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Biomedical subjects

E J Kim

Publications and source records attributed to E J Kim.

At least 73 records · Page 4Linked to original sources
PubMed2000

Association of focal adhesion kinase with fibronectin and paxillin is required for precartilage condensation of chick mesenchymal cells.

We show that tyrosine phosphorylation of FAK was increased as precartilage condensation occurred, followed by a subsequent decrease in proliferation of in vitro micromass culture of wing bud mesenchymal cells. FAK was associated with fibronectin and paxillin, which were maximal at day 3 of culture. FAK was also associated with signaling molecules such as PLC-gamma and PI3-kinase through c-Src. The beta1 integrin antibody and several inhibitors of signaling molecules such as herbimycin A, U73122, LY294002, as well as cytochalasin D, an actin depolymerizing agent, remarkably decreased tyrosine phosphorylation of FAK and its association with fibronectin and paxillin during condensation. resulting in a marked inhibition of condensation and chondrogenesis. Taken together, our findings suggest that beta1 integrin-mediated interaction of mesenchymal cells and fibronectin signals to accelerate the precartilage condensation through tyrosine phosphorylation of FAK and its association with paxillin. This signaling pathway is required for precartilage condensation and subsequent cartilage nodule formation in chondrogenesis.

Animals↗
PubMed2000

Heart cell transplantation improves heart function in dilated cardiomyopathic hamsters.

BACKGROUND: Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium. This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters. METHODS AND RESULTS: Ventricular heart cells were isolated from 4-week-old BIO 53. 58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4 x 10(6) cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, n=12 each). Sham-operated hamsters (n=12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater (P:<0. 001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915+/-253 versus control 453+/-120 and sham 530+/-187 mm Hg/s, P:<0.001, balloon volume of 15 microL). No differences in ventricular function were found between control and sham-operated hamsters. CONCLUSIONS: The transplanted ventricular heart cells formed cardiac-like tissue in cardiomyopathic myocardium and improved its contractile function.

Animals↗
PubMed2000

Stereoselective determination of cetirizine and studies on pharmacokinetics in rat plasma.

Enantiomers may confer benefits over racemates in therapeutic uses and we developed a chiral separation method of cetirizine enantiomers, a second generation H1 histamine receptor antagonist, in rat plasma. alpha1-Acidglycoprotein based chiral stationary phase(AGP-CSP), monitored with UV at 230 nm was used to separate the enantiomers. Observed enantioselectivity (alpha) was 2.0. The AGP-CSP was also used at a preparative scale to isolate the enantiomers with an optical purity of greater than ee 99%. In addition, an analysis was carried out for the cetirizine enantiomers in rat plasma to study the differences of enantiomers in pharmacokinetics. Both (+)- and (-)-cetirizine were separated using a reversed-phase column of AGP, and were detected at the range of 2.5-200 microg ml(-1) in plasma. Although there was no recognizable differences in pharmacokinetics between the enantiomers in rat, the method appears to be useful for their pharmacokinetic studies.

Animals↗
PubMed2000

Role of glucose utilization in the restoration of hypophysectomy-induced hepatic cytochrome P450 2E1 by growth hormone in rats.

Growth hormone and insulin are the primary determinants for cytochrome P450 2E1 (CYP2E1) expression. The role of glucose on the induction of CYP2E1 by hypophysectomy and on the restorative effect by growth hormone was investigated in the rat liver. Western and Northern blot analyses revealed that hypophysectomy induced CYP2E1 by 5-fold at 1-4 weeks, relative to control, with a concomitant increase in CYP2E1 mRNA. Hypophysectomized rats (HXR) showed a 20% reduction in the plasma glucose level. Hypophysectomy-induced increase in the CYP2E1 mRNA was completely abolished by glucose feeding in drinking water (10%) for 7 days. Treatment of HXR with hGH (2 I.U./kg, twice a day, for 7 days) inhibited the increases in CYP2E1 protein and mRNA levels with restoration of the plasma glucose level. In contrast to the effect of human growth hormone (hGH) on CYP2E1 in HXR with free access to foods, CYP2E1 expression failed to be restored by hGH in starving HXR. However, glucose feeding of starving HXR abolished the induction of CYP2E1. Effects of hypophysectomy and hGH treatment were studied in streptozotocin-induced diabetic rats. Insulin, but not hGH, prevented an increase in CYP2E1 mRNA in diabetic rats. The hepatic CYP2E1 induction in hypophysectomized diabetic rats was inhibited by hGH treatment, indicating that the hGH effect on CYP2E1 expression did not involve insulin production. These results provide evidence that the induction of hepatic CYP2E1 by hypophysectomy may result from reduced glucose utilization, and that the effect of hGH on CYP2E1 expression may be mediated with enhanced glucose utilization, but not with insulin production.

