Showing papers by "Pusan National University published in 2000"

Pandemic Spread of an O3:K6 Clone of Vibrio parahaemolyticus and Emergence of Related Strains Evidenced by Arbitrarily Primed PCR and toxRS Sequence Analyses

Abstract: Some strains of Vibrio parahaemolyticus, a marine bacterium, can cause gastroenteritis in humans through consumption of seafood. It was reported in the late 1960s that almost all clinical strains, but very few environmental strains, manifest Kanagawa phenomenon (KP), β-type hemolysis on Wagatsuma agar (8, 19). KP is caused by high-level production of thermostable direct hemolysin. Thermostable direct hemolysin is encoded by the tdh gene (13, 17), which was detected almost exclusively in clinical strains in an early study (11). The role of thermostable direct hemolysin in enterotoxigenicity was demonstrated by construction and examination of the tdh-deficient mutant of a KP-positive strain (10). Investigation of an outbreak in the Maldives in 1985 revealed that some clinical strains do not possess the tdh gene but carry the tdh-related hemolysin (trh) gene (14). The trh sequence was approximately 70% identical to the tdh sequence. There is much greater strain-to-strain divergence among trh sequences than among tdh sequences. The trh sequences in different strains, however, can be clustered into two groups represented by the trh1 and trh2 genes, which have 84% sequence identity (5). Strains possessing either the tdh gene, the trh gene, or both were shown to be strongly associated with gastroenteritis (5, 20). Surveillance for V. parahaemolyticus infection was initiated in January 1994 in Calcutta, India. A group of strains belonging to serovar O3:K6 and possessing the tdh gene but not the trh gene appeared suddenly in February 1996 and was shown to be responsible for the high incidence of V. parahaemolyticus infection since then in Calcutta (16). Serovar O3:K6 was not isolated before February 1996 in Calcutta. In addition, the O3:K6 strains isolated in Calcutta were shown to exhibit unique profiles in an arbitrarily primed PCR (AP-PCR) analysis (16). Strains belonging to the same group, i.e., O3:K6 strains possessing the tdh gene but not the trh gene and showing the unique AP-PCR profiles, were also detected among those isolated from travelers arriving in Japan from Southeast Asian countries from 1995 on (16). Thus, the Calcutta O3:K6 strains and the above strains from the travelers were considered to belong to a single clone (16). These results suggested that this unique clone, referred to below as a new O3:K6 clone, might have emerged recently and become prevalent not only in Calcutta, India, but also in other parts of the world. We examined this hypothesis, and we present evidence in this study for the first pandemicity in the history of V. parahaemolyticus. Clinical strains isolated over 22 years, starting from 1977, in a hospital in Bangladesh were available. The emergence of the new O3:K6 clone in 1996 but not earlier was demonstrated by examination of these strains. Next, we showed by AP-PCR analysis that the clinical strains of serovar O3:K6 isolated in six other countries, including the United States, from 1997 on belong to the same clone. We then developed a novel PCR method to identify the strains belonging to the new O3:K6 clone. We utilized the toxRS operon sequence to develop this PCR method. The toxR and toxS genes in the toxRS operon encode transmembrane proteins involved in the regulation of virulence-associated genes and are well conserved in the genus Vibrio (3, 7, 18; J. H. Rhee, S. E. Lee, S. Y. Kim, S. H. Shin, C. M. Kim, P. Y. Ryu, K. C. Leong, S. H. Choi, and S. S. Chung, Abstr. 98th Gen. Meet. Am. Soc. Microbiol., abstr. B-171, p. 84, 1998; V. Vuddhakul, T. Nakai, C. Matsumoto, T. Oh, T. Nishino, M. Nishibuchi, and J. Okuda, submitted for publication). We used the intraspecies variation of the toxRS sequence to develop a cluster-specific PCR method that allowed for confirmation of the clonality of the new O3:K6 strains. By using this PCR method in our investigation, we found emerging strains that were almost indistinguishable from the new O3:K6 clone, although the strains belonged to different serovars.

