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Biomedical subjects

J W Kim

Publications and source records attributed to J W Kim.

At least 73 records · Page 4Linked to original sources

Binding aspects of baicalein to HIV-1 integrase.

Human immunodeficiency virus type 1 (HIV-1) integrase is an essential enzyme in the life cycle of the virus. It is responsible for catalyzing the insertion of the viral genome into the host cell chromosome. This integrase is an attractive target for the design of a HIV antiviral drug, because integrase has no human counterpart. In order to know the interaction mode of HIV-1 integrase with its inhibitor, we investigated the effect of the inhibitor, baicalein, on the conformation of the HIV-1 integrase catalytic domain [IN-(50-212/F185K)] using fluorescence and circular dichroism (CD) spectroscopy. We found that baicalein binds to the hydrophobic region of the HIV-1 integrase catalytic core domain. This binding of baicalein induces the conformational change of the enzyme. We also found that the binding ratio of baicalein to the HIV-1 integrase catalytic domain is 2:1.

Circular Dichroism↗

Production of granular activated carbon from waste walnut shell and its adsorption characteristics for Cu(2+) ion.

Production of granular activated carbon by chemical activation has been attempted employing walnut shells as the raw material. The thermal characteristics of walnut shell were investigated by TG/DTA and the adsorption capacity of the produced activated carbon was evaluated using the titration method. As the activation temperature increased, the iodine value increased. However, a temperature higher than 400 degrees C resulted in a thermal degradation, which was substantiated by scanning electron microscopy (SEM) analysis, and the adsorption capacity decreased. Activation longer than 1h at 375 degrees C resulted in the destruction of the microporous structure of activated carbon. The iodine value increased with the increase in the concentration of ZnCl2 solution. However, excessive ZnCl2 in the solution decreased the iodine value. The extent of activation by ZnCl2 was compared with that by CaCl2 activation. Enhanced activation was achieved when walnut shell was activated by ZnCl2. Applicability of the activated carbon as adsorbent was examined for synthetic copper wastewater. Adsorption of copper ion followed the Freundlich model. Thermodynamic aspects of adsorption have been discussed based on experimental results. The adsorption capacity of the produced activated carbon met the conditions for commercialization and was found to be superior to that made from coconut shell.

Adsorption↗

Depletion of praziquantel in plasma and muscle tissue of cultured rockfish Sebastes schlegeli after oral and bath treatment.

Depletion of praziquantel in plasma and muscle tissue after oral and bath treatments was studied in cultured rockfish Sebastes schlegeli. In the oral treatment, a single dose of 400 mg praziquantel kg(-1) body weight was administered by intubation of the stomach. A bath treatment at 100 ppm of praziquantel for 4 min was also carried out. Plasma and muscle tissue samples were collected at 3, 6, 12, 24, 48, 72, 96, 120, 144 and 168 h post-treatment, and analyzed for praziquantel by reversed-phase HPLC using diazepam as the internal standard. Following oral treatment, praziquantel was detected in plasma and muscle tissue until 96 h after treatment. In plasma the praziquantel concentration was highest at the 9 h sampling time and declined sharply at the 48 h sampling point. The concentrations of praziquantel in the muscle tissue were lower than those in the plasma, and the highest value was found at the 9 h sampling time. Following bath treatment, praziquantel was found in plasma and muscle tissue until 72 and 24 h after treatment, respectively. In plasma the praziquantel concentration was highest at the 12 h sampling time and declined sharply thereafter. The concentrations of praziquantel in the muscle tissue were significantly lower than those in the plasma, and the concentrations declined consistently with time.

Administration, Oral↗

Expression of exo-polygalacturonases in Botrytis cinerea.

The pathogenic fungus, Botrytis cinerea, causing gray mold disease in a variety of plant species, secretes at least four polygalacturonases (PGs), cell wall degrading enzymes. Among them, we prepared polyclonal antibody against purified 66-kDa exo-PG in rabbit. Immunoblot analysis revealed that the antibody recognized two exo-PGs, 66 kDa and 70 kDa in molecular mass, secreted from B. cinerea cultured in the medium containing citrus pectin as a carbon source. By immunohistochemical analysis, the expression of exo-PGs was identified in cucumber leaves inoculated with spores of B. cinerea. The exo-PGs were observed 9 h after inoculation, and the amount of exo-PGs increased with time in the leaves. The exo-PGs were induced by polygalacturonic acid as well as its monomer, galacturonic acid, in vitro. The expression of 66-kDa exo-PG (exo-PG I) increased with time of culture, while 70-kDa exo-PG (exo-PG II) was transiently expressed soon after the start of culture. Therefore, exo-PGs might play an important role in pathogenesis at an early stage of infection as well as in tissue maceration of host plant.