Animals↗
PubMed2000

Involvement of SPARC in in vitro differentiation of skeletal myoblasts.

SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca(2+)-binding glycoprotein associated with the morphogenesis and remodeling of various tissues. Here, involvement of SPARC in the myogenesis of skeletal myoblasts was investigated in vitro. First, the differential expression of SPARC mRNA during the myogenesis was initially identified by a differential display reverse transcription (DDRT)-PCR method. The expression of the SPARC gene was significantly up-regulated during the differentiation of C2C12 mouse myoblasts. Second, the treatment with anti-SPARC antibody almost completely prevented the differentiation of myoblasts. Third, the treatment with EGTA, a Ca(2+) chelator that is known to inhibit the fusion of C2C12 myoblasts, reversibly inhibited the up-regulation of SPARC gene expression. On the other hand, the treatment with A23187, a Ca(2+) ionophore, rapidly and dramatically increased the level of SPARC transcript. Taken together, these results suggest that SPARC may play a critical role(s) in the morphological change of myoblasts, and that the expression of SPARC gene may be controlled by Ca(2+)-dependent pathway in myogenesis.

Animals↗
PubMed2000

Cloning, sequencing and expression in Escherichia coli of a thermophilic lipase from Bacillus thermoleovorans ID-1.

A thermophilic lipase of Bacillus thermoleovorans ID-1 was cloned and sequenced. The lipase gene codes 416 amino acid residues and contains the conserved pentapeptide Ala-X-Ser-X-Gly as other Bacillus lipase genes. The optimum temperature of the lipase is 75 degrees C, which is higher than other known Bacillus lipases. For expression in Escherichia coli, the lipase gene was subcloned in pET-22b(+) vector with a strong T7 promoter. Lipase activity was approximately 1.4-fold greater than under the native promoter.

Amino Acid Sequence↗
PubMed2000

Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis.

In studying biological roles of interferon regulatory factor (IRF)-1 tumor suppressor in cervical carcinogenesis, we found that HPV E7 is functionally associated with IRF-1. Binding assays indicate a physical interaction between IRF-1 and HPV E7 in vivo and in vitro. The carboxyl-terminal transactivation domain of IRF-1 was required for the interaction. Transient co-expression of E7 significantly inhibits the IRF-1-mediated activation of IFN-beta promoter in NIH-3T3 cells. Co-transfection of E7 mutants reveals that the pRb-binding portion of E7 is necessary for the E7-mediated inactivation of IRF-1. It was next determined whether histone deacetylase (HDAC) is involved in the inactivation mechanism as recently suggested, where the carboxyl-terminal zinc finger domain of E7 associates with NURD complex containing HDAC. When trichostatin A, an inhibitor of HDAC, was treated, the repressing activity of E7 was released in a dose-dependent manner. Furthermore, the mutation of zinc finger abrogates such activity without effect on the interaction with IRF-1. These results suggest that HPV E7 interferes with the transactivation function of IRF-1 by recruiting HDAC to the promoter. The immune-promoting role of IRF-1 evokes the idea that our novel finding might be important for the elucidation of the E7-mediated immune evading mechanism that is frequently found in cervical cancer.

DNA-Binding Proteins↗
PubMed2000

Antiproliferative effects of retinoic acid/interferon in cervical carcinoma cell lines: cooperative growth suppression of IRF-1 and p53.

Retinoids and interferons have been implicated in the growth regulation of cervical cancer cells. However, the molecular mechanisms are not fully defined. To analyze detailed mechanisms, HPV-positive (HeLa, CaSki), HPV-negative (C33A, HT-3) and non-cervical Cos-1 cell lines were treated with I microM all-trans-retinoic acid (RA) and/or 10 ng/ml interferon-gamma (IFN-gamma). The growth of RA-treated HeLa cells was less effectively suppressed than that of IFN-gamma-treated ones. A combination of RA and IFN-gamma leads to an additive antiproliferative effect on the cell growth. CaSki cell growth was also inhibited by IFN-gamma but was little stimulated by RA treatment, and the IFN effect was attenuated when IFN-gamma was combined with RA. HPV-negative C33A and HT-3 cells, which are defective in p53 and Rb, and Cos- 1 cells were weakly or not responsive to all combined treatments. The molecular mechanism underlying the differential effects of RA/IFN on HeLa and C33A cells was investigated. Combined RA/IFN-gamma treatment caused a marked increase in the level of IFN regulatory factor-1 (IRF-1) in HeLa, whereas no induction of IRF-1 was observed in C33A, consistent with the findings that IFN signaling is functional in HeLa but is defective in C33A cells. The increase of p53 in HeLa cells might account for the down-regulation of HPV-18 E6 gene expression by RA/IFN-gamma. Furthermore, RA/IFN-gamma treatment resulted in the concurrent induction of p21WAF1 CDK inhibitor and dephosphorylation of Rb protein. Transient co-expression of IRF-1 and p53 led to the cooperative activation of the p21WAF1 promoter. Our results indicate that 2 transcription factors, increased in response to RA/IFN-gamma, cooperate functionally to regulate the cell cycle through the activation of a common p21WAF1 gene in HeLa cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Intestinal first-pass effect of bumetanide in rats.

