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Biomedical subjects

Hideyuki Hayashi

Publications and source records attributed to Hideyuki Hayashi.

At least 19 recordsLinked to original sources

Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase.

Catechins have recently been reported to increase the cellular content of the hypoxia-inducible factor (HIF)-1alpha within mammalian cells. These catechins have a gallate moiety as a common structure. We now report that n-propyl gallate (nPG) also increases the HIF-1alpha protein in the rat heart-derived H9c2 cells. The increase was dose-dependent and reached a maximum at 2-4h after the addition of nPG to the cells. nPG did not change the HIF-1alpha mRNA level, showing that the increase is a posttranscriptional event. Although nPG did not inhibit the HIF prolyl hydroxylase, gallate, the hydrolysis product of nPG, inhibited the enzyme completely at submillimolar concentrations. Model building studies on the human HIF prolyl hydroxylase 2 showed that the two phenolate oxygen atoms of gallate form a chelate with the active site Fe(2+), while the carboxyl group of gallate forms a strong ionic/hydrogen bonding interaction with Arg383, explaining why nPG, which has an esterified carboxyl group, is unable to inhibit the hydroxylase. Together with the observation that gallate was detected in the H9c2 cells treated with nPG, these results suggest that nPG incorporated into the cells is hydrolyzed and the released gallate inhibits the HIF prolyl hydroxylase, thereby reducing the HIF degradation rate and increasing the HIF-1alpha content.

Animals↗

Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (gamma-resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005.

Reversible 2,6-dihydroxybenzoate decarboxylase from Rhizobium sp. strain MTP-10005 belongs to a nonoxidative decarboxylase family. We have determined the structures of the following three forms of the enzyme: the native form, the complex with the true substrate (2,6-dihydroxybenzoate), and the complex with 2,3-dihydroxybenzaldehyde at 1.7-, 1.9-, and 1.7-A resolution, respectively. The enzyme exists as a tetramer, and the subunit consists of one (alphabeta)8 triose-phosphate isomerase-barrel domain with three functional linkers and one C-terminal tail. The native enzyme possesses one Zn2+ ion liganded by Glu8, His10, His164, Asp287, and a water molecule at the active site center, although the enzyme has been reported to require no cofactor for its catalysis. The substrate carboxylate takes the place of the water molecule and is coordinated to the Zn2+ ion. The 2-hydroxy group of the substrate is hydrogen-bonded to Asp287, which forms a triad together with His218 and Glu221 and is assumed to be the catalytic base. On the basis of the geometrical consideration, substrate specificity is uncovered, and the catalytic mechanism is proposed for the novel Zn2+-dependent decarboxylation.

Benzaldehydes↗

Molecular cloning, expression and characterization of pyridoxamine-pyruvate aminotransferase.

Pyridoxamine-pyruvate aminotransferase is a PLP (pyridoxal 5'-phosphate) (a coenzyme form of vitamin B6)-independent aminotransferase which catalyses a reversible transamination reaction between pyridoxamine and pyruvate to form pyridoxal and L-alanine. The gene encoding the enzyme has been identified, cloned and overexpressed for the first time. The mlr6806 gene on the chromosome of a symbiotic nitrogen-fixing bacterium, Mesorhizobium loti, encoded the enzyme, which consists of 393 amino acid residues. The primary sequence was identical with those of archaeal aspartate aminotransferase and rat serine-pyruvate aminotransferase, which are PLP-dependent aminotransferases. The results of fold-type analysis and the consensus amino acid residues found around the active-site lysine residue identified in the present study showed that the enzyme could be classified into class V aminotransferases of fold type I or the AT IV subfamily of the alpha family of the PLP-dependent enzymes. Analyses of the absorption and CD spectra of the wild-type and point-mutated enzymes showed that Lys197 was essential for the enzyme activity, and was the active-site lysine residue that corresponded to that found in the PLP-dependent aminotransferases, as had been suggested previously [Hodsdon, Kolb, Snell and Cole (1978) Biochem. J. 169, 429-432]. The K(d) value for pyridoxal determined by means of CD was 100-fold lower than the K(m) value for it, suggesting that Schiff base formation between pyridoxal and the active-site lysine residue is partially rate determining in the catalysis of pyridoxal. The active-site structure and evolutionary aspects of the enzyme are discussed.

