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Biomedical subjects

Hiroshi Noguchi

Publications and source records attributed to Hiroshi Noguchi.

At least 19 recordsLinked to original sources

Hybrid layer seals the cementum/4-META/MMA-TBB resin interface.

Although 4-META/MMA-TBB resin has adhesive properties to dentin, and has been clinically used for the bonding treatment of vertically fractured roots and apicoectomy, there has not been any investigation on the adhesion of 4-META/MMA-TBB resin to cementum. The purpose of this in vitro study was to evaluate the bonding and the sealing ability of 4-META/MMA-TBB resin to cementum. Bovine root cementum and dentin surfaces were treated with a citric acid and ferric chloride solution, and the 4-META/MMA-TBB resin was applied on the treated surfaces before testing. The microtensile bond strength and the leakage levels obtained for the cementum were almost equal to those for the dentin. In SEM and TEM observations, a hybrid layer approximately 2-3 microm in thickness was observed at the interface between the resin and the cementum. It is concluded that 4-META/MMA-TBB resin adhered to cementum via a hybrid layer on cementum, as previously reported for dentin.

Acid Etching, Dental↗

Spinal cord herniation into associated pseudomeningocele after brachial plexus avulsion injury: case report.

OBJECTIVE: Posttraumatic spinal cord herniation is a rare condition. We describe a case of spinal cord herniation into an associated pseudomeningocele after a brachial plexus avulsion injury. CLINICAL PRESENTATION: A 33-year-old man began to develop progressive Horner's syndrome 14 years after a brachial plexus avulsion injury. At a clinical presentation 17 years after that injury, sensory disturbance and a unilateral pyramidal sign were also evident. In addition to myelography and computed tomographic myelography findings, coronal magnetic resonance imaging scans clearly demonstrated herniation of the spinal cord into a large pseudomeningocele inside the C7-T1 intervertebral foramen. Another pseudomeningocele inside the T1-T2 intervertebral foramen was also noted. INTERVENTION: The patient underwent a C6-T2 laminectomy, during which the spinal cord was found to be herniated through a dural defect into a pseudomeningocele at the C8 root level, and a second dural defect was also shown, with an arachnoid outpouching that included an avulsed T1 root. The spinal cord herniation was reduced and the dural defects were repaired. After surgery, the patient showed no significant neurological changes, and his condition stabilized. CONCLUSION: Brachial plexus root avulsions may result in the formation of pseudomeningoceles and can lead to spinal cord herniation. Coronal magnetic resonance imaging is useful to demonstrate spinal cord herniation as well as pseudomeningoceles. Surgical treatment is recommended for such cases with progressive symptoms to prevent further deterioration.

Adult↗

Coordination symmetry-dependent structure restoration function of one-dimensional MOFs by molecular respiration.

One-dimensional metal-organic compounds with cis, trans symmetry-controlled counter anions were synthesized (cis compound {[Cu(azpy)(H2O)2(OTs)2]*2H2O*(acetone)} (1) and trans compound {[Cu(H2O)4Cu(azpy)2(OTs)2(H2O)2]*2(OTs)*2H2O*2EtOH} (2)). Only 2, having trans conformation, exhibited a complete structure-restoration effect with a mechanism involving layering of molecular "bricks" of water and solvent molecules.

Journal Article↗

Enzymatic formation of quinolone alkaloids by a plant type III polyketide synthase.

[Structure: see text] Benzalacetone synthase from Rheum palmatum efficiently catalyzed condensation of N-methylanthraniloyl-CoA (or anthraniloyl-CoA) with malonyl-CoA (or methylmalonyl-CoA) to produce 4-hydroxy-2(1H)-quinolones, a novel alkaloidal scaffold produced by a type III polyketide synthase (PKS). Manipulation of the functionally divergent type III PKSs by a nonphysiological substrate thus provides an efficient method for production of pharmaceutically important quinolone alkaloids.

Alkaloids↗

A new index of the autonomic nervous balance and its clinical usefulness; a power law 1/f like scale of a spectral analysis of the heart rate variability.

