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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 127 records · Page 7Linked to original sources

Role of anti-parietal cell antibody in Helicobacter pylori-associated atrophic gastritis: evaluation in a country of high prevalence of atrophic gastritis.

BACKGROUND: Helicobacter pylori plays an important part in the progression of atrophic gastritis; however, markers for predicting the progression of atrophic gastritis remain unidentified. We investigated the relation between the degree of atrophic gastritis and the amount of anti-parietal cell antibodies (APCAs) present. METHODS: In 219 Japanese patients, APCA was investigated by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The grade of corpus atrophy was estimated by histology and serum pepsinogen levels. Serum levels of pepsinogen were evaluated by radioimmunoassay. RESULTS: Helicobacter pylori infection did not affect the APCA levels determined by ELISA. Long-term administration of proton-pump inhibitors and H. pylori eradication did not influence the levels of APCAs. However, in H. pylori-positive patients, the levels of APCA determined by ELISA were statistically higher in patients with severe atrophy than in those with mild atrophy as determined histologically (0.67+/-0.48 versus 0.45+/-0.40; A492, mean+/-s, P=0.01) and serologically by pepsinogen levels (0.66+/-0.51 versus 0.44+/-0.40. P=0.002). The levels of pepsinogen I/II ratio were correlated with APCA levels only in the H. pylori-positive group. Western blotting showed that major antigen was identical with the beta-subunit of H+,K+-ATPase. CONCLUSION: APCA plays an important part in the progression of corpus atrophy after H. pylori infection.

Adolescent↗

Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells.

BACKGROUND: The transcription factor encoded by the intestinal Cdx2 homeobox gene and treatment with sodium butyrate (NaB), a byproduct of fibre fermentation by colonic bacteria, exert similar effects on colon cancer cell lines as they both inhibit cell growth and stimulate cell differentiation and apoptosis. AIM: To investigate whether NaB regulates expression of the Cdx2 gene in colon cancer cell lines. METHODS: Human adenocarcinoma cell lines Caco2 and HT29 were grown in the presence or absence of NaB. Cells were analysed for Cdx2 mRNA expression by reverse transcription-polymerase chain reaction, for protein expression by western blotting and electromobility shift assays, and for transcriptional activity of the Cdx2 promoter by transfection with luciferase reporter plasmids. RESULTS: In HT29 and Caco2 cells, NaB stimulated Cdx2 mRNA and protein expression as well as transcriptional activity of the Cdx2 promoter. Stimulation of the activity of the Cdx2 promoter by NaB was dose and time dependent. The Cdx2 promoter contains discrete regions that participate in or inversely that blunt the stimulatory effect exerted by NaB. In addition, NaB stimulated the transcriptional activity of the Cdx2 promoter downregulated by oncogenic ras. CONCLUSION: This study is the first report of an intestine specific transcription factor, Cdx2, stimulated by butyrate. Thus it provides a new mechanism whereby butyrate controls proliferation and differentiation of colon cancer cells.

Adenocarcinoma↗

The prototype of sex chromosomes found in Korean populations of Rana rugosa.

The seventh largest chromosome in Japanese populations of the frog Rana rugosa morphologically evolved as a sex chromosome. The sex chromosome is XX/XY type in one geographic form and ZZ/ZW type in another. In contrast, the seventh chromosomes are still homomorphic between the sexes in the other two geographic forms: they are more subtelocentric in the Kanto form and subtelocentric in the western Japanese form. To identify a prototype of the sex chromosomes, we extended our investigation in this study to the Korean form, which is supposed to be close to the phylogenetic origin of this species. The karyotype, a sex-linked gene sequence, and mechanisms of sex determination and gonadal differentiation were all examined. In addition, phylogenetic analyses were performed based on mitochondrial gene sequences and the results of crossings between the Korean and Japanese forms. As a consequence, the more subtelocentric seventh chromosome, shared by the Korean and Japanese Kanto forms, was concluded to be the prototype of the sex chromosomes. Starting at the prototype, a whole process of morphological sex chromosome evolution was reconstructed.

Animals↗

Demonstration of enhanced potency of a chimeric somatostatin-dopamine molecule, BIM-23A387, in suppressing growth hormone and prolactin secretion from human pituitary somatotroph adenoma cells.

