Biomedical subjects

S Y Kim

Publications and source records attributed to S Y Kim.

At least 73 records · Page 4Linked to original sources

PubMed2001

Dual role of inflammatory stimuli in activation-induced cell death of mouse microglial cells. Initiation of two separate apoptotic pathways via induction of interferon regulatory factor-1 and caspase-11.

We have previously shown that mouse microglial cells undergo apoptosis upon inflammatory activation and that nitric oxide (NO) is the major autocrine mediator in this process (Lee, P., Lee, J., Kim, S., Yagita, H., Lee, M. S., Kim, S. Y., Kim, H., and Suk, K. (2001) Brain Res. 892, 380-385). Here, we present evidence that interferon regulatory factor-1 (IRF-1) and caspase-11 are the essential molecules in activation-induced cell death of microglial cells. The apoptogenic action of inflammatory stimuli such as lipopolysaccharide (LPS) and interferon-gamma (IFNgamma) was mediated through the induction of IRF-1 and caspase-11 expression in two separate events. Although IRF-1 was required for NO synthesis, caspase-11 induction was necessary for NO-independent apoptotic pathway. Microglial cells from IRF-1-deficient mice showed markedly decreased NO production, and they were partially resistant to apoptosis in response to LPS/IFNgamma but were sensitive to NO donor exposure. LPS/IFNgamma treatment resulted in the induction of caspase-11 followed by activation of caspase-11, -1, and -3. Inactivation of caspase-11 by the transfection of dominant-negative mutant or treatment with the caspase inhibitors rendered microglial cells partially resistant to LPS/IFNgamma-induced apoptosis. Inhibition of both NO synthesis and caspase-11 completely blocked LPS/IFNgamma-induced cytotoxicity. These results indicated that LPS/IFNgamma not only induced the production of cytotoxic NO through IRF-1 but also initiated the NO-independent apoptotic pathway through the induction of caspase-11 expression.

Animals↗

PubMed2001

Density of states, Potts zeros, and Fisher zeros of the Q-state Potts model for continuous Q.

The Q-state Potts model can be extended to noninteger and even complex Q by expressing the partition function in the Fortuin-Kasteleyn (F-K) representation. In the F-K representation the partition function Z(Q,a) is a polynomial in Q and v=a-1 (a=e(betaJ)) and the coefficients of this polynomial, Phi(b,c), are the number of graphs on the lattice consisting of b bonds and c connected clusters. We introduce the random-cluster transfer matrix to compute Phi(b,c) exactly on finite square lattices with several types of boundary conditions. Given the F-K representation of the partition function we begin by studying the critical Potts model Z(CP)=Z(Q,a(c)(Q)), where a(c)(Q)=1+square root[Q]. We find a set of zeros in the complex w=square root[Q] plane that map to (or close to) the Beraha numbers for real positive Q. We also identify Q(c)(L), the value of Q for a lattice of width L above which the locus of zeros in the complex p=v/square root[Q] plane lies on the unit circle. By finite-size scaling we find that 1/Q(c)(L)-->0 as L-->infinity. We then study zeros of the antiferromagnetic (AF) Potts model in the complex Q plane and determine Q(c)(a), the largest value of Q for a fixed value of a below which there is AF order. We find excellent agreement with Baxter's conjecture Q(AF)(c)(a)=(1-a)(a+3). We also investigate the locus of zeros of the ferromagnetic Potts model in the complex Q plane and confirm that Q(FM)(c)(a)=(a-1)(2). We show that the edge singularity in the complex Q plane approaches Q(c) as Q(c)(L) approximately Q(c)+AL(-y(q)), and determine the scaling exponent y(q) for several values of Q. Finally, by finite-size scaling of the Fisher zeros near the antiferromagnetic critical point we determine the thermal exponent y(t) as a function of Q in the range 2</=Q</=3. Using data for lattices of size 3</=L</=8 we find that y(t) is a smooth function of Q and is well fitted by y(t)=(1+Au+Bu2)/(C+Du) where u=-(2/pi)cos(-1)(squareroot[Q]/2). For Q=3 we find y(t) approximately 0.6; however if we include lattices up to L=12 we find y(t) approximately 0.50(8) in rough agreement with a recent result of Ferreira and Sokal [J. Stat. Phys. 96, 461 (1999)].