Properties of Cosmic Shock Waves in Large-Scale Structure Formation

Abstract: We have examined the properties of shock waves in simulations of large-scale structure formation. Two cosmological scenarios have been considered: a standard cold dark matter model with ΩM = 1 (SCDM), and a cold dark matter model with cosmological constant and ΩM + ΩΛ = 1 (ΛCDM) having ΩΛ = 0.55. Large-scale shocks result from accretion onto sheets, filaments, and knots of mass distribution on a scale of the order of ~5 h-1 Mpc in both scenarios. Energetic motions, partly residuals of past accretion processes and partly caused by current asymmetric inflow along filaments, end up generating additional shocks. These extend on a scale of the order of ~1 h-1 Mpc and envelop and penetrate deep inside the clusters. Collisions between substructures inside clusters also form merger shocks. Consequently, the topology of the shocks is very complex and highly connected. During cosmic evolution the comoving shock surface density decreases, reflecting the ongoing structure merger process in both scenarios. Accretion shocks have very high Mach numbers, typically between 10 and a few ×103, when photoheating of the preshock gas is not included. The characteristic shock velocity is of the order of vsh(z) = H(z)λnl(z), where λnl(z) is the wavelength scale of the nonlinear perturbation at the given epoch. However, the Mach number for merger and flow shocks (which occur within clusters) is usually smaller, in the range of ~3-10, corresponding to the fact that the intracluster gas is hot (i.e., already shock heated). Statistical fits of shock velocities around clusters as a function of cluster temperature give power-law functions in accord with those predicted by one-dimensional solutions. On the other hand, a very different result is obtained for the shock radius, reflecting extremely complex shock structures surrounding clusters of galaxies in three-dimensional simulations. The amount of inflowing kinetic energy across the shocks around clusters, which represents the power available for cosmic-ray acceleration, is comparable to the cluster X-ray luminosity emitted from a central region of radius 0.5 h-1 Mpc. Considering their large size and long lifetimes, those shocks are potentially interesting sites for cosmic-ray acceleration, if modest magnetic fields exist within them.

Interaction of the Postsynaptic Density-95/Guanylate Kinase Domain-Associated Protein Complex with a Light Chain of Myosin-V and Dynein

Abstract: NMDA receptors interact directly with postsynaptic density-95 (PSD-95), a scaffold protein that organizes a cytoskeletal- signaling complex at the postsynaptic membrane. The molecular mechanism by which the PSD-95-based protein complex is trafficked to the postsynaptic site is unknown but presumably involves specific motor proteins. Here we demonstrate a direct interaction between the PSD-95-associated protein guanylate kinase domain-associated protein (GKAP) and dynein light chain (DLC), a light chain subunit shared by myosin-V (an actin-based motor) and cytoplasmic dynein (a microtubule-based motor). A yeast two-hybrid screen with GKAP isolated DLC2, a novel protein 93% identical to the previously cloned 8 kDa dynein light chain (DLC1). A complex containing PSD-95, GKAP, DLC, and myosin-V can be immunoprecipitated from rat brain extracts. DLC colocalizes with PSD-95 and F-actin in dendritic spines of cultured neurons and is enriched in biochemical purifications of PSD. Immunogold electron microscopy reveals a concentration of DLC in the postsynaptic compartment of asymmetric synapses of brain in which it is associated with the PSD and the spine apparatus. We discuss the possibility that the GKAP/DLC interaction may be involved in trafficking of the PSD-95 complex by motor proteins.

A new approach for minimum-torque-ripple maximum-efficiency control of BLDC motor

Abstract: Torque-ripple control of the brushless DC motor has been the main issue of the servo drive systems in which the speed fluctuation, vibration, and acoustic noise should be minimized. Most methods for suppressing the torque ripples require Fourier series analysis and either iterative or least-mean-square minimization. In this paper, a novel approach to achieve ripple-free torque control with maximum efficiency based on the d-q-0 reference frame is presented. The proposed method optimizes the reference phase current waveforms which include the case of three-phase unbalanced conditions. As a result, the proposed approach provides a simple way to obtain optimal motor excitation currents. The validity and practical applications of the proposed control scheme are verified through the simulations and experimental results.

Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study.

