Biomedical subjects

K S Oh

Publications and source records attributed to K S Oh.

At least 19 recordsLinked to original sources

PubMed2006

The elevation of the constructed auricle with a temporoparietal fascial flap wrapping a resorbable plate.

During the second stage reconstruction of the auricle in patients with microtia, we modified Nagata's method and two technical improvements were possible. After the implanted auricle was separated from the bed, we harvested the temporoparietal fascial flap through helical rim incision instead of incising the temporal scalp. So the surgical scar over the temporal region was avoided. Thereafter, a costal cartilage wedge was carved and grafted to the posterior aspect of the conchal region to get a firm projection. But in cases of unavailable costal cartilage wedge graft, we used a resorbable plate composed of polylactic and polyglycolic acid as a substitute for the former so that we could create firm elevation and sufficient ear projection. Between June 2002 and May 2004, 28 patients underwent this operation with the temporoparietal fascial flap and resorbable plating system. There was no complication resulting from our technique. It was possible to create firm elevation and good frontal projection even if there was no available cartilage wedge. Additionally, by harvesting the temporoparietal fascia through helical rim incision, we avoid creating additional scars on the scalp.

Biocompatible Materials↗

PubMed2001

Mechanistic insight into the inactivation of carboxypeptidase A by alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid, a novel type of irreversible inhibitor for carboxypeptidase A with no stereospecificity.

On the basis of the active site topology and enzymic catalytic mechanism of carboxypeptidase A (CPA), a prototypical zinc-containing proteolytic enzyme, alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (1), was designed as a novel type of mechanism-based inactivator of the enzyme. All four possible stereoisomers of the inhibitor were synthesized in an enantiomerically pure form starting with optically active aspartic acid, and their CPA inhibitory activities were evaluated to find that surprisingly all of the four stereoisomers inhibit CPA in a time dependent manner. The inhibited enzyme did not regain its enzymic activity upon dialysis. The inactivations were prevented by 2-benzylsuccinic acid, a competitive inhibitor that is known to bind the active site of the enzyme. These kinetic results strongly support that the inactivators attach covalently to the enzyme at the active site. The analysis of ESI mass spectral data of the inactivated CPA ascertained the conclusion from the kinetic results. The values of second-order inhibitory rate constants (k(obs)/[I](o)) fall in the range of 1.7-3.6 M(-1) min(-1). The lack of stereospecificity shown in the inactivation led us to propose that the ring cleavage occurs by the nucleophilic attack at the 2-position rather than at the 5-position and the ring opening takes place in an addition-elimination mechanism. The tetrahedral transition state that would be generated in this pathway is thought to be stabilized by the active site zinc ion, which was supported by the PM3 semiemprical calculations. In addition, alpha-benzyl-2-oxo-1,3-oxazolidine-5-acetic acid (18), a structural isomer of 1 was also found to inactivate CPA in an irreversible manner, reinforcing the nucleophilic addition-elimination mechanism. The present study demonstrates that the transition state for the inactivation pathway plays a critical role in determining stereochemistry of the inactivation.

Carboxypeptidases↗

PubMed2001

The need for scoliosis screening in Malaysia.

Conflicting recommendations exist on the issue of scoliosis screening in the general population. Worldwide, opponents cite the relative inaccuracy of screening tests, cost-ineffectiveness and psychosocial effect of 'labelled' patients but advocates quote the successes in many centres and the advantages of timely intervention. We studied 205 patients with idiopathic scoliosis and found they presented at relatively later ages and with curves that showed rapid annual progression. We suggest that screening in Malaysia may identify patients early for treatment besides promoting health awareness.

Adolescent↗

PubMed2001

An audit of the Scoliosis Service at Hospital Kuala Lumpur.