OBJECTIVE: This study was undertaken to develop a new autonomic scoring scale distinct from the conventional sympathetic or parasympathetic parameters cardiac autonomic response. METHODS: The parameters were obtained from a log-log scale of frequency (f ) vs. power spectral (P) amplitude of heart rate variability (HRV). A gradient value in which the graph decreases towards a high frequencies on the X-axis, while showing an absolute value beta itself based on the formula 'P = f (-beta)' was newly named the 'Balance index' by implying a balanced state in the living body. The index was categorized into four bands based on the appearance of the whole frequency ranges (T-Balance Index). Therefore, we compared the responses of the following groups: the patient test group (Group PT), the normal test group (Group NT), and the normal non-test group (group NN). RESULTS: Significant differences in parameters were observed among the three groups. In addition, the difference between the 'High-side Balance Index' and the 'Low-side Balance Index' was 0.75 +/- 0.12 vs. 0.07 +/- 0.04 (p < 0.005) for groups NT vs. PT. This novel analyzing method was useful for evaluating the subtle changes in a living body to regulate the living-power (strength of vitality). Moreover, the difference between the 'T-Balance Index' and 'SV-Balance Index' was 0.18 +/- 0.12 vs. -0.21 +/- 0.15 (p < 0.01) for groups NT vs. PT. CONCLUSIONS: One application of new parameters 'Balance Index' is its ability to evaluate the vital or emotional functions of unconscious patients in a critical condition undergoing a sense challenge test. This method assists in improving our ability to measure the early stage of conscious recovery with greater accuracy by using our novel analysis method for performing senses challenge test, with the aid of media such as music.

Adolescent↗

Site-directed mutagenesis of conserved aromatic residues in rat squalene epoxidase.

Squalene epoxidase catalyzes the conversion of squalene to (3S)2,3-oxidosqualene, which is a rate-limiting step of the cholesterol biogenesis. To evaluate the importance of conserved aromatic residues, 15 alanine-substituted mutants were constructed and tested for the enzyme activity. Except F203A, all the mutants significantly lost the enzyme activity, confirming the importance of the residues, either for correct folding of the protein, or for the catalytic machinery of the enzyme. Further, interestingly, F223A mutant no longer accepted (3S)2,3-oxidosqualene as a substrate, while Y473A mutant converted (3S)2,3-oxidosqualene to (3S,22S)2,3:22,23-dioxidosqualene twice more efficiently than wild-type enzyme. It is remarkable that the single amino acid replacement yielded mutants with altered substrate and product specificities. These aromatic residues are likely to be located at the substrate-binding domain of the active-site, and control the stereochemical course of the enzyme reaction.

Alanine↗

Dynamics of vesicle self-assembly and dissolution.

The dynamics of membranes is studied on the basis of a particle-based meshless surface model, which was introduced earlier [Phys. Rev. E 73, 021903 (2006)]. The model describes fluid membranes with bending energy and-in the case of membranes with boundaries-line tension. The effects of hydrodynamic interactions are investigated by comparing Brownian dynamics with a particle-based mesoscale solvent simulation (multiparticle collision dynamics). Particles self-assemble into vesicles via disk-shaped membrane patches. The time evolution of assembly is found to consist of three steps: particle assembly into discoidal clusters, aggregation of clusters into larger membrane patches, and finally vesicle formation. The time dependence of the cluster distribution and the mean cluster size is evaluated and compared with the predictions of Smoluchowski rate equations. On the other hand, when the line tension is suddenly decreased (or the temperature is increased), vesicles dissolve via pore formation in the membrane. Hydrodynamic interactions are found to speed up the dynamics in both cases. Furthermore, hydrodynamics makes vesicle more spherical in the membrane-closure process.

Computer Simulation↗

Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone.

Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase that catalyzes the formation of 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. Recombinant PCS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group P2(1), with unit-cell parameters a = 73.2, b = 88.4, c = 70.0 A, alpha = gamma = 90.0, beta = 95.6 degrees . Diffraction data were collected to 1.6 A resolution using synchrotron radiation at BL24XU of SPring-8.

Aloe↗

Meshless membrane model based on the moving least-squares method.

A meshless particle-based membrane model is proposed. The particles possess no internal degree of freedom and interact via a potential, which has three different contributions: a short-range repulsive pair potential, an attractive multibody potential, and a curvature potential based on the moving least-squares method. Brownian dynamics simulations are employed to demonstrate that the particles self-assemble into a membrane and to study equilibrium properties, such as bending rigidity, surface tension, line tension, and diffusion constant. The bending rigidity and line tension are shown to depend on different potential parameters and can therefore be varied independently. The finite-size effects of nearly planar membranes are investigated. This model is well suited to study the membrane dynamics with topological changes.

Computer Simulation↗

Engineered biosynthesis of plant polyketides: manipulation of chalcone synthase.

[reaction: see text]. Chalcone synthase (CHS) is a plant-specific type III polyketide synthase catalyzing condensation of 4-coumaroyl-CoA with three molecules of malonyl-CoA. Surprisingly, it was demonstrated that S338V mutant of Scutellaria baicalensis CHS produced octaketides SEK4/SEK4b from eight molecules of malonyl-CoA. Further, the octaketides-forming activity was dramatically increased in a CHS triple mutant (T197G/G256L/S338T). The functional conversion is based on the simple steric modulation of a chemically inert residue lining the active-site cavity.

Acyltransferases↗

Protective effect of brain-derived neurotrophic factor on pancreatic islets in obese diabetic mice.

