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Biomedical subjects

Y C Kim

Publications and source records attributed to Y C Kim.

At least 181 records · Page 10Linked to original sources
PubMed1998

The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients.

In patients with non-small cell lung cancer (NSCLC), tumor expression of P21-Ras, HER2, P53, and Bcl-2 has been reported as independent predictors of prognosis. However, the prognostic information carried by these proteins has usually been determined separately, and their potential interaction has not been taken into account. We conducted immunostaining for P21-Ras, HER2, P53 and Bcl-2 on 238 cases of NSCLC in a Korean population with 203 squamous cell carcinomas, and 35 adenocarcinomas. P21-Ras, HER2, P53 or Bcl-2 was expressed at high levels in 54.6, 42.0, 18.1 and 71.8% of the NSCLC studied, respectively. A total of 59 tumors (24.8%) expressed only one protein, while 70 (29.4%) expressed two, 59 (24.8) expressed three, and 17 tumors (7.1%) expressed all four proteins. Univariate analysis testing the association of marker expression with survival found Bcl-2 expression to be significantly associated with a poor prognosis, as well as the co-expression of Bcl-2 + HER2, Bcl-2 + HER2 + P53, and Bcl-2 + HER2 + P53 + P21-ras with an increasing hazard ratio. By multivariate analysis controlling for age, tumor stage and tumor type, only the combination of Bcl-2 + HER2 expression was an independent marker of poor prognosis (hazard ratio = 1.91, P = 0.003). Thus, a prospective analysis of the co-expression of Bcl-2 + HER2 in NSCLC patients may identify patients with a poor prognosis who may benefit from more aggressive therapy.

Adenocarcinoma↗
PubMed1998

Effects of singly administered betaine on hepatotoxicity of chloroform in mice.

Effects of a single dose of betaine on the chloroform-induced hepatotoxicity were examined in adult male ICR mice. Administration of betaine (1000 mg/kg, ip) 1 to 7 hr prior to a chloroform challenge (0.25 ml/kg, ip) resulted in remarkable enhancement of hepatotoxicity as indicated by increases in serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. The potentiation of hepatotoxicity was most significant when mice were treated with betaine 4 hr earlier than chloroform. However, a 24 hr prior administration of betaine protected the animals from induction of the chloroform hepatotoxicity. Thus, its effect appeared to be highly dependent on the time lapse from the betaine pretreatment to the challenge of mice with chloroform. Betaine treated either 4 or 24 hr prior to sacrifice did not alter the hepatic contents of cytochrome P-450, cytochrome b5, or NADPH cytochrome P-450 reductase activity. Accordingly the hepatic microsomal p-nitroanisole O-demethylase, aminopyrine N-demethylase, or p-nitrophenol hydroxylase activities were not influenced by the betaine pretreatment. Betaine was shown not to affect any of the enzyme activities associated with glutathione (GSH) conjugation reaction, such as glutathione S-transferases (GSTs), glutathione disulfide (GSSG) reductase and GSH peroxidase irrespective of the time of its administration. When betaine was administered to mice 2-6 hr prior to sacrifice, hepatic GSH level, but not plasma GSH, was decreased significantly. Enhancement of the chloroform hepatotoxicity by betaine correlated well with the reduction in hepatic GSH levels. Both hepatic and plasma GSH levels were elevated in mice 24 hr following the betaine treatment. The results suggest that betaine affects induction of the chloroform hepatotoxicity by modulating the availability of hepatic GSH, which appears to be associated with its role in the transsulfuration pathway in the liver.

Alanine Transaminase↗
PubMed1998

Inhibition of nitric oxide synthesis by butanol fraction of the methanol extract of Ulmus davidiana in murine macrophages.