Abstract: Study design: Construction of an international walking scale by a modified Delphi technique. Objective: The purpose of the study was to develop a more precise walking scale for use in clinical trials of subjects with spinal cord injury (SCI) and to determine its validity and reliability. Setting: Eight SCI centers in Australia, Brazil, Canada (2), Korea, Italy, the UK and the US. Methods: Original items were constructed by experts at two SCI centers (Italy and the US) and blindly ranked in an hierarchical order (pilot data). These items were compared to the Functional Independence Measure (FIM) for concurrent validity. Subsequent independent blind rank ordering of items was completed at all eight centers (24 individuals and eight teams). Final consensus on rank ordering was reached during an international meeting (face validation). A videotape comprised of 40 clips of patients walking was forwarded to all eight centers and inter-rater reliability data collected. Results: Kendall coeAcient of concordance for the pilot data was significant (W=0.843, P50.001) indicating agreement among the experts in rank ordering of original items. FIM comparison (Spearman’s rank correlation coeAcient=0.765, P50.001) showed a theoretical relationship, however a practical diAerence in what is measured by each scale. Kendall coeAcient of concordance for the international blind hierarchical ranking showed significance (W=0.860, P50.001) indicating agreement in rank ordering across all eight centers. Group consensus meeting resulted in a 19 item hierarchical rank ordered ‘Walking Index for Spinal Cord Injury (WISCI)’. Inter-rater reliability scoring of the 40 video clips showed 100% agreement. Conclusions: This is the first time a walking scale for SCI of this complexity has been developed and judged by an international group of experts. The WISCI showed good validity and reliability, but needs to be assessed in clinical settings for responsiveness. Spinal Cord (2000) 38, 234‐243

Narrowband to wideband conversion of speech using GMM based transformation

Abstract: Reconstruction of wideband speech from its narrowband version is an attractive issue, since it can enhance the speech quality without modifying the existing communication networks. This paper proposes a new recovery method of wideband speech from narrowband speech. In the proposed method, the narrowband spectral envelope of input speech is transformed to a wideband spectral envelope based on the Gaussian mixture model (GMM), whose parameters are calculated by a joint density estimation technique. Then the lowband and highband speech signal is reconstructed by the LPC synthesizer using the reconstructed spectral envelope. This paper also proposes a codeword-dependent power estimation method. Both the objective and subjective test results shows that the proposed algorithm outperforms the conventional codebook mapping method.

Hypoxia-induced VEGF enhances tumor survivability via suppression of serum deprivation-induced apoptosis

Abstract: Low oxygen and nutrient depletion play critical roles in tumorigenesis, but little is known about how they interact to produce tumor survival and tumor malignancy. In the present study, we investigated the mechanism underlying hypoxia-modulated apoptosis of serum-deprived HepG2 cells. Our results showed that hypoxia blocked the apoptosis, which was accompanied with decreased Bax/Bcl-2 ratio, inhibited cytochrome c release, and reduced caspase-3 activity. More importantly, increased expressions of VEGF and its receptor-2 (KDR) under hypoxic/serum-deprived condition suggest that VEGF may act as a survival factor in a self-promoting manner. Data were further supported by results that recombinant human VEGF (rhVEGF) suppressed the serum deprivation-induced apoptosis, and anti-VEGF neutralizing antibody block anti-apoptotic activity of hypoxia. In addition, inhibitors of receptor tyrosine kinase blocked anti-apoptosis of hypoxia. Our study further showed that rhVEGF or hypoxia induced ERK phosphorylation in serum-deprived cells, and that a specific inhibitor of MAPK/ERK, PD98059 eliminated the anti-apoptotic activity of rhVEGF or hypoxia by increasing Bax/Bcl-2 ratio and caspase-3 activity. Our data led us to conclude that induction of ERK phosphorylation and decrease of Bax/Bcl-2 ratio by rhVEGF implies that hypoxia-induced VEGF prevents apoptosis of serum-deprived cells by activating the MAPK/ERK pathway. Taken together, we propose that hypoxia enhances survival of nutrient-depleted tumor cells by reducing susceptibility to apoptosis, which consequently leads to tumor malignancy.

Cogging torque and acoustic noise reduction in permanent magnet motors by teeth pairing

Abstract: This paper investigates reduction of cogging torque and acoustic noise in permanent magnet motors with larger stator slot opening. Using an energy method with Fourier series expansion, cogging torque is analytically determined with airgap MMF function and airgap permeance function. It shows that there exist several tooth widths which minimize the cogging torque. It also proposes a teeth pairing with two different types of tooth width which can effectively reduce the cogging torque and thus the acoustic noise. Experimental results show that the proposed teeth pairing reduces the cogging torque by 85% and the acoustic noise by 3.1 dB.