This is a study of patients referred to the Scoliosis Service of Hospital Kuala Lumpur. Three hundred and thirty five (335) consecutive patients who were seen between 1985 and 2000 were reviewed to determine the presentation of scoliosis, the treatment received and the compliance to follow up. Data were determined by measuring the frontal spinal radiographs. Two hundred and ninety eight (298) patients met inclusion criteria. Idiopathic scoliosis accounted for 203 patients (68.1%), 31 (10.4%) were neuromuscular scoliosis; and 44 (14.8%) had congenital scoliosis. Twenty-five point five percent of patients had surgery, 10.4% were treated with brace, while the remaining 69.1% of patients were observed, or had no treatment at all. Congenital scoliosis patients had better compliance compared to idiopathic or neuromuscular scoliosis patients.

Adolescent↗

PubMed2001

The natural history of scoliosis: curve progression of untreated curves of different aetiology, with early (mean 2 year) follow up in surgically treated curves.

We studied the curve progression of untreated curves presenting to the Scoliosis Service of Hospital Kuala Lumpur. One hundred and fifty-two (152) patients were included in this study. The median rate of curve progression of idiopathic scoliosis curves was 7.03 degrees per year, for neuromuscular scoliosis curves was 17.39 degrees per year; and congenital scoliosis curves were 3.67 degrees per year. These rates are similar to the reported rates in the literature. Data for sixty-one (61) surgically treated patients were reviewed to determine the early curve correction of the curves of different aetiology. The mean age of surgery was 14.15 years old, the mean preoperative curve size was 71.61 degrees; and the mean postoperative curve size was 43.78 degrees. The mean duration of follow up after surgery was 2.44 years. The revision and removal of instrumentation rate was 8.3%.

Adolescent↗

PubMed2000

Role of catalytic residues in enzymatic mechanisms of homologous ketosteroid isomerases.

Ketosteroid isomerase (KSI) is one of the most proficient enzymes catalyzing an allylic isomerization reaction at a diffusion-controlled rate. In this study of KSI, we have detailed the structures of its active site, the role of various catalytic residues, and have explained the origin of the its fast reactivity by carrying out a detailed investigation of the enzymatic reaction mechanism. This investigation included the X-ray determination of 15 crystal structures of two homologous enzymes in free and complexed states (with inhibitors) and extensive ab initio calculations of the interactions between the active sites and the reaction intermediates. The catalytic residues, through short strong hydrogen bonds, play the role of charge buffer to stabilize the negative charge built up on the intermediates in the course of the reaction. The hydrogen bond distances in the intermediate analogues are found to be about 0.2 A shorter in the product analogues both experimentally and theoretically.

Aspartic Acid↗

PubMed2000

Origin of the high affinity and selectivity of novel receptors for NH4+ over K+: charged hydrogen bonds vs cation-pi interaction.

[structure: see text]Given the recent report of a novel pyrazole receptor exhibiting a high selectivity for NH4+ over K+, it would be interesting to investigate the origin of this selectivity and affinity so that better receptors could be designed. On the basis of extensive theoretical studies, we conclude that the origin arises from a subtle interplay of charged H-bonds and cation-pi interactions. The approach employed herein would be very useful in the rational design of novel functional molecular systems.

Cations↗

PubMed2000

Catalytic role of enzymes: short strong H-bond-induced partial proton shuttles and charge redistributions.

A two-step reaction mechanism (catalyzed alternatively by acid and base) with partial proton shuttles and charge redistributions promoted by short strong H bonds (SSHBs) (playing a dual role as an amphi-acid/base catalyst) is proposed to explain the enormous rate enhancement observed in enzymatic reactions involving carbanion intermediates. The SSHBs in the two-step reactions are found to be responsible for enhancing enzyme-substrate interactions in favor of the transition state structure over that of reactant. The detailed quantum theoretical studies of ketosteroid isomerase provide evidence of assisting roles of SSHB in enzymatic activity. The understanding of the two-step reaction mechanism would be a useful aid in designing novel functional enzymes and abzymes.

Binding Sites↗

PubMed2000

High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion.