Since there is increasing evidence that nitric oxide (NO) plays a crucial role in the pathogenesis of inflammatory diseases, this study was undertaken to address whether the methanol (MeOH) extract and its fractions of the bark of Ulmus davidiana Planch (Ulmaceae) could modulate the expression of inducible NO synthase (iNOS) in thioglycollate-elicited murine peritoneal macrophages and murine macrophage cell line, RAW264.7 cells. Stimulation of the peritoneal macrophages and RAW264.7 cells with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) resulted in increased production of NO in the medium. However, the butanol (BuOH) fraction of the MeOH extract of U. davidiana barks showed marked inhibition of NO synthesis in a dose-dependent manner. The inhibition of NO synthesis was reflected in the decreased amount of iNOS protein, as determined by Western blotting. The BuOH fraction did not affect the viability of RAW264.7 cells, as assessed by methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay; rather, it reduced endogenous NO-induced apoptotic cell death via inhibition of NO synthesis in RAW264.7 cells. On the other hand, the BuOH fraction showed no inhibitory effect on the synthesis of NO by RAW264.7 cells, when iNOS was already expressed by the stimulation with IFN-gamma and LPS. Collectively, these results demonstrate that the BuOH fraction inhibits NO synthesis by inhibition of the induction of iNOS in murine macrophages.

Animals↗
PubMed1998

A new sesquiterpene ester from Celastrus orbiculatus reversing multidrug resistance in cancer cells.

In a search for revertants of multidrug-resistance in cancer cells, a novel (1) and two known (2,3) sesquiterpene esters were isolated from the root of Celastrus orbiculatus. The structure of 1 was elucidated as 1 beta,2 beta-diacetoxy-6 alpha,9 alpha-bis(benzoyloxy)dihydro-beta-agarofuran. Compounds 1-3 partially or completely reversed resistance to adriamycin, vinblastine, and paclitaxel of multidrug-resistant KB-V1 and MCF7/ADR cells.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Mode of action of torilin in multidrug-resistant cancer cell lines.

The mechanism of action of multidrug-resistance reversing activity of torilin was studied. In vitro experiments for the accumulation and efflux of vinblastine clearly indicated that MDR reversing effects of torilin would directly be associated with the increase of the intracellular accumulation of anticancer drugs by blocking the drug efflux. Furthermore, torilin increased the membrane ATPase activity from KB-V1 cells, suggesting that torilin might function by inhibiting drug transport mediated by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Spreading pattern of epidurally administered contrast medium in rabbits.

BACKGROUND: The aim of this study was to examine the precise spreading pattern of epidurally administered contrast medium with small increments of injection volume for determining both the exact volume of the dose required and the site of epidural injection according to different target segments of the spinal cord in a rabbit epidural model. METHOD: Following pentobarbital anesthesia, the epidural puncture was done surgically with a round-tipped blunt hook. The tip of the epidural catheter was located at either the mid-portion of T7 (T7 group, n = 7) or T12 (T12 group, n = 8). Injection of the contrast medium was started at 0.1 ml/kg and increased by 0.1 ml/kg up to a maximum of 0.6 ml/kg. RESULTS: In both groups, the extent of spread increased continuously with increasing injected volume (T7 group: r2 = 0.91, P = 0.0001; T12 group: r2 = 0.86, P = 0.0001) and the total spread of contrast medium was similar. However, the spread was not linearly volume dependent. The total number of segments (y) through which the contrast medium spread during changes in its volume (x) in the T7 and T12 groups was calculated as y = 4.0 + 41.8x - 28.1x2 and y = 0.2 + 57.7x - 43.5x2, respectively. The contrast medium spread in both rostral and caudal directions, equally from the catheter tip in the T7 group, whereas it spread rostrally about twice as far as it spread caudally in the T12 group (P < 0.05). CONCLUSION: In rabbits, it is recommended that at the lower thoracic or lumbar segments the tip of the epidural catheter should be located 1-3 segments below the target segment because of more rostral spread. In the case of mid-thoracic segments, however, placement at the target segment is recommended. In addition, a small titration of volume to achieve a particular range of epidural spread should be required.

Animals↗
PubMed1998

Relationship between global cytosolic Ca2+ concentration and Ca2+-activated K+ current in rabbit cerebral arterial myocyte.

