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ABSTRACT: BACKGROUND: Intraocular pressure (IOP) may vary according to the change of ocular conditions. In this study, we want to assess the effect and mechanism of pupil dilation on IOP in normal subjects. METHODS: We prospectively evaluated 32 eyes of 32 patients (age; 61.7 +/- 8.2 years) with normal open angles under diurnal IOP. IOP was measured every two hours from 9 AM to 11 PM for one day to establish baseline values and was measured again for one day to assess the differences after dilation. To induce dilation, we administered 2.5% phenylephrine and 1% tropicamide every 5 minutes from 8:30 AM to 8:45 AM and for every two hours from 11 AM to 9 PM to keep the pupil dilated. Diurnal IOP, biometry, Visante OCT, and laser flare photometry were measured before and after dilation. RESULTS: We observed a significant increase in IOP after dilation, 1.85 +/- 2.01 mmHg (p = 0.002). IOP elevation remained significant until about four hours after dilation. Thereafter, IOP decreased slowly and eventually reached pre-dilation level (p > 0.05). Flare values decreased, and the anterior chamber angle became wider after mydriasis. CONCLUSIONS: Dilation of the pupil significantly and incidentally elevated IOP in normal subjects. Further related studies are warranted to characterize the mechanism of the increased IOP after dilation.
BMC Ophthalmology 09/2012; 12(1):53. · 1.00 Impact Factor
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Chaeyoung Kim,
Dong Woo Nam,
Sang Yoon Park,
Hyundong Song,
Hyun Seok Hong,
Jung Hyun Boo,
Eun Sun Jung,
Yoonhee Kim,
Ju Yuel Baek, Kwan Soo Kim,
Jin Won Cho,
Inhee Mook-Jung
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ABSTRACT: Deposition of β-amyloid (Aβ) as senile plaques and disrupted glucose metabolism are two main characteristics of Alzheimer's disease (AD). It is unknown, however, how these two processes are related in AD. Here we examined the relationship between O-GlcNAcylation, which is a glucose level-dependent post-translational modification that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins, and Aβ production in a mouse model of AD carrying 5XFAD genes. We found that 1,2-dideoxy-2'-propyl-α-d-glucopyranoso-[2,1-d]-Δ2'-thiazoline (NButGT), a specific inhibitor of O-GlcNAcase, reduces Aβ production by lowering γ-secretase activity both in vitro and in vivo. We also found that O-GlcNAcylation takes place at the S708 residue of nicastrin, which is a component of γ-secretase. Moreover, NButGT attenuated the accumulation of Aβ, neuroinflammation, and memory impairment in the 5XFAD mice. This is the first study to show the relationship between Aβ generation and O-GlcNAcylation in vivo. These results suggest that O-GlcNAcylation may be a suitable therapeutic target for the treatment of AD.
Neurobiology of aging 04/2012; · 5.94 Impact Factor
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ABSTRACT: Modification of nuclear and cytosolic proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) is ubiquitous in cells. The in vivo function of the protein O-GlcNAcylation, however, is not well understood. Here, we manipulated the cellular O-GlcNAcylation level in Drosophila and found that it promotes developmental growth by enhancing insulin signaling. This increase in growth is due mainly to cell growth and not to cell proliferation. Our data suggest that the increase in the insulin signaling activity is mediated, at least in part, through O-GlcNAcylation of Akt. These results indicate that O-GlcNAcylation is one of the crucial mechanisms involved in control of insulin signaling during Drosophila development.
Cellular and Molecular Life Sciences CMLS 03/2011; 68(20):3377-84. · 6.57 Impact Factor
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ABSTRACT: Here we review the equatorial β-directing effects of electron-withdrawing protecting groups at remote positions of mannopyranosyl donors, mannuronate donors, rhamnopyranosyl donors, and 2,6-dideoxyglucopyranosyl donors. We discuss the equatorial α-directing effect of an electron-withdrawing group at the N-5 position of sialyl donors. The proposed mechanism and origin of some of the equatorial β-directing effects are described. We also review the effects of potentially participating, electron-withdrawing protecting groups at remote positions of glycopyranosyl and glycofuranosyl donors on the glycosylation stereochemistries. Further, we present substantial evidence in favor of the remote participation by the electron-withdrawing protecting groups and also include reports that are opposed to remote participation.