OBJECTIVE: The enzymes cyclooxygenase (COX)-1 and -2 are necessary for the synthesis of prostaglandins. COX-2 is usually absent in normal cells and is upregulated and expressed as a product of the "immediate early" gene during inflammatory processes. In previous studies, the expression of COX-2 has been shown to be induced by proinflammatory cytokines, and suggestions have been made that overexpression of COX-2 suppresses apoptosis and is directly related to tumor growth. We have attempted to determine a relationship between tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis, COX-1, and COX-2 in tumor tissues. METHODS: The subjects were 36 patients who were FIGO stage IB uterine cervical cancer patients who underwent surgery at Ajou University Hospital. There were 12 cases with lymph node or parametrial involvement. All tissues were subjected to immunohistochemical staining for COX-1, -2, and TUNEL method for apoptosis detection, and the following results were obtained. RESULTS: Tumor tissues confirmed by cytokeratin were separated into tumor surface, tumor stroma, and invasion site portions, in which decreased apoptosis was observed in the invasion sites. COX-2 expression was observed in all tumor tissues and was especially strong in the tumor invasion site. Therefore, it is suggested that COX-2 expression may suppress cell apoptosis at the tumor invasion site. When COX-2 expression was investigated according to the groups with regard to the presence of lymph node or parametrial involvement, there was a statistically significant (Mann-Whitney U test) COX-2 expression difference in the tumor invasion site (P value = 0.040) and the tumor stroma (P value = 0. 028). CONCLUSIONS: In surgically treated stage IB cervical cancer patients, COX-2 was significantly expressed when lymph node or parametrial involvement was present. These results suggest that the expression of COX-2 in stage IB cervical cancer may downregulate apoptotic processes and thus enhance tumor invasion and metastasis.

Apoptosis↗

PubMed2000

Inhibition of nicotinic receptor-mediated catecholamine secretion by Dryobalanops aromatica in bovine adrenal chromaffin cells.

Effect of the aqueous extract from a medicinal plant Dryobalanops aromatica(Dipterocarpaceae) on catecholamine secretion was investigated in bovine adrenal chromaffin cells. The aqueous extract inhibited [(3)H]norepinephrine ([(3)H]NE) secretion induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic acetylcholine receptor (nAChR) agonist, with a half-maximal inhibitory concentration (IC(50)) of 8.4 +/- 1.7 microgml(-1). Increases in cytosolic calcium ([Ca(2+)](i)) and sodium ([Na(+)](i)) induced by DMPP were also inhibited by the extract. However, the binding of [(3)H]nicotine to nAChRs was not affected by the addition of the extract in receptor binding competition analysis, suggesting that active components in the extract and nicotine do not share the binding site in the nAChR. On the other hand, [Ca(2+)](i)increases induced by high K(+), ionomycin, bradykinin, angiotensin II, and thapsigargin were not inhibited by the extract. The data suggest that the extract from D. aromatica specifically inhibits catecholamine secretion by blocking nAChR in a noncompetitive manner.

Animals↗

PubMed2000

Expression of protein kinase C genes in normal (+/+) and W mutant alleles (Wsh/Wsh, W/Wv) mice testes.

In the present study, we investigated the expression of mRNA of protein kinase C (PKC) isoenzymes (alpha, beta, gamma, delta, epsilon, zeta, eta, and theta) in normal (+/+) and W mutant alleles mice testes. In +/+ mice testes, abundant expression of PKCdelta and PKCtheta was observed, while other PKCs (alpha, beta, gamma, epsilon, zeta, and eta) generally were not detected by Northern blotting. The PKCdelta and PKCtheta isoenzymes demonstrated a distinctive cellular distribution when evaluated by in situ hybridization. We have previously shown that PKCdelta gene was selectively expressed in spermatid of +/+ testes. Here we show that PKCdelta gene is also present in spermatid of Wsh/Wsh mice testes and PKCtheta gene was present in interstitial cells of +/+, Wsh/Wsh, and W/Wv mice testes. These studies provide the evidence of selective cell distributions of the PKC isoenzymes and suggest that PKC has the functional significance in testes.