In acromegaly, the combination of somatostatin (SS) and dopamine (DA) agonists has been shown to enhance suppression of GH secretion. In the present study, a new chimeric molecule, BIM-23A387, which selectively binds to the SS subtype 2 receptor (sst(2); K(i) = 0.10 nM) and to the DA D2 receptor (D2DR; K(i) = 22.1 nM) was tested in cultures prepared from 11 human GH-secreting tumors for its ability to suppress GH and prolactin (PRL) secretion. The chimeric compound was compared with individual sst(2) and D2DR agonists of comparable activity at the individual receptors. All tumors expressed both sst(2) and D2DR mRNAs (0.8 +/- 0.2 and 4.7 +/- 0.7 copy/copy beta-glucuronidase mRNA, respectively). In cell cultures from seven octreotide-sensitive tumors, the maximal inhibition of GH release induced by the individual sst(2) and D2DR analogs and by BIM-23A387 was similar. However, the mean EC(50) for GH suppression by BIM-23A387 (0.2 pM) was 50 times lower than that of the individual sst(2) and D2DR analogs, either used individually or combined. Similar data were obtained in four tumors that were only partially responsive to octreotide. The inhibition of GH release by BIM-23A387 was only partially reversed by the D2R2 antagonist, sulpiride, or by the sst(2) antagonist, BIM-23454. Only when both antagonists were combined was the GH suppressive effect of BIM-23A387 totally reversed. Finally, BIM-23A387 produced a mean 73 +/- 6% inhibition of PRL in six mixed GH plus PRL tumors. These data demonstrate an enhanced potency of the chimeric molecule, BIM-23A387, in suppressing GH and PRL secretion from acromegalic tumors, which cannot be explained merely on the basis of binding affinity for SS and/or DA receptors.

Adenoma↗

Evaluation of several respirometry-based activated sludge toxicity control strategies.

Four different strategies including influent storage and reintroduction, step-feeding, rapid sludge recycle and waste sludge storage were evaluated using the denitrification layout of the IWA simulation benchmark. The control objective was to minimise deterioration in effluent quality caused by a certain toxic input event. In these strategies the maximum specific respiration rate (Rmax) was selected as a measured and controlled variable. To simplify the analysis, the toxicant was assumed to be a soluble and nonbiodegradable substance. Two toxic influent files were developed with square-wave input lasting 3 hours. To detect the influent toxicity, a pseudo-online flow-through respirometer was applied. A number of simulations were performed and the results suggested that the influent storage and reintroduction strategy provided the most optimistic results and other strategies could not mitigate the toxic effect. The influent storage and reintroduction strategy strongly depended on reintroduction flow rate from the storage tank. The simulation according to reintroduction flow could estimate the time required for completely treating toxic wastewater stored in the storage tank. Also the IWA simulation benchmark was enhanced to evaluate toxicity effect on the activated sludge process.

Benchmarking↗

Genetic algorithms for the application of Activated Sludge Model No. 1.

The genetic algorithm (GA) has been integrated into the IWA ASM No. 1 to calibrate important stoichiometric and kinetic parameters. The evolutionary feature of GA was used to configure the multiple local optima as well as the global optimum. The objective function of optimization was designed to minimize the difference between estimated and measured effluent concentrations at the activated sludge system. Both steady state and dynamic data of the simulation benchmark were used for calibration using denitrification layout. Depending upon the confidence intervals and objective functions, the proposed method provided distributions of parameter space. Field data have been collected and applied to validate calibration capacity of GA. Dynamic calibration was suggested to capture periodic variations of inflow concentrations. Also, in order to verify this proposed method in real wastewater treatment plant, measured data sets for substrate concentrations were obtained from Haeundae wastewater treatment plant and used to estimate parameters in the dynamic system. The simulation results with calibrated parameters matched well with the observed concentrations of effluent COD.

Algorithms↗

Application of cDNA microarray technique to detection of gene expression in host cells infected with viruses.

cDNA microarray technique was used to monitor changes in mRNA levels in cells after Hantaan virus (HTNV) infection. The values of the ratio of medians for HTNV and Japanese encephalitis virus (JEV) at the early stage of infection were compared and found similar, suggesting that the same or similar genes are associated with the early events of infection with either virus. The reproducibility of values of the "ratio of medians" for HTNV was examined. We found that applying cluster analysis to the gene expression data groups efficiently together genes with the same function. Therefore, in analyzing the effects of viral infection on host cells by the cDNA microarray technique, clustering data appear to be necessary for gaining biological meaning from a dump of gene expression profiles obtained from virus-infected cells.

Animals↗

Cytological observation of two environmental genic male-sterile lines of rice.

We report here two environmental genic male-sterilities (EGMS) in rice. These two EGMS rice lines, thermo-sensitive genic male-sterility (TGMS) and photoperiod-sensitive genic male-sterility (PGMS), are controlled by temperature and photoperiod, respectively, in determining their male-sterility. Male-sterility of the TGMS and PGMS was found to be induced when they were grown at 32 degrees C/26 degrees C (day/night) with 14 h daylight, while they were fertile at 26 degrees C/20 degrees C (day/night) with 10 h daylight in a growth chamber. We also examined their anther structures under a light microscope. The light microscopic observation revealed that the EGMS lines showed a complete pollen abortion at the sterile growth condition while they produced normal fertile pollens at the fertile growth condition.

