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Biomedical subjects

I H Kim

Publications and source records attributed to I H Kim.

At least 19 recordsLinked to original sources
PubMed2006

Pioglitazone, a synthetic ligand for PPARgamma, induces apoptosis in RB-deficient human colorectal cancer cells.

No published data are available about the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the role of PPARgamma in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to investigate whether PPARgamma is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying the effect of pioglitazone, a synthetic ligand for PPARgamma, on cell growth in these cell lines. RT-PCR and Western blot analysis showed that both human CRC cell lines expressed PPARgamma mRNA and protein. Pioglitazone inhibited the cell growth of both cell lines through G2/M phase block and apoptosis. In addition, pioglitazone caused a down-regulation of the X chromosome-linked inhibitor of apoptosis (XIAP), Bcl-2, and cyclooxygenase-2 (COX-2) under conditions leading to PPARgamma down-regulation. These results suggest that pioglitazone may have therapeutic relevance or significance in the treatment of human CRC, and the down-regulation of XIAP, Bcl-2, and COX-2 may contribute to pioglitazone-induced apoptosis in these and other RB-deficient cell lines and tumors.

Apoptosis↗
PubMed2005

Comparative study on biologic and immunologic characteristics of the pancreas islet cell between 24 degrees C and 37 degrees C culture in the rat.

The aim of this study was to investigate the effect of culture at 24 degrees C on cell viability, cellular function, immunogenicity, and cytokine profiles of rat pancreatic islets. Pancreatic islets were isolated from Lewis rats and cultured at either 24 degrees C or 37 degrees C for 14 days. Islet recovery was counted as islet equivalents; islet viability was examined with fluorescent vital staining. Islet function was measured with a glucose stimulation test. Annexin V, and MHC class I and II expression were measured using flow cytometric assay for apoptosis and immunogenicity, respectively. Lymphocyte cell proliferation was examined with WST-1 proliferation assay. Cytokine profiles were analyzed with quantitative real time RT-PCR. All these parameters were measured on 1, 3, 5, 7 and 14 culture days after islet isolation. Islet recovery was higher in islets cultured at 24 degrees C than 37 degrees C without a change in viability. Insulin secretion after glucose stimulation was more effective in 24 degrees C culture conditions. Decreased apoptotic cell death was demonstrated in 24 degrees C cultured islets. Both MHC class I and II expression on islets and lymphocyte proliferation upon coculture with islets were less prominent in 24 degrees C cultured islets. TNF-alpha expression was lower in islets cultured at 24 degrees C than in islets cultured at 37 degrees C. Both IL-1beta and IL-10 cytokine expressions were similar under both culture conditions. This study demonstrated that cell recovery and function are increased in islets cultured at 24 degrees C than those at 37 degrees C with decreased antigenicity and proinflammatory cytokine expression.

Animals↗
PubMed2005

Effects of feeding antibiotic-free creep feed supplemented with oligofructose, probiotics or synbiotics to suckling piglets increases the preweaning weight gain and composition of intestinal microbiota.

The objective of this study was to determine whether feeding an antibiotic-free creep feed supplemented with either oligofructose, probiotics or synbiotics to suckling piglets influences growth performance, the gut microflora, gut morphology and hematological traits at weaning. Twenty sows with 10 piglets each were randomly assigned to one of four treatments. The treatments consisted of a control (antibiotic-free) diet, 0.2% oligofructose (OF), 0.3% probiotics or 0.5% synbiotics (mixture of 0.2% OF+0.3% probiotics). Piglets were offered the diet ad libitum from 7 d after birth until one day after weaning (21 d of age). At the day after weaning, blood samples were collected from the jugular vein to determine the immune response. Digesta samples of the ileum and colon were collected to determine the microbial composition. Tissue segments from the duodenum and ileum were collected for morphometric measurements of the small intestine. The average daily weight gain was significantly higher for piglets fed the OF or synbiotics diet compared with the pigs fed the control diet. The hematological traits (the concentration of lymphocytes and neutrophils in whole blood) were not affected by the diet. Piglets fed the OF, probiotics or synbiotics diet had a significantly decreased number of total coliform bacteria in the colon. Feeding OF, probiotics or synbiotics significantly increased the population of bifidobacteria in the ileum compared to the control. In the colon, the probiotics and synbiotics diet significantly increased the number of bifidobacteria compared with the control diet. The results of this experiment showed that supplementation of oligofructose or synbiotics to an antibiotic-free creep feed during the preweaning period affected gut microbial population and performance of piglets.

