Biomedical subjects

K Bae

Publications and source records attributed to K Bae.

At least 19 recordsLinked to original sources

PubMed2006

Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma.

In the course of searching for BACE1 (beta-secretase) inhibitors from natural products, the ethyl acetate soluble fraction of Smilax Rhizoma (the dried rhizomes of Smilax china L.) showed potent inhibitory activity. The active compounds were identified as a trans/cis-resveratrol mixture, oxyresveratrol, veraphenol, and cis-scirpusin A. They were shown to non-competitively inhibit BACE1 with the Ki values of 5.4 x 10(-6), 5.4 x 10(-6), 3.4 x 10(-6), and 5.4 x 10(-6)M and IC(50) values of 1.5 x 10(-5), 7.6 x 10(-6), 4.2 x 10(-6), and 1.0 x 10(-5)M, respectively. The active compounds were less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.

Amyloid Precursor Protein Secretases↗

PubMed2006

Effect of water-soluble reduced chitosan on Streptococcus mutans, plaque regrowth and biofilm vitality.

The purpose of the present study was to examine the effects of a newly developed water-soluble reduced chitosan on Streptococcus mutans, plaque regrowth, and biofilm vitality. A 1.0%, water-soluble reduced chitosan, with pH ranging from 6.0 to 6.5, molecular weights between 3,000 and 5,000 Da, and 70% degree of deacetylation, was used. To determine antibacterial and antiplaque potency of chitosan, minimal inhibitory concentrations (MICs) for S. mutans and S. sanguinis (formerly S. sanguis), short-term exposure to S. mutans, and clinical trial of plaque regrowth and biofilm vitality were conducted. Twelve dental students volunteered to participate in the 6-week, double blind, randomized clinical trial using the classical 4-day plaque regrowth design. The MIC of water-soluble reduced chitosan for S. mutans was 1.25 g/l. While the cells exposed to distilled water (DW) grew rapidly, with a maximum turbidity reached by 16 h postinoculation, S. mutans exposed to chitosan (5.0 g/l) exhibited a substantial delay in growth and reached a maximum turbidity by 32 h postinoculation. The chitosan solution reduced the plaque index and the vitality of the plaque flora significantly when compared to DW, but this was less than the reductions found with the positive control of 0.1% chlorhexidine solution. The water-soluble reduced chitosan exhibited potent antibacterial effect on S. mutans, and displayed a significant antibacterial and plaque-reducing action during the 4-day plaque regrowth.

Adult↗

PubMed2006

CT findings of malarial spleen.

Malaria is one of the most frequent causes of fever among travellers to tropical countries. We report the CT imaging findings of poor contrast enhancement of the spleen on arterial phase in a case of malaria presenting as splenomegaly. To the best of our knowledge, this is the first report of malarial spleen diagnosed by these CT results.

Adult↗

PubMed2001

A new naphthoquinone from Pyrola japonica.

A new naphthoquinone, 5,8-dihydro-2,7-dimethyl-[1,4]naphthoquinone (1), which was named 5,8-dihydrochimaphilin, isolated from an ethyl acetate soluble fraction from the root of Pyrola japonica, together with chimaphilin (2). Compound 1 was transformed rapidly to 2 upon exposure to air by HPLC analysis. This fact supported that chimaphilin (2) may be an artifact from 1.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Cytotoxic triterpenoides from Alismatis Rhizoma.

Four prostane-type triterpenes were isolated from a methanol extract of Alismatis Rhizoma by bioassay-guided isolation using in vitro cytotoxic assay. The compounds were identified as alisol B 23-acetate (1), alisol C 23-acetate (2), alisol B (3), alisol A 24-acetate (4) by spectroscopic methods. Amongst the compounds, alisol B (3) showed significant cytotoxicity against SK-OV3, B16-F10, and HT1080 cancer cell lines with ED50 values of 7.5, 7.5, 4.9 microg/ml, respectively.

Animals↗

PubMed2001

A cytotoxic secocycloartenoid from Abies koreana.