The intestinal first-pass effect of bumetanide was investigated after intravenous and intraportal infusion, and intragastric and intraduodenal instillation of the drug to rats. The AUC(0-->8 h) values of bumetanide after intragastric and intraduodenal instillation of the drug, 10 and 20 mg/kg, were significantly smaller than AUC values after intraportal administration, suggesting that the gastrointestinal first-pass effect of bumetanide was considerable in rats. However, the AUC(0-->8 h) values of bumetanide between intragastric and intraduodenal instillation were comparable, suggesting that the gastric first-pass effect of bumetanide was almost negligible in rats. The AUC(0-->8 h) values of bumetanide after intraduodenal instillation were significantly smaller than AUC values after intraportal infusion at 10 (89.8 vs 569 microg min per ml) and 20 (304 vs 1230 microg min per ml) mg/kg, indicating that the first-pass organ(s) of bumetanide was intestine. The F values were 15.8 and 24.7% after intraduodenal instillation of bumetanide, 10 and 20 mg/kg, respectively. Approximately 76.1 and 76.5% of intraduodenally instilled bumetanide disappeared (as a result of absorption and first-pass effect) after 10 and 20 mg/kg, respectively. Therefore, it could be concluded that approximately 60. 3 and 51.8% of the oral dose of bumetanide disappeared by intestinal first-pass effect at 10 and 20 mg/kg, respectively.

Animals↗
PubMed2000

Enantioselective determination of cetirizine in human urine by HPLC.

In order to study the simultaneous determination of (+)- and (-)-cetirizine in human urine we have developed a chiral separation method by HPLC. A chiral stationary phase of alpha1-acidglycoprotein, the AGP-CSP, was used to separate the enantiomers. The pH of the phosphate buffer, as well as the content of the organic modifier in the mobile phase, markedly affected the chromatographic separation of (+)- and (-)-cetirizine. A mobile phase of 10 mmol/l phosphate buffer (pH 7.0)-acetonitrile (95: 5, v/v) was used for the urine assays. Ultraviolet absorption was monitored at 230 nm and roxatidine was employed as the internal standard for quantification. (+)-Cetirizine, (-)-cetirizine and the internal standard were eluted at retention times of 12, 16, and 32 mins, respectively. The detection limit for cetirizine enantiomers was 400 ng/ml of urine. A pharmacokinetic study was conducted with the help of 5 healthy female volunteers who were administered with a single oral dose of racemic cetirizine (20 mg). The peak area ratios provided by the cetirizine enantiomers were linear (r>0.997) over a concentration range of 2.5-200 microg/ml. The peak of the excreted cetirizine enantiomers appeared in the urine sample during the period of 1-2 hrs following the administration of the oral dose. The excreted level of (+)-cetirizine was slightly higher than (-)-cetirizine but the difference was not statistically significant. However, this method appears to have applications for enantioselective pharmacokinetic studies of racemic drugs.

Adult↗
PubMed2000

Carrier detection and prenatal diagnosis of hemophilia A in a Korean population by PCR-based analysis of the BclI/intron 18 and St14 VNTR polymorphisms.