Journal Article↗

PubMed2001

Protective role of superoxide dismutases against ionizing radiation in yeast.

The protective role of superoxide dismutases (SODs) against ionizing radiation, which generates reactive oxygen species (ROS) harmful to cellular function, was investigated in the wild-type and in mutant yeast strains lacking cytosolic CuZnSOD (sod1Delta), mitochondrial MnSOD (sod2Delta), or both SODs (sod1Deltasod2Delta). Upon exposure to ionizing radiation, there was a distinct difference between these strains in regard to viability and the level of protein carbonyl content, which is the indicative marker of oxidative damage to protein, intracellular H2O2 level, as well as lipid peroxidation. When the oxidation of 2',7'-dichlorofluorescin was used to examine the hydroperoxide production in yeast cells, the SOD mutants showed a higher degree of increase in fluorescence upon exposure to ionizing radiation as compared to wild-type cells. These results indicated that mutants deleted for SOD genes were more sensitive to ionizing radiation than isogenic wild-type cells. Induction and inactivation of other antioxidant enzymes, such as catalase, glucose 6-phosphate dehydrogenase, and glutathione reductase, were observed after their exposure to ionizing radiation both in wild-type and in mutant cells. However, wild-type cells maintained significantly higher activities of antioxidant enzymes than did mutant cells. These results suggest that both CuZnSOD and MnSOD may play a central role in protecting cells against ionizing radiation through the removal of ROS, as well as in the protection of antioxidant enzymes.

Catalase↗

PubMed2001

Morphology of calretinin and tyrosine hydroxylase-immunoreactive neurons in the pig retina.

The morphology of calretinin- and tyrosine hydroxylase-immunoreactive (IR) neurons in adult pig retina was studied. These neurons were identified using antibody immunocytochemistry. Calretinin immunoreactivity was found in numerous cell bodies in the ganglion cell layer. Large ganglion cells, however, were not labeled. In the inner nuclear layer, the regular distribution of calretinin-IR neurons, the inner marginal location of their cell bodies in the inner nuclear layer, and the distinctive bilaminar morphologies of their dendritic arbors in the inner plexiform layer suggested that these calretinin-IR cells were AII amacrine cells. Calretinin immunoreactivity was observed in both A-and B-type horizontal cells. Neurons in the photoreceptor cell layer were not labeled by this antibody. The great majority of tyrosine hydroxylase-IR neurons were located at the innermost border of the inner nuclear layer (conventional amacrines). The processes were monostratified and ran laterally within layer 1 of the inner plexiform layer. Some of the tyrosine hydroxylase-IR neurons were located in the ganglion cell layer (displaced amacrines). The processes of displaced tyrosine hydroxylase-IR amacrine cells were also located within layer 1 of the inner plexiform layer. Some processes of a few neurons were located in the outer plexiform layer. A very low density of neurons had additional bands of tyrosine hydroxylase-IR processes in the middle and deep layers of the inner plexiform layer. The processes of tyrosine hydroxylase-IR neurons extended radially over a wide area and formed large, moderately branched dendritic fields. These processes occasionally had varicosities and formed "dendritic rings". These results indicate that calretinin- and tyrosine hydroxylase-IR neurons represent specific neuronal cell types in the pig retina.

Animals↗

PubMed2001

An improved strategy for a genetic assay for site-specific proteolysis.

We have previously reported a genetic assay that is suitable for the study of substrate specificity of a protease in vivo, and herein present a simplified version of the method. In this procedure, expressed in Saccharomyces cerevisiae by using the constitutive alcohol dehydrogenase promoter is a fusion protein in which a transcription factor is linked to the intracellular domain of an integral membrane protein by a protease substrate sequence. Following this, a protease is expressed by using the inducible GAL promoter in the same yeast cells. The cleavage of the substrate sequence by the specific protease results in the release of the transcription factor and subsequent activation of reporter genes in nucleus. Since the expression of a protease is strictly under the control of the inducible GAL promoter, false substrate sequences that are cleaved by endogenous yeast proteases can be easily recognized and eliminated from further characterization. This suggests that the modified strategy provides an efficient tool for the analysis of substrate sequences of a protease in vivo.