Optical and electrical properties of some electron and proton irradiated polymers

Abstract: Ion beam treatment studies have been carried out to investigate the potential for improvements in conductivity properties of the polymers Polytetrafluroethylene (PTFE), Polyimide (PI), Polyethyleneterepthalate (PET) and Polypropylene (PP), after 2 MeV electron and 62 MeV proton irradiation. The shift in optical absorption edges as observed by UV–VIS spectra of the irradiated polymers has been correlated to the optical band-gap using Tauc’s expression. A decrease in the optical band-gap has been observed in irradiated PP and PTFE, but no considerable change was found for the optical band-gaps of PET and PI. Further AC conductivity measurements confirmed an increase in conductivity in electron irradiated PP.

An Investigation of the Initial Voluntary Environmental Disclosures Made in Korean Semi-Annual Financial Reports

Abstract: In 1997, a group of Korean companies listed on the Korean Stock Exchange disclosed environmental information in their 1997 semi-annual financial reports, which was the first incidence of corporate social and environmental disclosure made in financial reports in Korea. The purpose of this study is to examine these initial environmental disclosures in terms of their quality and quantity and to test for possible relationships between the propensity to disclose and a variety of corporate characteristics. Content analysis is conducted to evaluate the overall standards of disclosure and then a variety of association tests are performed to determine whether the propensity to disclose is associated with selected corporate characteristics. Using a sample of disclosing and non-disclosing firms, I find that industry type and firm size are significantly associated with the propensity to disclose. When the analysis is confined within the discloser group only, financial leverage emerges as a significant explanatory variable for the level of disclosure especially in high-profile industries.

A masquerade-like serine proteinase homologue is necessary for phenoloxidase activity in the coleopteran insect, Holotrichia diomphalia larvae

Abstract: Previously, we reported the molecular cloning of cDNA for the prophenoloxidase activating factor-I (PPAF-I) that encoded a member of the serine proteinase group with a disulfide-knotted motif at the N-terminus and a trypsin-like catalytic domain at the C-terminus [Lee, S.Y., Cho, M.Y., Hyun, J.H., Lee, K.M., Homma, K.I., Natori, S., Kawabata, S.I., Iwanaga, S. & Lee, B.L. (1998) Eur. J. Biochem. 257, 615–621]. PPAF-I is directly involved in the activation of pro-phenoloxidase (pro-PO) by limited proteolysis and the overall structure is highly similar to that of Drosophila easter serine protease, an essential serine protease zymogen for pattern formation in normal embryonic development. Here, we report purification and molecular cloning of cDNA for another 45-kDa novel PPAF from the hemocyte lysate of Holotrichia diomphalia larvae. The gene encodes a serine proteinase homologue consisting of 415 amino-acid residues with a molecular mass of 45 256 Da. The overall structure of the 45-kDa protein is similar to that of masquerade, a serine proteinase homologue expressed during embryogenesis, larval, and pupal development in Drosophila melanogaster. The 45-kDa protein contained a trypsin-like serine proteinase domain at the C-terminus, except for the substitution of Ser of the active site triad to Gly and had a disulfide-knotted domain at the N-terminus. A highly similar 45-kDa serine proteinase homologue was also cloned from the larval cDNA library of another coleopteran, Tenebrio molitor. By in vitro reconstitution experiments, we found that the purified 45-kDa serine proteinase homologue, the purified active PPAF-I and the purified pro-PO were necessary for expressing phenoloxidase activity in the Holotrichia pro-PO system. However, incubation of pro-PO with either PPAF-I or 45-kDa protein, no phenoloxidase activity was observed. Interestingly, when the 45-kDa protein was incubated with PPAF-I and pro-PO in the absence, but not in the presence of Ca2+, the 45-kDa protein was cleaved to a 35-kDa protein. RNA blot hybridization revealed that expression of the 45-kDa protein was increased in the Holotrichia hemolymph after Escherichia coli challenge.

p53‐independent Induction of p21 (WAF1/CIP1), Reduction of Cyclin B1 and G2/M Arrest by the Isoflavone Genistein in Human Prostate Carcinoma Cells