We have previously demonstrated that brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. In the present study, the effect of BDNF treatment on pancreatic islets of db/db mice was examined, using vehicle-treated pair-fed db/db mice as controls. Brain-derived neurotrophic factor (10 mg/kg) or vehicle was subcutaneously administered to male db/db mice for 4 weeks. The food intake of vehicle-treated db/db mice was restricted and precisely synchronized with that of BDNF-treated db/db mice using a pellet pair-feeding apparatus because BDNF decreases food intake in hyperphagic mice. Repetitive administration of BDNF significantly lowered the blood glucose concentration compared with pair-fed vehicle-treated db/db mice. The pancreatic insulin and glucagon concentrations were measured in db/db mice to evaluate the effect of BDNF on the pancreas. Although the insulin concentration in the pancreas of pair-fed vehicle-treated db/db mice was lower than in nondiabetic control +m/+m mice, it was higher in BDNF-treated db/db mice than in vehicle-treated pair-fed db/db mice and comparable to the concentration in +m/+m mice. The glucagon concentration in the pancreas of vehicle-treated pair-fed db/db mice was higher than in +m/+m mice, and BDNF partially decreased the glucagon concentration in the pancreas of db/db mice compared with vehicle. Histologic analyses of pancreatic sections were performed to characterize the mechanism through which BDNF modulates the hormonal concentration in the pancreas of db/db mice. Although there were no significant differences in the number and total area of islets between the BDNF- and vehicle-treated groups, immunostaining with an anti-insulin antibody indicated that the islet beta-cell area in BDNF-treated db/db mice was larger than that in vehicle-treated pair-fed db/db mice. Furthermore, immunostaining with an antiglucagon antibody indicated that BDNF normalized the delocalization of non-beta cells in islets of db/db mice. Electron microscopic images of beta cells indicated a decrease in secretory granules in vehicle-treated pair-fed db/db mice; this change was reversed in BDNF-treated db/db mice and reached a level comparable to that found in +m/+m mice. These findings suggest that BDNF prevents exhaustion of the pancreas in diabetic mice by maintaining the histologic cellular organization of beta cells and non-beta cells in pancreatic islets and restoring the level of insulin-secreting granules in beta cells.

Animals↗

Novel expansion/shrinkage modulation of 2D layered MOF triggered by clathrate formation with CO(2) molecules.

Crystal-to-crystal transformation from a 3D interpenetrated-type MOF {[Cu(BF(4))(2)(bpy)(H(2)O)(2)] (bpy)} (1) to a 2D square-grid-type [Cu(BF(4))(2)(bpy)(2)] (2) (bpy = 4,4'-bipyridine) was observed. It was derived from dehydration and confirmed by in situ FT-IR, TG, and elemental analysis. Moreover, we elucidate the novel expansion/shrinkage dynamic modulation of 2 triggered by clathrate formation with gas molecules.

Adsorption↗

Concentration and daily excretion of uranium in urine of Japanese.

A study was undertaken to investigate uranium concentrations in urine samples for unexposed Japanese individuals and to evaluate uranium daily excretion. Uranium concentrations were measured with inductively coupled plasma mass spectrometry after microwave-assisted digestion and online separation using the UTEVA extraction chromatographic resin. The concentrations ranged from 0.8 to 35.6 ng of uranium per liter of urine (median 4.5 ng L(-1)). Urinary uranium was normalized relative to the creatinine concentration in order to compensate for the degree of urine dilution. Creatinine-normalized values ranged from 1.2 to 17.8 ng of uranium per gram of creatinine (median 7.4 ng g(-1) creatinine). These results corresponded to the lower end of urinary uranium reported for unexposed populations. The level of daily excreted uranium was calculated as 6.45 ng d(-1) (median value) using ICRP recommended values for 24-h creatinine excretion. These data along with literature data on uranium dietary intake for Japanese populations were used to estimate the uranium gastrointestinal absorption fraction (f(1)). The median f(1) value was calculated to be 0.007. Statistical analysis was done to investigate statistical differences and relationships between the studied variables.

Adult↗

Active site residues governing substrate selectivity and polyketide chain length in aloesone synthase.

