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Biomedical subjects

C O Lee

Publications and source records attributed to C O Lee.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of isoprenaline, carbachol, and Cs+ on Na+ activity and pacemaker potential in rabbit SA node cells.

Effects of isoprenaline, carbachol, and Cs+ on intracellular Na+ activity (a(i)Na) and spontaneous action potentials were studied in multicellular and single cell preparations isolated from rabbit sinoatrial (SA) nodes. a(i)Na was measured with double-barreled Na+-selective microelectrodes and the fluorescent Na+-indicator sodium-binding benzofuran isophthalate (SBFI). In spontaneously beating cells, aiNa measured with Na+-selective microelectrodes and SBFI were 4.5 +/- 1.2 mM (means +/- SD, n = 21) in multicellular preparations and 4.0 +/- 1.1 mM (n = 16) in single cells, respectively. Measurements of a(i)Na with microelectrodes showed that isoprenaline increased a(i)Na from 4.7 +/- 1.2 to 5.5 +/- 1.6 mM (n = 16, P < 0.01) and shortened the action potential cycle length (ACL) from 338 +/- 46 to 269 +/- 35 ms (n = 16, P < 0.01). However, increasing the action potential rate by pacing produced a much smaller increase in a(i)Na. Changes in a(i)Na and ACL produced by isoprenaline were blocked by Cs+. The selective hyperpolarization-activated inward current (If) blocker ZD-7288 decreased a(i)Na from 5.2 +/- 1.0 to 4.6 +/- 1.3 mM (n = 4, P < 0.01) and prolonged ACL from 394 +/- 20 to 553 +/- 68 ms (n = 4, P < 0.01). The If blocker substantially inhibited the increase in a(i)Na produced by isoprenaline. Carbachol and Cs+ decreased aiNa from 4.6 +/- 1.4 to 3.9 +/- 1.2 mM (n = 15, P < 0.01) and from 4.9 +/- 1.0 to 3.9 +/- 1.3 mM (n = 18, P < 0.01), respectively. In addition, carbachol and Cs+ prolonged ACL from 345 +/- 44 to 587 +/- 100 ms (n = 15, P < 0.01) and from 353 +/- 30 to 464 +/- 87 ms (n = 18, P < 0.01), respectively. However, carbachol and Cs+ almost did not change a(i)Na when SA node cells became quiescent in a 25.4 mM extracellular K+ concentration. The results suggest that isoprenaline, ZD-7288, carbachol, or Cs+ might have changed a(i)Na and action potential rate by possibly stimulating or inhibiting If carried by Na+. Measurements of a(i)Na with SBFI showed that isoprenaline, carbachol, and Cs+ produced a(i)Na changes that were similar to those measured with the microelectrodes.

Action Potentials↗
PubMed1998

Vanadate-sensitive microsomal ATPases and microsomal 45Ca2+ uptake in tracheal epithelial cells.

Cytosolic free Ca2+ plays important roles in the regulation of physiological processes in tracheal epithelial cells and is probably regulated by many ion-transporting ATPases in these cells. Therefore, the effect of vanadate was investigated to characterize microsomal ion-transporting ATPases. Dose response experiments showed that vanadate had a biphasic effect on the microsomal ATPase activity: a decrease at the vanadate concentration below 100 microM, and a steep decrease at the concentration above 100 microM. The dose response data were fitted to two sigmoidal functions, corresponding to a low-affinity vanadate-sensitive (LAVS) ATPase and a high-affinity vanadate-sensitive (HAVS) ATPase. In 45Ca2+ uptake experiments, both LAVS and HAVS ATPases mediated microsomal 45Ca2+ uptake. The LAVS ATPase was selectively sensitive to thapsigargin in both ATPase activity and 45Ca2+ uptake, suggesting that it is an ER/SR-type intracellular Ca2+-ATPase. Although the HAVS ATPase mediated one-fourth of microsomal 45Ca2+ uptake, its activity was not sensitive to thapsigargin. These results indicate that the activities of these two vanadate-sensitive ATPases are mediated by different enzymes, since thapsigargin only blocks the activity of LAVS ATPase. In conclusion, there are two types of vanadate-sensitive microsomal ATPases, and these ATPases mediate microsomal 45Ca2+ uptake in airway epithelial cells.

Adenosine Triphosphatases↗
PubMed1998

Voltage-dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+.