We have undertaken this study to identify the usefulness of polymerase chain reaction (PCR)-based analysis of DNA polymorphisms in the BclI/intron 18 and St14 variable number of tandem repeats (VNTR) loci for carrier detection and prenatal diagnosis of hemophilia A in the Korean population. We have analyzed these polymorphisms in members of 105 unrelated Korean families with severe hemophilia A. The observed heterozygosity rates for the BclI/intron 18 and St14 VNTR polymorphisms were 21.0% and 71.3%, respectively. The BclI/intron 18 polymorphism was less informative in Koreans when compared with Caucasians and Japanese. The allele frequencies for St14 VNTR in Koreans were different from those in Caucasians. Compared with Caucasians, there was a markedly higher occurrence of low molecular weight alleles in Koreans. The observed heterozygosity for the St14 VNTR polymorphism in combination with the BclI/intron 18 polymorphism was 81.9%. These two polymorphisms were applied to determine the carrier status of 107 women from 65 unrelated families, and to assess fetal status in 37 pregnancies. So far, we have experienced one case of misdiagnosis of carriership. Our study demonstrated that the PCR-based analysis of the BclI/intron 18 and St14 VNTR polymorphisms was useful in the carrier detection and prenatal diagnosis of hemophilia A in the Korean population.

DNA↗
PubMed2000

Autologous porcine heart cell transplantation improved heart function after a myocardial infarction.

OBJECTIVE: Fetal cardiomyocyte transplantation improved heart function after cardiac injury. However, cellular allografts were rejected despite cyclosporine (INN: ciclosporin) therapy. We therefore evaluated autologous heart cell transplantation in an adult swine model of a myocardial infarction. METHODS: In 16 adult swine a myocardial infarction was created by occlusion of the distal left anterior descending coronary artery by an intraluminal coil. Four weeks after infarction, technetium 99m-sestamibi single photon emission tomography showed minimal perfusion and viability in the infarcted region. Porcine heart cells were isolated and cultured from the interventricular septum at the time of infarction and grown in vitro for 4 weeks. Through a left thoracotomy, either cells (N = 8) or culture medium (N = 8) was injected into the infarct zone. RESULTS: Four weeks after cell transplantation, technetium 99m-sestamibi single photon emission tomography demonstrated greater wall motion scores in the pigs receiving transplantation than in control animals (P =.01). Pigs receiving transplantation were more likely to have an improvement in perfusion scores (P =.03). Preload recruitable stroke work (P =.009) and end-systolic elastance (P =. 02) were greater in the pigs receiving transplantation than in control animals. Scar areas were not different, but scar thickness was greater (P =.02) in pigs receiving transplantation. Cells labeled with bromodeoxyuridine in vitro could be identified in the infarct zone 4 weeks after transplantation. Swine receiving transplantation gained more weight than control animals (P =.02). CONCLUSION: Autologous porcine heart cell transplantation improved regional perfusion and global ventricular function after a myocardial infarction.

Analysis of Variance↗
PubMed2000

CoMed: a real-time collaborative medicine system.

CoMed is a prototype of a real-time collaborative medicine system that allows medical specialists to share patient records and to communicate with each other on the Internet. CoMed consists of a multimedia medical database containing relevant information about laryngeal diseases and a real-time collaboration system including a teleconferencing system, a whiteboard and a chatting system. CoMed is web-based. We adopted the object database O2 and CORBA technologies for the multimedia medical database. Therefore, our system can provide the flexibility, extensibility and location transparency of patient databases. We developed a SeeYou Active X control for the teleconferencing system and a Java applet for the whiteboard and chatting system. CoMed improves the efficiency of the overall system by separating the servers on a UNIX machine and a Windows NT machine. CoMed can be utilized for stand-alone research, for collaborative consultations among medical specialists and for a telemedicine in participation with the patients and medical specialists. Our system can be extended easily into other types of the collaborative systems, such as collaborative distance learning, collaborative science system, etc.

Humans↗
PubMed2000

Asitrocin, (2,4)-cis- and trans-asitrocinones: novel bioactive mono-tetrahydrofuran acetogenins from Asimina triloba seeds.

Asitrocin (1) and the mixture of (2,4)-cis- and trans-asitrocinones (2 and 3), new bioactive Annonaceous acetogenins, were isolated from the seeds of Asimina triloba by activity-directed fractionation using the brine shrimp lethality test. Asitrocin and the mixture of (2,4)-cis- and trans-asitrocinones have a configuration of erythro/trans/threo from C-15 to C-20, the mono-THF moiety with two flanking hydroxyl groups. The structures were determined by spectroscopic methods. These acetogenins showed potent bioactivities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the prostate (PC-3) and the pancreatic (MIA PaCa-2) cell lines at 10-100 times the potency of adriamycin.

Animals↗
PubMed2000

General pharmacology of the new antiviral agent SK 1899.