Botrytis↗

Fatal submassive hepatic necrosis associated with tyrosine-methionine-aspartate-aspartate-motif mutation of hepatitis B virus after long-term lamivudine therapy.

We present a case of infection with lamivudine-resistant mutant hepatitis B virus (HBV) that fatally exacerbated hepatitis following the emergence of HBV with mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif in an immunocompetent patient who was receiving long-term lamivudine therapy. Restriction fragment length polymorphism analysis showed that the YMDD-motif mutant was the predominant form of circulating HBV at the time of the fatal exacerbation, and a necropsy specimen of the liver revealed submassive hepatic necrosis without steatosis.

Amino Acid Motifs↗

Front propagation of spatiotemporal chaos.

We study the dynamics of the front separating a spatiotemporally chaotic region from a stable steady region using a simple model applicable to periodically forced systems. In particular, we investigate both the coarsening of the front induced by the inherent "noise" of the chaotic region, and the long wavelength dynamics causing the front to develop cusps.

Journal Article↗

Role of receptor-interacting protein in tumor necrosis factor-alpha -dependent MEKK1 activation.

Receptor-interacting protein (RIP), a death domain serine/threonine kinase, has been shown to play a critical role in tumor necrosis factor-alpha (TNF-alpha)-induced activation of the nuclear factor-kappaB signaling pathway. We demonstrate here that ectopically expressed RIP induces I-kappaB kinase-beta (IKKbeta) activation in intact cells and that RIP-induced IKKbeta activation can be blocked by a kinase-inactive form of MEKK1, MEKK1(K1253M). Interestingly, RIP physically associated with MEKK1 both in vitro and in vivo. RIP phosphorylated MEKK1 at Ser-957 and Ser-994. Our data also indicate that RIP induced the stimulation of MEKK1 but not MEKK1(S957A/S994A) in transfected cells. Furthermore, overexpressed MEKK1(S957A/S994A) inhibited the RIP-induced activation of both IKKbeta and nuclear factor-kappaB. We also demonstrated that the TNF-alpha-induced MEKK1 activation was defective in RIP-deficient Jurkat cells. Taken together, our results suggest that RIP phosphorylates and activates MEKK1 and that RIP is involved in TNF-alpha-induced MEKK1 activation.

Cell Line↗

Negative regulation of the SAPK/JNK signaling pathway by presenilin 1.

Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid beta-protein. To understand intracellular signaling events downstream of PS1, we investigated in this study the action of PS1 on mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two functionally inactive PS1 mutants, PS1(D257A) and PS1(D385A), failed to inhibit UV-stimulated SAPK/JNK. Furthermore, H(2)O(2-) or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS(+/+) mice. MEF(PS1(-/-)) cells were more sensitive to the H(2)O(2)-induced apoptosis than MEF(PS1(+/+)) cells. Ectopic expression of PS1 in MEF(PS1(-/-)) cells suppressed H(2)O(2)-stimulated SAPK/JNK activity and apoptotic cell death. Together, our data suggest that PS1 inhibits the stress-activated signaling by suppressing the SAPK/JNK pathway.

Animals↗

Up-Regulation of ninjurin expression in human hepatocellular carcinoma associated with cirrhosis and chronic viral hepatitis.

The cDNA clones, which were highly expressed in liver tissues of hepatocellular carcinoma (HCC) patients, were identified using dot hybridization and reconfirmed by Northern blot analysis. One of the clones, ninjurin (nerve injury induced protein), showed a much higher expression level in the liver tissue of HCC patients than in normal liver tissue. Interestingly, the presence of ninjurin mRNA transcripts was detected with high intensity in HCC tissues when combined with viral infection and cirrhosis, but not with a normal liver or HCC tissue unrelated with viral infection and cirrhosis. We produced a N-terminal part of recombinant ninjurin protein, as well as a monoclonal antibody specific to this polypeptide. The intensity of immunohistochemical staining of the liver tumor tissue, and regenerating tissue for the ninjurin protein, was stronger than that of normal liver tissue. These results suggest that ninjurin may play an important role in the development of HCC combined with cirrhosis and viral infection.

Animals↗

Properties of the Corynebacterium glutamicum metC gene encoding cystathionine beta-lyase.

