Biomedical subjects

S Oh

Publications and source records attributed to S Oh.

At least 19 recordsLinked to original sources

PubMed2003

Two histidine residues in the juxta-membrane cytoplasmic domain of Na+/H+ exchanger isoform 3 (NHE3) determine the set point.

Histidine residues in Na+/H+ exchangers are believed to participate in proton binding and influence the Na+/H+ exchanger activity. In the present study, the function of three highly conserved histidines in the juxtamembrane cytoplasmic domain of NHE3 was studied. His-479, His-485, and His-499 were mutated to Leu, Gln or Asp and expressed in an Na+/H+ exchanger null cell line and functional consequences on Na+/H+ exchange kinetics were characterized. None of the histidines were essential for NHE3 activity, with all mutated NHE3 resulting in functional exchangers. However, the mutation in His-475 and His-499 significantly lowered NHE3 transport activity, whereas the mutation in H485 showed no apparent effect. In addition, the pH profiles of the H479 and H499 mutants were shifted to a more acidic region, and lowered its set point, the intracellular pH value above which the Na+/H+ exchanger becomes inactive, by approximately 0.3-0.6 pH units. The changes in set point by the mutations were further shifted to more acidic values by ATP depletion, indicating that the mechanism by which the mutations on the histidine residues altered the NHE3 set point differs from that caused by ATP depletion. We suggest that His-479 and His-499 are part of the H+ sensor, which is involved in determining the sensitivity to the intracellular H+ concentration and Na+/H+ exchange rate.

Adenosine Triphosphate↗

PubMed2003

The association of cholesteryl ester transfer protein polymorphism with high-density lipoprotein cholesterol and coronary artery disease in Koreans.

Cholesteryl ester transfer protein (CETP) is a key protein involved in high-density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma HDL-C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C levels in females (p = 0.049) and non-smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL-C levels (p = 0.046) and explained 5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL-C levels in females and non-smoking males, and may be an independent genetic risk factor of CAD in the Korean population.

Carrier Proteins↗

PubMed2003

A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.

BACKGROUND: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. METHODS: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation ('treated' patients, n = 9) or conventional management ('untreated' patients, n = 6). RESULTS: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6-8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. CONCLUSION: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

Adult↗

PubMed2002

Atomic scale imaging and spectroscopy of a CuO(2) plane at the surface of Bi(2)Sr(2)CaCu(2)O(8+delta).

We have used a scanning tunneling microscope to demonstrate that a single CuO2 plane can form a stable and atomically ordered layer at the surface of Bi(2)Sr(2)CaCu(2)O(8+delta). In contrast to previous studies on high-T(c) surfaces, the CuO2-terminated surface exhibits a strongly suppressed tunneling conductance at low voltages. We consider a number of different explanations for this phenomena and propose that it may be caused by how the orbital symmetry of the CuO2 plane's electronic states affects the tunneling process.

Journal Article↗

PubMed2001

Effects of ginsenosides on vanilloid receptor (VR1) channels expressed in Xenopus oocytes.

Ginsenosides, or ginseng saponins, are biologically active ingredients of Panax ginseng. Accumulating evidence suggests that ginsenosides can alleviate pain from injections of noxious chemicals, such as capsaicin [Nah et al. (2000)]. In this study we examined the effects of ginsenoside Rc on the capsaicin-induced inward current in Xenopus oocytes that expresses the vanilloid receptor 1 (VR1). Ginsenoside Rc enhanced the capsaicin-induced inward current in a concentration-dependent and reversible manner, but ginsenoside Rc itself elicited no membrane currents. The VR1 antagonist capsazepine almost completely blocked the inward current that was elicited by capsaicin plus ginsenoside Rc. We also tested the effect of seven other fractionated ginsenosides (i.e., Rb1, Rb2, Rd, Re, Rf, Rg1, and Rg2) in addition to ginsenoside Rc. We found that six of them significantly enhanced the inward current that is induced by capsaicin with the following order of potency: Rc > Rf > Rg1 approximately Rd > Rb2 > Rb1. These results show the possibility that the in vivo effect of ginsenosides against capsaicin-induced pain is derived from their modulation of the VR1 channel function.

Analgesics↗

PubMed2001

An aspartic protease analogue: intermolecular catalysis of peptide hydrolysis by carboxyl groups.

Two aspartic carboxyl groups act as key catalytic groups in the active site of an aspartic protease. We synthesized an aspartic protease analogue by positioning three salicylate residues in close proximity on a cross-linked polystyrene. The immobile artificial protease effectively hydrolyzed albumin into many small fragments by the catalytic action of carboxyl groups contained in the active site. The artificial protease manifested optimum activity at pH 3 just as aspartic proteases.

