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Biomedical subjects

J Oh

Publications and source records attributed to J Oh.

At least 19 recordsLinked to original sources
PubMed2006

TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118.

We previously demonstrated that TIMP-2 increases the association of Crk with C3G and via subsequent activation of Rap1 enhances the expression of RECK, a membrane-anchored MMP inhibitor. In the present study, we investigate the mechanism of how the TIMP-2 signal is transduced from the alpha3beta1 integrin receptor to the Crk-C3G-Rap1 molecular complex. TIMP-2 treatment of human microvascular endothelial cells (hMVECs) increased the phosphorylation levels of Src at Tyr-527, the negative regulatory site, through enhanced association of Src with Csk. This results in the reduction of Src kinase activity and dephosphorylation of paxillin at Tyr-31/118, the target sites for Src kinase phosphorylation and also the binding sites for the downstream effector Crk. Such TIMP-2 effects accompany the disassembly of paxillin-Crk-DOCK180 molecular complex and, in turn, Rac1 inactivation. On the contrary, levels of paxillin-Crk-C3G complex formation are not reduced, rather slightly increased, which is consistent with our previous finding. Therefore, TIMP-2-mediated inhibition of Src kinase activity leads to the signaling switch from Rac1 to Rap1, thereby leading to enhanced RECK expression.

Cells, Cultured↗
PubMed2004

Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging.

OBJECTIVES: To investigate the extent of tissue damage in a region of normal appearing corpus callosum (NACC) for different forms of multiple sclerosis (MS) using diffusion tensor and proton magnetic resonance (MR) spectroscopic imaging. METHODS: A total of 47 patients with MS and 15 controls were included. Regions of interest from the NACC were manually segmented using high resolution anatomical images. Diffusion tensor eigenvalues and metabolite ratio of N-acetyl-aspartate (NAA) to creatine/phosphocreatine (Cr) were calculated in the NACC region. RESULTS: Increased apparent diffusion coefficients (ADCs) and decreased anisotropy were observed in the NACC for patients with MS relative to the control subjects. These resulted from increased diffusion tensor eigenvalues perpendicular to the maximum diffusion direction. The NAA:Cr ratio was decreased in the NACC for patients with MS relative to the control subjects. Significant correlations between pericallosal T1 lesion load and MR modalities in the NACC were observed for patients with relapsing remitting/secondary progressive MS (RR/SPMS), but not for patients with primary progressive MS (PPMS). CONCLUSION: This study provides further insight into changes in the ADC and diffusion anisotropy based on the diffusion tensor eigenvalues for patients with MS. The changes in the diffusion tensor eigenvalues and NAA:Cr ratio in the NACC for patients with RR/SPMS suggest axonal injury and/or dysfunction induced by wallerian degeneration. The lack of correlation between these variables in the NACC and focal MS lesions for patients with PPMS further supports intrinsic differences related to tissue injury between these subtypes of MS.

Adult↗
PubMed2003

Factors affecting the quality of life in patients with epilepsy in Seoul, South Korea.

OBJECTIVES: The level of, and factors affecting the quality of life (QOL) in patients with epilepsy may be different in Korea where social prejudice toward them is still pronounced. However, these issues have not yet been addressed properly. METHODS: We consecutively identified 154 epilepsy patients who visited the outpatient clinic at the Seoul National University Hospital. An interview was performed by two research nurses with the use of a standardized questionnaire, which included data pertaining to seizure characteristics, symptoms of depression/anxiety, social support, family life/social life satisfaction, and the activities of daily living (ADLs). The QOL was assessed with the use of QOL in Epilepsy Inventory (QOLIE-31). RESULTS: Factors affecting the QOL were: age (P<0.01), education in years (P<0.01), employment status (P<0.05), employment type (P<0.05), current economic status (P<0.05), seizure frequency (P<0.01), the number of antiepileptic drugs (P<0.01), family life/social life dissatisfaction (P<0.01, respectively), social support (P<0.01), the symptoms of anxiety and depression (P<0.01, respectively) and ADL dysfunction (P<0.01). In multiple regression analysis, the symptom of anxiety was the most important factor in explaining lower QOL in patients with epilepsy, while depression (P<0.01), social life dissatisfaction (P<0.01), ADL dysfunction (P<0.05) and seizure frequency (P<0.05) were also significant factors. CONCLUSION: Psycho-social factors outweighed the physical factors in determining QOL in Korean epilepsy patients. Recognition of these factors will lead health professionals to develop different strategies to improve the QOL of these patients.