Topics in current chemistry 01/2011; 301:109-40. · 4.29 Impact Factor
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ABSTRACT: A highly sensitive electrochemical lectin biosensor has been developed for the first time using carbohydrate-stabilized gold nanoparticles and silver-enhancement technique. A target lectin protein, Concanavalin A (Con A), was specifically bound to the self-assembled monolayer of thiolated mannose on a gold electrode. Mannose-stabilized gold nanoparticles were added to form a sandwich-type complex with the Con A and were followed by silver-enhancement process to coat the mannose-stabilized gold nanoparticles with silver metal. The coated metallic silver was dissolved in an acidic solution and the resulting silver ions were detected by anodic stripping voltammetry. The present lectin biosensor gave a linear response (R(2)=0.999) for Con A concentration from 0.084 μg/mL to 50.0 μg/mL with a remarkable detection limit (S/N=3) of 0.070 μg/mL, which is much lower compared to those obtained with the reported microgravimetric and colorimetric detection methods.
Biosensors & bioelectronics 12/2010; 26(4):1326-31. · 5.43 Impact Factor
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ABSTRACT: To examine the survival function and prognostic factors of the adjacent segments based on a second operation after thoracolumbar spinal fusion.
This retrospective study reviewed 3,188 patients (3,193 cases) who underwent a thoracolumbar spinal fusion at the author's hospital. Survival analysis was performed on the event of a second operation due to adjacent segment degeneration. The prognostic factors, such as the cause of the disease, surgical procedure, age, gender and number of fusion segments, were examined. Sagittal alignment and the location of the adjacent segment were measured in the second operation cases, and their association with the types of degeneration was investigated.
One hundred seven patients, 112 cases (3.5%), underwent a second operation due to adjacent segment degeneration. The survival function was 97% and 94% at 5 and 10 years after surgery, respectively, showing a 0.6% linear reduction per year. The significant prognostic factors were old age, degenerative disease, multiple-level fusion and male. Among the second operation cases, the locations of the adjacent segments were the thoracolumbar junctional area and lumbosacral area in 11.6% and 88.4% of cases, respectively. Sagittal alignment was negative or neutral, positive and strongly positive in 47.3%, 38.9%, and 15.7%, respectively. Regarding the type of degeneration, spondylolisthesis or kyphosis, retrolisthesis, and neutral balance in the sagittal view was noted in 13.4%, 36.6%, and 50% of cases, respectively. There was a significant difference according to the location of the adjacent segment (p = 0.000) and sagittal alignment (p = 0.041).
The survival function of the adjacent segments was 94% at 10 years, which had decreased linearly by 0.6% per a year. The likelihood of a second operation was high in those with old age, degenerative disease, multiple-level fusion and male. There was a tendency for the type of degeneration to be spondylolisthesis or kyphosis in cases of the thoracolumbar junctional area and strongly positive sagittal alignment, but retrolisthesis in cases of the lumbosacral area and neutral or positive sagittal alignment.
Clinics in orthopedic surgery 09/2010; 2(3):140-7.
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ABSTRACT: Mannosylations of various acceptors with donors possessing an electron-withdrawing o-trifluoromethylbenzenesulfonyl, benzylsulfonyl, p-nitrobenzoyl, benzoyl, or acetyl group at O-3, O-4, or O-6 positions were found to be beta-selective except when donors had 3-O-acyl and 6-O-acetyl groups, which afforded alpha-mannosides as major products. The alpha-directing effect of 3-O-acyl and 6-O-acetyl groups was attributed to their remote participation, and the isolation of a stable bicyclic trichlorooxazine ring resulting from the intramolecular trapping of the anomeric oxocarbenium ion by 3-O-trichloroacetimidoyl group provided evidence for this remote participation. The triflate anion, counteranion of the mannosyl oxocarbenium ion, was essential for the beta-selectivity, and covalent alpha-mannosyl triflates with an electron-withdrawing group at O-3, O-4, or O-6 were detected by low-temperature NMR. The strongly electron-withdrawing sulfonyl groups, which exhibited a higher beta-directing effect in the mannosylation, made the alpha-mannosyl triflates more stable than the weakly electron-withdrawing acyl groups. We therefore proposed the mechanism for the beta-mannosylation and the origin of the beta-directing effect: the electron-withdrawing groups would stabilize the alpha-mannosyl triflate intermediate, and the subsequent reaction of the alpha-triflate (or its contact ion pair) with the acceptor would afford the beta-mannoside. The beta-selective mannosylation of a sterically demanding acceptor was achieved by employing a donor possessing two strongly electron-withdrawing benzylsulfonyl groups at O-4 and O-6 positions.