Alleles↗

PubMed1999

Crystal structure of delta(5)-3-ketosteroid isomerase from Pseudomonas testosteroni in complex with equilenin settles the correct hydrogen bonding scheme for transition state stabilization.

Delta(5)-3-Ketosteroid isomerase from Pseudomonas testosteroni has been intensively studied as a prototype to understand an enzyme-catalyzed allylic isomerization. Asp(38) (pK(a) approximately 4.7) was identified as the general base abstracting the steroid C4beta proton (pK(a) approximately 12.7) to form a dienolate intermediate. A key and common enigmatic issue involved in the proton abstraction is the question of how the energy required for the unfavorable proton transfer can be provided at the active site of the enzyme and/or how the thermodynamic barrier can be drastically reduced. Answering this question has been hindered by the existence of two differently proposed enzyme reaction mechanisms. The 2.26 A crystal structure of the enzyme in complex with a reaction intermediate analogue equilenin reveals clearly that both the Tyr(14) OH and Asp(99) COOH provide direct hydrogen bonds to the oxyanion of equilenin. The result negates the catalytic dyad mechanism in which Asp(99) donates the hydrogen bond to Tyr(14), which in turn is hydrogen bonded to the steroid. A theoretical calculation also favors the doubly hydrogen-bonded system over the dyad system. Proton nuclear magnetic resonance analyses of several mutant enzymes indicate that the Tyr(14) OH forms a low barrier hydrogen bond with the dienolic oxyanion of the intermediate.

Binding Sites↗

PubMed1999

Effects of low oxygen condition on the generation of reactive oxygen species and the development in mouse embryos cultured in vitro.

OBJECTIVE(S): To elucidate the relationship between intracellular H2O2 production and embryo development in different oxygen culture conditions. METHODS: Pronuclear stage embryos were obtained from C57BL/CBA F1 and ICR mice. Measurement of H2O2 level was performed with 2',7'-dichlorodihydroflourescein diacetate and the number of blastomeres was counted after staining with 4',6'-diamidino-2-phenylindole. RESULTS: Regardless of strains, H2O2 level reached a peak at the 2-cell stage in 20% O2. But in embryos cultured in 5% O2 it was significantly lower at the 2-cell and 4-cell stages compared to those from 20% O2. The embryos cultured in 20% O2 showed developmental delay or block, but in 5% O2 these phenomena were overcome and the development was significantly increased with an infrequent fragmentation. CONCLUSIONS: Our data suggest that the 5% O2 decreases the relative concentration of H2O2 and results in improved embryo development in terms of quantity and quality without regard to type of strains.

Animals↗

PubMed1999

Homocyst(e)ine and atherosclerosis in patients on chronic hemodialysis.

Hyperhomocyst(e)inemia is an established risk factor for atherosclerosis. We performed this study to identify the correlating variables and risk factors for atherosclerosis, as measured by the atherosclerotic score (AS), and to determine the relative risk for cardiovascular disease in relation to plasma homocyst(e)ine levels in patients on chronic hemodialysis. We evaluated and measured 61 patients on chronic hemodialysis for clinical and biochemical parameters including atherosclerotic score (AS) and plasma homocyst(e)ine. We divided patients into high and low groups, first, by the mean AS, and second, by the median value of plasma total homocyst(e)ine levels. Then we compared the variables between the two groups. Out of the 61 patients, the median plasma total homocyst(e)ine level was 24.4 micromol/L (mean+/-SD, 27.7+/-17.4; range, 9.8-127.4 micromol/L), and the median AS was 5 (mean+/-SD, 6.2+/-2.8; range, 3-13) out of a possible 20 points. AS was significantly correlated with plasma total homocyst(e)ine levels (r=0.37) and age (r=0.67). Through multivariate analysis, plasma total homocyst(e)ine level and age were determined as significant risk factors for the high-AS group (p<0.05). However, plasma total homocyst(e)ine level did not correlate with age (p>0.05). Eighteen of the 61 patients, presented with cardiovascular disease until the present study, had an AS>6. Cardiovascular disease was found more often in the high-homocyst(e)ine group (>24.4 micromol/L) than in the low-homocyst(e)ine group (odds ratio, 9.3; 95% confidence interval, 2.3-37.4). Regardless of age, hyperhomocyst(e)inemia (especially homocyst(e)ine levels >24.4 micromol/L) is a risk factor that can be modified for the development of cardiovascular disease in patients on chronic hemodialysis.

