Biomedical subjects

Y C Kim

Publications and source records attributed to Y C Kim.

At least 127 records · Page 7Linked to original sources

PubMed2000

Antioxidant lignans from Machilus thunbergii protect CCl4-injured primary cultures of rat hepatocytes.

Eleven lignans (1-11) were isolated from the CH2Cl2 fraction of the bark of Machilus thunbergii Sieb. et Zucc. (Lauraceae). These were identified as (-)-acuminatin (1), (-)-isoguaiacin (2), meso-dihydroguaiaretic acid (3), (+)-galbacin (4), (-)-sesamin (5), (+)-galbelgin (6), machilin A (7), machilin G (8), licarin A (9), and nectandrin A (10) and B (11). Primary cultures of rat hepatocytes were co-incubated for 90 min with the hepatotoxin CCl4 and each of the 11 lignans (50 microM). Hepatoprotective activity was determined by measuring the level of glutamic pyruvic transaminase released into the medium from the primary cultures of rat hepatocytes. (-)-Acuminatin, (-)-isoguaiacin and meso-dihydroguaiaretic acid all significantly reduced the level of glutamic pyruvic transaminase released. Further investigation revealed that these three compounds significantly preserved the levels and the activities of glutathione, superoxide dismutase, glutathione peroxidase and catalase. (-)-Acuminatin, (-)-isoguaiacin and meso-dihydroguaiaretic acid also ameliorated lipid peroxidation as demonstrated by a reduction of malondialdehyde production. These results suggest that (-)-acuminatin, (-)-isoguaiacin and meso-dihydroguaiaretic acid exert diverse hepatoprotective activities, perhaps by serving as potent antioxidants.

Animals↗

PubMed2000

Dammarane derivatives protect cultured rat cortical cells from glutamate-induced neurotoxicity.

We previously reported that ginsenosides Rb1 and Rg3, dammarane glycosides, of Panax ginseng C. A. Meyer (Araliaceae), significantly attenuated glutamate-induced neurotoxicity in primary cultures of rat cortical cells. To seek more potent neuroprotective compounds, we attempted to modify the chemical structure of dammarane glycosides and obtained six derivatives, MA-11, PT-11, PT-111, POA-101, POA-111 and N-001. The neuroprotective activity of these dammarane derivatives were evaluated employing primary cultures of rat corticoid cells. The glutamate-induced neuronal cell damage was significantly reduced by a pre-treatment with protopanaxadiol, MA-11 or PT-11 at concentrations ranging from 100 nM to 10 microM. Both MA-11 and PT-11, preserved the levels of catalase and inhibited decreases in glutathione reductase in glutamate-injured cells. Furthermore, the dammarane derivatives reduced the content of intracellular peroxide in glutamate-intoxicated cells. Finally, they inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, in glutamate-insulted cells. These results show that the dammarane derivatives, MA-11 and PT-11, exert significant neuroprotective effects on cultured cortical cells by a mechanism seemingly distinct from that afforded by ginsenosides Rb1 and Rg3. As such, the dammarane derivatives may be efficacious in protecting neurons from oxidative damage caused by exposure to excess glutamate.

Animals↗

PubMed2000

Sauchinone, a lignan from Saururus chinensis, attenuates CCl4-induced toxicity in primary cultures of rat hepatocytes.

We used primary cultures of rat hepatocytes injured by the hepatotoxin, carbon tetrachloride (CCl4), as a test system to screen for hepatoprotective compounds from natural products. Sauchinone was isolated from the aerial parts of Saururus chinensis (Saururaceae) by this method. At a concentration of 50 microM, sauchinone significantly reduced the release into the culture medium of glutamic pyruvic transaminase from CCl4-damaged cultures of rat hepatocytes. It has been determined that glutathione, superoxide dismutase and glutathione peroxidase all play important roles in the cellular defense against oxidative stress. Sauchinone appeared to protect primary cultured rat hepatocytes exposed to CCl4 from significant drops in the levels of each of these three specific markers, respectively. Sauchinone also seemed to ameliorate lipid peroxidation as demonstrated by a reduction in the production of the oxidized lipid byproduct, malondialdehyde. These results suggest that sauchinone may exert hepatoprotective activity through antioxidant activity.