Animal Feed↗
PubMed2003

Liposome-complexed adenoviral gene transfer in cancer cells expressing various levels of coxsackievirus and adenovirus receptor.

PURPOSE: Loss of coxsackievirus and adenovirus receptor (CAR) is frequently observed in malignant cancer, hampering adenoviral gene therapy approaches. Complexing adenovirus with cationic liposomes can increase adenoviral transgene expression, particularly in cells with CAR-deficiency. We investigated whether other factors such as lipid composition might be involved in determining the efficiency of liposome-complexed adenoviral gene transfer in cancer cells. MATERIAL AND METHODS: Human cancer cell lines with different expression levels of CAR were infected with a GFP transgene. The efficiency of transgene expression was assessed by determining GFP expression using FACS analysis. RESULTS: The efficiency of liposome-complexed adenoviral gene transfer was dependent on the lipid composition constituting liposomes. Polyethylene glycol (PEG)-containing liposomes were most effective in increasing liposome-complexed adenoviral gene transfer. In CAR-deficient cells, use of PEG-containing liposomes enhanced adenoviral gene transfer, whereas in CAR-expressing cells enhancement varied depending on cell type. In some CAR-expressing cells, the effect of liposome complexing was even comparable to that in CAR-deficient cells. Increased adenoviral transgene expression following complexing with PEG-containing liposomes correlated with liposome uptake in cancer cells. CONCLUSIONS: Liposome-complexed adenoviral gene transfer appears to depend on lipid composition and the level of liposome uptake by cancer cells, in addition to CAR levels. Our study suggest that these multiple factors should be considered in designing liposome-complexed adenoviral vectors to improve outcomes of current adenoviral cancer gene therapies.

Adenoviridae↗
PubMed2003

Independent exponential feeding of glycerol and methanol for fed-batch culture of recombinant Hansenula polymorpha DL-1.

As a novel feeding strategy for optimizing human epidermal growth factor (hEGF) production with a recombinant Hansenula polymorpha DL-1 using the methanol oxidase (MOX) promoter in H. polymorpha DL-1, independent exponential feeding of two substrates was used. A simple kinetic model considering the cell growth on two substrates was established and used to calculate the respective feeding rates of glycerol and methanol. In the fedbatch culture with methanol-only feeding, the optimal set point of specific growth rate on methanol was found to be 0.10 h-1. When the fed-batch cultures were conducted by the independent feeding of glycerol and methanol, the actual specific growth rate on glycerol and methanol was slightly lower than the set point of specific growth rate. By the uncoupled feeding of glycerol and methanol the volumetric productivity of hEGF increased from 6.4 to 8.0 mg/(L.h), compared with methanol-only feeding.

Alcohol Oxidoreductases↗
PubMed2002

Radiosurgery of intracranial cavernous malformations.