In smooth muscle cells, the sarcoplasmic reticulum (SR) has been identified as the primary storage site for intracellular Ca2+. The peripheral SR is in close proximity with plasma membrane to make a narrow subsarcolemmal space. In this study, we investigated the regulation of subsarcolemmal [Ca2+] ([Ca2+]sl) and global cytosolic [Ca2+] ([Ca2+]c) of rabbit arterial smooth muscle using whole cell patch clamp technique and microspectrofluorimetry. The Ca2+-activated K+ current (IK(Ca)) and the ratio of fura-2 fluorescence (R340/380) were considered to reflect the [Ca2+]sl and [Ca2+]c, respectively. At a holding potential of 0 mV, extracellular application of 10 mM caffeine, a well known Ca2+-releasing agent, induced transient increase of IK(Ca) and R340/380 (IK(Ca)-transient and R340/380-transient, respectively). The increase and decay of IK(Ca) transient was faster than R340/380-transient. By repetitive application of caffeine, when the refilling state of SR was supposed to be lower than the control condition, IK(Ca)-transient and R340/380 transient were suppressed to different levels; e.g. the second application 20 sec after the first could induce smaller IK(Ca) transient than R340/380-transient. Dissociation of IK(Ca)-transient and R340/380-transient was removed by sufficient (>3 min) washout of caffeine. Recovery from the dissociation was also dependent upon the membrane potential; faster recovery was observed at negative (-40 mV) holding potential than at depolarized (0 mV) condition. Dissociation of IK(Ca) from [Ca2+]c was also partially prevented by perfusion with Na+-free (replaced by NMDG+) extracellular solution. These results suggest that, 1) there is prominent spatial inhomogeneity of [Ca2+] in cerebral arterial myocyte, 2) [Ca2+]Sl is preferentially affected by the interference from nearby plasmalemmal Ca2+ regulation mechanism which is partly dependent upon extracellular Na+.

Animals↗
PubMed1998

Rehabilitation of a triple amputee including a hip disarticulation.

A multiple amputee more severe than a triple amputee is uncommon. There have been no reports on the rehabilitation outcome of a triple amputee, including hip disarticulation and transtibial amputation. The authors report the rehabilitation of a patient with left hip disarticulation, right trans-tibial amputation, and left trans-humeral amputation due to a train accident. He has successfully completed the rehabilitation programme and has become independent in prosthetic ambulation, activities of daily living, and driving.

Adult↗
PubMed1998

Technetium-99m-MIBI uptake in small cell lung cancer.

UNLABELLED: Patients with small cell lung cancer (SCLC) often fail to respond to chemotherapy due to multidrug resistance (MDR). Technetium-99m-MIBI was reported to be a suitable transport substrate of P-glycoprotein, which is a cytoplasmic membrane protein encoded by the MDR gene. The purpose of this study was to evaluate whether or not the degree of MIBI uptake in SCLC or its retention on delayed imaging correlated with response to chemotherapy. METHODS: Twenty-five patients (19 men, 6 women; mean age 59 +/- 10 yr) with biopsy-proven SCLC had MIBI SPECT 3-7 days before starting chemotherapy. Imaging was acquired 1 and 4 hr after injection of 740 MBq MIBI using a single-head rotating gamma camera. Tumor-to-normal lung uptake ratio (T/NL) was measured. Percent retention (%R) was measured as: %R = 100 x (T/NL at 4 hr)/(T/NL at 1 hr). All patients received VAP chemotherapy (VP-16 100 mg/m2, adriamycin 40 mg/m2, cisplatin 25 mg/m2) every 4 wk for at least three times. Response to chemotherapy was grouped as complete remission, partial remission and no remission according to the change of tumor size on chest radiograph and CT images. Differences in T/NL and %R among the three groups were analyzed using ANOVA. RESULTS: T/NL of patients with complete remission (n = 7) and partial remission (n = 10) were significantly higher than that of no remission (n = 8) in 1 hr and 4 hr. T/NL at 1 hr in three groups were 2.75 +/- 0.78, 2.35 +/- 0.31 and 1.65 +/- 0.36, respectively. T/NL at 4 hr in three groups was 2.61 +/- 0.94, 2.48 +/- 0.50 and 1.66 +/- 0.42, respectively. However, %R was not different among three groups. Percent retention in three groups was 109.40 +/- 22.10, 96.71 +/- 14.25 and 103.59 +/- 28.43, respectively. CONCLUSION: SCLC with a higher MIBI uptake was more likely to respond to chemotherapy than that with a lower uptake. However, there was a considerable overlap of MIBI uptake among subjects. No significant correlation between the MIBI retention between 1 hr and 4 hr, and the response to chemotherapy was noted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Cell death and cytoskeletal alterations in cultured hepatic fat-storing cells induced by 6-hydroxydopamine.