Animals↗

PubMed2000

Background nonselective cationic current and the resting membrane potential in rabbit aorta endothelial cells.

The ion channel conductances that regulate the membrane potential was investigated by using a perforated patch-clamp technique in rabbit aorta endothelial cells (RAECs). The whole-cell current/voltage (I-V) relation showed a slight outward rectification under physiological ionic conditions. The resting membrane potential was -23.3 +/- 1.1 mV (mean +/- SEM, n = 19). The slope conductances at the potentials of -80 and 50 mV were 31.0 +/- 4.0 and 62.8 +/- 7.1 pS pF(-1), respectively (n = 15). Changes in the extracellular and intracellular Cl(-) concentrations did not affect the reversal potential on I-V curves. The background nonselective cationic (NSC) current was isolated after the K(+) current was suppressed. The relative permeabilities calculated from the changes in reversal potentials using the constant-field theory were P(K):P(Cs):P(Na):P(Li) = 1:0.87:0.40:0.27 and P(Cs):P(Ca) = 1:0.21. Increases in the external Ca(2+) decreased the background NSC current in a dose-dependent manner. The concentration for half block by Ca(2+) was 1.1 +/- 0.3 mM (n = 7). Through the continuous recording of the membrane potential in a current-clamp mode, it was found that the background NSC conductance is the major determinant of resting membrane potential. Taken together, it could be concluded that the background NSC channels function as the major determinant for the resting membrane potential and can be responsible for the background Ca(2+) entry pathway in freshly isolated RAECs.

Animals↗

PubMed2000

Vascular endothelial growth factor in malignant and tuberculous pleural effusions.

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.

Endothelial Growth Factors↗

PubMed2000

The role of E-cadherin expression in non-small cell lung cancer.

The purpose of this study is to evaluate the clinical significance of E-cadherin expression in lung cancer. E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1). Strongly positive (++) E-cadherin tumors were classified as a type of preserved E-cadherin expression (Pr type), while the others (+, - tumors) were classified as a type of reduced E-cadherin expression (Rd type). The frequency of Pr type in squamous cell carcinomas (59.0%) was higher than Rd type. However, in adenocarcinomas, the frequency of Rd type was higher than Pr type. E-cadherin expression pattern was significantly correlated with differentiated state (Pearson correlation coefficient 0.394, p<0.001). E-cadherin expression of well-differentiated tumors was more frequently preserved than that of poorly differentiated tumors (60.0% vs. 25.9%). With regard to the correlation between E-cadherin expression and stages of lymph node metastasis in non-small cell lung cancers, the percentage of tumors with Pr type E-cadherin expression declined from 66.3% (< or = N1) to 38.6% (> or = N2), indicating that loss of E-cadherin expression is responsible for acquisition of invasive potential of lung cancer as well as the possible role of E-cadherin in the histological differentiation of lung cancer.

Adult↗

PubMed2000

Successful treatment in the patient with serum sodium level greater than 200 mEq/L.

Hypernatremia developing in nonhospitalized adults is predominantly a disease of the elderly and mentally handicapped patients, possibly revealing inadequate nursing care of these patients. It has long been claimed that the duration of hypernatremia and its rate of correction are correlated with improvement in patients' neurologic status. Since there are only a handful of cases with serum sodium levels greater than 200 mEq/L until recently, it is not clear at what rate plasma sodium concentration can be safely normalized in severe hypernatremic patients. We report a case of severe hypernatremia with survival. This patient underwent rapid correction of serum sodium concentration during the management of this metabolic derangement using isotonic solution.

Female↗

PubMed2000

A case of Cushing's syndrome in ACTH-secreting mediastinal paraganglioma.