Endopeptidases↗

PubMed2001

Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.

The structure activity relationship on a series of ester and hydroxamate analogues of methionyl and isoleucyl adenylate has been investigated through introducing linkers between the 1'-position of ribose and adenine surrogates as methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The results indicate that ester analogue 23 was found to be a potent inhibitor of Escherichia coli methionyl-tRNA synthetase, and its interaction with the active site was proposed by a molecular modeling study.

Adenosine↗

PubMed2001

Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.

As aminoacyl adenylate surrogates, a series of methionyl and isoleucyl phenolic analogues containing bioisosteric linkers mimicking ribose have been investigated. Inhibition of synthesized compounds to the aminoacylation reaction by the corresponding Escherichia coli methionyl-tRNA and isoleucyl-tRNA synthetases indicated that 18 was found to be a potent inhibitor of isoleucyl-tRNA synthetase. A molecular modeling study demonstrated that in 18, isovanillate and hydroxamate served as proper surrogates for adenine and ribose in isoleucyl adenylate, respectively.

Adenine↗

PubMed2001

Cloning and characterization of the Hansenula polymorpha homologue of the Saccharomyces cerevisiae MNN9 gene.

A gene homologous to Saccharomyces cerevisiae MNN9 has been cloned and characterized in the methylotrophic yeast Hansenula polymorpha. This gene was cloned from a H. polymorpha genomic DNA library using the S. cerevisiae MNN9 gene as a probe. The H. polymorpha MNN9 homologue (HpMNN9) contained a 1062 bp open reading frame encoding a predicted protein of 354 amino acids. The deduced amino acid sequence showed 58% and 51% identity, respectively, with the S. cerevisiae and Candida albicans Mnn9 proteins. Disruption of HpMNN9 leads to phenotypic effects suggestive of cell wall defects, including detergent sensitivity and hygromycin B sensitivity. The hygromycin B sensitivity of S. cerevisiae mnn9 null mutant was complemented in the presence of the HpMNN9 gene. The DNA sequence of the H. polymorpha homologue has been submitted to GenBank with the Accession No. AF264786.

Amino Acid Sequence↗

PubMed2001

Effect of total sleep deprivation on the dimensional complexity of the waking EEG.

STUDY OBJECTIVES: Sleep deprivation can affect the waking EEG that may reflect information processing of the brain. We examined the effect of total sleep deprivation (TSD) on nonlinear dynamics of the waking EEG. DESIGN: Paired-group design. SETTING: A sleep disorders laboratory in a hospital. PARTICIPANTS: Twenty healthy male volunteers. INTERVENTIONS: Waking EEG data were recorded from subjects with eyes closed after (a) an 8-hour night's sleep and (b) TSD for 24 hours. The dimensional complexity (D2), as a nonlinear measure of complexity, of the EEG after a full night sleep were compared with those of the EEG after TSD. MEASUREMENTS AND RESULTS: The sleep-deprived states had lower D2 values at three channels (P4, O2, and C3) than normal states. CONCLUSIONS: TSD results in the decrease of complexity in the brain, which may imply sub-optimal information processing of the cerebral cortex. We suggest that the investigation of the relation between nonlinear dynamics of the waking EEG induced by TSD and cognitive performance may offer fruitful clues for understanding the role of sleep and the effects of sleep deprivation on brain function.

Adult↗

PubMed2001

Long-term delivery of all-trans-retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres.

All-trans-retinoic acid (atRA) has been proved to be effective against several malignancies in human clinical trials. However, in many patients who were treated with atRA, the cancer relapsed after a brief remission. One reason for such relapse is that atRA is metabolized by specific P450s that are induced in the liver during prolonged atRA treatments. In order to overcome such a drawback of atRA, we prepared biodegradable microspheres to provide continuous release of atRA for a long period of time. These biodegradable microspheres were prepared by poly(L-lactide) (PLLA) and polyethylene glycol (PEG)-PLLA diblock copolymers (PLE) in various blending ratios to control the release rate of atRA. As the PLE content in microsphere was increased, the density of the hydrophilic PEG block of PLE on microsphere surfaces increased and the microspheres were dispersed well in PBS without any surfactants. Various release patterns of atRA were obtained according to PLE and atRA contents in the microspheres. Especially, the pseudo-zero-order release profiles were observed for 5 weeks when the contents of PLE and atRA in the microspheres were above 4 wt.%.