Journal of the American Chemical Society 11/2009; 131(48):17705-13. · 9.91 Impact Factor
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ABSTRACT: We wanted to investigate the results of surgical treatment and analyze the factors that have an influence on the neurologic symptoms and prognosis of spinal intradural extramedullary (IDEM) tumors.
The spinal IDEM tumor patients (11 cases) who had been treated by surgical excision and who were followed up more than 1 year were retrospectively analyzed. Pain was evaluated by the visual analogue scale (VAS) and the neurologic function was assessed by Nurick's grade. The pathological diagnosis, the preoperative symptom duration, the tumor location on the sagittal and axial planes and the percentage of tumor occupying the intradural space were investigated. In addition, all these factors were analyzed in relation to the degree of the preoperative symptoms and the prognosis. On the last follow-up, the MRI was checked to evaluate whether or not the tumor had recurred.
The most common diagnosis was schwannomas (73%), followed by meningiomas (18%). The percentage of tumor occupying the intradural space was 82.9 +/- 9.4%. The VAS score was reduced in all cases from 8.0 +/- 1.2 to 1.2 +/- 0.8 (p = 0.003) and the Nurick's grade was improved in all cases from 3.0 +/- 1.3 to 1.0 +/- 0.0 (p = 0.005). The preoperative symptoms were correlated with only the percentage of tumor occupying the intradural space (VAS; r(2) = 0.75, p = 0.010, Nurick's grade; r(2) = 0.69, p = 0.019). One case of schwannoma recurred.
The degree of neurologic symptoms was correlated with the percentage of tumor occupying the intradural space. All the tumors were able to be excised through the posterior approach. The postoperative neurologic recovery was excellent in all the cases regardless of any condition. Therefore, aggressive surgical excision is recommended even for cases with a long duration of symptoms or a severe neurologic deficit.
Clinics in orthopedic surgery 09/2009; 1(3):165-72.
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ABSTRACT: Synthesis of a suitably protected form of the hexasaccharide repeating unit of the cell wall polymer from Kineosporia aurantiaca VKM Ac-720 T has been achieved by the stereoselective direct glycosylation of a trisaccharide acceptor with a trisaccharide donor having an anomeric hydroxy group involving a glycosyl phthalate intermediate. Both the trisaccharide acceptor and the trisaccharide donor were obtained from a common trisaccharide, of which two β-mannopyranosyl linkages were constructed stereoselectively by employing the direct glycosylation method with the anomeric hydroxy sugar involving a glycosyl phthalate intermediate and the 2′-carboxybenzyl glycoside method, respectively.
Journal of Carbohydrate Chemistry. 08/2009; 28(6):317-329.
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ABSTRACT: The transcription factor NFkappaB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. Additionally, posttranslational modification of the NFkappaB p65 subunit by O-linked N-acetylglucosamine (O-GlcNAc) has been reported, but the modification site of O-GlcNAc on NFkappaB p65 and its exact function have not been elucidated. In this work, we show that O-GlcNAcylation of NFkappaB p65 decreases binding to IkappaB alpha and increases transcriptional activity under hyperglycemic conditions. Also, we demonstrate that both Thr-322 and Thr-352 of NFkappaB p65 can be modified with O-GlcNAc, but modification on Thr-352, not Thr-322, is important for transcriptional activation. Our findings suggest that site-specific O-GlcNAcylation may be a reason why NFkappaB activity increases continuously under hyperglycemic conditions.
Proceedings of the National Academy of Sciences 12/2008; 105(45):17345-50. · 9.68 Impact Factor
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ABSTRACT: A highly sensitive microgravimetric lectin biosensor has been developed using carbohydrate-stabilized Au nanoparticles as a signal amplifier; mannose-stabilized Au nanoparticles formed a sandwich-type complex with the target Con A specifically bound to a mannose-modified Au QCM electrode to give an amplified frequency response.