Alphaproteobacteria↗

Kinetic and structural studies on the catalytic role of the aspartic acid residue conserved in copper amine oxidase.

Copper amine oxidase contains a post-translationally generated quinone cofactor, topa quinone (TPQ), which mediates electron transfer from the amine substrate to molecular oxygen. The overall catalytic reaction is divided into the former reductive and the latter oxidative half-reactions based on the redox state of TPQ. In the reductive half-reaction, substrate amine reacts with the C5 carbonyl group of the oxidized TPQ, forming the substrate Schiff base (TPQ(ssb)), which is then converted to the product Schiff base (TPQ(psb)). During this step, an invariant Asp residue with an elevated pKa is presumed to serve as a general base accepting the alpha proton of the substrate. When Asp298, the putative active-site base in the recombinant enzyme from Arthrobacter globiformis, was mutated into Ala, the catalytic efficiency dropped to a level of about 10(6) orders of magnitude smaller than the wild-type (WT) enzyme, consistent with the essentiality of Asp298. Global analysis of the slow UV/vis spectral changes observed during the reductive half-reaction of the D298A mutant with 2-phenylethylamine provided apparent rate constants for the formation and decay of TPQ(ssb) (k(obs) = 4.7 and 4.8 x 10(-4) s(-1), respectively), both of which are markedly smaller than those of the WT enzyme determined by rapid-scan stopped-flow analysis (k(obs) = 699 and 411 s(-1), respectively). Thus, Asp298 plays important roles not only in the alpha-proton abstraction from TPQ(ssb) but also in other steps in the reductive half-reaction. X-ray diffraction analyses of D298A crystals soaked with the substrate for 1 h and 1 week revealed the structures of TPQ(ssb) and TPQ(psb), respectively, as pre-assigned by single-crystal microspectrophotometry. Consistent with the stereospecificity of alpha-proton abstraction, the pro-S alpha-proton of TPQ(ssb) to be abstracted is positioned nearly perpendicularly to the plane formed by the Schiff-base imine double bond conjugating with the quinone ring of TPQ, so that the orbitals of sigma and pi electrons maximally overlap in the conjugate system. More intriguingly, the pro-S alpha proton of the substrate is released stereospecifically even in the reaction catalyzed by the base-lacking D298A mutant. On the basis of these results, we propose that the stereospecificity of alpha-proton abstraction is primarily determined by the conformation of TPQ(ssb), rather than the relative geometry of TPQ and the catalytic base.

Amine Oxidase (Copper-Containing)↗

Quantum mechanical hydrogen tunneling in bacterial copper amine oxidase reaction.

A key step decisively affecting the catalytic efficiency of copper amine oxidase is stereospecific abstraction of substrate alpha-proton by a conserved Asp residue. We analyzed this step by pre-steady-state kinetics using a bacterial enzyme and stereospecifically deuterium-labeled substrates, 2-phenylethylamine and tyramine. A small and temperature-dependent kinetic isotope effect (KIE) was observed with 2-phenylethylamine, whereas a large and temperature-independent KIE was observed with tyramine in the alpha-proton abstraction step, showing that this step is driven by quantum mechanical hydrogen tunneling rather than the classical transition-state mechanism. Furthermore, an Arrhenius-type preexponential factor ratio approaching a transition-state value was obtained in the reaction of a mutant enzyme lacking the critical Asp. These results provide strong evidence for enzyme-enhanced hydrogen tunneling. X-ray crystallographic structures of the reaction intermediates revealed a small difference in the binding mode of distal parts of substrates, which would modulate hydrogen tunneling proceeding through either active or passive dynamics.

Amine Oxidase (Copper-Containing)↗

Long-term changes in corneal surface configuration after penetrating keratoplasty.