BACKGROUND: The efficacy of radiosurgery in cases of surgically high risk symptomatic cavernous malformations (CMs) for reducing haemorrhagic risk and for seizure control has not been clearly documented and the radiation-induced complications of radiosurgery remain problematic. The authors present a retrospective clinical analysis of 22 cases of CMs treated by radiosurgery. METHODS: Twenty-two patients with symptomatic CMs were treated by linear accelerator (LINAC) radiosurgery or Gamma knife (GK) between 1995 and 1998. Medical records including radiological investigations were carefully reviewed to the last follow-up. The mean age of the patients was 34.1 years (12-56) and the male to female ratio was 12:10. Twenty patients reported at least one episode of bleeding and four had undergone microsurgery before radiosurgery. The remaining two patients presented with seizure without evidence of recent haemorrhage. In 16 cases, the CMs were deep-seated, and the others were located in the cerebral hemispheres; four were located at an eloquent area. LINAC radiosurgery using computed tomography scan was performed in 11 cases until May 1997, after which GK radiosurgery using magnetic resonance (MR) image was performed in 11 cases. The volume of the lesion ranged from 0.09 cc to 4.8 cc (mean 1.42 cc) and the mean marginal dose was 16.1 Gy (8-24). The median follow-up period after radiosurgery was 38.3 months (21-67). The rate of haemorrhage, seizure, and neurological deterioration following radiosurgery was analyzed, and the rate of haemorrhage was compared to that seen in natural course reports. FINDINGS: There was one case of haemorrhage during the follow-up period and the seizure was well controlled with anticonvulsants. In the group with prior haemorrhage, the bleeding rate of cavernous malformation after radiosurgery (1.55%/year) was lower than that of pre-radiosurgical period (35.5%/year, t=1.296, P=0.04). Six patients showed neurological deterioration following radiosurgery, however, the neurological deficits persisted in only two of the patients with LINAC. The radiosurgical modality (LINAC vs. GK) showed a possible correlation to radiation induced neurological deficits (P=0.06). On the MR images at the last follow-up, the lesion was decreased in eleven patients, increased in one, and no change was found in 10 cases. The T2 weighted MR images revealed a perilesional high signal change in nine patients. This signal change was not statistically related to lesion size (P=0.236), location (P=0.658), nor radiation dose (P=0.363), but was dependent on the treatment modality (P=0.02). New-enhancing lesion and a new cyst were each found in one case, respectively, during the follow-up. INTERPRETATION: Radiosurgery may be a good alternative option for treatment of surgically high risk CMs. However, the optimal radiosurgical technique, dose adjustment, and proper delineation of the mass are prerequisites. Radiosurgery induced complications are still problematic and post-radiosurgery MR image changes need to be further elucidated.

Adolescent↗
PubMed2002

Evaluation of endoscopic hemostasis in upper gastrointestinal bleeding related to Mallory-Weiss syndrome.

BACKGROUND AND STUDY AIMS: The endoscopic hemostatic method has been introduced as a safe and effective mechanical approach to hemostasis for upper gastrointestinal bleeding related to Mallory-Weiss syndrome (MWS). However, the indications for when to use endoscopic treatment are debatable because many patients need only medical observation. The study was designed to evaluate the necessity and efficacy of endoscopic hemostasis in upper gastrointestinal bleeding related to MWS. PATIENTS AND METHODS: From July 1994 to May 2000, we conducted a clinical trial in 76 patients who were found by endoscopy to have active bleeding (I, spurting; II, oozing), protruding visible vessels (III), and/or adherent clots (IV). Two study periods can be differentiated: in the first 3 years endoscopic treatment (n = 30) was prospectively analyzed and in the final 3 years medical treatment (n = 46) was analyzed in both cases to compare the outcome in MWS bleeding II-IV. In the first study period, in addition, endoscopic treatment was randomised to an injection method, using a mixture of hypertonic saline and epinephrine (HSE) (n = 14) and a hemoclipping or band ligation method (n = 16). RESULTS: Rebleeding was observed in four of 14 patients who had received endoscopic hemostasis with HSE injection and one of 46 patients who had been managed with medical treatment. No rebleeding was found following hemoclipping or band ligation. While all rebleeding was in bleeding stigmata of the I (1) and II (4) grades, there was no rebleeding in protruding visible vessels (III) or in adherent clots (IV), regardless of treatment methods. CONCLUSIONS: Our results suggested that endoscopic hemostasis is not necessary in patients without active bleeding stigmata, and the mechanical hemostatic method is more effective than HSE injection in patients with active bleeding stigmata.

Adult↗
PubMed2001

A divalent recombinant immunotoxin formed by a disulfide bond between the extension peptide chains.