We studied the effects of the neurotoxin, 6-hydroxydopamine (6-OHDA), on cultured fat-storing cells (FSCs) and hepatocytes. If either FSCs or hepatocytes were exposed to 6-OHDA for 4 hr, the neurotoxicant induced cell death in FSCs but not in hepatocytes. We decided to investigate why hepatocytes were refractile to injury from 6-OHDA while FSCs were labile. The activity of antioxidant enzymes within FSCs grown in vitro is remarkably lower than the activity in hepatocytes. Indeed, some specific antioxidant enzymes in FSCs were undetectable by our assays, but were easily detected in hepatocytes. Furthermore, the profile of antioxidant activity in FSCs was found to be almost identical to the profiles seen in cultured fibroblasts or myocytes. However, indirect immunolocalization of tyrosine hydroxylase in FSCs using anti-tyrosine hydroxylase antibodies was negative. Mazindol, a dopaminergic receptor antagonist, did not alleviate the toxicity of 6-OHDA suggesting that FSCs do not appear to possess a dopaminergic receptor. When the cell morphology of FSCs was examined by an indirect immunofluorescence technique, treatment of FSCs with 6-OHDA at a concentration of 200 microM for 2 hr modified the organization of alpha-smooth muscle actin into an irregular punctate pattern. Indeed, we found that the effects of 6-OHDA on cytoskeletal alterations and on the cell viability of FSCs were irreversible. These data suggest that : (1) 6-OHDA can cause irreparable injury to FSCs, but not hepatocytes; (2) hepatocytes are specially adapted to withstand an oxidative attack in contrast to FSCs. fibroblast and myocytes; (3) FSCs resemble other somatic cells in their low levels of antioxidant enzymes; and (4) this low profile of antioxidant activity may be responsible for the cell death and cytoskeletal alterations observed in FSCs in response to 6-OHDA.

Actins↗
PubMed1998

Blood sampling site-dependent plasma concentrations and hepatotoxic parameters in serum after intraperitoneal administration of acetaminophen to rats.

Blood sampling site-dependent (the dorsal aorta, the jugular vein, and the retro-orbital sinus) plasma concentrations of acetaminophen and its glucuronide and sulfate conjugates, and acetaminophen-induced hepatotoxic parameters (such as ALT and SDH activity) in serum were evaluated after intraperitoneal administration of acetaminophen, 500 mg/kg body weight, to rats. The plasma concentrations and the resultant AUC0-12 h of acetaminophen, acetaminophen-glucuronide, and acetaminophen-sulfate were significantly higher when blood samples were collected from the retro-orbital sinus than those from the jugular vein. The serum ALT activity at 3 and 24 h after administration of acetaminophen were significantly higher when the blood samples were collected from the retro-orbital sinus than those from the dorsal aorta.

Acetaminophen↗
PubMed1997

Nucleotide sequence of the Pseudomonas sp. DJ77 phnG gene encoding 2-hydroxymuconic semialdehyde dehydrogenase.

The nucleotide sequence of a 1520 bp region, spanning the coding region for the meta-cleavage pathway enzyme, 2-hydroxymuconic semialdehyde dehydrogenase, was determined. This enzyme, encoded by the phnG, is the first of three sequential enzymes required for conversion of 2-hydroxymuconic semialdehyde, which is produced from catechol by the PhnE catechol 2,3-dioxygenase, to 2-hydroxypent-2,4-dienoate in the dehydrogenative branch of the pathway. The deduced protein sequence is 484 amino acid residues long with a M(r) of 51504. The phnG has a high degree of homology with genes encoding isofunctional proteins from other Pseudomonas strains. We now show that the relative position of the phnG dehydrogenase gene in the phn operon is unique compared to the other meta-cleavage operons which have a dehydrogenative branch of the pathway.