Adolescent↗

PubMed1998

Gas chromatographic profiling and pattern recognition analysis of urinary organic acids from uterine myoma patients and cervical cancer patients.

An efficient organic acid profiling and pattern recognition method is described for the correlation between urinary organic acid profiles and uterine cervical cancer. After methoximation of keto acids in alkalinized urine samples, all free organic acids were recovered by a dual solid-phase extraction procedure, followed by conversion to tert.-butyldimethylsilyl derivatives for the profiling analysis by dual-capillary column gas chromatography (GC) with subsequent screening for acids by retention index (I) library matching. A total of 50 organic acids were positively identified in urine samples (0.25 ml) from 12 uterine myoma (benign tumor group) and 14 uterine cervical cancer (malignant tumor group) patients studied. When the GC profiles were simplified to their corresponding organic acid I spectra in bar graphical form, characteristic patterns were obtained for each average of benign and malignant tumor groups. Stepwise discriminant analysis performed on the GC data selected 16 acids as the variables discriminating between the two groups. Canonical discriminant analysis applied to these 16 variables correctly classified 26 urine samples into two separate clusters according to tumor types in the canonical plot.

Adult↗

PubMed1998

Sintering of TCP-TiO2 biocomposites: influence of secondary phases.

TCP-TiO2 ceramic biocomposites with various alpha-to-beta TCP ratios can be prepared by quenching the alpha phase. The presence of dopants (Ca, P, or Na) leads to the precipitation of secondary phases, which decreases the densification of titania. In the system TCP-TiO2, there is a eutectic with a composition of 63 wt% TCP-37 wt% TiO2 at a temperature of 1380 degrees C.

Biocompatible Materials↗

PubMed1998

Conservative therapy of adnexal torsion employing color Doppler sonography.

STUDY OBJECTIVE: To ascertain if color Doppler sonography (CDS) can detect viability of adnexa in torsion. DESIGN: Concurrent, nonrandomized study (Canadian Task Force classification II-2). SETTING: Tertiary medical care center in a university hospital. PATIENTS: Twenty-seven women suspected of having torsion of the ovary in which a benign tumor was present. INTERVENTIONS: Color Doppler sonography of the ovarian pedicle suggested torsion. Laparoscopy or laparotomy was performed in 19 patients and confirmed the diagnosis. MEASUREMENTS AND MAIN RESULTS: We identified a twisted vascular pedicle of the ovarian tumor by CDS in 24 (88%) of 27 women. Pedicle arterial and venous blood flow was observed in 10 women; pathology specimens revealed normal tissue, edema with congestion, or early hemorrhage. In all nine in whom only arterial blood flow or no blood flow was observed, pathology revealed hemorrhagic necrosis. In five women with arterial and venous blood flow the tumor was managed conservatively, either by detorsion or cystectomy, after which no embolism or tumor recurrence was seen at follow-up ultrasonography. Normal follicular development and ovulation occurred in these patients. CONCLUSION: For women of childbearing age in whom torsion of benign adnexal tumors is suspected, CDS should be performed to confirm the diagnosis and ascertain whether or not pedicle arterial and venous blood flow is present. If such blood flow is detected, the adnexa is considered to be viable and detorsion or cystectomy may be performed, thus preserving the ovary. It is recommended that further studies with a larger group be undertaken to provide a basis for statistical analysis.

Abdomen, Acute↗

PubMed1998

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos.

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.

Apoptosis↗