Recombinant immunotoxin for the treatment of cancer was made by connecting toxins to 'carcinoma-specific' antibodies that selectively bind to cancer cells, then kills them without harming the normal cells. The divalent recombinant immunotoxin, [B3(Fab)-ext-PE38]2, is a derivative of B3(Fab)-PE38. B3(Fab)-PE38 was made by fusing the Fab domain of the monoclonal antibody (MAb) B3 to PE38, a truncated mutant form of Pseudomonas exotoxin (PE). In this study, B3(Fab)-ext-PE38 was constructed, which has the hinge region of the B3(Fab)-PE38 extended with the peptide extension, G4C(G4S)2, and connected to the C3 connector. The Cys residue of the extension peptide chain makes the disulfide bond between the two Fab domains. The extension sequence (ext) makes the dimerization of B3(Fab)-ext-PE38 easier to form the divalent immunotoxin, because it decreases the steric hindrance between the two PE38s. The constructed genes were expressed in E. coli as inclusion bodies. Polypeptides that were obtained from the inclusion body were refolded, and the active forms were purified. The ID50 values of the divalent molecule, [B3(Fab)-ext-PE38]2, were about 4 ng/ml on A431 cell lines, about 1 ng/ml on CRL1739 cell lines, and 5 ng/ml on MCF-7 cell lines. The [B3(Fab)-ext-PE38]2 showed about a 12-fold higher cytotoxicity on CRL1739 cell lines than B3(scFv)-PE40 did.

Antibodies, Monoclonal↗
PubMed2001

Blocking of acidosis-mediated apoptosis by a reduction of lactate dehydrogenase activity through antisense mRNA expression.

Lactic acid produced from the cells is a potential cause of extra- and intracellular acidification. Due to scarce technical tools, lactic acid that leads to acidification could not be reduced and direct evidence of the relationship between metabolic lactate and apoptosis has not yet been elucidated. In this study, we designed a cellular pH regulation system in CHO cells by a reduction of lactate dehydrogenase (LDH) activity through LDH antisense mRNA expression. This inhibited lactate production and, therefore, acidification of the cytosol. Under HCO3(-)-buffered growth conditions, both the parent CHO cells and the engineered CHO cells maintained their extracellular pH and intracellular pH fairly well. However, upon acidification of the cytosol, only the parent CHO cells underwent apoptosis under HCO3(-)-free conditions. In fact, we observed a number of apoptosis-related events only in control cells, including mitochondrial dysfunction, cytochrome c release, and an increase in caspase-3 enzymatic activity.

Acidosis, Lactic↗
PubMed2001

Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector.

Ideally, somatic gene therapy should result in lifetime reversal of genetic deficiencies. However, to date, phenotypic correction of monogenic hyperlipidemia in mouse models by in vivo gene therapy has been short-lived and associated with substantial toxicity. We have developed a helper-dependent adenoviral vector (HD-Ad) containing the apolipoprotein (apo) E gene. A single i.v. injection of this vector completely and stably corrected the hypercholesterolemia in apoE-deficient mice, an effect that lasted the natural lifespan of the mice. At 2.5 years, control aorta was covered 100% by atherosclerotic lesion, whereas aorta of treated mice was essentially lesion-free. There was negligible toxicity associated with the treatment. We also developed a method for repeated HD-Ad vector administration that could be applied to organisms, e.g., humans, with life spans longer than 2-3 years. These studies indicate that HD-Ad is a promising system for liver-directed gene therapy of metabolic diseases.

Adenoviridae↗
PubMed2001

Human neutrophil lactoferrin trans-activates the matrix metalloproteinase 1 gene through stress-activated MAPK signaling modules.

