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Biomedical subjects

J O Lee

Publications and source records attributed to J O Lee.

At least 19 recordsLinked to original sources

Arthroplasty for advanced Kienböck's disease using a radial bone flap with a vascularised wrapping of pronator quadratus.

We have performed a form of lunate replacement arthroplasty, which included excision of the lunate and insertion of a vascularised radial bone flap wrapped in pronator quadratus, for stage IIIB or stage IV Kienböck's disease, in 41 patients who have been followed up for more than three years. All patients reported an improvement in their symptoms, and 20 of the 41 became free of pain after the operation. Extension and flexion of the wrist were increased by a mean of 9 degrees and 6 degrees , respectively (p < 0.05). The radioscaphoid angle and the carpal height ratio were not significantly changed and only minimal deterioration was observed due to degenerative change. The size, density or location of the inserted bone did not change with time. A vascularised radial bone flap wrapped in pronator quadratus can be a reliable treatment option for advanced Kienböck's disease, when the pedicled bone and muscle envelope acts as a stable spacer for the excised lunate.

Adult↗

Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans.

Sensorineural hearing loss associated with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene. In western populations, less than one-half of the affected individuals with EVA have two mutant SLC26A4 alleles, and EVA is frequently caused by unknown genetic or environmental factors alone or in combination with a single SLC26A4 mutation as part of a complex trait. In this study, we ascertained 26 Korean probands with EVA and performed nucleotide sequence analysis to detect SLC26A4 mutations. All subjects had bilateral EVA, and 20 of 26 were sporadic (simplex) cases. Fourteen different mutations were identified, including nine novel mutations. Five mutations were recurrent and accounted for 80% of all mutant alleles, providing a basis for the design and interpretation of cost-efficient mutation detection algorithms. Two mutant alleles were identified in 21 (81%), one mutant allele was detected in three (11%), and zero mutant allele was detected in two (8%) of 26 probands. The high proportion of Korean probands with two SLC26A4 mutations may reflect a reduced frequency of other genetic or environmental factors causing EVA in comparison to western populations.

Adolescent↗

Survey of nitrate and nitrite contents of vegetables grown in Korea.

A scientific basis for the evaluation of the risk to public health arising from excessive dietary intake of nitrate in Korea is provided. The nitrate () and nitrite () contents of various vegetables (Chinese cabbage, radish, lettuce, spinach, soybean sprouts, onion, pumpkin, green onion, cucumber, potato, carrot, garlic, green pepper, cabbage and Allium tuberosum Roth known as Crown daisy) are reported. Six hundred samples of 15 vegetables cultivated during different seasons were analysed for nitrate and nitrite by ion chromatography and ultraviolet spectrophotometry, respectively. No significant variance in nitrate levels was found for most vegetables cultivated during the summer and winter harvests. The mean nitrates level was higher in A. tuberosum Roth (5150 mg kg(-1)) and spinach (4259 mg kg(-1)), intermediate in radish (1878 mg kg(-1)) and Chinese cabbage (1740 mg kg(-1)), and lower in onion (23 mg kg(-1)), soybean sprouts (56 mg kg(-1)) and green pepper (76 mg kg(-1)) compared with those in other vegetables. The average nitrite contents in various vegetables were about 0.6 mg kg(-1), and the values were not significantly different among most vegetables. It was observed that nitrate contents in vegetables varied depending on the type of vegetables and were similar to those in vegetables grown in other countries. From the results of our studies and other information from foreign sources, it can be concluded that it is not necessary to establish limits of nitrates contents of vegetables cultivated in Korea due to the co-presence of beneficial elements such as ascorbic acid and alpha-tocopherol which are known to inhibit the formation of nitrosamine.

Allium↗

The microbial community analysis of a 5-stage BNR process with step feed system.