PURPOSE: To examine the long-term longitudinal changes in corneal surface configuration as determined by Fourier series harmonic analysis of videokeratography data and of visual acuity and refraction after penetrating keratoplasty (PK). DESIGN: Interventional case series. METHODS: One hundred thirty eyes of 130 consecutive patients who were scheduled for PK using 16 interrupted 10-0 nylon sutures were recruited. Spherical equivalent power, regular astigmatism component, irregular astigmatism (asymmetry and higher-order irregularity) component of the central cornea as determined by Fourier analysis of videokeragraphic data, spectacle-corrected visual acuity, and spherical equivalent were examined at 1 week, and at 1, 3, 6, 9, 12, 18, and 24 months after PK. RESULTS: Spherical equivalent power increased considerably for up to 1 month after PK, but thereafter showed no further appreciable change up to the final follow-up at 24 months. The regular astigmatism component decreased markedly for up to 6 months after PK, while the total irregular astigmatism (sum of the asymmetry and higher-order irregularity) component decreased considerably up to approximately 3 months, and then these showed no further relevant change for up to 24 months. Spectacle-corrected visual acuity also improved markedly until approximately 3 months after PK, after which it was virtually stable. Furthermore, important correlations were found between regular and irregular astigmatism and the spectacle-corrected visual acuity. CONCLUSIONS: Corneal surface configuration after PK appears to be stable by approximately 6 months after PK, concurrent with postkeratoplasty stabilization of visual acuity.

Adult↗

Posterior capsule opacification in myopic eyes.

PURPOSE: To determine whether posterior capsule opacification (PCO) is extensive in eyes with myopia or long axial length when an intraocular lens (IOL) of low-power, zero-power, or minus-power, is implanted. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: Ninety eyes of 90 patients scheduled for phacoemulsification surgery were recruited. These consisted of 30 eyes with high (> or =-8 diopters [D]) myopia, 30 eyes with moderate (<-8 D and > or =-3 D) myopia, and 30 eyes with low (<-3 D) myopia. All eyes had implantation of an acrylic IOL-low-power, zero-power, or minus-power-with a sharp optic edge (AcrySof MA60BM or MA60MA, Alcon Surgical). The PCO in these eyes was measured using a Scheimpflug videophotography system (EAS-1000, Nidek) 1, 3, 6, 12, 18, and 24 months after surgery. Visual acuity and the incidence of neodymium:YAG (Nd:YAG) laser posterior capsulotomy were also examined. RESULTS: No significant difference was observed in the mean PCO value or in the Nd:YAG capsulotomy rate between the high myopia, moderate myopia, or low myopia groups throughout the follow-up period. There was also no significant correlation between PCO value and the actual spherical power or axial length of the eye. Furthermore, although mean visual acuity tended to be worse in proportion to the degree of myopia, the difference was not statistically significant. CONCLUSION: When an acrylic IOL of low-power, zero-power, or minus-power with a sharp optic edge was implanted, high myopia and long axial length were not associated with the degree of PCO.

Acrylic Resins↗

Simultaneous versus sequential penetrating keratoplasty and cataract surgery.

PURPOSE: To compare the surgical outcomes of simultaneous penetrating keratoplasty and cataract surgery with those of sequential surgery. METHODS: Thirty-nine eyes of 39 patients scheduled for simultaneous keratoplasty and cataract surgery and 23 eyes of 23 patients scheduled for sequential keratoplasty and secondary phacoemulsification surgery were recruited. Refractive error, regular and irregular corneal astigmatism determined by Fourier analysis, and endothelial cell loss were studied at 1 week and 3, 6, and 12 months after combined surgery in the simultaneous surgery group or after subsequent phacoemulsification surgery in the sequential surgery group. RESULTS: At 3 and more months after surgery, mean refractive error was significantly greater in the simultaneous surgery group than in the sequential surgery group, although no difference was seen at 1 week. The refractive error at 12 months was within 2 D of that targeted in 15 eyes (39%) in the simultaneous surgery group and within 2 D in 16 eyes (70%) in the sequential surgery group; the incidence was significantly greater in the sequential group (P = 0.0344). The regular and irregular astigmatism was not significantly different between the groups at 3 and more months after surgery. No significant difference was also found in the percentage of endothelial cell loss between the groups. CONCLUSION: Although corneal astigmatism and endothelial cell loss were not different, refractive error from target refraction was greater after simultaneous keratoplasty and cataract surgery than after sequential surgery, indicating a better outcome after sequential surgery than after simultaneous surgery.