Paragangliomas are unusual neuroendocrine cell tumors arising from paraganglia, of which ACTH-secreting cases in the mediastinum are extremely rare. A 51-year-old woman was admitted for generalized edema and weakness which began 5 months ago. Chest X-ray and CT scan revealed a tumor mass in the anterior mediastinum. The plasma cortisol and ACTH levels were very high. Other sources secreting ACTH, except mediastinal mass, were not found. Surgical excision of mediastinal mass and left supraclavicular lymph node was performed. The postoperative microscopic finding and immunohistochemical staining revealed organoid tumor cell nests (zellballen) and S-100 protein positive sustentacular cells which are characteristics of paraganglioma. This was thus a case of Cushing's syndrome resulting from ectopic ACTH production in anterior mediastinal paraganglioma.

Adrenocorticotropic Hormone↗

PubMed2000

Differential regulation of the stearoyl-CoA desaturase genes by thiazolidinediones in 3T3-L1 adipocytes.

Two stearoyl-CoA desaturase (SCD) isoforms can be expressed during the differentiation of 3T3-L1 preadipocytes into adipocytes. Here we report on the effects of the peroxisome proliferator-activated receptor gamma ligand troglitazone (TRO) on scd1 and scd2 mRNA levels as determined by Northern blotting, on SCD protein expression as determined by Western blotting, and on total lipid composition as determined by GC during differentiation. In preadipocytes, scd1 mRNA and SCD protein were not detected, whereas scd2 mRNA was detected. These cells have high levels of palmitate (16:0), stearate (18:0), and monounsaturated oleate (Delta(9)-18:1) and low levels of monounsaturated palmitoleate (Delta(9)-16:1). In MDI (methylisobutylxanthine, dexamethasone, and insulin)-treated cells, scd1 mRNA and SCD protein were increased approximately 100-fold relative to preadipocyte levels, the scd2 mRNA level was increased 2-fold, Delta(9)-16:1 was increased approximately 20-fold, and 18:0 was decreased approximately 3-fold. In TRO-treated cells, the scd1 mRNA level was lower than that observed in preadipocytes, while the scd2 mRNA level was similar. TRO also decreased scd1 mRNA in primary adipocytes. The TRO-treated cells contained a Delta(9)-18:1 level typical of MDI-treated cells whereas, conversely, these cells also contained a low Delta(9)-16:1 level typical of preadipocytes. The implications of these correlations for the regulatory and enzymatic mechanism(s) used to establish and maintain lipid composition are discussed.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Effects of neostigmine on the pharmacokinetics of intravenous parathion in rats.

It was reported that the area under the plasma concentration-time curve from time zero to time infinity (AUC) of parathion was significantly smaller and the time-averaged total body clearance (CL) of parathion was significantly faster after intravenous administration of parathion to rats pretreated with dexamethasone than those in control rats. This was supported by significantly faster intrinsic clearance of parathion to form paraoxon in hepatic microsomal fraction of rats pretreated with dexamethasone. The above data suggested that parathion was metabolized to paraoxon by dexamethasone-inducible hepatic cytochrome P450 (CYP) 3A in rats. The purpose of this study is to explain the protective effects of neostigmine against paraoxon toxicity by suppressing CYP3A and hence decreasing formation of toxic metabolite, paraoxon by neostigmine. The pharmacokinetic changes of parathion and its active metabolite, paraoxon, were investigated after intravenous administration of parathion, 3 mg/kg, to control Sprague-Dawley rats and the rats pretreated with neostigmine (200 microg/kg, intraperitoneal injection 30 min before parathion administration). After 1-min intravenous infusion of parathion to rats pretreated with neostigmine, the AUC of parathion (65.1 versus 74.3 microg min/ml) was significantly greater and the CL of parathion (45.1 versus 40.4 ml/min/kg) was significantly slower than those in control rats. Based on in vitro hepatic microsomal studies, neostigmine inhibited significantly the erythromycin N-demethylase activity (1.03 versus 0.871 nmol/mg protein/min), mainly mediated by hepatic cytochrome P450 3A in rats. The above data suggested that the formation of paraoxon was inhibited in rats pretreated with neostigmine by inhibiting CYP3A.