Abstract: Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase II activities. Genistein has been shown to have anticancer proliferation, differentiation and chemopreventive effects. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of p53-null human prostate carcinoma cells. Genistein significantly inhibited the cell growth, which effect was reversible, and induced dendrite-like structure. The inhibitory effects of genistein on cell growth proliferation were associated with a G2/M arrest in cell cycle progression concomitant with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 (WAF1/CIP1) in a p53-independent manner. Following genistein treatment of cells, an increased binding of p21 with Cdk2 and Cdc2 paralleled a significant decrease in Cdc2 and Cdk2 kinase activity with no change in Cdk2 and Cdc2 expression. Genistein also induced the activation of a p21 promoter reporter construct, utilizing a sequence distinct from the p53-binding site. Analysis of deletion constructs of the p21 promoter indicated that the response to genistein could be localized to the 300 base pairs proximal to the transcription start site. These data suggest that genistein may exert a strong anticarcinogenic effect, and that this effect possibly involves an induction of p21, which inhibits the threshold kinase activities of Cdks and associated cyclins, leading to a G2/M arrest in the cell cycle progression.

Shape-memory behavior of segmented polyurethanes with an amorphous reversible phase: The effect of block length and content

Abstract: Segmented thermoplastic polyurethanes (TPU)s with amorphous soft segments from the reaction of hexamethylene diisocyanate and 1,2-butanediol and crystalline hard segments from 4,4′-methylenediphenyl diisocyanate and 1,6-hexanediol showed sharp glass-transition temperatures that could be used as shape-recovery temperatures The thermal, mechanical, and shape-memory effect of these TPUs of various block compositions and lengths were studied by differential scanning calorimetry, dynamic mechanical testing, and tensile testing As the block lengths decreased, phase mixing increased and hysteresis in the shape-memory behavior decreased Too low a content of hard segments increased the hysteresis in the shape-memory behavior © 2000 John Wiley & Sons, Inc J Polym Sci B: Polym Phys 38: 2652–2657, 2000

Detection and Identification of Mycobacteria by Amplification of the Internal Transcribed Spacer Regions with Genus- and Species-Specific PCR Primers

Abstract: We evaluated the usefulness of PCR assays that target the internal transcribed spacer (ITS) region for identifying mycobacteria at the species level. The conservative and species-specific ITS sequences of 33 species of mycobacteria were analyzed in a multialignment analysis. One pair of panmycobacterial primers and seven pairs of mycobacterial species-specific primers were designed. All PCRs were performed under the same conditions. The specificities of the primers were tested with type strains of 20 mycobacterial species from the American Type Culture Collection; 205 clinical isolates of mycobacteria, including 118 Mycobacterium tuberculosis isolates and 87 isolates of nontuberculous mycobacteria from 10 species; and 76 clinical isolates of 28 nonmycobacterial pathogenic bacterial species. PCR with the panmycobacterial primers amplified fragments of approximately 270 to 400 bp in all mycobacteria. PCR with the M. tuberculosis complex-specific primers amplified an approximately 120-bp fragment only for the M. tuberculosis complex. Multiplex PCR with the panmycobacterial primers and the M. tuberculosis complex-specific primers amplified two fragments that were specific for all mycobacteria and the M. tuberculosis complex, respectively. PCR with M. avium complex-, M. fortuitum-, M. chelonae-, M. gordonae-, M. scrofulaceum-, and M. szulgai-specific primers amplified specific fragments only for the respective target organisms. These novel primers can be used to detect and identify mycobacteria simultaneously under the same PCR conditions. Furthermore, this protocol facilitates early and accurate diagnosis of mycobacteriosis.

Shape memory polyurethane containing amorphous reversible phase

Abstract: Segmented thermoplastic polyurethanes (TPUs), which consist of an amorphous soft segment from 1,3-butanediol and hexamethylene diisocyanate (HDI) and a crystalline hard segment from 4,4′-bis-(6-hydroxy hexoxy)biphenyl and tolylene 2,4-diisocyanate were synthesized. Their thermal and mechanical properties, shape memory effect, utilizing amorphous soft segment domain as reversible phase and crystalline hard segment domain as frozen phase, were examined. The reversibility observed on repeated deformation was improved as the magnitude of deformation was reduced and the hard segment content was increased, or by crosslinking with excess HDI.