The metC gene encoding the cystathionine beta-lyase, the third enzyme in the methionine biosynthetic pathway, was isolated from Corynebacterium glutamicum by heterologous complementation of the Escherichia coli metC mutant. A DNA-sequence analysis of the cloned DNA identified two open-reading frames (ORFs) of ORF1 and ORF2 that consisted of 1,107 and 978 bp, respectively. A SDS-PAGE analysis identified a putative cystathionine beta-lyase band with approximate Mr of 41,000 that consisted of 368 amino acids encoded from ORF1. The translational product of the gene showed no significant homology with that of the metC gene from other organisms. Introduction of the plasmid containing the metC gene into C. glutamicum resulted in a 5-fold increase in the activity of the cystathionine beta-lyase. The putative protein product of ORF2, encoding a protein product of 35,574 Da, consisted of 325 amino acids and was identical to the previously reported aecD gene product, except for the existence of two different amino acids. Like the aecD gene, when present in multiple copies, the metC gene conferred resistance to S-(betaaminoethyl)-cysteine, which is a toxic lysine analog. However, genetic and biochemical evidence suggests that the natural activity of the metC gene product is to mediate methionine biosynthesis in C. glutamicum. Mutant strains of metC were constructed, and the strains showed methionine prototrophy. The mutant strains completely lost their ability to show resistance to the S-(beta-aminoethyl)-cysteine. These results suggest that, in addition to the transsulfuration, other biosynthetic pathway(s), such as a direct sulfhydrylation pathway, may be functional in C. glutamicum as a parallel biosynthetic route for methionine.

Amino Acid Sequence↗

Short peptides with induced beta-turn inhibit the interaction between HIV-1 gp120 and CD4.

To identify novel peptides that inhibit the interaction between human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 and CD4, we constructed a targeted phage-displayed peptide library in which phenylalanine and proline were fixed at the fourth and sixth positions, respectively, because Phe43 and the adjacent beta-turn of CD4 are critical for interaction with gp120. Two synthetic peptides were selected after three rounds of biopanning against gp120, and one of them, G1 peptide (ARQPSFDLQCGF), exhibited specific inhibition of the interaction between gp120 and CD4 with an IC(50) of about 50 microM. Structural analysis using NMR demonstrated that G1 peptide forms a compact cyclic structure similar to the CD4 region interacting with gp120. Two derivatives of G1 peptide, a linear hexameric peptide (G1-6) and a cyclic nonameric peptide (G1-c), were synthesized based on the structure of the G1 peptide. Interestingly, they showed higher inhibitory activities than did G1 peptide with IC(50)'s of 6 and 1 microM, respectively. Thus, this study might provide a new insight into the development of anti-HIV-1 inhibitors.

Amino Acid Sequence↗

Alpha-1 antichymotrypsin and alpha-2 macroglobulin gene polymorphisms are not associated with Korean late-onset Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder with possible involvement of several genetic and environmental factors. For late-onset AD (LOAD), the epsilon4 allele of apolipoprotein E (APOE) has been identified as a major susceptible gene. However, the observation that APOE epsilon4 accounted for approximately one half of the genetic variance of LOAD prompted many researchers to undertake genome surveys to identify other susceptible genes. Recently, several candidate genes such as alpha-1 antichymotrypsin (ACT) and alpha-2 macroglobulin (A2M) were reported to be associated with LOAD. To evaluate the possible association between these genes and LOAD in Korean population, we genotyped ACT A/T and A2M 5-bp deletion (exon 18) polymorphisms in 89 LOAD cases and 50 age-matched healthy controls. The frequencies of ACT A and A2M 5-bp deletion alleles in LOAD and controls were 0.39 vs. 0.37, and 0.05 vs. 0.05, respectively. Although APOE epsilon4 clearly showed higher frequency in LOAD (0.34) than that in controls (0.09), giving an odds ratio of 5.14 (95% confidence interval, 2.31-11.76), neither ACT nor A2M showed statistically significant difference between LOAD and controls regardless of APOE carrier status. Our results do not support previously reported association of ACT and A2M with LOAD, at least in Korean population.

Aged↗

Increases in cell proliferation and apoptosis in dentate gyrus of anorexia (anx/anx) mice.

The homozygous anorexia mutant (anx/anx) mice present with premature death during the third or fourth postnatal week: this phenotype is caused by a lethal mutation, anx, on chromosome 2, which has an autosomal recessive mode of inheritance. These animals also present phenotypically with decreased food intake, weight loss, and neurological deficits such as hyperactivity, body tremors, uncoordinated gait, and head weaving. In order to investigate changes in the occurrence of cell proliferation and apoptosis in the dentate gyrus of the hippocampus of anx/anx mice, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay were performed in this study. In addition, the volume of the dentate gyrus was estimated via stereological analysis. anx/anx mice showed significantly higher numbers of both BrdU- and TUNEL-positive cells in the dentate gyrus than those of the control mice. Furthermore, the volume of the dentate gyrus of anx/anx mice was significantly reduced compared to that of the control mice.