Fertility↗

A reaction-induced FT-IR study of cyanobacterial photosystem I.

In oxygenic photosynthesis, photosystem I (PSI) conducts light-driven electron transfer from plastocyanin to ferredoxin. The reactions are initiated when the primary chlorophyll donor, P(700), is photooxidized. P(700) is a chlorophyll dimer ligated by the core subunits psaA and psaB. A difference Fourier transform infrared spectrum, associated with P(700)(+)-minus-P(700), can be acquired using PSI from the cyanobacterium Synechocystis sp. PCC 6803. This spectrum reflects contributions from oxidation-sensitive modes of chlorophyll, as well as from oxidation-induced structural changes in amino acid residues and the peptide backbone. Oxidation-induced structural changes may play a role in the facilitation and control of electron-transfer reactions involving the primary donor. In this paper, we report that photooxidation of P(700) in cyanobacterial PSI perturbs a cysteine residue. At 264 and 80 K, a downshift of a SH stretching vibration from 2560 to 2551 cm(-1) is observed. Such a downshift is consistent with an increase in hydrogen bonding, with a change in C-S-H conformation, or with an electric field effect. Deuterium exchange experiments were also performed. While the perturbed cysteine is in a protein region that is resistant to exchange, other (2)H-sensitive vibrational chl and amino acid bands were observed. From the (2)H exchange experiments, we conclude that photooxidation of P(700) perturbs internal or bound water molecules in PSI and that the P(700)(+)-minus-P(700) spectrum is (2)H exchange-sensitive. The results are consistent with structural complexity in the PSI primary donor, as previously suggested [Kim, S., and Barry, B. A. (2000) J. Am. Chem. Soc. 122, 4980-4981]. Possible explanations, including a partial enolization of P(700)(+), are discussed.

Amino Acid Sequence↗

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Agrobacterium tumefaciens↗

Low M(r) protein tyrosine phosphatase inhibits growth and migration of vascular smooth muscle cells induced by platelet-derived growth factor.

Vascular smooth muscle cell (VSMC) migration and growth are positively regulated by protein tyrosine phosphorylation. Therefore, a dephosphorylation process controlled by protein tyrosine phosphatases (PTPs) must also be critical. The present study identified six cytoplasmic PTPs expressed in VSMCs: low M(r) protein tyrosine phosphatase (LMW-PTP), SHP-2, PTP36, PTP2, PTP1B, and FAP1. We further examined the functions of LMW-PTP in VSMCs using the adenovirus-mediated gene transfer of recombinant LMW-PTP. PDGF-induced activation of p38, but not of ERK MAP kinase, was blocked by LMW-PTP. LMW-PTP as well as the p38 inhibitor SB203580 inhibited DNA synthesis and cell migration upon PDGF stimulation. LMW-PTP dephosphorylated activated PDGF receptors in NIH3T3 cells, but not in VSMCs. Thus, LMW-PTP negatively regulates PDGF functions by inhibiting the p38 pathway in VSMCs although its substrate is unclear. These findings strongly demonstrate that PTPs are important as negative regulators for VSMC growth and migration, processes that are closely related to the progression of atherosclerosis.

3T3 Cells↗

C-terminal heparin-binding domain of fibronectin regulates integrin-mediated cell spreading but not the activation of mitogen-activated protein kinase.

Fibronectin (FN) stimulates multiple signalling events including mitogen-activated protein kinase (MAPK) activation. During cell spreading, both the cell-binding domain and the C-terminal heparin-binding domain (HepII) of FN co-operatively regulate cytoskeleton organization. However, in comparison with the large number of studies on the functions of cell-binding domain, there is little information about the role of HepII. We therefore investigated the effect of HepII on integrin-mediated cell spreading and adhesion on FN and MAPK activation. In contrast with cells on FN substrates, rat embryo fibroblasts on FN120, which lacks HepII, were less spread, had weaker adhesion to FN and failed to form focal adhesions and actin stress fibres. Phosphotyrosine was present in the focal contacts of rat embryo fibroblasts on FN within 30 min but was absent from cells on FN120. Overall, tyrosine phosphorylation was much less in cell lysates from cells on FN120, with decreased phosphorylation of focal adhesion kinase ('pp125FAK') on tyrosine-397, implying additional regulation of tyrosine phosphorylation by HepII. Nevertheless, adhesion-mediated MAPK activity was similar in cells on FN and on FN120. Furthermore, cells spread on FN and on FN120 substrates showed similar MAPK activation in response to treatment with epidermal growth factor and with platelet-derived growth factor. Consistently, overexpression of syndecan-4, which binds to HepII, enhanced cell spreading and adhesion on FN but did not affect integrin-mediated MAPK activation. We therefore conclude that both HepII and syndecan-4 regulate integrin-mediated cell spreading but not MAPK activation.

