotensin levels were observed with enalapril treatment. Direct infusion of enalapril into the renal medullary interstitium decreased mean arterial blood pressure in association with the reduction of renal tissue angiotensin II concentration without changes in plasma angiotensin II concentration in SHR. These observations suggest that the inhibition of angiotensin conversion in the kidney is important for the hypotensive action of enalapril.

Administration, Oral↗
PubMed1999

Three-dimensional structure analysis of PROSITE patterns.

Pattern matches for each of the sequence patterns in PROSITE, a database of sequence patterns, were searched in all protein sequences in the Brookhaven Protein Data Bank (PDB). The three-dimensional structures of the pattern matches for the 20 patterns with the largest numbers of hits were analysed. We found that the true positives have a common three-dimensional structure for each pattern; the structures of false positives, found for six of the 20 patterns, were clearly different from those of the true positives. The results suggest that the true pattern matches each have a characteristic common three-dimensional structure, which could be used to create a template to define a three-dimensional functional pattern.

Adenosine Triphosphate↗
PubMed1999

Structure-activity relationship of HIV-1 protease inhibitors containing alpha-hydroxy-beta-amino acids. Detailed study of P1 site.

The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing alpha-hydroxy-beta-amino acids is discussed. We demonstrated that substituent groups on the P1 aromatic rings of the inhibitors exert significant influence on their biological activity. Inhibitors bearing an alkyl or a fluorine atom at the meta and para position on their P1 benzene ring were found to be good inhibitors. We also discovered that the substitution positions of the P2 benzamides were crucial for good antiviral potency. In this study, inhibitor 48 was the most potent [IC90 (CEM/HIV-1 IIIB) 27 nM] and showed good pharmacokinetics in rats.

Amino Acids↗
PubMed1999

Inhibitory effect of nitric oxide on the renin-angiotensin system in Dahl salt-sensitive rats.

1. To explore the role of nitric oxide (NO) in the regulation of the renin-angiotensin system (RAS) in Dahl salt-sensitive (DS) rats, the effects of NG-nitro-L-arginine methyl ester (L-NAME) on plasma renin activity (PRA), and concentrations of angiotensin (Ang)I and AngII in the plasma, aorta and kidney were investigated in DS and Dahl salt-resistant (DR) rats. 2. NG-Nitro-L-arginine methyl ester (12-18 mg/kg per day) administration for 1 week increased mean arterial pressure (MAP) in DS and DR rats fed a 0.3% NaCl diet and in DR rats fed an 8% NaCl diet compared with corresponding vehicle (water)-treated groups. However, L-NAME administration did not change MAP in DS rats fed an 8% NaCl diet. 3. NG-Nitro-L-arginine methyl ester administration increased PRA in DS rats fed an 8% NaCl diet, but not in DR rats fed an 8% NaCl diet. NG-Nitro-L-arginine methyl ester administration increased AngI and AngII concentrations in plasma, aorta and kidney only in DS rats fed an 8% NaCl diet. The ratio of AngI to AngII did not change following L-NAME administration in any rats. 4. These results suggest that NO has an inhibitory role on renin release in DS rats fed a high-salt diet.

Animals↗
PubMed1998

Structure-activity relationship of HIV-1 protease inhibitors containing AHPBA. Part III: Modification of P2 site.

The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing AHPBA (3-amino-2-hydroxy-4-phenylbutanoic acid) is discussed. In order to solve the problem of poor oral bioavailability, small-sized dipeptide HIV-1 protease inhibitors containing cyclic urethanes or benzamides at the P2 site were designed and prepared. The substitution patterns of the benzamides contributed significantly to their HIV-1 PR inhibitory activities, and it was shown that the choice of P2-residues was very important. Highly potent inhibitors possessing subnanomolar IC50 values and exhibiting good antiviral potency have been identified. In this class, inhibitor 18 was the most potent (IC90 (CEM/HIV-1 IIIB) 0.11 microM) and showed good oral bioavailability in dogs.

Animals↗
PubMed1998

Species variation in pharmacokinetics and opsonization of palmitoyl rhizoxin (RS-1541) incorporated in lipid emulsions.

Highly lipophilic antitumor agent, palmitoyl rhizoxin (RS-1541), was incorporated into stable lipid emulsions about 100-1000nm in mean diameter consisting of triglyceride ODO and surfactant HCO-60. The pharmacokinetics of RS-1541 were studied after i.v. injection in mice, rats, rabbits, and dogs. Dog showed characteristic pharmacokinetics of RS-1541, compared with other species. RS-1541 was much more rapidly eliminated from plasma with emulsion particles in dogs than in mice, rats, and rabbits. Most amounts of injected RS-1541 were recovered in the liver six hours after administration to dogs, while less than 20% recoveries were observed for mice and rats. To clarify this species variation, opsonization of emulsion particles were evaluated. When emulsions (about 200nm in size) were opsonized by dog plasma, and intravenously injected to rats, total clearance and liver uptake of RS-1541 were increased to 1.8 fold and 2.7 fold of control values, respectively. In contrasts, emulsions opsonized by mouse, rabbit and human plasma did not show such drastic changes in pharmacokinetics of RS-1541 in rats. Furthermore, total clearance of RS-1541 for emulsions opsonized by dog plasma was increased to 1.9 fold of controls after injection to rabbits. These results indicate that opsonizing activities of dog plasma for RS-1541 emulsions are high, compared with other species. This species variation in opsonizing process probably caused the species variation in the pharmacokinetics of RS-1541 incorporated in lipid emulsions.

Animals↗
PubMed1997

Inhibition of HIV-1 protease by oxim derivatives.

In cell-free proteolytic processing using recombinant HIV-1 protease and Gag precursor polypeptide, certain simple oxim derivatives containing halogenomethylketone and phenyl moieties displayed HIV-1 protease inhibitory activity. Their Ki values ranged from 2.1 microM to 6.3 microM and they did not inhibit significantly other aspartic acid proteases. Both the halogenomethylketone moiety and the oxim structure were essential for the observed inhibition. Molecular modeling analysis suggested that these compounds are recognized by the HIV-1 protease as the P1 and P1' part of the substrate. In addition, one potent derivative showed inhibition of viral maturation in HIV-1IIIB chronically infected Molt-4 cells. These results indicate that it is possible to develop new and specific nonpeptidyl HIV protease inhibitors of low molecular weight.

Binding, Competitive↗
PubMed1996

Reconstruction of the 3D coordinates of alpha-carbon atoms of proteins from a pair of stereographic figures.

In an attempt to promptly use the experimentally determined structures of proteins in modeling studies, we have developed the program ReconstC alpha to generate the 3D coordinates of alpha-carbon atoms from a pair of stereographic figures. Calculations of the 3D coordinates were performed by estimating the stereo parameters systematically. Geometrical features of C alpha traces were used to evaluate the integrity of the calculated structure. The program was applied to four kinds of protein structures to examine the performance. It was found that the root-mean-square deviation of atomic positions between constructed and reference crystal structures ranged from 0.36 to 0.78 A. The range represents a reasonable accuracy and its automatic feature suggests that our approach would be expedient for providing initial structures for protein modeling studies.

Crystallography, X-Ray↗
PubMed1996

Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA--II. Modification of pyrrolidine ring at P1' proline.

Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed Ki = 4.5 nM against HIV PR and IC90S 0.58 microM and 0.06 microM in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-CI atom and fused bicyclic heterocycles may be effective in improving their cellular penetration.

Cells, Cultured↗