Albumins↗

PubMed2001

Interaction of FACT, SSRP1, and the high mobility group (HMG) domain of SSRP1 with DNA damaged by the anticancer drug cisplatin.

The structure-specific recognition protein SSRP1, initially isolated from expression screening of a human B-cell cDNA library for proteins that bind to cisplatin (cis-diamminedichloroplatinum(II))-modified DNA, contains a single DNA-binding high mobility group (HMG) domain. Human SSRP1 purifies as a heterodimer of SSRP1 and Spt16 (FACT) that alleviates the nucleosomal block to transcription elongation by RNAPII in vitro. The affinity and specificity of FACT, SSRP1, and the isolated HMG domain of SSRP1 for cisplatin-damaged DNA were investigated by gel mobility shift assays. FACT exhibits both affinity and specificity for DNA damaged globally with cisplatin compared with unmodified DNA or DNA damaged globally with the clinically ineffective trans-DDP isomer. FACT binds the major 1,2-d(GpG) intrastrand cisplatin adduct, but its isolated SSRP1 subunit fails to form discrete, high affinity complexes with cisplatin-modified DNA under similar conditions. These results suggest that Spt16 primes SSRP1 for cisplatin-damaged DNA recognition by unveiling its HMG domain. As expected, the isolated HMG domain of SSRP1 is sufficient for specific binding to cisplatin-damaged DNA and binds the major cisplatin 1,2-d(GpG) intrastrand cross-link. The affinity and specificity of FACT for cisplatin-modified DNA, as well as its importance for transcription of chromatin, suggests that the interaction of FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin.

Amino Acid Sequence↗

PubMed2001

Cosmology from MAXIMA-1, BOOMERANG, and COBE DMR cosmic microwave background observations.

Recent results from BOOMERANG-98 and MAXIMA-1, taken together with COBE DMR, provide consistent and high signal-to-noise measurements of the cosmic microwave background power spectrum at spherical harmonic multipole bands over 2<l less similar to 800. Analysis of the combined data yields 68% (95%) confidence limits on the total density, Omega(tot) approximately 1.11+/-0.07 (+0.13)(-0.12), the baryon density, Omega(b)h(2) approximately 0.032(+0.005)(-0.004) (+0.009)(-0.008), and the scalar spectral tilt, n(s) approximately 1.01(+0.09)(-0.07) (+0.17)(-0.14). These data are consistent with inflationary initial conditions for structure formation. Taken together with other cosmological observations, they imply the existence of both nonbaryonic dark matter and dark energy in the Universe.

Journal Article↗

PubMed2001

The evolving treatment of anal cancer: How are we doing?

HYPOTHESIS: The adaptation of new techniques in treatment of epidermoid carcinoma of the anal canal during the past 3 decades has improved clinical outcomes. DESIGN: Retrospective consecutive case review. SETTING: A university hospital and Veterans Affairs medical center. PATIENTS: Medical records of 76 consecutive patients treated for invasive epidermoid cancer of the anal canal between 1970 and 1999 were reviewed. Twenty-one patients were excluded because of inadequate staging information and/or follow-up of less than 12 months. MAIN OUTCOME MEASURES: Locoregional recurrence, survival, colostomy-free survival, and morbidity. RESULTS: Fifty-five patients composed the study population. Ten were treated during decade 1 (1970-1979), 16 in decade 2 (1980-1989), and 29 in decade 3 (1990-1999). Mean age and sex distributions were similar. The prevailing primary treatment modality changed during the course of the study from sequential treatment (chemotherapy then radiation therapy then radical surgery) to concurrent chemoradiation (70% and 0% of cases, respectively, in decade 1 to 7% and 76% of cases, respectively, in decade 3). Locoregional control (50%, 81%, and 93%; P =.01), crude survival (median, 28, 30, and 76 months), and colostomy-free survival (mean, 13, 90, and 80 months) improved during the 3 decades. There were no differences in major complications during the 3 decades (40%, 56%, and 41%). CONCLUSION: Primary treatment with concurrent chemoradiation has improved the local recurrence, survival, and colostomy-free survival rates in patients with invasive epidermoid carcinoma of the anal canal without increasing major morbidity.

Adult↗

PubMed2001

Aberrant expression of Smad4 results in resistance against the growth-inhibitory effect of transforming growth factor-beta in the SiHa human cervical carcinoma cell line.