Excipients↗

PubMed2001

Baryon rapidity loss in relativistic Au + Au collisions.

An excitation function of proton rapidity distributions for different centralities is reported from AGS Experiment E917 for Au+Au collisions at 6, 8, and 10.8 GeV/nucleon. The rapidity distributions from peripheral collisions have a valley at midrapidity which smoothly change to distributions that display a broad peak at midrapidity for central collisions. The mean rapidity loss increases with increasing beam energy, whereas the fraction of protons consistent with isotropic emission from a stationary source at midrapidity decreases with increasing beam energy. The data suggest that the stopping is substantially less than complete at these energies.

Journal Article↗

PubMed2001

Bicritical scaling behavior in unidirectionally coupled oscillators.

We study the scaling behavior of period doublings in a system of two unidirectionally coupled parametrically forced pendulums near a bicritical point where two critical lines of period-doubling transition to chaos in both subsystems meet. When crossing a bicritical point, a hyperchaotic attractor with two positive Lyapunov exponents appears, i.e., a transition to hyperchaos occurs. Varying the control parameters of the two subsystems, the unidirectionally coupled parametrically forced pendulums exhibit multiple period-doubling transitions to hyperchaos. For each transition to hyperchaos, using both a "residue-matching" renormalization group method and a direct numerical method, we make an analysis of the bicritical scaling behavior. It is thus found that the second response subsystem exhibits a new type of non-Feigenbaum scaling behavior, while the first drive subsystem is in the usual Feigenbaum critical state. The universality of the bicriticality is also examined for several different types of unidirectional couplings.

Journal Article↗

PubMed2001

NO as an autocrine mediator in the apoptosis of activated microglial cells: correlation between activation and apoptosis of microglial cells.

Abnormal activation of microglial cells has been implicated in various neurodegenerative diseases. Microglial activation needs to be tightly regulated for physiological maintenance and normal functioning of the central nervous system. Potential mechanisms for the down-regulation of activated microglial cells are the deactivation or elimination of activated cells. We hypothesized that the elimination of activated microglial cells by apoptosis is one of the key mechanisms of auto-regulation of activated microglial cells. To test this hypothesis, we utilized BV-2 mouse microglial cells and rat primary microglial cultures exposed to activating agents such as lipopolysaccharide and interferon-gamma, and investigated a possible correlation between apoptosis and activation of these cells. We found that the activation of microglial cells led to apoptotic death, and the activation state of microglial cells inversely correlated with cell viability. We have also demonstrated that: (i) NO was produced by activated microglial cells in a manner dependent on time and dose of activating agents; (ii) inhibition of NO synthesis by iNOS inhibitor blocked the apoptosis of activated microglial cells; (iii) an exogenous NO donor induced apoptosis of microglial cells; and (iv) inhibition of TNFalpha or FasL using neutralizing antibodies did not affect activation-induced apoptosis of microglial cells. These results indicated that activation of microglial cells leads to the production of NO, which in turn acts as the major mediator of cellular apoptosis in an autocrine fashion. Our work suggests the presence of auto-regulatory mechanism for microglial activation, which may have relevance in the pathogenesis of various neurodegenerative diseases possibly resulting from 'over-activation' of microglial cells.

Animals↗

PubMed2001

Association of alpha-2-macroglobulin deletion polymorphism with sporadic Alzheimer's disease in Koreans.

Alpha-2-macroglobulin (A2M) deletion polymorphism was recently reported to be associated with Alzheimer's disease (AD) in a way comparable to apolipoprotein E (APOE) polymorphism in a family-based study. However, the association of A2M deletion polymorphism with AD has not been consistently replicated in successive case-controlled studies. In order to evaluate whether this A2M polymorphism is associated with AD in Koreans, we examined the frequencies of the A2M deletion (D) allele and D-bearing genotypes in a group of Koreans composed of 100 sporadic AD patients and 203 control subjects. The frequency of the deletion (D) allele (P=0.046) was significantly different between the total group of AD patients and the controls, although the frequency of the D-bearing genotypes did not attain significance (P=0.078). When the subjects were stratified according to age at onset, there was significant difference in the frequencies of the D allele (P=0.044) and D-bearing genotypes (P=0.041) between late-onset AD patients (> or =65 years) and the controls. However, no significant difference was observed between early-onset AD patients (<65 years) and the control group. Additionally, when we divided the late-onset AD and control subjects by APOE epsilon4 status, the difference of the A2M D allelic frequency was significant only in the APOE epsilon4 negative subjects (P=0.015). In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects.