The microbial communities of 5-stage BNR activated sludge samples were analyzed using fluorescence in-situ hybridization (FISH) and 16S rDNA characterization. The total cell numbers of each reactor were from 2.36 x 10(9) cells/ml to 2.83 x 10(9) cells/ml. From 56.5% to 62.0% of total DAPI cell counts were hybridized to the most bacterial specific probe EUB 338. Among them, beta-proteobacteria were most dominant in each tank. The number of phosphate accumulating organisms (PAOs) was almost 50% of the total cell number in anoxic-1 tank, and these results indicate that this process has a high content of denitrifying phosphorus accumulating organisms (dPAOs). In contrast with FISH, 16S rDNA analysis showed that dominant groups were the Cytophaga-Flavobacterium group and high G+C% gram-positive bacteria, which were determined as PAOs in anoxic-1 tank. The beta subclass Proteobacteria did not accumulate a large amount of polyphosphate. The overall results indicate that high G+C% gram-positive bacteria and the Cytophaga-Flavobacterium group might play a key role as dPAOs in this process.

Bioreactors↗

Electrical conduction through poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA molecules.

We report direct measurements of electrical transport through poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA molecules containing identical base pairs. The observed experimental results suggest that electrical transport through DNA molecules occurs by polaron hopping. We have also investigated the effect of gate voltage on the current-voltage curve. It demonstrates the possibility of a DNA field-effect transistor operating at room temperature. Moreover, the gate-voltage dependent transport measurements show that poly(dA)-poly(dT) behaves as an n-type semiconductor, whereas poly(dG)-poly(dC) behaves as a p-type semiconductor.

DNA↗

Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.

The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. The structure also reveals that PTEN has a C2 domain. The PTEN C2 domain binds phospholipid membranes in vitro, and mutation of basic residues that could mediate this reduces PTEN's membrane affinity and its ability to suppress the growth of glioblastoma tumor cells. The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane.

Amino Acid Sequence↗

Cytotoxic constituents from Solidago virga-aurea var. gigantea MIQ.

Activity-guided fractionation of the whole plant of Solidago virga-aurea var. gigantea M(IQ). (Compositae) has led to the isolation of three cytotoxic compounds, erythrodiol-3-acetate (1), alpha-tocopherol-quinone (2), and trans-phytol (3) from the hexane soluble fraction. It is the first report of those compounds from the genus.

Antineoplastic Agents↗

Two new lignans from Lindera obtusiloba blume.

Two new furanolignans (3, 5), together with three known lignans (1, 2, 4), were isolated from the stem of Lindera obtusiloba (Lauraceae). The structures of the compounds were determined as actifolin (1), pluviatilol (2), 5,6-dihydroxymatairesinol (3), (+)-syringaresinol (4), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (5) on the basis of physicochemical and spectroscopic evidences. Compounds 1, 2, 3, and 5 showed cytotoxicity against a small panel of human tumor cell lines with ED50 values of 3.40 to approximately 19.27 microg/ml.

Antineoplastic Agents, Phytogenic↗

Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a.

The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of the catalytic cleft, opposite where the activating cyclin subunit binds. They prevent cyclin binding indirectly by causing structural changes that propagate to the cyclin-binding site. The INK4 inhibitors also distort the kinase catalytic cleft and interfere with ATP binding, which explains how they can inhibit the preassembled Cdk4/6-cyclin D complexes as well. Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a.

Adenosine Triphosphate↗

Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7.

The pocket domain of the retinoblastoma (Rb) tumour suppressor is central to Rb function, and is frequently inactivated by the binding of the human papilloma virus E7 oncoprotein in cervical cancer. The crystal structure of the Rb pocket bound to a nine-residue E7 peptide containing the LxCxE motif, shared by other Rb-binding viral and cellular proteins, shows that the LxCxE peptide binds a highly conserved groove on the B-box portion of the pocket; the A-box portion appears to be required for the stable folding of the B box. Also highly conserved is the extensive A-B interface, suggesting that it may be an additional protein-binding site. The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB.

Amino Acid Sequence↗

Identification of apo(a) phenotypes in a Korean population using a standardized nomenclature system based on the number of kringle IV repeats.