Animals↗

PubMed1999

Regulation of stearoyl-CoA desaturase genes: role in cellular metabolism and preadipocyte differentiation.

The degree of fatty acid unsaturation in cell membrane lipids determines membrane fluidity, whose alteration has been implicated in a variety of disease states including diabetes, obesity, hypertension, cancer, and neurological and heart diseases. Stearoyl-CoA desaturase (SCD) is a key rate-limiting enzyme in the synthesis of unsaturated fatty acids by insertion of a cis-double bond in the Delta9 position of fatty acid substrates. Palmitate and stearate are the preferred substrates, which are converted to palmitoleate and oleate, respectively. These monounsaturated fatty acids are the major constituents of cellular membrane phospholipids and triacylglycerol stores found in adipose tissue. Two mouse and rat SCD genes (SCD1 and SCD2) have been cloned and characterized. During the differentiation of 3T3-L1 preadipocytes into adipocytes, SCD1 and SCD2 mRNAs are induced concomitant with increased de novo synthesis of palmitoleate and oleate. The physiological significance of expressing the two isoforms in the adipocytes is currently unknown. In this review we discuss the role of the SCD isoforms in metabolism and the recent findings on the differential regulation of mouse SCD genes by the antidiabetic thiazolidinediones (TZDs), during preadipocyte differentiation.

Adipocytes↗

PubMed1999

Transcriptional regulation by iron of genes encoding iron- and manganese-superoxide dismutases from Pseudomonas putida.

Genes from Pseudomonas putida (Pp), sodA, encoding manganese-superoxide dismutase (MnSOD) and, sodB, iron-superoxide dismutase (FeSOD) were cloned by hybridization with digoxigenin (dig)-labeled PCR products generated from Pp genomic DNA. The sodB gene had a 594 bp open reading frame (ORF), corresponding to 198 amino acids (aa), and a transcript of 880 bases. The sodA gene contained a 609 bp ORF encoding 203 aa and was transcribed as part of a polycistronic operon, consisting of orfY-fumC-orfX-sodA. Pp sodA or sodB genes both restored aerobic growth, growth on paraquat, and growth on minimal medium to an Escherichia coli (Ec) mutant deficient in SOD activity. Paraquat treatment did not enhance mRNA transcription of the sod genes or increase SOD activity in Pp. The Pp sodB gene was highly expressed throughout logarithmic-(log) growth phase and stationary-phase cells grown in medium supplemented with FeCl3, but was down-regulated in iron-deficient conditions, such as in stationary-phase or generated by 2,2'-dipyridyl (DP) treatment. This is the first evidence that iron regulates expression of the sodB gene at the transcriptional level. In contrast, iron-deficient conditions, or addition of MnCl2 to the growth medium, induced transcripts (2.4 kb and 1.2 kb) from the sodA operon. Our results reveal an intricate role of iron in the transcriptional regulation of both Pp sodA and sodB genes.

Cell Division↗

PubMed1999

Structure-activity relationships of bisphosphate nucleotide derivatives as P2Y1 receptor antagonists and partial agonists.