Adult↗
PubMed2003

MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy.

OBJECTIVES: To investigate whether axonal damage in primary progressive (PP) multiple sclerosis (MS), as measured by proton magnetic resonance spectroscopy (HMRS) imaging and brain atrophy, is a function of T2 weighted brain lesion volume. METHODS: 34 PP MS patients were divided into two categories: low (<3 cm(3), n = 18) or high (>or=3 cm(3), n = 16) T2 lesion load (LL). An Index of Brain Atrophy (IBA) was calculated and HMRS metabolite ratios were derived from a central brain area centred at the corpus callosum. RESULTS: Patient groups did not differ with regard to clinical characteristics and showed lower mean IBA and mean N-acetylaspartate:creatinine (NAA:Cr) ratios compared to healthy controls. CONCLUSION: PP patients with low and high brain T2LL have detectable brain atrophy and NAA:Cr reduction compared to healthy controls. In PP MS, T2 lesions alone are insufficient to explain the presence of brain atrophy and decrease in NAA:Cr.

Aspartic Acid↗
PubMed2002

Role of the CC chemokine receptor 9/TECK interaction in apoptosis.

Chemokine receptors are members of the G protein coupled receptor (GPCR) supergene family whose expression is highly restricted to hematopoietic cells. Although the primary role of chemokine and chemokine receptor interaction is believed to be regulation of chemotaxis of leukocytes, subsequent information clearly suggests that multiple immune regulatory functions are attributed to chemokine receptor signaling. We recently showed that activation of the CC chemokine 9 receptor (CCR9), a thymus-specific chemokine receptor, led to potent cFLIP(L)-independent resistance to cycloheximide-induced apoptosis and modest resistance to Fas-mediated apoptosis possibly via activation of multiple signaling components involving Akt and glycogen synthase kinase 3beta. The fact that these two apoptotic signals involve activation of similar arrays of death execution machinery such as caspase-8, caspase-9, or caspase-3, suggests that chemokine receptor signaling may provide a wide range of antiapoptotic activities to hematopoietic cells under certain biological conditions. GPCR is a large family of cell surface receptors, many of which are critically involved in hormonal and behavioral control. Recent observations also suggest that GPCR signaling plays a pivotal role in immune cell activation. Heterotrimeric G protein is an integral part of GPCR signaling. Thus, dissection of signaling components involved in the CCR9-mediated antiapoptosis could be a framework for cell survival mechanisms and may provide options for therapeutic interventions for neurdegenerative diseases or T cell malfunctioning.

Animals↗
PubMed2001

The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.

Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.

Animals↗
PubMed2001

Bicaudal-D is essential for egg chamber formation and cytoskeletal organization in drosophila oogenesis.

Bicaudal-D (Bic-D) is required for the transport of determinant mRNAs and proteins to the presumptive oocyte, an essential step in the differentiation of the oocyte. Bic-D protein contains four well-defined heptad repeat domains characteristic of intermediate filament proteins. We characterized the ovarian phenotypes of females expressing mutant Bic-D proteins (Bic-D(H)) deleted for each of the heptad repeat domains. The altered migration of follicle cells we observe in mutant ovaries suggests that Bic-D functions in the germline and directs the inward migration of somatic follicle cells. In the germarium Bic-D is required for the organization of the egg chamber and the structural integrity of the oocyte and nurse cells. Examination of the polarized microtubule network in Bic-D(H) ovaries shows that Bic-D function is required for both the establishment of the polarized microtubule network and its maintenance throughout oogenesis. To explain the multiple functions suggested by the pleiotropic Bic-D phenotype, we propose that Bic-D protein could form itself a filamentous structure and represent an integral, essential part of the cytoskeleton.