Aged↗

Expression and characterization of the peptidase domain of Streptococcus pneumoniae ComA, a bifunctional ATP-binding cassette transporter involved in quorum sensing pathway.

ComA, a member of the bacteriocin ATP-binding cassette transporters, is postulated to be responsible for both the processing of the propeptide ComC and secretion of the mature competence-stimulating peptide, which regulates the competence and subsequent genetic transformation in Streptococcus pneumoniae. A recombinant N-terminal peptidase domain of ComA, designated PEP, was expressed as a soluble protein in Escherichia coli, purified to homogeneity, and characterized. Gel-filtration analysis revealed that PEP functions as a monomer. The purified PEP exhibited an efficient proteolytic activity for the substrate ComC, which was cleaved after the double glycine site. The stability of PEP was examined by circular dichroism analyses. A convenient method for analyzing the proteolytic activity of PEP was developed, and the kinetic parameters for ComC were determined (k(cat) = 1.5 +/- 0.083 min(-1) and Km = 62 +/- 9.0 microM). Replacements of Cys17 of PEP with Ser or Ala and His96 with Ala resulted in complete loss of activity, indicating that both Cys17 and His96 are essential for the catalysis. Together with information from a protease data base, the N-terminal domain of ComA was concluded to belong to the same clan as the papain-like cysteine proteases. Mutant substrates, in which each of the double glycines was replaced with Ala, were cleaved very poorly by PEP. The mechanism of this strict substrate specificity is discussed on the basis of the sequence alignment with other cysteine proteases.

Adenosine Triphosphate↗

Binding of C5-dicarboxylic substrate to aspartate aminotransferase: implications for the conformational change at the transaldimination step.

The mechanism for the reaction of aspartate aminotransferase with the C4 substrate, l-aspartate, has been well established. The binding of the C4 substrate induces conformational change in the enzyme from the open to the closed form, and the entire reaction proceeds in the closed form of the enzyme. On the contrary, little is known about the reaction with the C5 substrate, l-glutamate. In this study, we analyzed the pH-dependent binding of 2-methyl-l-glutamate to the enzyme and showed that the interaction between the amino group of 2-methyl-l-glutamate and the pyridoxal 5'-phosphate aldimine is weak compared to that between 2-methyl-l-aspartate and the aldimine. The structures of the Michaelis complexes of the enzyme with l-aspartate and l-glutamate were modeled on the basis of the maleate and glutarate complex structures of the enzyme. The result showed that l-glutamate binds to the open form of the enzyme in an extended conformation, and its alpha-amino group points in the opposite direction of the aldimine, while that of l-aspartate is close to the aldimine. These models explain the observations for 2-methyl-l-glutamate and 2-methyl-l-aspartate. The crystal structures of the complexes of aspartate aminotransferase with phosphopyridoxyl derivatives of l-glutamate, d-glutamate, and 2-methyl-l-glutamate were solved as the models for the external aldimine and ketimine complexes of l-glutamate. All the structures were in the closed form, and the two carboxylate groups and the arginine residues binding them are superimposable on the external aldimine complex with 2-methyl-l-aspartate. Taking these facts altogether, it was strongly suggested that the binding of l-glutamate to aspartate aminotransferase to form the Michaelis complex does not induce a conformational change in the enzyme, and that the conformational change to the closed form occurs during the transaldimination step. The hydrophobic residues of the entrance of the active site, including Tyr70, are considered to be important for promoting the transaldimination process and hence the recognition of the C5 substrate.

Amines↗

Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.