The P2Y1 receptor is present in the heart, in skeletal and various smooth muscles, and in platelets, where its activation is linked to aggregation. Adenosine 3',5'- and 2',5'-bisphosphates have been identified as selective antagonists at the P2Y1 receptor (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329) and have been modified structurally to increase receptor affinity (Camaioni et al. J. Med. Chem. 1998, 41, 183-190). We have extended the structure-activity relationships to a new series of deoxyadenosine bisphosphates with substitutions in the adenine base, ribose moiety, and phosphate groups. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-(methylthio)adenosine 5'-diphosphate (antagonist effect). 2'-Deoxyadenosine bisphosphate analogues containing halo, amino, and thioether groups at the 2-position of the adenine ring were more potent P2Y1 receptor antagonists than analogues containing various heteroatom substitutions at the 8-position. An N6-methyl-2-chloro analogue, 6, was a full antagonist and displayed an IC50 of 206 nM. Similarly, N6-methyl-2-alkylthio derivatives 10, 14, and 15 were nearly full antagonists of IC50 < 0.5 microM. On the ribose moiety, 2'-hydroxy, 4'-thio, carbocyclic, and six-membered anhydrohexitol ring modifications have been prepared and resulted in enhanced agonist properties. The 1,5-anhydrohexitol analogue 36 was a pure agonist with an EC50 of 3 microM, i.e., similar in potency to ATP. 5'-Phosphate groups have been modified in the form of triphosphate, methyl phosphate, and cyclic 3',5'-diphosphate derivatives. The carbocyclic analogue had enhanced agonist efficacy, and the 5'-O-phosphonylmethyl modification was tolerated, suggesting that deviations from the nucleotide structure may result in improved utility as pharmacological probes. The N6-methoxy modification eliminated receptor affinity. Pyrimidine nucleoside 3', 5'-bisphosphate derivatives were inactive as agonists or antagonists at P2Y receptor subtypes.

Animals↗

PubMed1999

Cloning and sequencing of the fcbB gene encoding 4-chlorobenzoate-coenzyme A dehalogenase from Pseudomonas sp. DJ-12.

Pseudomonas sp. DJ-12 degrades 4-chlorobenzoate through hydrolytic dechlorination to produce 4-hydroxybenzoate and a chloride ion. The fcbB gene encoding the 4-chlorobenzoate-coenzyme A (4CBA-CoA) dehalogenase which catalyzes the nucleophilic substitution reaction to convert 4CBA-CoA to 4-hydroxybenzoate-coenzyme A (4HBA-CoA) in the consecutive steps of dechlorination was cloned from the chromosome of the organism. A nucleotide sequence analysis of the gene showed an open reading frame consisting of 810 nucleotides, which can encode for a polypeptide of molecular mass 30 kDa, containing 269 amino acid residues. A promoter-like sequence (-35 and -10 region) and a putative ribosome-binding sequence were identified. A deduced amino acid sequence of the 4CBA-CoA dehalogenase showed 86%, 50%, and 50% identity with those of corresponding enzymes in the Pseudomonas sp. CBS3, Arthrobacter sp. SU, and Arthrobacter sp. TM1, respectively.

Amino Acid Sequence↗

PubMed1999

The phnIJ genes encoding acetaldehyde dehydrogenase (acylating) and 4-hydroxy-2-oxovalerate aldolase in Pseudomonas sp. DJ77 and their evolutionary implications.

The two final steps of meta-cleavage pathway for catechol degradation involve conversion of 4-hydroxy-2-oxovalerate, via acetaldehyde, to acetyl coenzyme A. We report here the complete nucleotide sequences and overexpression of the phnIJ genes for an acetaldehyde dehydrogenase (acylating) (ADA) and a 4-hydroxy-2-oxovalerate aldolase (HOA) from the meta-pathway operon of the phenanthrene-degrading bacterium, Pseudomonas sp. strain DJ77. Additional partial sequence analysis of adjacent DNA shows the gene order within the operon to be phnHIJ, identical to the order found for the isofunctional genes in the other meta-pathway operons. The deduced amino acid sequences of the PhnI (312 amino acids) and PhnJ (343 amino acids) have identities of 51-71% with the corresponding genes of dmp, xyl, nah, bph_LB400, bph_KKS102, tod, cum, cmt, and MTCY03C7 operons. The phylogenetic analyses reveal the evolutionary relationships of HOA and ADA.

Acetaldehyde↗

PubMed1999

Purification and characterization of a serine protease with fibrinolytic activity from Tenodera sinensis (praying mantis).