Animals↗
PubMed2001

Protective effects of morphine in peroxynitrite-induced apoptosis of primary rat neonatal astrocytes: potential involvement of G protein and phosphatidylinositol 3-kinase (PI3 kinase).

Opiates, such as morphine, have been used extensively in the clinical management of pain due to their potent analgesic effect. Astrocytes, representing a major non-neuronal cell population in the CNS, contain opioid receptors that are actively involved in several brain functions. This study was designed to evaluate the effects by which morphine, a preferential mu-opioid receptor agonist, contributes to cytotoxicity of nitric oxide (NO) species, including NO and peroxynitrite (ONOO-), in primary rat neonatal astrocytes. Primary astrocytes isolated from the cerebral cortex of 1- to 2-day-old Sprague-Dawley rats were treated with morphine, naloxone, and 3-morpholinosydnonimine (SIN-1), a donor of peroxynitrite. Morphine significantly protected primary rat astrocytes from apoptosis mediated by sodium nitroprusside, an NO donor, and SIN-1 in a dose-dependent manner, whereas it did not in other types of cells including C6 glioma, RAW 264.7, and HL-60 cells. Moreover, naloxone antagonized the protective effects of morphine on SIN-1-induced apoptosis. Morphine also inhibited the nuclear condensation and fragmentation of SIN-1-treated cells that was antagonized by naloxone pretreatment. The protective role of morphine in SIN-1-induced apoptosis was dependent on an intracellular antioxidant system such as GSH. Furthermore, the effects of morphine on SIN-1-induced cytotoxicity were prohibited by pretreatment with the G(i) protein inhibitor, pertussis toxin, and the phosphatidylinositol 3-kinase (PI3 kinase) inhibitors, wortmannin and LY294002. Taken together, these results suggest that morphine may protect primary rat astrocytes from apoptosis by NO species via the signaling cascades that involve both G protein and PI3 kinase.

Animals↗
PubMed2001

Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel.

CV787, a PSA+ prostate cell-specific adenovirus variant, is currently in Phase I/II clinical trials for the treatment of prostate cancer. We have previously demonstrated that a single administration of CV787 at 1 x 10(11) particle/animal could eliminate established tumors within 6 weeks in nude mouse xenografts (Yu et al., Cancer Res., 59: 4200-4203, 1999). We now demonstrate that CV787-mediated replication-dependent cytotoxicity is synergistic with the chemotherapeutic agents paclitaxel (Taxol) or docetaxel (Taxotere) both in vitro and in vivo. In vitro, cells were pretreated with CV787 24 h before taxane, pretreated with taxane 24 h before CV787, or treated with both agents simultaneously. Cell viability was determined at various time points by 3-[4,5-dimethylthiazole-2-4]-2,5-diphenyl-2H-tetrazolium bromide assay, and virus yield was examined by plaque assay. Addition of taxane to CV787 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP, regardless of the timing of administration. There was no reduction in virus replication or specificity of CV787-based cytopathogenicity for prostate cancer cells (approximately 10,000 to 1) with the taxanes. p53 expression was significantly elevated in the cells treated with CV787 and taxane. In vivo, using the PSA+ LNCaP xenograft model of prostate cancer, a single i.v. dose of 1 x 10(8) particles CV787 and docetaxel in combination eliminates large preexistent distant tumors. Toxicity studies do not show a synergistic increase of toxicity of CV787 and taxane. These experiments demonstrate a synergistic antitumor efficacy for CV787 when combined with taxane and demonstrate an in vivo single-dose curative therapeutic index for CV787 of over 1000:1.