Two triterpenoids, 24-methylene-3,4-seco-cycloart-4(28)-en-3-oic acid (1) and 3-oxo-9beta-lanosta-7,22Z,24-trien-26,23-olide (6) were isolated from Abies koreana, together with beta-sitosterol (2), maltol (3), beta-sitosterol-O-beta-D-glucoside (4), and hexacosylferulate (5). The structures of the compounds were established based on the spectroscopic data. The cytotoxic activities of triterpenoids have been evaluated using the sulforhodamine B (SRB) method. Compound 1 showed moderate cytotoxicities against human lung carcinoma (A549), ovarian carcinoma (SK-OV-3), malignant melanoma (SK-MEL-2), and colon carcinoma (HCT-15) cell lines.

Abies↗

PubMed2001

Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.

The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes.

Animals↗

PubMed2001

Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy.

Hypertriglyceridemia, peripheral insulin resistance, and trunk adiposity are metabolic complications recently recognized in people infected with human immunodeficiency virus (HIV) and treated with highly active antiretroviral therapy (HAART). These complications may respond favorably to exercise training. Using a paired design, we determined whether 16 wk of weight-lifting exercise increased muscle mass and strength and decreased fasting serum triglycerides and adipose tissue mass in 18 HIV-infected men. The resistance exercise regimen consisted of three upper and four lower body exercises done for 1-1.5 h/day, 4 days/wk for 64 sessions. Dual-energy X-ray absorptiometry indicated that exercise training increased whole body lean mass 1.4 kg (P = 0.005) but did not reduce adipose tissue mass (P = NS). Axial proton-magnetic resonance imaging indicated that thigh muscle cross-sectional area increased 5-7 cm(2) (P < 0.005). Muscle strength increased 23-38% (P < 0.0001) on all exercises. Fasting serum triglycerides were decreased at the end of training (281-204 mg/dl; P = 0.02). These findings imply that resistance exercise training-induced muscle hypertrophy may promote triglyceride clearance from the circulation of hypertriglyceridemic HIV-infected men treated with antiviral therapy.

Adipose Tissue↗

PubMed2000

Platelet-activating factor (PAF)-dependent transacetylase and its relationship with PAF acetylhydrolases.

Platelet-activating factor (PAF)-dependent transacetylase (TA) is an enzyme that transfers an acetyl group from PAF to acceptor lipids such as lysophospholipids and sphingosine. This enzyme is distributed in membrane and cytosol of the cells. We previously revealed that TA purified from rat kidney membrane showed an amino acid sequence similarity to that of bovine PAF-acetylhydrolase (AH) (II). In the present study, we purified TA from the rat kidney cytosol and analyzed its amino acid sequence. The amino acid sequence of the cytosolic TA is similar to that of bovine PAF-AH (II) and membrane TA. To clarify the relationship between TA and PAF-AH (II), we isolated cDNA of rat PAF-AH (II). The predicted amino acid sequence of rat PAF-AH (II) from isolated cDNA included all the sequences found in TAs purified from the membrane and cytosolic TAs. In addition, monoclonal antibody to recombinant PAF-AH (II) cross-reacted with both cytosolic and membrane TAs. Consistent with sequence identity, recombinant PAF-AH (II) showed TA activity, whereas recombinant PAF-AH Ib, which is a different subtype of intracellular PAF-AHs, did not possess TA activity. Analysis of a series of site-directed mutant PAF-AH (II) proteins showed that TA activity was decreased, whereas PAF-AH activity was not affected in C120S and G2A mutant proteins. Thus, Cys(120) and Gly(2) are implicated in the catalysis of TA reaction in this enzyme. Furthermore, the transfer of acetate from PAF to endogenous acceptor lipids was significantly increased in a time-dependent manner in CHO-K1 cells transfected with PAF-AH (II) gene. These results demonstrate that PAF-AH (II) can function, as a TA in intact cells, and PAF-AH (II) and TA are the same enzyme.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2000

Characteristics of levan fructotransferase from Arthrobacter ureafaciens K2032 and difructose anhydride IV formation from levan.