The general pharmacological properties of 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (CAS 247081-81-8, SK 1899), a new potential antiviral agent, were investigated in mice, rats, guinea pigs, rabbits, and dogs. The oral administration of 50, 150, and 500 mg/kg of SK 1899 had no effects on the central nervous system except that it slightly increased the spontaneous locomotor activity in mice at a dose of 500 mg/kg. SK 1899 did not disturb either the spontaneous motility or contractor-induced contraction of the isolated organs such as guinea pig ileum, rat uterus, guinea pig vas deferens, and guinea pig trachea at concentrations up to 10(-4) mol/l. It slightly increased the contractile force in the isolated guinea pig atrium at a concentration of 10(-4) mol/l. Following intravenous infusion of 5, 15, and 50 mg/kg of SK 1899 to anesthetized dogs, it did not change the mean arterial pressure, heart rate, left ventricular systolic pressure (LVSP), and respiratory rate, while it slightly increased the left ventricular positive dP/dtmax (LV + dP/dtmax) at a dose of 50 mg/kg. SK 1899 did not induce any significant changes in the intestinal charcoal meal transit in mice, basal gastric juice secretion in rats, and renal function in rats. It did not affect the blood coagulation system and phenolsulfonphthalein secretion in rats. These findings suggest that SK 1899 has a very low potential to induce any adverse pharmacological effects at the doses showing antiviral activity.

Animals↗
PubMed2000

Bleeding Dieulafoy's lesions and the choice of endoscopic method: comparing the hemostatic efficacy of mechanical and injection methods.

BACKGROUND: Dieulafoy's lesion has unique endoscopic and histopathologic characteristics. This is a clinical trial of endoscopic therapy in 24 patients with Dieulafoy's lesions. METHODS: Patients were divided into 2 groups according to initial endoscopic treatment method. Data were analyzed with respect to clinical and endoscopic characteristics as well as outcomes. The 24 patients were evenly divided into mechanical (9 hemoclipping, 3 band ligation) and injection groups (12). RESULTS: The average number of therapeutic endoscopic sessions needed to achieve permanent hemostasis for the mechanical and injection groups were 1.17 and 1.67, respectively. Initial hemostasis was achieved in 91.7% of patients undergoing mechanical therapy and 75% of those undergoing injection therapy, with none in the former group needing subsequent surgery in comparison to 17% of the latter group. The rate of recurrent bleeding in the mechanical therapy group was significantly lower in comparison to the injection therapy group (8.3% versus 33.3%, p < 0. 05). CONCLUSIONS: Higher efficacy in terms of initial hemostasis and less recurrent bleeding was achieved by mechanical hemostatic therapy with hemoclip and band ligation compared with injection therapy. Endoscopic mechanical therapy is recommended as effective for bleeding Dieulafoy's lesions.

Adult↗
PubMed2000

The Arabidopsis HKT1 gene homolog mediates inward Na(+) currents in xenopus laevis oocytes and Na(+) uptake in Saccharomyces cerevisiae.

The Na(+)-K(+) co-transporter HKT1, first isolated from wheat, mediates high-affinity K(+) uptake. The function of HKT1 in plants, however, remains to be elucidated, and the isolation of HKT1 homologs from Arabidopsis would further studies of the roles of HKT1 genes in plants. We report here the isolation of a cDNA homologous to HKT1 from Arabidopsis (AtHKT1) and the characterization of its mode of ion transport in heterologous systems. The deduced amino acid sequence of AtHKT1 is 41% identical to that of HKT1, and the hydropathy profiles are very similar. AtHKT1 is expressed in roots and, to a lesser extent, in other tissues. Interestingly, we found that the ion transport properties of AtHKT1 are significantly different from the wheat counterpart. As detected by electrophysiological measurements, AtHKT1 functioned as a selective Na(+) uptake transporter in Xenopus laevis oocytes, and the presence of external K(+) did not affect the AtHKT1-mediated ion conductance (unlike that of HKT1). When expressed in Saccharomyces cerevisiae, AtHKT1 inhibited growth of the yeast in a medium containing high levels of Na(+), which correlates to the large inward Na(+) currents found in the oocytes. Furthermore, in contrast to HKT1, AtHKT1 did not complement the growth of yeast cells deficient in K(+) uptake when cultured in K(+)-limiting medium. However, expression of AtHKT1 did rescue Escherichia coli mutants carrying deletions in K(+) transporters. The rescue was associated with a less than 2-fold stimulation of K(+) uptake into K(+)-depleted cells. These data demonstrate that AtHKT1 differs in its transport properties from the wheat HKT1, and that AtHKT1 can mediate Na(+) and, to a small degree, K(+) transport in heterologous expression systems.

Amino Acid Sequence↗