We determined serum lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) [apo(a)] phenotypes in 193 healthy Koreans. We analysed the apo(a) phenotypes by a simplified sodium dodecyl sulphate-polyacrylamide gel electrophoresis method and classified apo(a) isoforms objectively using an apo(a) phenotype standard with a known number of kringle IV repeats. The frequency distribution of Lp(a) levels showed marked positive skew with a mean of 0.143 g/L and a median of 0.052 g/L. Of the 193 subjects tested, no bands were detected in three, and single- and double-band phenotypes were observed in 103 and 87, respectively. Among the Koreans, the most frequent phenotype was S5(39.4%), followed by S4S5(17.1%), S5S5(14.0%), S4(11.4%), S3S5(5.2%), and the remaining phenotypes (13.0%). The calculated apo(a) allele frequencies were LpF, 0.003; LpS1, 0.013; LpS2, 0.010; LpS3, 0.048; LpS4, 0.198; LpS5, 0.563 and Lp0, 0.165. We found that the serum Lp(a) concentration in Koreans was similar to that of Caucasians, but the apo(a) allele size distribution was shifted toward higher molecular weights.

Adult↗

Relation between lipoprotein(a) concentrations in patients with acute-phase response and risk analysis for coronary heart disease.

This study investigated whether lipoprotein(a) [Lp(a)] is an acute-phase reactant that can cause important bias in risk factor analysis for coronary heart disease among patients with an acute-phase response (APR patients). To determine whether serum Lp(a) concentrations increase among APR patients, we compared the Lp(a) concentrations and apolipoprotein(a) [apo(a)] phenotypes of 100 controls with those of a random sampling of 100 APR patients. Serum Lp(a) concentration was measured by ELISA; Lp(a) phenotyping was performed by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel. Lp(a) was significantly (P <0.0001) higher among APR patients (mean +/- SD 0.300 +/- 0.284 g/L) than among controls (0.118 +/- 0.193 g/L) even though the distribution of apo(a) phenotypes did not differ significantly. The 100 APR patients were grouped into 4 categories: 48 patients with infections, 25 postoperative patients, 17 patients with tumors, and 10 patients with other diseases, all of whom showed substantially higher Lp(a) values than did the controls. For the S5, S4S5, S5S5, and S4 phenotypes, the mean concentrations of serum Lp(a) were substantially higher among the APR patients.

Acute-Phase Reaction↗

Characterization of the rcsA and rcsB genes from Salmonella typhi: rcsB through tviA is involved in regulation of Vi antigen synthesis.

Synthesis of Vi antigen, a capsular polysaccharide expressed by Salmonella typhi, is controlled by the viaA and viaB chromosomal loci. It was previously shown that Vi antigen expression was regulated by a system similar to the rcs regulatory system involved in colanic acid synthesis in Escherichia coli. We have cloned the rcsA, rcsB, and rcsC genes from S. typhi. The predicted amino sequences of the RcsA and RcsB proteins showed a high degree of similarity to their E. coli homologs. The nucleotide sequence of the rcsC gene was partially determined and was shown to be homologous to that of its E. coli counterpart. Complementation experiments indicated that rcsB and rcsC were encompassed within the viaA locus. The RcsA protein was not involved in Vi antigen synthesis. In contrast, the RcsB protein acted as a positive regulator of Vi polysaccharide expression. By mRNA and gene fusion analyses, we studied the role of RcsB and TviA, a via-B-encoded regulatory protein characterized previously, in regulating Vi antigen synthesis. The transcriptional start point of tviA mRNA was not influenced by RcsB or TviA. In the absence of RcsB or TviA protein, transcription of tviA gave rise to only a monocistronic tviA-specific mRNA. The presence of RcsB and TriA not only increased the amount of monocistronic tviA-specific mRNA but also resulted in countranscription of tviA and tviB, which is located immediately downstream of tviA on the viaB locus. In addition, TviA protein did not appear to be subject to degradation by the Lon protease. These results strongly suggest that TviA might act in concert with RcsB at the tviA promoter to activate transcription of the genes involved in Vi polymer synthesis in S. typhi in a Lon-independent manner.