Animals↗

Platelet-activating factor-induced early activation of NF-kappa B plays a crucial role for organ clearance of Candida albicans.

In this study, we have investigated the mechanisms underlying organ susceptibility to candida infection. Infection of BALB/c mice with Candida albicans led to both an early (1-8 h) and late (24-48 h) activation of NF-kappaB in the organs resistant to C. albicans, including the lung and spleen. In susceptible organs such as the kidneys, early activation of NF-kappaB was not observed. The kinetics of TNF-alpha mRNA expression paralleled those of NF-kappaB activation in all organs examined. Blocking the effects of endogenous platelet-activating factor (PAF) by pretreatment with the PAF antagonist BN50739 or antioxidants significantly reduced the early activity of NF-kappaB and TNF-alpha mRNA expression, and increased the recovery of C. albicans in the lung and spleen. Importantly, administration of PAF 5 min prior to the infection resulted in the appearance of early activities of NF-kappaB and TNF-alpha mRNA expression, followed by a nearly complete clearance of the organisms in the kidneys. Pretreatment with anti-TNF-alpha Ab resulted in an enhanced susceptibility to C. albicans, and the PAF-mediated resistance was abrogated by anti-TNF-alpha in all organs examined. These data indicated that endogenously produced PAF in response to C. albicans is a key molecule involved in the early activation of NF-kappaB, which, in turn, renders the organ resistant to the fungus by promoting the production of anti-candidal proinflammatory cytokines such as TNF-alpha. Susceptible organs, including the kidneys, lack the capacity to generate a sufficient PAF-induced early NF-kappaB response.

Adjuvants, Immunologic↗

Characterization of a lytic Lactobacillus plantarum bacteriophage and molecular cloning of a lysin gene in Escherichia coli.

Bacteriophage SC921, which can infect Lactobacillus plantarum specifically, was isolated from a fermented vegetable source, Kimchi. This phage is active against six of 11 strains of L. plantarum tested as hosts. Morphologically, it has an isometric head (60 nm in diameter) and a non-contractile tail (260 nm long and 9-11 nm wide), indicating that it belongs to Bradley's group B or the Siphoviridae family according to the International Committee on Taxonomy of Viruses (ICTV). The bouyant density was 1.58 g/cm3. SDS-PAGE experimentation indicated that the phage particle contains two major structural proteins and several minor proteins. The genome was a double stranded linear DNA molecule with cohesive ends and 66.5 kb long by mapping genomic DNA digested with the restriction endonucleases: KpnI, SmaI, and XbaI. The [G + C] content of the phage DNA is 39.4%. For this lysin gene study, 9.4 kb of KpnI-digested DNA fragment was cloned into pUC19 and expressed in Escherichia coli. The KpnI fragment was considered as the genetic element responsible for the lysis gene of L. plantarum bacteriophage. The cloned fragment in pUC19 was hybridized to a 9.4-kb fragment generated by KpnI digestion of SC 921 as a probe. This confirmed that the fragment in pUC19 originated from phage DNA. The lysin gene was near the middle of the phage genome.

Bacteriophages↗

MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells.

Transcriptional repression of the transforming growth factor (TGF)-1P type II receptor (TPRII) gene appears to be a major mechanism to inactivate TGF-beta responsiveness in many human cancers. Because histone acetylation/deacetylation plays a role in transcriptional regulation, we have examined the effect of MS-275, a synthetic inhibitor of histone deacetylase, in human breast cancer cell lines. MS-275 showed antiproliferative activity against all human breast cancer cell lines examined and induced TbetaRII mRNA, but not TGF-beta type I receptor mRNA. MS-275 caused an accumulation of acetylated histones H3 and H4 in total cellular chromatin. An increase in the accumulation of acetylated histones H3 and H4 was detected in the TbetaRII promoter after treatment with MS-275. However, the level of histone acetylation did not change in chromatin associated with the TGF-beta type I receptor gene. MS-275 treatment enhanced TGF-beta1-induced plasminogen activator inhibitor 1 expression. Thus, antitumor activity of MS-275 may be mediated in part through the induction of TbetaRII expression and consequent potentiation of TGF-beta signaling.

Acetylation↗