A microorganism producing levan fructotransferase was isolated from sugar-disclosed soil and it was identified as Arthrobacter ureafaciens. The major product from levan by enzyme reaction was identified as di-D-fructofuranose 2,6':6,2' dianhydride by mass spectrometry, nuclear magnetic resonance, and chemical analyses. Small amounts of several oligosaccharides and free fructose were also formed by enzyme reaction. An extracellular enzyme that produces di-D-fructofuranose 2,6':6,2' dianhydride from levan was purified from the culture broth of A. ureafaciens K2032. The enzyme had optimum activity around pH 5.8 and 45 degrees C and had a dimeric form in solution. The N-terminal amino acid residues of the purified enzyme were SAPGSLRAVYHMTPPSGXLXDPQ. The enzyme has narrow substrate range and converts the levan to di-D-fructofuranose 2,6':6,2' dianhydride with around 62.5% conversion yield.

Journal Article↗

PubMed2000

Role of follicular dendritic cells in the apoptosis of germinal center B cells.

Follicular dendritic cells (FDCs) provide the most obvious source of antigens, which are essential for the differentiation of GC B cells. It has been reported that most proliferating B cells in germinal centers undergo apoptosis. Quantitative histology shows macrophages with apoptotic debris throughout the germinal center, the highest frequency of these cells being found in the dense FDC network. Based on these findings, we hypothesized that FDC may be involved in an apoptotic pathway of the germinal center B cells. To prove this hypothesis, we performed double immunohistochemical analysis using anti-FDC mAb and peanut agglutinin (PNA), with their respective TUNEL kits. Collated data showed that a great proportion of the apoptotic cells, most of which were positive for PNA, were in close contact with FDC, which indicated an interaction between FDC and B cells in the apoptotic pathway. Further studies using double immunohistochemical staining and FACS analyses demonstrated the expression of Fas-ligand (FasL) in a subset of the FDC. These results suggest that FDC may play a role in the apoptosis of germinal center B cells via Fas-FasL interaction.

Animals↗

PubMed2000

dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex.

In Drosophila melanogaster four circadian clock proteins termed PERIOD (PER), TIMELESS (TIM), dCLOCK (dCLK), and CYCLE (CYC/dBMAL1) function in a transcriptional feedback loop that is a core element of the oscillator mechanism. dCLK and CYC are members of the basic helix-loop-helix (bHLH)/PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of per and tim and repression of dClk, whereas PER and TIM inhibit dCLK-CYC-mediated transcription and lead to the activation of dClk. To understand further the dynamic regulation within the circadian oscillator mechanism, we biochemically characterized in vivo-produced CYC, determined the interactions of the four clock proteins, and calculated their absolute levels as a function of time. Our results indicate that throughout a daily cycle the majority of the dCLK present in adult heads stably interacts with CYC, indicating that CYC is the primary in vivo partner of dCLK. dCLK-CYC dimers are bound by PER and TIM during the late evening and early morning, suggesting the formation of a tetrameric complex with impaired transcriptional activity. Although dCLK is present in limiting amounts and CYC is by far the most abundant of the four clock proteins that have been examined, PER and TIM appear to interact preferentially with dCLK. Our results suggest that dCLK is the main component regulating the daily abundance of transcriptionally active dCLK-CYC complexes.

ARNTL Transcription Factors↗

PubMed2000

Cytotoxic triterpenes from Crataegus pinnatifida.

Bioassay-guided fractionation of Crataegus pinnatifida (Rosaceae) gave two cytotoxic ursane-type triterpenes which were identified as uvaol (1) and ursolic acid (2) by physicochemical and spectroscopic methods. 3-Oxo-ursolic acid (3) was synthesized from ursolic acid (2) by Jones method. The cytotoxic activities of these compounds were tested against murine L1210 and human cancer cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15) in vitro. Compounds 1 and 2 showed moderate cytotoxicities against L1210, whereas they showed weak activities against human cancer cell lines. However, compound 3 exhibited potent cytotoxic activities both in murine and in human cancer cell lines.

Animals↗

PubMed2000

Purification and characterization of extracellular medium-chain-length polyhydroxyalkanoate depolymerase from Pseudomonas sp. RY-1.