It has been proposed that human neutrophil lactoferrin (Lf) could be involved in gene expression as a DNA-binding protein after its translocation into the nucleus. However, the molecular basis of Lf action has not been defined, and Lf-regulated target genes have not been identified. We report here that overexpressed Lf functions as a specific trans-activator of matrix metalloproteinase 1 (MMP1) gene, and that induction of this AP-1-responsive gene is mediated via the stress-activated MAPK signaling modules. Transactivation of the MMP1 promoter by overexpressed Lf requires the presence of an AP-1 binding site. In gel shift experiments, Lf did not interact directly with AP-1-containing fragments of the MMP1 promoter. However, nuclear extracts from Lf-expressing cells contained increased levels of proteins that bound to AP-1 elements. This Lf-induced AP-1 DNA binding activity was reduced by a p38 MAPK inhibitor. Inhibitors of the MEK kinases had little effect on Lf-induced AP-1. However, expression of dominant-negative MKK4 or JNK1 inhibited Lf-induced gene expression. The JNK activity stimulated by Lf correlates with the enhanced AP-1 binding ability. These findings demonstrate that the Lf-induced activation of AP-1 is mediated via JNK and p38 MAPK pathways.

3T3 Cells↗
PubMed2001

Synthesis of 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine as potential in vivo precursors of fluorinated norepinephrines.

The title compounds were prepared by the aldol condensation of 3,4-dibenzyloxy-2-fluorobenzaldehyde and 4,5-dibenzyloxy-2-fluorobenzaldehyde with the oxazolidinone 2, a chiral glycine equivalent. Removal of the chiral auxiliary and blocking groups produced the target amino acids 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine (1b and 1c) in >98% ee.

Adrenergic Agonists↗
PubMed2001

Long-term stable correction of low-density lipoprotein receptor-deficient mice with a helper-dependent adenoviral vector expressing the very low-density lipoprotein receptor.

BACKGROUND: Familial hypercholesterolemia (FH) that results from LDL receptor (LDLR) deficiency affects approximately 1 in 500 persons in the heterozygous state and approximately 1 in 1 million persons in the homozygous state. We tested a novel gene therapy strategy for the treatment of FH in a mouse model. METHODS AND RESULTS: We delivered the VLDL receptor (VLDLR) to the liver of LDLR-deficient mice and compared the effect of a helper-dependent adenoviral vector with all viral coding sequences deleted (HD-Ad-mVLDLR) with a first-generation vector (FG-Ad-mVLDLR), an HD-Ad (HD-Ad-0) that contained no expression cassette, and dialysis buffer (DB). A single intravenous injection of HD-Ad-mVLDLR led to a lowering of plasma cholesterol that lasted >/=6 months. Acute liver toxicity (as measured with liver enzyme elevation) occurred after FG-Ad-mVLDLR but not after HD-Ad-mVLDLR, HD-Ad-0, or DB treatment. At 6 months, VLDLR was detected in the liver with Western blotting and with immunofluorescence staining only in HD-Ad-mVLDLR-treated mice. Aortic atherosclerosis was almost completely prevented in these animals. CONCLUSIONS: HD-Ad-mediated intravenous delivery of VLDLR to hepatocytes is well tolerated. It produces long-term lowering of plasma cholesterol and prevents atherosclerosis development in LDLR-deficient mice. These data provide support for the feasibility and safety of this approach for therapy of human subjects.

Adenoviridae↗
PubMed2001

Effect of dominant follicle removal before superstimulation on follicular growth, ovulation and embryo production in Holstein cows.