Aged↗

PubMed2001

Mechanism for the riddling transition in coupled chaotic systems.

We investigate the loss of chaos synchronization in coupled chaotic systems without symmetry from the point of view of bifurcations of unstable periodic orbits embedded in the synchronous chaotic attractor (SCA). A mechanism for direct transition to global riddling through a transcritical contact bifurcation between a periodic saddle embedded in the SCA and a repeller on the boundary of its basin of attraction is thus found. Note that this bifurcation mechanism is different from that in coupled chaotic systems with symmetry. After such a riddling transition, the basin becomes globally riddled with a dense set of repelling tongues leading to divergent orbits. This riddled basin is also characterized by divergence and uncertainty exponents, and thus typical power-law scaling is found.

Journal Article↗

PubMed2001

Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma.

Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.

Humans↗

PubMed2001

Somatic mutations in the death domain of the Fas (Apo-1/CD95) gene in gastric cancer.

It is now believed that genes regulating apoptosis are also important variables in cancer development. Fas, a transmembrane protein of the tumour necrosis factor receptor family, is a key molecule for cell death signalling. The mutation of the primary structure of the Fas gene might also be one of the possible mechanisms that disrupt Fas-mediated apoptosis in tumour cells. The purpose of this study was to determine whether somatic mutation of the Fas gene could be involved in the tumourigenesis of gastric cancer. Polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) analysis with two intragenic polymorphic markers, and mutation analysis for the entire coding regions of the Fas gene were performed in 43 cases of gastric cancer, using PCR-single-strand conformational polymorphism sequencing. Five (11.6%) missense mutations were detected, only in the death domain of the Fas gene. Although these mutations were observed only in intestinal-type gastric cancers, there was no statistically significant difference in the frequency of Fas mutation between intestinal- and diffuse-type gastric cancer (p=0.068). Nine LOH out of 22 informative cases were also detected with one or both markers (41%). Three of them demonstrated a somatic mutation in the remaining allele, indicating the inactivation of both alleles. These results suggest that genetic alterations of the Fas gene may not only be limited to gastric cancer cell protection through Fas resistance, but may also play an important role in tumour promotion and/or progression in a subset of gastric cancer.

Adenocarcinoma↗

PubMed2001

Nuclear localization of beta-catenin is an important prognostic factor in hepatoblastoma.

In this study, mutational and immunohistochemical analyses of beta-catenin were performed in 30 hepatoblastomas, to assess the prevalence of alterations of the Wnt pathway with respect to clinicopathological parameters and survival. Four missense mutations of beta-catenin (13.3%) were detected and there was strong immunoreactivity for beta-catenin in the cytoplasm and/or the nucleus in 97% of hepatoblastomas. Nuclear and cytoplasmic staining was demonstrated in 19 of 30 tumours (63%), while ten revealed only cytoplasmic staining. Statistically, this nuclear beta-catenin staining was significantly higher in the embryonal (Fisher exact test; p=0.00393) or undifferentiated type (p=0.00156) of hepatoblastoma than in the fetal type, but there was no difference between clinical stages I and II and clinical stages III and IV (p=0.175). Cumulative survival curves showed that nuclear beta-catenin staining (generalized Wilcoxon test; p=0.0088), undifferentiated histological type (p=0.0305), and clinical stages III and IV (p=0.0107) were significantly correlated with shorter survival time in these patients. Moreover, Cox multivariate analysis provides evidence that nuclear beta-catenin staining is the most important prognostic factor for survival (p=0.0090). It is therefore concluded that immunohistochemical analysis of beta-catenin might be a useful clinical tool for estimating the prognosis for patients with hepatoblastoma.

Biomarkers, Tumor↗