PhyloDraw: a phylogenetic tree drawing system

Abstract: Summary: PhyloDraw is a unified viewing tool for phylogenetic trees. PhyloDraw supports various kinds of multi-alignment formats (Dialign2, Clustal-W, Phylip format, NEXUS, MEGA, and pairwise distance matrix) and visualizes various kinds of tree diagrams, e.g. rectangular cladogram, slanted cladogram, phylogram, unrooted tree, and radial tree. By using several control parameters, users can easily and interactively manipulate the shape of phylogenetic trees. This program can export the final tree layout to BMP (bitmap image format) and PostScript. Availability: http:// pearl.cs.pusan.ac.kr/ phylodraw/

The properties of AlN-filled epoxy molding compounds by the effects of filler size distribution

Abstract: AlN filler was compared with crystalline silica as a filler for advanced epoxy molding compounds. Properties such as the thermal conductivity, dielectric constant, CTE, flexural strength, elastic modullus and water absorption ratio of water-resistant grade AlN-filled molding compounds according to the contents or size of AlN and the filler size distribution were evaluated. A spiral flow test was also carried out to measure the change in viscosity according to the AlN size distribution for improved fluidity. The properties of EMC that is filled with a 70 vol.% of 12 micron AlN was compared with a crystalline silica-filled EMC. Thermal conductivity was improved by 2.2 times, the dielectric constant was reduced to less than one-half, the flexural strength was improved, and the CTE was also reduced. A binary mixture of an AlN-filled (65 vol.%) EMC showed improved fluidity, thermal conductivity, dielectric constant, flexural strength and water resistance compared to a single-size AlN-filled EMC. The maximum improvement was obtained when the fraction of small particles in the binary mixture of the AlN is 0.2–0.3. The CTE of EMC was decreased by increasing the volume fraction of small particles in the binary mixture of the AlN.

CO2-sensing characteristics of SnO2 thick film by coating lanthanum oxide

Abstract: CO2 gas-sensor was fabricated by coating and heat-treating the drop of LaCl3⋅7H2O solution on the surface of SnO2 thick film. The effects of several factors, such as heat-treatment temperature, La concentration of coating-drop and humidity on CO2 sensitivity of thick film sensor were investigated in this work. The starting material, LaCl3⋅7H2O, for coating was phase-transformed by heat-treating, from LaCl3 to LaOCl at temperature range of 367–738°C, and from LaOCl to La2O3 over 773°C. The maximum sensitivity appeared at heat-treatment temperature of 1000°C and La concentration of 1×10−2 M La. The sensitivity showed a tendency to decrease remarkably with increasing humidity as well as with decreasing oxygen partial pressure.

The multi-item newsvendor problem with a budget constraint and fixed ordering costs

Abstract: This paper deals with a multi-item newsvendor problem subject to a budget constraint on the total value of the replenishment quantities. Fixed costs for non-zero replenishments have been explicitly considered. Dynamic programming procedures are presented for two situations: (i) where the end item demand distributions are assumed known (illustrated for the case of normally distributed demand) and (ii) a distribution free approach where only the first two moments of the distributions are assumed known. In addition, simple and efficient heuristic algorithms have been developed. Computational experiments show that the performance of the heuristics are excellent based on a set of test problems.

Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of dna replication

Abstract: Ursolic acid (UA), a pentacyclic triterpene acid, has been reported to exhibit anti-tumor activity. In this study, we investigated the pro-apoptotic effect of UA on HepG2 human hepatoblastoma cells. Treatment with UA decreased the viability of HepG2 cells in a concentration- and time-dependent manner. Furthermore, 30 μM of UA induced DNA fragmentation and subdiploid cells and enhanced the release of cytochrome c and the activation of caspase-3. These results suggest that UA induces cell death through apoptosis, which may be mediated by cytochrome c-dependent caspase-3 activation. In addition, cell-cycle analysis revealed that UA-treated cells were arrested predominantly in the G0 and G1 phases with a concomitant decrease in the cell population of S phase. Moreover, expression of p21WAF1, a cell-cycle regulator, was increased by UA, indicating that p21WAF1 might mediate UA-induced cell-cycle arrest. However, UA markedly inhibited SV40 DNA replication in the initiation stage in vitro and significantly reduced the DNA cleaving of topoisomerase I and the ssDNA binding activity of replication protein A. These results indicate that the inhibition of DNA replication by UA may result from blockade of the establishment of the replication fork during initiation stage, consequently contributing to UA-induced cell-cycle arrest. Taken together, we suggest that UA-induced cell-cycle arrest may be mediated by inhibition of DNA replication and the increase of p21WAF1 expression, which induces the release of cytochrome c and the activation of caspase-3, leading to apoptosis of HepG2 cells. Int. J. Cancer 87:629–636, 2000. © 2000 Wiley-Liss, Inc.