A novel bacterial strain capable of growing in a medium containing a medium-chain-length polyhydroxyalkanoate (MCL-PHA) as the sole carbon source was isolated from a soil sample. The isolate, which was identified as Pseudomonas sp. RY-1, secreted MCL-PHA depolymerase into the culture fluid only when it was cultivated in a medium containing a MCL-PHA, such as polyhydroxyoctanoate (PHO) or polyhydroxynonanoate (PHN). The extracellular MCL-PHA depolymerase of this organism was purified to electrophoretic homogeneity. The enzyme was a tetramer with identical subunits and a total molecular mass of 115 kDa. The isoelectric point of this enzyme was estimated to be 5.9 by isoelectric focusing. The maximal activity was observed at pH 8.5 and 35 degrees C. The enzyme was insensitive to phenylmethylsulfonyl fluoride and dithiothreitol, unlike other short-chain-length (SCL) PHA depolymerases. The K(m) values for PHO and PHN were 0.86 and 1.47 mg/ml, respectively. The enzyme could not hydrolyze SCL-PHAs and p-nitrophenyl esters of fatty acids.

Journal Article↗

PubMed2000

Potentiating effect of obacunone from Dictamnus dasycarpus on cytotoxicity of microtuble inhibitors, vincristine, vinblastine and taxol.

The limonoid triterpene, obacunone, was found to enhance the cytotoxicity of vincristine against L1210 cells by approximately 10-fold. Further, it was found that the cytotoxicity of other microtubule inhibitors such as vinblastine and taxol in drug-sensitive KB-3-1 cells as well as in multidrug-resistant KB-V1 cells was enhanced greatly in the presence of obacunone. On the other hand, there was no remarkable potentiating effect of obacunone on the cytotoxicity of other antineoplastic drugs such as adriamycin, cisplatin or 5-fluorouracil. From these results, it is implied that the potentiating action of obacunone may be limited to microtubule inhibitors.

Animals↗

PubMed1999

Inhibitory effect of triterpenes from Crataegus pinatifida on HIV-I protease.

The methanol extracts of the leaves of Crataegus pinnatifida showed potent inhibitory activities against HIV-1 protease at a concentration of 100 micrograms/ml. The subsequent fractionation and isolation of the extract gave two active compounds. Their structures were identified as uvaol (1) and ursolic acid (2) by spectral data. These active compounds inhibit HIV-1 protease with IC50 values of 5.5 and 8.0 microM, respectively.

Anti-HIV Agents↗

PubMed1999

PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription.

The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1) proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of the circadian clock genes period (per) and timeless (tim). Several lines of evidence indicate that PER, TIM, or a PER-TIM heterodimer somehow inhibit the transcriptional activity of a putative dCLOCK-CYC complex, generating a negative-feedback loop that is a core element of the Drosophila circadian oscillator. In this report we show that PER and/or TIM inhibits the binding of a dCLOCK-CYC heterodimer to an E-box-containing DNA fragment that is present in the 5' nontranscribed region of per and acts as a circadian enhancer element. Surprisingly, inhibition of this DNA binding activity by PER, TIM, or both is not accompanied by disruption of the association between dCLOCK and CYC. The results suggest that the interaction of PER, TIM, or both with the dCLOCK-CYC heterodimer induces a conformational change or masks protein regions in the heterodimer, leading to a reduction in DNA binding activity. Together with other findings, our results strongly suggest that daily cycles in the association of PER and TIM with the dCLOCK-CYC complex probably contribute to rhythmic expression of per and tim.

ARNTL Transcription Factors↗

PubMed1998

The Drosophila CLOCK protein undergoes daily rhythms in abundance, phosphorylation, and interactions with the PER-TIM complex.

We report the in vivo characterization of the Drosophila CLOCK protein (dCLOCK), a transcription factor that is required for the expression of the circadian clock genes period (per) and timeless (tim). dCLOCK undergoes circadian fluctuations in abundance, is phosphorylated throughout a daily cycle, and interacts with PER, TIM, and/or the PER-TIM complex during the night but not during most of the day. Our results suggest that PER and TIM participate in transcriptional autoinhibition by physically interacting with dCLOCK or a dCLOCK-containing complex. Nevertheless, in the absence of PER or TIM, the levels of dCLOCK are constitutively low, indicating that PER and TIM also act as positive elements in the feedback loop by stimulating the production of dCLOCK.

Animals↗