Smad proteins activated by TGF-beta form complexes with Smad4. Upon activation, these complexes translocate to the nucleus of the cell, where they induce transcription of genes related to inhibition of cell growth, cell differentiation and apoptosis. We investigated the role of Smads in the TGF-beta-mediated signal-transduction cascade in 4 human cervical cancer cell lines: HeLa, Caski, HT-3 and SiHa. Based on our results, SiHa cells show low mRNA expression of mutated Smad4 (Gly(230)Ala, Ala(488)Val) and of Smads 2, 3, 5 and 6. SiHa cells were likewise defective in TGF-beta signaling, as evidenced by a lack of significant growth inhibition following TGF-beta treatment. In addition, TGF-beta did not induce transcription of the PAI-1 gene or change Smad protein levels. Introduction of Smad3 and/or Smad4 into SiHa cells restored TGF-beta signaling, as determined by activation of the 3TP-lux reporter gene and by prominent apoptotic cell death with PAI-1 induction. Analysis of the downstream targets activated by TGF-beta yielded rapid activation of p38 with subsequent phosphorylation of the transcription factor ATF-2 but unchanged SAPK/JNK activation in the 4 cervical cancer cell lines. Our findings demonstrate that (i) decrease of Smad4 mRNA expression is closely associated with defective TGF-beta response and lack of growth inhibition, (ii) activation of PAI-1 by TGF-beta may be Smad4-dependent and (iii) the Smad and the p38 cascades are triggered by TGF-beta independently of each other in human cervical cancer.

Adenoviridae↗

PubMed2001

Changes of [3H]MK-801, [3H]muscimol and [3H]flunitrazepam binding in rat brain by the prolonged ventricular infusion of ginsenoside Rc and Rg1.

In the present study, we have investigated the effects of centrally administered ginsenoside Rc and Rg1 on the modulation of the NMDA receptor and GABA(A)receptor binding in rat brain. The NMDA receptor binding was analysed by quantitative autoradiography using [(3)H]MK-801 binding, and the GABA(A)receptor bindings were analysed by using [(3)H]muscimol and [(3)H]flunitrazepam binding in rat brain slices. Rats were infused with ginsenoside Rc or Rg1 (10 microg/10 microl h(-1), i.c.v.) for 7 days, through pre-implanted cannula using osmotic minipumps (Alzet, model 2ML). The levels of [(3)H]MK-801 binding were highly decreased in part of the parietal layers of the cortex and cingulated by ginsenoside Rc and Rg1. The levels of [(3)H]muscimol binding were strongly elevated in almost all regions of the frontal cortex by the treatment of ginsenoside Rc but decreased by ginsenoside Rg1. However, the [(3)H]flunitrazepam binding was not modulated by ginsenoside Rc or Rg1 infusion. These results suggest that prolonged infusion of ginsenosides could differentially modulate [(3)H]MK-801 and [(3)H]muscimol binding in a region-specific manner.

Animals↗

PubMed2001

Hepatic fibrosis: are any of the serum markers useful?

There is a clinical need for noninvasive measurement of liver fibrosis both to diagnose significant liver fibrosis and to monitor the effects of therapy on fibrogenesis and fibrolysis. Multiple clinical markers have been evaluated over the years, and as our understanding of the molecular process of liver scarring has advanced, newer markers have appeared. Serum markers include extracellular matrix proteins such as the N-terminal propeptide of collagen III, hyaluronan, YKL-40, laminin, metalloproteinases, and their inhibitors. Use of multiple markers has led to 90% sensitivity in diagnosing cirrhosis, but specificity is variable at about 60%. Automated systems to measure these markers are under development and are being evaluated for their ability to monitor fibrosis during and after therapy in multiple liver diseases, including hepatitis B and C. Although no individual fibrosis marker is clinically applicable today, we foresee a future in which monitoring fibrosis markers will replace sequential liver biopsy as a standard of care.

Biomarkers↗

PubMed2001

Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids.

To examine a role of N-methyl-D-aspartate (NMDA) receptors in the locus coeruleus (LC) in the expression of the withdrawal signs from opioids, rats were continuously infused with morphine (a mu-opioid agonist, 26 nmol/microl per h) or butorphanol (a mu/delta/kappa-mixed opioid agonist, 26 nmol/microl per h) intracerebroventricularly (i.c.v.) through osmotic minipumps for 3 days. An LC injection of NMDA (0.1 and 1 nmol/5 microl) induced withdrawal signs in opioid-dependent animals. However, it did not precipitate any abnormal behaviors in saline-treated control rats. The expression of the withdrawal signs precipitated by NMDA (1 nmol/5 microl), glutamate (10 nmol/5 microl), or naloxone (an opioid antagonist, 24 nmol/5 microl) was completely blocked by pretreatment with a NMDA antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine), 0.1 mg/kg, i.p. In animals that had been infused with opioids in the same manner, naloxone (48 nmol/5 microl, i.c.v.) precipitated withdrawal signs and increased extracellular glutamate levels in the LC of opioid-dependent rats measured by in vivo microdialysis method. Pretreatment with MK-801, however, did not affect the increases of glutamate levels in the LC. These results further demonstrate that the expression of opioid withdrawal induced by an expeditious release of glutamate in the LC region of opioid-dependent animals might be mainly mediated by the postsynaptic NMDA receptors.