Familial exudative vitreoretinopathy (FEVR) is a hereditary blinding disorder that features defects in retinal vascular development. The mutations in the genes encoding the Wnt receptor pair, frizzled 4 (FZD4) and low-density-lipoprotein receptor-related protein 5 (LRP5), have been shown to cause FEVR. In this study we screened 56 unrelated patients with FEVR (31 familial and 25 simplex cases) for possible mutations in LRP5 and FZD4. Six novel mutations in either LRP5 or FZD4 were identified in six familial cases. Four novel mutations in LRP5 and one known mutation in FZD4 were detected in three simplex cases, and two of these patients carried compound heterozygous mutations in LRP5. Remarkably, c.1330C>T [p.R444C] in LRP5 was found in the family in which c.1250G>A [p.R417Q] in FZD4 had previously been identified. The phenotype of these patients suggested a synergistic effect of the two mutations in the independent FEVR-causing genes. We also demonstrated that reduced bone density is a common feature in patients with FEVR who harbor LRP5 mutations. The profile of the mutations obtained in the current study further illustrates the complexity of the disease and provides a better understanding of the spectrum, frequencies, and genotype-phenotype correlation.

Adult↗

Intravitreal versus retrobulbar injections of triamcinolone for macular edema associated with branch retinal vein occlusion.

PURPOSE: To compare the short-term effect of intravitreal versus retrobulbar injection of triamcinolone acetonide for the treatment of macular edema caused by branch retinal vein occlusion. DESIGN: Randomized clinical trial. METHODS: Sixty eyes of 60 patients who had macular edema associated with branch retinal vein occlusion were randomly assigned to receive a single intravitreal injection (4 mg) or repeated retrobulbar injections (40 mg, three times) of triamcinolone. These injections (first injection in the retrobulbar group) were given approximately 1 week after focal laser photocoagulation. Using optical coherence tomography, the central retinal (foveal) thickness and total macular volume were measured before and at 1 and 3 months after injection. Visual acuity, intraocular pressure, and the incidence of reinjection were also examined. Fifty-two patients (86.7%) completed the 3-month follow-up. RESULTS: The mean foveal thickness and total macular volume decreased significantly after either intravitreal or repeated retrobulbar triamcinolone injections. Foveal thickness and macular volume were significantly less after intravitreal injection than after repeated retrobulbar injections, although there had been no significant differences at baseline. The percent reductions in foveal thickness and macular volume were also greater after intravitreal injection than after retrobulbar injections. Improvement in visual acuity was significantly better after intravitreal injection than after the retrobulbar injections. The incidence of intraocular pressure rise (to > or =20 mm Hg) was greater in the intravitreal group than in the retrobulbar group, but this was readily controlled by the use of antiglaucoma medications. After completion of the 3-month follow-up, 24 patients (46.2%) underwent reinjection. The need for reinjections was significantly greater in the retrobulbar group than in the intravitreal group (P = .0001). CONCLUSIONS: A single intravitreal injection of triamcinolone is significantly more effective than are repeated retrobulbar injections in reducing macular edema associated with branch retinal vein occlusion, and leads to greater improvement in visual acuity.

Adult↗

Vitamin A up-regulates the expression of thrombospondin-1 and pigment epithelium-derived factor in retinal pigment epithelial cells.

Vitamin A is essential for the visual system. It is metabolized in the retina and the resulting product, retinoic acid (RA), greatly affects the structure and functions of retinal pigment epithelial (RPE) cells. RPE cells produce a variety of extracellular matrix (ECM) proteins and angiogenic factors, both of which are expressed at varying levels in the normal RPE layer. In this study, we investigated the effect of all-trans-retinoic acid on the production of an ECM protein, thrombospondin-1 (TSP-1), and two angiogenic factors, pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) by RPE cells. RA increased the release of TSP-1 and PEDF, but not that of VEGF, from human RPE cells in vitro. In vitamin A-deficient mice, the expression of TSP-1 and PEDF in the RPE layer considerably decreased compared with that of normal control mice. The vitamin A deficiency hardly affected the accumulation of VEGF in the RPE layer. These findings suggest that vitamin A modulates the structure and anti-angiogenic functions of the RPE layer partly by up-regulating the expression of the angiogenesis-related ECM protein, TSP-1, and the anti-angiogenic factor, PEDF.