1. We expressed the human eag-related gene (HERG), which is known to encode the delayed rectifier K+ current (IKr) in cardiac muscle, in Xenopus oocytes. Using a two-microelectrode voltage clamp technique, the effect of external Ca2+ and Mg2+ on the HERG current (IHERG) was investigated. 2. When [Ca2+]o was increased, the amplitude of outward IHERG elicited by depolarization decreased, and the rate of current onset slowed. The rate of current decay observed on repolarization was greatly accelerated. The threshold and fully activated potential of IHERG shifted to a more positive potential. On the other hand, the inactivation property represented by the negative slope of the I-V curve and the instantaneous conductance of IHERG were little affected by [Ca2+]o. 3. The effect of [Ca2+]o on IHERG can be interpreted using the channel blockade model. The blockade is voltage dependent; smaller dissociation constants (KM) at more negative potentials indicate that block is facilitated by hyperpolarization. KM changes e-fold for 14.5 mV and the fractional electrical distance of the binding site calculated from this value is 0.86. 4. Blockade by a low concentration of Ca2+ (0.5 mM) was inhibited by increasing [K+]o (from 2 to 20 mM), whereas blockade by a high concentration of Ca2+ (5 mM) was not affected by varying [K+]o, indicating that there is competition between permeating ions and blocking ions. 5. The effect of [Mg2+]o on IHERG was qualitatively similar to that of [Ca2+]o, but the potency was lower. 6. These results suggest that external Ca2+ and Mg2+ block the HERG channel in a voltage- and time-dependent manner, resulting in a voltage dependence which has been regarded as a property of the activation gate.

Animals↗
PubMed1998

Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents.

To investigate the structure-activity relationship of 7,8-dimethoxy-2- methyl-3-(4,5-methylenedioxy-2-vinylphenyl)isoquinolin-1(2H) -one 2, diverse substituted 3-arylisoquinolines were synthesized and tested in vitro antitumor activity against five human tumor cell lines. The results showed a broad antitumor spectrum for a series of 3-arylisoquinolines.

Antineoplastic Agents↗
PubMed1998

Persistent and heterogenous expression of the cyclin-dependent kinase inhibitor, p27KIP1, in rat hearts during development.

We have previously shown that there were differential and dramatic decreases of cyclin and cyclin-dependent kinase (CDK) activities in cardiomyocytes during the neonatal period. The activity of CDKs control cell cycle progression, and this activity is regulated positively and negatively by association of CDKs with cyclins and cyclin-dependent kinase inhibitors (CKIs), respectively. While the INK family (p15(INK4B)/p16(INK4A)/p18(INK4C)/p19(INK4D)) of CKIs is not detectable in hearts, the KIP/CIP family (p21(CIP1), p27(KIP1) and p57(KIP2)) of CKIs is detectable in most organs including the heart. Differential and dramatic changes of the KIP/CIP family (p21(CIP1), p27(KIP1) and p57(KIP2)) of CKIs were detected in rat hearts during development. The mRNA and protein levels of p21(CIP1) and p57(KIP2) were readily detectable in hearts at gestational and early postnatal periods and decreased thereafter. The mRNA levels of p27(KIP1) in ventricles were high during the gestational period, and did not change until day 30 postnatal, then were decreased slightly in 90-day-old rats. The protein levels of p27(KIP1) increased significantly in the early postnatal period, then were expressed persistently, although levels decreased slightly in the adult period. However, protein levels of p27(KIP1) in atria did not change during development. Variable immuno-staining patterns of p27(KIP1) were observed at different periods of development and in various locations in myocardium. During the gestational period, approximately 35-50% of myocardial cells in the cardiac wall were p27(KIP1) immuno-positive and were distributed diffusely. These p27(KIP1) immunopositive cells increased predominantly in endocardial and mid-portion areas of ventricular myocardium at the early postnatal period. This heterogenous pattern of p27(KIP1) protein expression persisted to adult hearts though the percentage of p27(KIP1) immuno-positive cells decreased slightly. High magnification revealed that more than 50% of adult cardiomyocytes were p27(KIP1) immuno-positive and that p27(KIP1) was located solely in nuclei. These results indicate that p27(KIP1) may be an important inhibitor of CDK activities in cardiomyocytes during early postnatal development and may block the re-entrance of adult cardiomyocytes into the cell cycle after injury.

Animals↗
PubMed1998

Synthesis and in vitro cytotoxicity of cinnamaldehydes to human solid tumor cells.

Cinnamaldehydes and related compounds were synthesized from various cinnamic acids based on the 2'-hydroxycinnamaldehyde isolated from the bark of Cinnamomum cassia Blume. The cytotoxicity to human solid tumor cells such as A549, SK-OV-3, SK-MEL-2, XF498 and HCT15 were measured. Cinnamic acid, cinnamates and cinnamyl alcohols did not show any cytotoxicity against the human tumor cells. Cinnamaldehydes and related compounds were resistant to A549 cell line up to 15 micrograms/ml. In contrast, HCT15 and SK-MEL-2 cells were much sensitive to these cinnamaldehyde analogues which showed ED50 values 0.63-8.1 micrograms/ml. Cytotoxicity of the saturated aldehydes was much weak compared to their unsaturated aldehydes. From these studies, it was found that the key functional group of the cinnamaldehyde-related compounds in the antitumor activity is the propenal group.