Adenoviridae↗
PubMed2001

Immunological alterations associated with Plasmodium vivax malaria in South Korea.

Various haematological and immunological studies on patients infected with Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemto-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3-/CD56+ and CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19+ lymphocytes gradually increased (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4+ appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.

Adolescent↗
PubMed2001

Retention and use of patient-centered interviewing skills after intensive training.

PURPOSE: Studies show that residents trained in patient-centered interviewing (PCI) are more effective in handling patients' emotions and are more skillful in gathering patients' data. This study evaluated the long-term use of PCI skills. METHOD: Fourteen residents received PCI training during internship, and their skills were evaluated before, immediately after, and two years after their training through directly observed patient interviews. A confidential survey evaluated the residents' actual use of PCI two years after the intensive training. Control groups of 14 interns prior to PCI training and 14 residents from another program not trained in PCI were also surveyed. RESULTS: Residents' use of PCI skills (optimization of setting, establishment of narrative thread, open-to-closed-ended questioning cone, avoid asking more than one question at a time, and (facilitation) were significantly improved, even two years after their training in PCI. The residents who received intensive block training reported using PCI techniques more frequently than did those in the control groups. However, the only significant difference in use of PCI skills between the intervention and control groups was found in reflection of patient's emotions. CONCLUSION: Medical residents retained PCI skills for two years. Further studies are needed to determine whether successful postgraduate training of physicians in PCI translates into a change in behaviors during their professional lives.

Case-Control Studies↗
PubMed2001

Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter.

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2-expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

Animals↗
PubMed2001

A multistage perceptual quality assessment for compressed digital angiogram images.

This paper describes a multistage perceptual quality assessment (MPQA) model for compressed images. The motivation for the development of a perceptual quality assessment is to measure (in)visible differences between original and processed images. The MPQA produces visible distortion maps and quantitative error measures informed by considerations of the human visual system (HVS). Original and decompressed images are decomposed into different spatial frequency bands and orientations modeling the human cortex. Contrast errors are calculated for each frequency and orientation, and masked as a function of contrast sensitivity and background uncertainty. Spatially masked contrast error measurements are then made across frequency bands and orientations to produce a single perceptual distortion visibility map (PDVM). A perceptual quality rating (PQR) is calculated from the PDVM and transformed into a one to five scale, PQR(1-5), for direct comparison with the mean opinion score, generally used in subjective ratings. The proposed MPQA model is based on existing perceptual quality assessment models, while it is differentiated by the inclusion of contrast masking as a function of background uncertainty. A pilot study of clinical experiments on wavelet-compressed digital angiogram has been performed on a sample set of angiogram images to identify diagnostically acceptable reconstruction. Our results show that the PQR(1-5) of diagnostically acceptable lossy image reconstructions have better agreement with cardiologists' responses than objective error measurement methods, such as peak signal-to-noise ratio A Perceptual thresholding and CSF-based Uniform quantization (PCU) method is also proposed using the vision models presented in this paper. The vision models are implemented in the thresholding and quantization stages of a compression algorithm and shown to produce improved compression ratio performance with less visible distortion than that of the embedded zerotrees wavelet (EZWs).

Algorithms↗
PubMed2001

In vitro generation of novel pyrimethamine resistance mutations in the Toxoplasma gondii dihydrofolate reductase.

Pyrimethamine is a potent inhibitor of dihydrofolate reductase and is widely used in the treatment of opportunistic infections caused by the protozoan parasite Toxoplasma gondii. In order to assess the potential role of dhfr sequence polymorphisms in drug treatment failures, we examined the dhfr-ts genes of representative isolates for T. gondii virulence types I, II, and III. These strains exhibit differences in their sensitivities to pyrimethamine but no differences in predicted dhfr-ts protein sequences. To assess the potential for pyrimethamine-resistant dhfr mutants to emerge, three drug-sensitive variants of the T. gondii dhfr-ts gene (the wild-type T. gondii sequence and two mutants engineered to reflect polymorphisms observed in drug-sensitive Plasmodium falciparum) were subjected to random mutagenesis and transfected into either wild-type T. gondii parasites or dhfr-deficient Saccharomyces cerevisiae under pyrimethamine selection. Three resistance mutations were identified, at amino acid residues 25 (Trp-->Arg), 98 (Leu-->Ser), and 134 (Leu-->His).