Animals↗

Comparison of the stability of 1-piece and 3-piece acrylic intraocular lenses in the lens capsule.

PURPOSE: To compare the degrees of intraocular lens (IOL) decentration, tilt, and longitudinal movement; the refractive change; and anterior capsule contraction after cataract surgery between eyes with a 1-piece acrylic IOL with soft acrylic loops and eyes with a 3-piece acrylic IOL with rigid poly(methyl methacrylate) loops. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: Fifty-six patients had implantation of a 1-piece acrylic IOL in 1 eye and a 3-piece acrylic IOL in the fellow eye. The degree of IOL decentration and tilt, the anterior chamber depth (ACD), and the area of anterior capsule opening were measured using Scheimpflug videophotography 3 days and 1, 3, and 6 months postoperatively. The postoperative refractive status was also examined. RESULTS: The mean degrees of decentration and tilt in the 1-piece IOL group were similar to those in the 3-piece IOL group throughout the follow-up. The ACD did not change after surgery in the 1-piece group but showed significant shallowing in the 3-piece group (P < .0001). The spherical equivalent (SE) did not change in the 1-piece group, while the SE had a significant myopic shift of approximately 0.4 diopter in the 3-piece group. The percentage of anterior capsule contraction was similar between the groups. CONCLUSIONS: The degree of IOL decentration and tilt and percentage of anterior capsule contraction in eyes with a 1-piece acrylic IOL with soft acrylic loops were similar to those in eyes with a 3-piece acrylic IOL. The longitudinal movement of the 1-piece IOL was less than the movement of the 3-piece IOL, resulting in less postoperative myopic shift.

Acrylic Resins↗

Intraocular lens factors that may affect anterior capsule contraction.

PURPOSE: To examine the various factors comprising intraocular lenses (IOLs) that may affect the degree of anterior capsule contraction after cataract surgery. DESIGN: Randomized controlled clinical trials. PARTICIPANTS: Three hundred thirty-one patients scheduled for bilateral cataract surgery were studied to compare the degree of anterior capsule contraction in fellow eyes that received different IOLs with regard to the following factors: (1) optic material-acrylic optic versus silicone optic; (2) optic design-round-edge optic versus sharp-edge optic; (3) haptic material-polymethyl methacrylate (PMMA) loop versus polyvinylidene fluoride loop; and (4) haptic material and design-single-piece acrylic haptic versus 3-piece PMMA haptic. The 2 IOLs implanted in the fellow eyes of each patient had almost the same material and design, except for the specific factor being compared. METHODS: All patients underwent phacoemulsification surgery with implantation of different IOLs in fellow eyes. MAIN OUTCOME MEASURES: The area of the anterior capsule opening was measured using the Scheimpflug videophotography system at 3 days or 1 week (baseline) and at 1, 3, and 6 months after surgery. The percent reduction in the anterior capsule opening area from baseline was determined at 1, 3, and 6 months after surgery. RESULTS: The mean percent reduction of the anterior capsule opening area was significantly greater in eyes with a silicone optic IOL than in eyes with an acrylic optic IOL. However, no significant difference was observed in the percent reduction between round-edge and sharp-edge optic IOLs, between PMMA and polyvinylidene fluoride loop IOLs, and between single-piece acrylic and 3-piece PMMA haptic IOLs. Strong associations were found in the percentage between round-edge and sharp-edge optic IOLs, between PMMA and polyvinylidene fluoride loop IOLs, and between single-piece acrylic and 3-piece PMMA haptic IOLs, whereas there was a relatively weak association between silicone and acrylic optic IOLs. CONCLUSIONS: Among the IOL factors examined, optic material affects most significantly the degree of anterior capsule contraction, whereas optic design and haptic material and design are not strongly related to anterior capsule contraction.

Acrylic Resins↗

Posterior capsule opacification in the presence of an intraocular lens with a sharp versus rounded optic edge.