Aloesone synthase (ALS) and chalcone synthase (CHS) are plant-specific type III poyketide synthases sharing 62% amino acid sequence identity. ALS selects acetyl-CoA as a starter and carries out six successive condensations with malonyl-CoA to produce a heptaketide aloesone, whereas CHS catalyses condensations of 4-coumaroyl-CoA with three malonyl-CoAs to generate chalcone. In ALS, CHS's Thr197, Gly256, and Ser338, the active site residues lining the initiation/elongation cavity, are uniquely replaced with Ala, Leu, and Thr, respectively. A homology model predicted that the active site architecture of ALS combines a 'horizontally restricting' G256L substitution with a 'downward expanding' T197A replacement relative to CHS. Moreover, ALS has an additional buried pocket that extends into the 'floor' of the active site cavity. The steric modulation thus facilitates ALS to utilize the smaller acetyl-CoA starter while providing adequate volume for the additional polyketide chain extensions. In fact, it was demonstrated that CHS-like point mutations at these positions (A197T, L256G, and T338S) completely abolished the heptaketide producing activity. Instead, A197T mutant yielded a pentaketide, 2,7-dihydroxy-5-methylchromone, while L256G and T338S just afforded a triketide, triacetic acid lactone. In contrast, L256G accepted 4-coumaroyl-CoA as starter to efficiently produce a tetraketide, 4-coumaroyltriacetic acid lactone. These results suggested that Gly256 determines starter substrate selectivity, while Thr197 located at the entrance of the buried pocket controls polyketide chain length. Finally, Ser338 in proximity of the catalytic Cys164 guides the linear polyketide intermediate to extend into the pocket, thus leading to formation of the hepataketide in Rheum palmatum ALS.

Acetyl Coenzyme A↗

Enzymatic formation of indole-containing unnatural cyclic polyprenoids by bacterial squalene:hopene cyclase.

[reaction: see text] Two indole-containing substrate analogues, in which a C20 isoprene unit is connected to indole (3-(geranylgeranyl)indole and 3-(farnesyldimethylallyl)indole), were synthesized and tested for enzymatic cyclization by squalene:hopene cyclase from Alicyclobacillus acidocaldarius. Interestingly, 3-(geranylgeranyl)indole was not a substrate for the bacterial squalene cyclase, while 3-(farnesyldimethylallyl)indole was efficiently converted to a 2:1 mixture of unnatural novel products.

Bacillus↗

Shape transitions of fluid vesicles and red blood cells in capillary flows.

The dynamics of fluid vesicles and red blood cells (RBCs) in cylindrical capillary flow is studied by using a three-dimensional mesoscopic simulation approach. As flow velocity increases, a model RBC is found to transit from a nonaxisymmetric discocyteto an axisymmetric parachute shape (coaxial with the flow axis), while a fluid vesicle is found to transit from a discocyte to a prolate ellipsoid. Both shape transitions reduce the flow resistance. The critical velocities of the shape transitions are linearly dependent on the bending rigidity and on the shear modulus of the membrane. Slipper-like shapes of the RBC model are observed around the transition velocities. Our results are in good agreement with experiments on RBCs.

Blood Circulation↗

Engineered biosynthesis of plant polyketides: chain length control in an octaketide-producing plant type III polyketide synthase.

The chalcone synthase (CHS) superfamily of type III polyketide synthases (PKSs) produces a variety of plant secondary metabolites with remarkable structural diversity and biological activities (e.g., chalcones, stilbenes, benzophenones, acrydones, phloroglucinols, resorcinols, pyrones, and chromones). Here we describe an octaketide-producing novel plant-specific type III PKS from aloe (Aloe arborescens) sharing 50-60% amino acid sequence identity with other plant CHS-superfamily enzymes. A recombinant enzyme expressed in Escherichia coli catalyzed seven successive decarboxylative condensations of malonyl-CoA to yield aromatic octaketides SEK4 and SEK4b, the longest polyketides known to be synthesized by the structurally simple type III PKS. Surprisingly, site-directed mutagenesis revealed that a single residue Gly207 (corresponding to the CHS's active site Thr197) determines the polyketide chain length and product specificity. Small-to-large substitutions (G207A, G207T, G207M, G207L, G207F, and G207W) resulted in loss of the octaketide-forming activity and concomitant formation of shorter chain length polyketides (from triketide to heptaketide) including a pentaketide chromone, 2,7-dihydroxy-5-methylchromone, and a hexaketide pyrone, 6-(2,4-dihydroxy-6-methylphenyl)-4-hydroxy-2-pyrone, depending on the size of the side chain. Notably, the functional diversity of the type III PKS was shown to evolve from simple steric modulation of the chemically inert single residue lining the active-site cavity accompanied by conservation of the Cys-His-Asn catalytic triad. This provided novel strategies for the engineered biosynthesis of pharmaceutically important plant polyketides.

Acyltransferases↗

Clathrate-formation mediated adsorption of methane on Cu-complex crystals.

We measured adsorption and desorption isotherms of methane on [Cu(4, 4'-bipyridine)2(BF4)2] (LPC) at 258, 273, and 303 K. Adsorption proceeds almost vertically at a definite pressure, which is named gate pressure. The lower the measurement temperature, the smaller the gate pressure. The temperature dependence of the gate pressure is expressed by the Clapeyron-Clausius equation, giving a thermodynamic evidence on the clathrate formation between the Cu complex and methane.

Letter↗