Acrolein↗
PubMed1998

Cytotoxic constituents of Saussurea lappa.

The crude extract of Saussurea lappa displayed significant lethality to brine shrimp larvae. Investigation of the causative components by bioactivity-directed fractionation resulted in the isolation of three C17-polyene alcohols. Based on various nmr spectral data, these compounds were identified as shikokiols which had been previously isolated from Cirsium nipponicum and/or Centaurea aegyptica. These C17-polyene alcohols exhibited moderate cytotoxicities against the human tumor cell lines, A549, SK-OV-3, SK-MEL-2, XF498, and HCT15.

Animals↗
PubMed1998

Synthesis of antineoplaston A10 analogs as potential antitumor agents.

Several aniline mustard analogues were obtained by introducing N,N-bis(2-chloroethyl)amino moiety to phenyl ring of A10 analogues in order to increase reactivity of A10 analogs and selectivity into DNA. The in vitro antitumor activity of synthesized compounds was evaluated using five different solid tumor cell lines by SRB method. Aniline mustard analogues exhibited more potent antitumor activity than A10 analogs. Especially, m-aniline mustard of benzoyl analogue displayed remarkable antitumor activity.

Antineoplastic Agents↗
PubMed1998

Synthesis and structure-activity relationship studies of substituted isoquinoline analogs as antitumor agent.

A number of substituted isoquinolin-1-ones, possible bioisosteres of the 5-aryl substituted 2,3-dihydroimidazo[2,1-a]isoquinolines, were synthesized and tested for their antitumor activity against five different human tumor cell lines. O-(3-hydroxypropyl) substituted compound (15) exhibited the best antitumor activity which is 3-5 times better than 5-[4'-(piperidinomethyl) phenyl]-2,3-dihydroimidazo[2,1-a]isoquinoline (1).

Antineoplastic Agents↗
PubMed1998

Synthesis and biological activity of 5-hydroxy-4-quinolones and 5-methoxy-4-quinolones as truncated acridones.

A series of 5-hydroxy-4-quinolone (3) and 5-methoxy-4-quinolone (4) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor, antiherpes and antituberculosis activities. Among them 5-hydroxy-8-methoxy-quinolone showed potent antitumor activity (IC50 = 17.7 microM for HL60) which was greater than that of acronycine. However, these compounds didn't show any significant antiherpes or antituberculosis activity.

Acridines↗
PubMed1998

Identification of alternatively spliced Na(+)-Ca2+ exchanger isoforms expressed in the heart.

Alternatively spliced isoforms of Na(+)-Ca2+ exchanger were found from various tissues and species. RT-PCR amplification was performed on the basis of our cloned mouse cardiac Na(+)-Ca2+ exchanger and four alternatively spliced isoforms of Na(+)-Ca2+ exchanger were identified. Three (NCX1.3, NCX1.4, and NCX1.12) of them were first identified in the heart, and one isoform (NCX1.12) was a novel spliced variant. These four spliced variants were present in the embryonic and adult atria and ventricles. Different cell types of the heart expressed different spliced isoforms of Na(+)-Ca2+ exchanger. Southern blot analysis indicated that the Na(+)-Ca2+ exchanger gene existed as a single copy in the mouse genome. Thus, the Na(+)-Ca2+ exchanger isoforms expressed in mouse heart are consistent with being produced by alternative splicing and they may have different functions in various cell types in the mouse heart.

Alternative Splicing↗
PubMed1998

Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives.

In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.721) was obtained through CoMFA.

Antineoplastic Agents↗
PubMed1998

Growth-inhibitory effects of Galla Rhois-derived tannins on intestinal bacteria.

The growth-inhibitory activity of Galla Rhois-derived materials towards 17 intestinal bacteria was evaluated using an impregnated paper disc method. The biologically active components of Galla Rhois were characterized as the tannins methyl gallate (MG) and gallic acid (GA) by spectral analysis. The growth responses varied with bacterial strain tested. In the test using 10 mg disc-1, MG and GA produced a clear inhibitory effect on harmful bacteria such as Clostridium perfringens, Cl. paraputrificum, Eubacterium limosum, Bacteroides fragilis, Staphylococcus aureus and Escherichia coli. Methyl gallate showed no growth-inhibitory activity towards Bifidobacterium adolescentis or B. longum whereas the growth of B. bifidum, B. breve, B. infantis, B. animalis, B. thermophilum, Lactobacillus acidophilus, Lact. plantarum and Streptococcus faecalis was slightly affected. However, GA did not adversely affect the growth of the bifidobacteria and lactobacilli. At 5 mg disc-1, MG significantly inhibited the growth of Cl. perfringens and Cl. paraputrificum but did not affect the growth of the bifidobacteria and lactobacilli. At 1 mg disc-1, MG greatly inhibited the growth of Cl. perfringens alone. These results may be an indication of at least one of the pharmacological actions of Galla Rhois.