Alcohol Oxidoreductases↗
PubMed1997

Identification of adjacent genes encoding the major catalase and a bacterioferritin from the plant-beneficial bacterium Pseudomonas putida.

The catA gene, encoding the major CatA from a root-colonizing isolate Pseudomonas putida (Pp), was cloned by complementation into a catalase (Cat)-deficient Escherichia coli (Ec) strain UM2. The ORF for catA consisted of 479 aa with a higher degree of identity with typical Cat from eukaryotes than prokaryotes. Chromosomal homologous exchange with a mutant gene bearing an insertion of a luxAB-npt cassette into the SfiI site of catA generated a CatA-deficient Pp isolate. This mutant and another mutant, J1M, derived by EMS mutagenesis, were highly sensitive to hydrogen peroxide. CatA activity and resistance to hydrogen peroxide were restored in both mutants by catA. Adjacent to the 3' end of catA was a potential ORF of 462 nt that had high identitity with other bfr genes that encode iron-storage proteins. Northern analysis of the bfr gene from Pp revealed a transcript of approximately 500 nt. CatA and bfr probes hybridized to the same size restriction fragments in genomic DNAs from other root-colonizing and plant pathogenic pseudomonads. Thus, the genes for an iron-storage protein and the heme-containing Cat appear to be conserved in adjacent loci in certain pseudomonads.

Amino Acid Sequence↗
PubMed1997

Localization and sequence analysis of the phnH gene encoding 2-hydroxypent-2,4-dienoate hydratase in Pseudomonas sp. strain DJ77.

The phnDEFG genes of Pseudomonas sp. DJ77, which are responsible for the degradation of polyaromatic hydrocarbons and chlorinated aromatics, were located previously on the 6.8 kb XhoI fragment of chromosomal DNA. Here, we sequenced a downstream region hitherto unknown and identified the phnH gene encoding a 2-hydroxypent-2,4-dienoate hydratase, which is required for the conversion of 2-hydroxypent-2,4-dienoate to 4-hydroxy-2-oxovalerate in the meta-cleavage pathway of catechols. The relative position of the hydratase gene in the phn operon is unique compared to the other meta-cleavage operons which have a dehydrogenative branch of the pathway. The PhnH hydratase contains 264 amino acids with a Mr of 28048. The deduced amino acid sequence of the PhnH enzyme is 60.9-31.6% identical to those of homologous enzymes encoded by the todG, bphE, cmtF, bphH, bphX1, xylJ, dmpE, cumE, MTCY03C7.20 and etbE genes.

Amino Acid Sequence↗
PubMed1997

Structure of catechol 2,3-dioxygenase gene encoded in TOM plasmid of Pseudomonas cepacia G4.

The catechol 2,3-dioxygenase is an extradiol-type dioxygenase which cleaves the C-C bond at the meta position of catechol to form 2-hydroxymuconic semialdehyde. A catechol 2,3-dioxygenase gene (tomB) in the TOM plasmid of P. cepacia G4 has been cloned and its nucleotide sequence was analyzed. The enzyme gene consisted of 945 base pairs with an ATG initiation codon and a TGA termination codon which can encode a polypeptide of molecular weight 35 kDa containing 314 amino acid residues, and a putative ribosome-binding sequence was identified at approximately 10 nucleotides upstream of the initiation codon. The deduced amino acid sequence of catechol 2,3-dioxygenase from P. cepacia G4 exhibited 79-82% homologies with those of 3-methylcatechol 2,3-dioxygenase of P. putida UCC2 and catechol 2,3-dioxygenase of P. pickettii PKO1.