This study was to investigate whether removing the dominant follicle 48 h before superstimulation influences follicular growth, ovulation and embryo production in Holstein cows. After synchronization, ovaries were scanned to assess the presence of a dominant follicle by ultrasonography with a real-time linear scanning ultrasound system on Days 4, 6 and 8 of the estrus cycle (Day 0 = day of estrus). Twenty-six Holstein cows with a dominant follicle were divided into 2 groups in which the dominant follicle was either removed (DFR group, n=13) by ultrasound-guided follicular aspiration or left intact (control group, n=13) on Day 8 of the estrus cycle. Superovulation treatment was initiated on Day 10. All donors were superovulated with injections of porcine FSH (Folltropin) twice daily with constant doses (total: 400 mg) over 4 d. On the 6th and 7th injections of Folltropin, 30 mg and 15 mg of PGF2alpha (Lutalyse) were given. Donors were inseminated twice at 12 h and 24 h after the onset of estrus. Embryos were recovered on Day 6 or 7 after AI. During superstimulation, the number of follicles 2 to 5 mm (small), 6 to 9 mm (medium) and > or = 10 mm (large) was determined by ultrasonography on a daily basis. At embryo recovery, the number of corpora lutea (CL) was also determined by ultrasonography and blood samples were collected for analysis of progesterone concentration. Follicular growth during superstimulation was earlier in the DFR group than in the control group. The number of medium and large follicles was greater (P < 0.01) in the DFR group than in the control group on Days 1 to 2 and Days 3 to 4 of superstimulation, respectively. The numbers of CL (9.6+/-1.1 vs 6.1+/-0.9) and progesterone concentration (30.9+/-5.4 vs 18.6+/-3.5 ng/mL) were greater (P < 0.05) in the DFR group than in the control group, respectively. The numbers of total ova (7.7+/-1.3 vs 3.9+/-1.0) and transferable embryos (4.6+/-0.9 vs 2.3+/-0.8) were also greater (P < 0.05) in the DFR group than in the control group, respectively. It is concluded that the removal of the dominant follicle 48 h before superstimulation promoted follicular growth, and increased ovulation and embryo production in Holstein cows.

Animals↗
PubMed2001

Thioredoxin-linked lipid hydroperoxide peroxidase activity of human serum albumin in the presence of palmitoyl coenzyme A.

Human Serum Albumin (HSA) exerted a significant lipid peroxidase activity with the use of a thiol-reducing equivalent such as dithiothreitol (DTT). Carboxyl group-modified HSA (CM-HSA) showed a 10-fold stronger lipid peroxidase activity (1.6 nmol/min/mg) than that of HSA (0.17 nmol/min/mg). Instead of DTT, thioredoxin (Trx) also supported reducing equivalent to the reduction of lipid hydroperoxide by CM-HSA. Contrast to CM-HSA, HSA did not reduce lipid peroxide with the use of Trx. In the presence of palmitoyl coenzyme A (palmitoyl-CoA) however, HSA used Trx as an electron donor to the reduction of lipid hydroperoxide. The Trx-linked peroxidase activity of HSA sharply increased with elongation in the carbon chain of the acyl moiety of acyl-CoA, showing an optimum activity in the presence of palmitoyl-CoA. Fluorescence study indicates the conformational changes of HSA induced by palmitoyl-CoA. Together, these data suggest that palmitoyl-CoA-bound HSA has a capability to remove lipid peroxide with the use of electrons given by Trx system.

Dithiothreitol↗
PubMed2001

Anti-inflammatory activity of methanol extract of Kalopanax pictus bark and its fractions.

The methanol extract of Kalopanax pictus bark was evaluated on anti-inflammatory and anti-nociceptive activities in animal models. The extract produced a significant inhibition of vascular permeability at doses of 1 and 3 g/kg, p.o. in mice and of leucocyte emigration at doses of 0.15 and 0.3 g/rat, s.c., in CMC-pouch of rats. However, the extract (0.25 and 3 g/kg, p.o.) did not show anti-inflammatory activity in carrageenan induced edema of rats. The extract at a dose of 2.5 g/kg, p.o. inhibited writhing syndromes, whereas it did not exhibit anti-nociceptive in Randall-Selitto assay. The methanol extract was then partitioned with n-hexane, chloroform, ethyl acetate and butanol to give each soluble fraction and finally water soluble fraction. Among those fractions, the inhibitory effect on vascular permeability in mice was produced by ethyl acetate soluble fraction in this activity-guided fractionation. The methanol extract showed low acute toxicity in mice. These results suggest that the methanol extract of Kalopanax pictus bark has an anti-inflammatory activity which is distributed in the ethyl acetate fraction.

Analgesia↗