Anti-Bacterial Agents↗
PubMed1998

Reversal of multidrug resistance by novel verapamil analogs in cancer cells.

The present study was performed to evaluate the ability of KR-30032 and KR-30035 to overcome multidrug resistance (MDR) by measuring the cytotoxicity and the accumulation rate of rhodamine. Additionally, the adverse cardiac toxicity of KR-30032 and KR-30035 was evaluated by measuring the changes of tension in isolated rat aorta and left ventricular pressure (LVP) in guinea pig heart. KR-30035 potentiated the paclitaxel-induced cytotoxicity to HCT15 [P-glycoprotein (P-gp)-expressed cells] to over 15-fold greater than that of verapamil and KR-30032 was equipotent with verapamil (EC50: 0.07, 5.0 and 3.3 nM at 1.0 microg/ml). KR-30032 and KR-30035 were without effect on cytotoxicity to SK-OV-3 cells (P-gp-non-expressing cells), as well as to tamoxifen-induced cytotoxicity in the above cell types. Maximal rhodamine accumulation rates with KR-30032, KR-30035 and verapamil were 290, 291 and 271% in HCT15 cells; and 451, 970 and 440% in HCT15/CL02 cells, respectively. KR-30032 and KR-30035 were 20- to 25-fold less potent than verapamil in relaxing aorta (EC50: 8.13, 6.40 and 0.32 microM, respectively) and were 12- to 35-fold less potent than verapamil in decreasing LVP in isolated hearts (EC50: 41.8, 14.1 and 1.2 microM, respectively). The results of this study suggest that KR-30032 and KR-30035 are active modulators of MDR with potentially minimal cardiovascular toxicity.

Adenocarcinoma↗
PubMed1998

The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistance-related drugs via modulation of P-glycoprotein.

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment and reducing drug accumulation by P-glycoprotein (P-gp) is one of the major mechanisms of multidrug resistance (MDR). The present study was performed to evaluate the MDR-reversal abilities of two bisbenzylisoquinoline alkaloids, tetrandine (TET) and fangchinoline (FAN), compared with verapamil (VER), a well-known P-gp modulator. TET (3.0 microM), FAN (3.0 microM) and VER (10.0 microM) reduced the paclitaxel (TAX) concentration required to achieve 50% inhibition of cell growth (EC50) to HCT15 (P-gp-positive) cells about 3100-, 1900- and 410-fold, and these compounds also reduced the EC50 value of actinomycin D (AMD) about 36.0-, 45.9- and 18.2-fold in the cells, respectively. Meanwhile, TET, FAN and VER had no effect on the cytotoxicity of the drugs to SK-OV-3 (P-gp-negative) cells. On the other hand, TET (3.0 microM), FAN (3.0 microM) and VER (10.0 microM) similarly enhanced the accumulation rates of rhodamine 123, a well known P-gp substrate, in HCT15 cells (200-250%). After efflux for 2 h with fresh medium, TET and FAN also enhanced the residual rate of rhodamine 123 about 5.0- and 2.6-fold in comparison with control, respectively. TET, FAN and VER could not affect the accumulation and residual rate of rhodamine 123 in SK-OV-3 cells. From the result, we conclude that TET and FAN enhanced the cytotoxicity of MDR-related drugs via modulation of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Four new cytotoxic germacranolides from Carpesium divaricatum.

In a bioassay-guided search for cytotoxic compounds from higher plants of South Korea, four new sesquiterpenes of the germacranolide type, named cardivins A (1), B (2), C (3), and D (4), have been isolated from the aerial parts of Carpesium divaricatum. Structures of these compounds were elucidated on the basis of spectroscopic techniques. Compounds 1, 2, 3, and 4 showed cytotoxicity to the human tumor cells, A-549 (nonsmall cell lung), SK-OV-3 (ovary), SK-MEL-2 (skin), XF-498 (central nervous system), and HCT-15 (colon).

Antineoplastic Agents, Phytogenic↗
PubMed1997

In vitro cytotoxicity of tanshinones from Salvia miltiorrhiza.

The cytotoxicity-guided fractionation of the roots of Salvia miltiorrhiza B. (Labiatae) extracts led to the isolation of eighteen active principles 1-18, responsible for the cytotoxicity against five cultured human tumor cell lines, i.e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon), using the SRB (sulfrhodamine-B) method in vitro. All active compounds 1-18 including two novel components 5 and 11 were comprised of tanshinone pigments, unusual diterpenes exclusively found in this species. The proliferation of each examined tumor cell line was significantly inhibited (IC50 values ranged from 0.2 to 8.1 micrograms/ml) during the continuous exposure of tumor cells to 1-18 for 48 hours, respectively.

Abietanes↗