Chemical Communications 11/2008; · 6.17 Impact Factor
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ABSTRACT: Periprosthetic fracture is a relatively rare but well-recognized complication after knee joint arthroplasty. We experienced a case of medial femoral condylar fracture among 700 cases of unicompartmental knee arthroplasty (UKA). The patient was a 56-year-old woman who underwent minimally invasive UKA for medial osteoarthritis of the knee. A displaced medial femoral condylar fracture occurred 3 years after UKA. A closed reduction and percutaneous fixation using 3 cannulated cancellous screws was performed. Union of the fracture was achieved, and a full recovery of knee motion was gained after 3 months. The Knee Society knee and function scores were 87 and 80, respectively, at the 2-year follow-up. They were the same as the scores before the fracture took place, and there was no evidence of component loosening or ligament instability.
The Journal of arthroplasty 11/2008; 24(7):1143.e21-4. · 1.79 Impact Factor
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ABSTRACT: The synthesis of dibenzyl 6-O-naphthylmethyl-2,3,5-tri-O-benzoyl-beta-D-galactofuranosyl-(1-->5)-2,3-di-O-benzoyl-6-O-benzyl-beta-D-galactofuranosyl-(1-->4)-3-O-benzyl-2-O-pivaloyl-alpha-l-rhamnopyranosyl-(1-->3)-2-acetamido-2-deoxy-4,6-di-O-benzoyl-alpha-D-glucopyranosyl phosphate (1), a protected form of the tetrasaccharide phosphate of the linkage region of the arabinogalactan-peptidoglycan complex in the mycobacterial cell wall, has been accomplished. Key steps include the coupling of four monosaccharide building blocks with complete stereoselectivity by glycosylations employing thioglycosides, 2'-carboxybenzyl glycosides, and glycosyl fluorides as glycosyl donors. The alpha-glycosyl phosphate linkage was also stereoselectively elaborated by reaction of a tetrasaccharide hemiacetal with tetrabenzyl pyrophosphate in the presence of a base.
Carbohydrate Research 08/2008; 343(10-11):1574-84. · 2.33 Impact Factor
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ABSTRACT: Here, we describe the enzymatic synthesis of novel inhibitors using acarviosine-glucose as a donor and 3-alpha-D-glucopyranosylpropen (alphaGP) as an acceptor. Maltogenic amylase from Thermus sp. (ThMA) catalyzed the transglycosylation of the acarviosine moiety to alphaGP. The two major reaction products were isolated using chromatographies. Structural analyses revealed that acarviosine was transferred to either C-7 or C-9 of the alphaGP, which correspond to C-4 and C-6 of glucose. Both inhibited rat intestine alpha-glucosidase competitively but displayed a mixed-type inhibition mode against human pancreatic alpha-amylase. The alpha-acarviosinyl-(1-->7)-3-alpha-D-glucopyranosylpropen showed weaker inhibition potency than acarbose against both alpha-glycosidases. In contrast, the alpha-acarviosinyl-(1-->9)-3-alpha-D-glucopyranosylpropen exhibited a 3.0-fold improved inhibition potency against rat intestine alpha-glucosidase with 0.3-fold inhibition potency against human pancreatic alpha-amylase relative to acarbose. In conclusion, alpha-acarviosinyl-(1-->9)-3-alpha-D-glucopyranosylpropen is a novel alpha-glucosidase-selective inhibitor with 10-fold enhanced selectivity toward alpha-glucosidase over alpha-amylase relative to acarbose, and it could be applied as a potent hypoglycemic agent.
Journal of Agricultural and Food Chemistry 07/2008; 56(13):5324-30. · 2.82 Impact Factor
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ABSTRACT: An efficient direct one-pot glycosylation method with anomeric hydroxy sugars as glycosyl donors employing phthalic anhydride and triflic anhydride as activating agents has been developed. Thus, highly stereoselective beta-mannopyranosylations were achieved by the reaction of 2,3-di-O-benzyl-4,6-O-benzylidene-D-mannopyranose (2) with phthalic anhydride in the presence of DBU at room temperature followed by sequential addition of DTBMP and Tf2O and glycosyl acceptors to the reaction mixture at -78 degrees C in one-pot. Stereoselective alpha-glucopyranosylations with 2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranose (25) and other glycosylations with glucopyranoses and mannopyranoses having tetra-O-benzyl- and tetra-O-benzoyl protecting groups were also possible by utilizing the present one-pot glycosylation protocol. The possible mechanism for the beta-mannosylation with 2 was proposed based on the NMR study, in which alpha-mannosyl phthalate 55alpha and alpha-mannosyl triflate 59 were detected as intermediates. The versatility and efficiency of the present glycosylation methodology, especially those of the beta-mannopyranosylation protocol, were readily demonstrated by the efficient synthesis of protected beta-(1-->4)-D-mannotriose 62 and beta-(1-->4)-D-mannotetraose 67 with perfect beta-stereoselectivity.