ATP-Dependent Proteases↗

Two conformations of the integrin A-domain (I-domain): a pathway for activation?

BACKGROUND: Integrins are plasma membrane proteins that mediate adhesion to other cells and to components of the extracellular matrix. Most integrins are constitutively inactive in resting cells, but are rapidly and reversibly activated in response to agonists, leading to highly regulated cell adhesion. This activation is associated with conformational changes in their extracellular portions, but the nature of the structural changes that lead to a change in adhesiveness is not understood. The interactions of several integrins with their extracellular ligands are mediated by an A-type domain (generally called the I-domain in integrins). Binding of the I-domain to protein ligands is dependent on divalent cations. We have described previously the structure of the I-domain from complement receptor 3 with bound Mg2+, in which the glutamate side chain from a second I-domain completes the octahedral coordination sphere of the metal, acting as a ligand mimetic. RESULTS: We now describe a new crystal form of the I-domain with bound Mn2+, in which water completes the metal coordination sphere and there is no equivalent of the glutamate ligand. Comparison of the two crystal forms reveals a change in metal coordination which is linked to a large (10 A) shift of the C-terminal helix and the burial of two phenylalanine residues into the hydrophobic core of the Mn2+ form. These structural changes, analogous to those seen in the signal-transducing G-proteins, alter the electrophilicity of the metal, reducing its ability to bind ligand-associated acidic residues, and dramatically alter the surface of the protein implicated in binding ligand. CONCLUSIONS: Our observations provide the first atomic resolution view of conformational changes in an integrin domain, and suggest how these changes are linked to a change in integrin adhesiveness. We propose that the Mg2+ form represents the conformation of the domain in the active state and the Mn2+ form the conformation in the inactive state of the integrin.

Allosteric Regulation↗

Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18).

We have determined the high resolution crystal structure of the A domain from the alpha chain of integrin CR3. The domain adopts a classic alpha/beta "Rossmann" fold and contains an unusual Mg2+ coordination site at its surface. One of the coordinating ligands is the glutamate side chain from another A domain molecule. We suggest that this site represents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands. We further propose that the beta subunits of integrins contain a MIDAS motif within a modified A domain. Our crystal structure will allow reliable models to be built for other members of the A domain superfamily and should facilitate development of novel adhesion modulatory drugs.

Amino Acid Sequence↗

A pathway for disulfide bond formation in vivo.

Protein disulfide bond formation in Escherichia coli requires the periplasmic protein DsbA. We describe here mutations in the gene for a second protein, DsbB, which is also necessary for disulfide bond formation. Evidence suggests that DsbB may act by reoxidizing DsbA, thereby regenerating its ability to donate its disulfide bond to target proteins. We propose that DsbB, an integral membrane protein, may be involved in transducing redox potential across the cytoplasmic membrane.

Amino Acid Sequence↗

Loss of retinoblastoma gene and amplification of N-myc gene in retinoblastoma.

We have analyzed paired samples of genomic DNA from peripheral leukocyte and primary tumor tissue from nine patients with retinoblastoma (RB) and from two RB cell lines, WERI-Rb-1 and Y79, to detect the molecular alterations of the retinoblastoma susceptibility gene (RB-1) and N-myc gene. In Southern analysis, RB-1 deletions in tumor tissues were detected in five patients (56%), one of these revealed a total loss of RB-1. N-myc amplification was found only in one (11.1%) out of nine patients. We also observed a total loss of RB-1 in WERI-Rb-1, and a more than 100-fold amplification of N-myc in Y79. The analysis of the relationship between molecular events and clinical characteristics such as age, sex, tumor laterality did not reveal any specific correlation. These results suggest that genetic backgrounds of RB in Korean patients are quite similar to those of reported cases elsewhere. The high sensitivity of our method in detecting the RB-1 loss indicates that this method can be a useful tool for initially screening a large number of tumors.

Child↗