Animals↗

PubMed2001

Modulation of the levels of NMDA receptor subunit mRNA and the bindings of [3H]MK-801 in rat brain by chronic infusion of subtoxic dose of MK-801.

The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.

Animals↗

PubMed2001

exo1-Dependent mutator mutations: model system for studying functional interactions in mismatch repair.

EXO1 interacts with MSH2 and MLH1 and has been proposed to be a redundant exonuclease that functions in mismatch repair (MMR). To better understand the role of EXO1 in mismatch repair, a genetic screen was performed to identify mutations that increase the mutation rates caused by weak mutator mutations such as exo1Delta and pms1-A130V mutations. In a screen starting with an exo1 mutation, exo1-dependent mutator mutations were obtained in MLH1, PMS1, MSH2, MSH3, POL30 (PCNA), POL32, and RNR1, whereas starting with the weak pms1 allele pms1-A130V, pms1-dependent mutator mutations were identified in MLH1, MSH2, MSH3, MSH6, and EXO1. These mutations only cause weak MMR defects as single mutants but cause strong MMR defects when combined with each other. Most of the mutations obtained caused amino acid substitutions in MLH1 or PMS1, and these clustered in either the ATP-binding region or the MLH1-PMS1 interaction regions of these proteins. The mutations showed two other types of interactions: specific pairs of mutations showed unlinked noncomplementation in diploid strains, and the defect caused by pairs of mutations could be suppressed by high-copy-number expression of a third gene, an effect that showed allele and overexpressed gene specificity. These results support a model in which EXO1 plays a structural role in MMR and stabilizes multiprotein complexes containing a number of MMR proteins. A similar role is proposed for PCNA based on the data presented.

Adenosine Triphosphate↗

PubMed2001

Tactual performance test trials: psychometric properties of the blocks-per-minute scores.

Internal consistency reliabilities were calculated for the Tactual Performance Test blocks-per-minute scores for the Preferred Hand (n=298), Nonpreferred Hand (n=302), and Both Hands (n=314) trials, and Total Time. Reliabilities are reported for the total sample and three groups of normal, alcoholic, and undiagnosed patients sent for assessment. The reliabilities ranged from .6102 to .9232. Only three of the discriminate indexes were poor.

Humans↗

PubMed2001

Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: secure blockade of ischemic neuronal death.

Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate. This neuroprotective behavior of complestatin was attributed to a blockade of Ca2+ ion entry and accumulation, after the activation of NMDA and AMPA/kainate receptors. Complestatin reversibly interfered with NMDA- and AMPA-mediated excitatory synaptic transmission. Complestatin also protected cortical neurons from prolonged deprivation of oxygen and glucose, more effectively than combined antagonists of NMDA and AMPA/kainate receptors. Neurotoxicity, evolving within 1 to 2 days after continuous exposure to combined NMDA and AMPA/kainate antagonists, was not observed in cortical cell cultures that were exposed to complestatin. Finally, complestatin dose dependently prevented neuronal death evolving within the inner nuclear and ganglion cell layers, after transient retinal ischemia. We conclude that complestatin possesses novel pharmacological properties that effectively prevent excitotoxicity under certain pathological conditions.

Animals↗

PubMed2000

Remarkable proteolytic activity of imidazoles attached to cross-linked polystyrene.

The insoluble resins synthesized by attaching imidazoles to poly(chloromethylstyrene-co-divinylbenzene) effectively hydrolyzed albumin with half-life as short as 20 min at pH 7 and 25 degrees C. Thus, peptide hydrolysis was accomplished with imidazole in an artificial system for the first time. The imidazole-based artificial proteinases manifested optimum activity at pH 7-8. The proteolytic activity of the imidazole-based artificial proteinases exceeded that of previously reported organic artificial proteinases including catalytic antibodies. High proteolytic activity was observed when imidazole was attached to the resin through the C-2 atom instead of the N atom. The catalytic activity was greatly reduced when the content of imidazole was lowered. This indicates catalytic cooperation of at least two proximal imidazole moieties attached to the resin. Possible mechanisms for the effective protein hydrolysis by the proximal imidazoles are presented.

Cross-Linking Reagents↗