Mantis egg fibrolase (MEF) was purified from the egg cases of Tenodera sinensis using ammonium sulfate fractionation, gel filtration on Bio-Gel P-60 and affinity chromatography on DEAE Affi-Gel blue gel. The protease was assessed homogeneous by SDS-polyacrylamide gel electrophoresis and has a molecular mass of 31500 Da. An isoelectric point of 6.1 was determined by isoelectric focusing. Amino acid sequencing of the N-terminal region established a primary structure composed of Ala-Asp-Val-Val-Gln-Gly-Asp-Ala-Pro-Ser. MEF readily digested the Aalpha- and Bbeta-chains of fibrinogen and more slowly the gamma-chain. The nonspecific action of the enzyme results in extensive hydrolysis of fibrinogen and fibrin releasing a variety of fibrinopeptide. The enzyme is inactivated by Cu2+ and Zn2+ and inhibited by PMSF and chymostatin, yet elastinal, aprotinin, TLCK, TPCK, EDTA, EGTA, cysteine, beta-mercaptoethanol, iodoacetate, E64, benzamidine and soybean trypsin inhibitor do not affect activity. Antiplasmin was not sensitive to MEF but antithrombin III inhibited the enzymatic activity of MEF. Among chromogenic protease substrates, the most sensitive to MEF hydrolysis was benzoyl-Phe-Val-Arg-p-nitroanilide with maximal activity at pH 7.0 and 30 degrees C. MEF preferentially cleaved the oxidized B-chain of insulin between Leu15 and Tyr16. D-Dimer concentrations increased on incubation of cross-linked fibrin with MEF, indicating the enzyme has a strong fibrinolytic activity.

Amino Acid Sequence↗

PubMed1999

A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region.

The centromeric part of chromosome segment 11p15.5 contains a region of frequent allele loss in many adult solid malignancies. This region, called LOH11A, is lost in 75% of lung cancers and is thought to contain a gene that may function as a metastasis suppressor. Genetic complementation studies have shown suppression of the malignant phenotype including reduction of metastasis formation. We constructed a high-resolution physical map and contig over 1.4 Mb that includes the beta-hemoglobin gene cluster and the gene for the large subunit of ribonucleotide reductase (RRM1). Through sequencing and computerized analysis, we determined that this region contains an unusually large number of transposable elements, which suggests that double-stranded DNA breaks occur frequently here. Twenty-two putative genes were identified. Because of its location at the site of maximal allele loss in the 650-kb LOH11A region and previous functional studies, RRM1 is the most likely candidate gene with metastasis suppressor function. The malignant phenotype, in this case, results from a relative loss of function rather than a complete loss.

Adenocarcinoma↗

PubMed1999

Non-ginsenoside nicotinic activity in ginseng species.

Amongst the many different therapeutic applications of ginseng are beneficial effects on age-related cognitive impairments. Ageing in the brain is associated with a loss of nicotinic receptor binding and receptor stimulation increases binding. Stimulation of the CNS (central nervous system) nicotinic receptor is considered to be beneficial in relation to symptomatic treatment and neuroprotection in age-associated cognitive disorders which involve a further receptor loss. We assessed Panax ginseng, Panax quinquefolium and several chemical constituents of these plants for nicotinic activity based on displacement of 3H-(-)nicotine from human brain cerebral cortex membranes in vitro. Dose-dependent displacement was evident in crude ethanol extracts of Panax ginseng and Panax quinquefolium. Assay of an extract of Panax ginseng showed the plant to have affinity for both the nicotinic receptor, and to a lesser extent the muscarinic receptor (IC50 2.12 mg/mL and 5.25 mg/mL respectively). Activity was largely conserved after the extraction of choline and other water soluble quaternary ammonium compounds (QAC), indicating that the activity of the plant extracts was not due to choline. Displacement binding assay of some purified chemical constituents, including a number of ginsenosides, showed that these were not primarily responsible for Panax activity. The active chemical constituent has yet to be identified, but the demonstrated nicotinic activity of ginseng warrants further investigation with reference to therapeutic activity in age-related conditions such as dementia.

Adult↗