Alleles↗
PubMed2001

gly gene cloning and expression and purification of glycinecin A, a bacteriocin produced by Xanthomonas campestris pv. glycines 8ra.

Glycinecin A, a bacteriocin produced by Xanthomonas campestris pv. glycines, inhibits the growth of X. campestris pv. vesicatoria. We have cloned and expressed the genes encoding glycinecin A in Escherichia coli. Recombinant glycinecin A was purified from cell extracts by ammonium sulfate precipitation followed by chromatography on Q-Sepharose, Mono Q (ion exchange), and size exclusion columns. Purified glycinecin A is composed of two polypeptides, is active over a wide pH range (6 to 9), and is stable at temperatures up to 60 degrees C. Glycinecin A is a heterodimer consisting of 39- and 14-kDa subunits, as revealed through size exclusion chromatography and cross-linking analysis. Two genes, glyA and glyB, encoding the 39- and 14-kDa subunits, respectively, were identified based on the N-terminal sequences of the subunits. From the nucleotide sequences of glyA and glyB, we conclude that both genes are translated as bacteriocin precursors that include N-terminal leader sequences. When expressed in E. coli, recombinant glycinecin A was found primarily in cell extracts. In contrast, most glycinecin A from Xanthomonas was found in the culture media. E. coli transformed with either glyA or glyB separately did not show the bacteriocin activity.

Bacteriocins↗
PubMed2001

Denitrification in submerged biofilters of concentrated-nitrate wastewater.

To understand the possibilities and limitations of the treatment of concentrated nitrate in wastewater, a space-saving biofilm process was introduced to investigate how efficiently concentrated nitrate was utilized in a biofilm process. Lab-scale submerged biofilters stuffed with plastic pall-ring media were developed for the treatment of wastewater containing high nitrate concentration. Two identical biofilters were operated at 2 and 4 hr media HRT in parallel and the concentration of nitrate in the influent was increased stepwise from 50 to 3000 mg-N/L. The concentration of NOx in the effluent was measured at various volumetric loading rates that were proportional to influent nitrate concentrations. There was a critical point for volumetric loading rate (9 kg NO3-N/m3/day) distinguishing the biofilter performances. At the volumetric loading rate below this critical point, the effluent NOx concentration was maintained steadily in spite of the drastic change in the loading rates. However, the effluent NOx concentration severely fluctuated for the small change when the loading rate was higher than the critical point. It was found that the reactor performance was closely related with the biomass concentration (g-dw/ring) in the biofilters.

Biofilms↗
PubMed2001

Experimental and modeling evaluation of upward and downward velocities in the coaxial flotation column.

This study was conducted to show the influence of upward velocity in the inner column and downward velocity in the outer column of the coaxial cylinder-type flotation column on the solids removal efficiency, solids concentration in the treated water, and so on. The SIMPLE (Semi-Implicit Method for Pressure Linked Equation) solution was applied to the coaxial flotation column to simulate the velocity vectors of the elements of water flowing in the column. The effects of solids loading and residence time in the agglomerate separation zone on the solids removal efficiency were also tested. In the pilot scale coaxial DAF column experiments with solids concentration of 1,000-2,000 mg of SS per liter and solids loading less than 350 kg/m2/day, approximately 90% of the solids removal efficiencies were obtained using the upward velocity of up to 110 cm/min in the contact zone of the inner column and the downward velocity of up to 30 cm/min in the outer column. In the simulation, similar results were observed as in the experiments. The solids loading in the excess of 350 kg/m2/day caused the instability of the sludge float layer and aggravated the quality of the treated water.

Air↗