PURPOSE: To compare the degree of posterior capsule opacification (PCO) and visual function in eyes implanted with an acrylic intraocular lens (IOL) with a sharp posterior optic edge with that in eyes implanted with an IOL with a rounded optic edge. DESIGN: Randomized clinical trial. PARTICIPANTS: Seventy-five consecutive patients scheduled for bilateral phacoemulsification were assigned randomly to 1 of 2 groups. One group received an acrylic IOL with a sharp edge (Sensar AR40e, AMO, Santa Ana, CA) in the left eye and an acrylic IOL of the same optic material and loops but with a rounded-edge optic (Sensar AR40) in the right eye. The other group received the sharp-edged IOL in the right eye and the rounded-edge IOL in the left eye. Sixty-nine patients (92%) completed follow-up. INTERVENTION: All patients underwent implantation of a sharp-edged IOL in 1 eye and a rounded-edge IOL in the fellow eye. MAIN OUTCOME MEASURES: The PCO value of these patients was measured using the Scheimpflug videophotography system at 1, 3, 6, 12, 18, and 24 months after surgery. The incidence of eyes that required a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy was examined. Visual acuity and contrast sensitivity with and without a glare source also were evaluated. RESULTS: The mean PCO value in the sharp-edge IOL group was significantly less than that in the rounded-edge IOL group throughout the follow-up period. The incidence of Nd:YAG capsulotomy also was significantly less in the sharp-edge group than in the rounded-edge group (P = 0.0095). No significant difference was found in mean visual acuity during the 24 months of follow-up. However, contrast visual acuity with and without glare was significantly better in the sharp-edge group than in the rounded-edge group at 24 months after surgery. CONCLUSIONS: The degree of posterior capsule opacification in eyes with an acrylic IOL with a sharp posterior optic edge is significantly less than that in eyes with a rounded-edge IOL, and the sharp-edge optic led to better contrast sensitivity with and without glare.

Acrylic Resins↗

Crystal structure of a putative aspartate aminotransferase belonging to subgroup IV.

Protein TT0402 from Thermus thermophilus HB8 exhibits about 30-35% sequence identity with proteins belonging to subgroup IV in the aminotransferase family of the fold-type I pyridoxal 5'-phosphate (PLP)-dependent enzymes. In this study, we determined the crystal structure of TT0402 at 2.3 A resolution (R(factor) = 19.9%, R(free) = 23.6%). The overall structure of TT0402 exhibits the fold conserved in aminotransferases, and is most similar to that of the Escherichia coli phosphoserine aminotransferase, which belongs to subgroup IV but shares as little as 13% sequence identity with TT0402. Kinetic assays confirmed that TT0402 has higher transamination activities with the amino group donor, L-glutamate, and somewhat lower activities with L-aspartate. These results indicate that TT0402 is a subgroup IV aminotransferase for the synthesis/degradation of either L-aspartate or a similar compound.

Amino Acid Sequence↗

Thrombospondin-1 accelerates wound healing of corneal epithelia.

To investigate a role of thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, in corneal epithelial wound healing, we analyzed the expression of TSP-1 in the normal and wounded mouse corneal epithelia and the effect of exogenous TSP-1 on the wound healing. In immunohistochemical analyses of unwounded corneas, TSP-1 was only detectable in endothelial cells. In contrast, TSP-1 appeared on the wounded corneal surface and on the corneal stroma, at 30 min and 8-16 h, respectively, after making an abrasion on the corneal epithelium. This expression of TSP-1 disappeared after 36-48 h, when re-epithelialization was completed. The TSP-1 mRNA level in the wounded corneas increased as much as three fold compared with that in the unwounded corneas. In organ culture, exogenous TSP-1 stimulated the re-epithelialization of corneal epithelial wounds whereas anti-TSP-1 antibody significantly inhibited the re-epithelialization. These findings suggest the possibility that epithelial defects in the corneas stimulate the expression of TSP-1 in the wound area, resulting in the accelerated re-epithelialization of the cornea.

Animals↗