Amino Acid Sequence↗
PubMed1997

8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and delta F508 first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis is an autosomal recessive disorder affecting chloride transport in pancreas, lung, and other tissues, which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Certain alkyl xanthines such as CPX (8-cyclopentyl-1,3-dipropylxanthine) stimulate Cl- efflux from cells bearing the delta F508 genotype common to most cases of cystic fibrosis. We have hypothesized that the CFTR molecule itself might be the site for CPX action, perhaps in the region of the first nucleotide binding fold (NBF-1) domain. Therefore, to test this hypothesis directly we have used a rapid membrane filtration assay to measure the kinetics of association and dissociation of [3H]CPX to both recombinant NBF-1 and recombinant NBF-1 bearing the delta F508 mutation. We report that [3H]CPX binds with higher affinity to the delta F508-NBF-1 of CFTR (Kd = 1.0 nM) than to the wild-type NBF-1 of CFTR (Kd = 17.0 nM). These Kd values were calculated from direct measurements of the association and dissociation rate constants. The rate constants for the dissociation reaction of the wild-type NBF-1 and delta F508-NBF-1 of CFTR were not different from each other. However, the corresponding rate constants for the association reaction were k(+1) (NBF-1) = 4.7 +/- 0.9 x 10(4) M(-1) s(-1) and k(+1) (delta F508-NBF-1) = 1.6 +/- 0.3 x 10(5) M(-1) s(-1), respectively. These Kd values were corroborated by equilibrium-binding experiments, which gave very similar values. We have also measured the relative displacement of various xanthines from both wild-type NBF-1 and delta F508-NBF-1, in anticipation that the order of potencies for binding might parallel the action of the different xanthines on CF cells. For wild-type NBF-1, the rank order was DA-CPX > DAX > CPX > caffeine > adenosine >> IBMX > 2-thioCPX. For delta F508-NBF-1, the rank order was DAX > CPX > caffeine > DA-CPX > adenosine >> IBMX > 2-thioCPX. These relative potencies show close parallels with previously observed relative potencies of these drugs on CF cells, and thus lend strong support to the hypothesis that the mechanism of action on CF cells may involve direct interaction with the CFTR molecule itself.

Adenosine↗
PubMed1997

Primers determine the sensitivity of PCR-mediated hepatitis B virus DNA detection and pretreatment of PCR mixture with 8-methoxypsoralen eliminates false-positive results.

Most methods for the diagnosis of hepatitis B virus (HBV) infection largely depend on viral DNA detection by polymerase chain reaction (PCR) or radioimmunological assay of viral antigens or antibodies. The quality assurance program recently established in Europe reported that PCR-mediated HBV DNA detection methods used in many laboratories produced a high rate of false-positive and false-negative results. Thus, we attempted to improve the conditions of current PCR methods for detection of HBV DNA. In the present study, we applied a recently developed method of releasing HBV DNA from virion by NaOH treatment of patient serum. Using four different primer sets specific to the HBV core region, we found that the sensitivity of first-round PCR can be improved by more than two orders of magnitude depending on the primers. The second round of PCR using nested primers was sensitive enough to detect up to 10(-6) pg of the HBV DNA, which is equivalent to approximately 3 copies of the HBV genome. Among the approximately 800 HBV-infected patient sera investigated in our laboratory, more than 60% of the tested samples gave positive results in the first-round PCR. The rate of positive results obtained using our experimental conditions is very high in comparison with other reports. The reamplification of the first-round PCR reaction mixture with the nested primers produced practically 100% positive results. For diagnosis of HBV infection, we routinely used 1 microliter of patient serum, which was found to be optimum in our laboratory. Surprisingly, from 20% of our positive results, even serum diluted to 1/100 (0.01 microliter) produced a stronger signal than 1 microliter. This observation suggests that direct PCR amplification of HBV DNA released from serum by NaOH treatment has to be compensated by other DNA detection methods for correct quantitation. In order to eliminate the false positive signal resulting from the carry-over due to massive screening of a large number of samples, PCR reaction mixture containing 8-methoxypsoralen was exposed to ultraviolet light prior to thermal cycle amplification. This exercise did not decrease the sensitivity of the detection method, but almost completely removed the false positive results caused by contaminated templates. We are in the process of improving PCR-mediated HBV DNA detection methods to attain more reliable and easily applicable methods.

Base Sequence↗