Journal of the American Chemical Society 07/2008; 130(26):8537-47. · 9.91 Impact Factor
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Acta ophthalmologica 06/2008; 86(8):925-7. · 2.44 Impact Factor
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ABSTRACT: Synthesis of cyclic tetra-, hexa- and octasaccharides containing alternating (1-->5)-beta- and (1-->6)-beta-galactofuranosyl linkages has been achieved by intramolecular cycloglycosylation of corresponding linear sugars and by cyclooligomerization of 1,6-linked and 1,5-linked disaccharides. In particular, cyclooligomerization of the (1-->6)-beta-galactofuranosyl disaccharide provides an efficient way to secure all three cyclic sugars in one operation.
Organic Letters 06/2008; 10(12):2373-6. · 5.86 Impact Factor
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ABSTRACT: PM0188 is a newly identified sialyltransferase from P. multocida which transfers sialic acid from cytidine 5'-monophosphonuraminic acid (CMP-NeuAc) to an acceptor sugar. Although sialyltransferases are involved in important biological functions like cell-cell recognition, cell differentiation and receptor-ligand interactions, little is known about their catalytic mechanism. Here, we report the X-ray crystal structures of PM0188 in the presence of an acceptor sugar and a donor sugar analogue, revealing the precise mechanism of sialic acid transfer. Site-directed mutagenesis, kinetic assays, and structural analysis show that Asp141, His311, Glu338, Ser355 and Ser356 are important catalytic residues; Asp141 is especially crucial as it acts as a general base. These complex structures provide insights into the mechanism of sialyltransferases and the structure-based design of specific inhibitors.
BMB reports 02/2008; 41(1):48-54. · 1.72 Impact Factor
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ABSTRACT: The concept of lactonization-mediated and related glycosylations led us to develop new methods of glycosylation such as the 2'-carboxybenzyl (CB) glycoside method, the glycosyl pentenoate/phenylselenyl trifluoromethanesulfonate (PhSeOTf) method, and the glycosyl aryl phthalate method. Highly stereoselective beta-mannopyranosylations were achieved by employing the CB glycoside and the glycosyl pentenoate/PhSeOTf methods. The CB glycoside method was also utilized for stereoselective 2-deoxyglycosylation, beta-arabinofuranosylation, and alpha-galactofuranosylation. In addition, these lactonization-mediated methods of glycosylation were employed for the synthesis of complex oligosaccharides. In particular, the CB glycoside method was successfully applied to the synthesis of repeating oligosaccharide subunits of the O-polysaccharide of the lipopolysaccharide from Danish Helicobacter pylori strains and Escherichia coli 077, the synthesis of oligoarabinofuranosides in mycobacterial cell walls, and the total synthesis of antineoplastic agelagalastatin.
The Chemical Record 02/2008; 8(1):46-65. · 4.38 Impact Factor
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ABSTRACT: The most representative anomeric ester
glycosyl donor is
glycosyl acetate
, which seems to be apromising and useful
glycosylating reagent due to avariety of advantageous
properties. Several other anomeric acyl and carbonate-type leaving
groups have been devised as new glycosyl donors. In particular, the
glycosyl acetate can be the precursor for glycosylating agents of
other types, for example, glycosyl halides, 1‑thioglycosides, and
glycosyl trichloroacetimidates. Therefore, use of glycosyl acetate
can make glycosylation reactions easier and less expensive.
Furthermore, the intramolecular glycosylation method through the
1-O-acyl linkage and the
glycosylation with glycosyl donors having remote acyl groups from
the anomeric center have been developed to increase the efficiency
and the stereoselectivity.
12/2007: pages 525-564;