Actins↗

A new selective and potent inhibitor of human cytochrome P450 1B1 and its application to antimutagenesis.

Human cytochrome P450 (P450) 1B1 is found mainly in extrahepatic tissues and is overexpressed in a variety of human tumors. Metabolic activation of 17beta-estradiol (E(2)) to 4-hydroxy E(2) by P450 1B1 has been postulated to be a factor in mammary carcinogenesis. The inhibition of recombinant human P450 1B1 by 2,4,3',5'-tetramethoxystilbene (TMS) was investigated using either bacterial membranes from a human P450/NADPH-P450 reductase bicistronic expression system or using purified enzymes. TMS showed potent and selective inhibition of the ethoxyresorufin O-deethylation (EROD) activity of P450 1B1 with an IC(50) value of 6 nM. TMS exhibited 50-fold selectivity for P450 1B1 over P450 1A1 (IC(50) = 300 nM) and 500-fold selectivity for P450 1B1 over P450 1A2 (IC(50) = 3 microM). The inhibitory effects of TMS on EROD activity of human liver microsomes were determined. TMS inhibited EROD activity of human liver microsomes at the same concentration as with recombinant human P450 1A2. TMS also strongly inhibited 4- and 2-hydroxylation of E(2) by P450 1B1-expressing membranes or purified P450 1B1. TMS was a competitive inhibitor of P450 1B1 with a K(i) of 3 nM. The inhibition by TMS was not mechanism-based, and the loss of activity was not blocked by the trapping agents glutathione, N-acetylcysteine, or dithiothreitol. Using purified histidine-tagged P450 1B1, the binding kinetic analysis was performed with TMS, yielding a K(d) of 3 microM. The activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline in an Escherichia coli lac-based mutagenicity tester system containing functional human P450 1B1 was strongly inhibited by TMS. Our results indicate that TMS is a very selective and potent competitive inhibitor of P450 1B1. TMS is selective for inhibiting P450 1B1 among other human P450s including 1A1, 1A2, and 3A4 and warrants consideration as a candidate for preventing mammary tumor formation by E(2) in humans.

Animals↗

Implication of co-measured platelet factor 4 in the reliability of the results of the plasma transforming growth factor-beta 1 measurement.

We examined the possible alteration of circulating transforming growth factor-beta1 (TGF-beta1) concentrations in a time-dependent fashion in human plasma. Plasma TGF-beta1 was measured three times at 2 week-intervals from each of 12 healthy participants. Platelet factor 4 (PF4) was measured in parallel with TGF-beta1 to estimate the degree of platelet degranulation. TGF-beta1 levels of the second and third plasma samples, in which PF4s were measured as < approximately 1000 IU/ml, were relatively low and fell in a narrow range. However, TGF-beta1 levels of the first samples, in most of which PF4s were > approximately 1000 IU/ml, appeared much higher and more variable than those of the second or third samples. These results indicate that the platelet degranulation accounted for the higher TGF-beta1 levels in the first samples, and thus did not support our initial assumption. We, nevertheless, could propose a useful guidance in the assessment of TGF-beta1 levels in plasma. When the PF4 level is measured as < approximately 1000 IU/ml under our assay conditions, the TGF-beta1 level in a given plasma sample might be accepted as a reliable value considering the effect of platelet degranulation on TGF-beta1 level.

Adult↗

Constitutive expression of rice MADS box gene using seed explants in hot pepper (Capsicum annuum L.).

Two transgenic pepper plants were obtained from 255 seed explants that were infected with Agrobacterium LBA4404 (pGA1209). One of them (PT2) showed morphological change, such as dwarfism and early flowering by the constitutive expression of the rice OsMADS1 gene. The in vitro condition of the plant regeneration has been optimized from hypocotyl explants on a MS medium that was supplemented with zeatin 3 mg/L, IAA 0.3 mg/L for shoot induction. The optimal rooting condition was at NAA 0.3 mg/L. The transformation frequency was 0.8% from the total hypocotyls. DNA and RNA hybridization analyses showed that the introduced gene was integrated and stably expressed in regenerated plants.

Capsicum↗

lyc1, a transgenic mutant of Lactuca sativa (lettuce) tightly linked to chloroplast biogenesis.

A T-DNA tagging mutant of lettuce was studied. The transgenic lettuce mutant, designated light yellowish cotyledon1 (lyc1), exhibited a chloroplast mutant phenotype in which the chloroplast development was arrested at the cotyledon stage and the cotyledon became a light yellowish due to the reduced level of chlorophyll content. A microscopic observation of the mutant showed that the chloroplasts failed to position along the cell wall, but were scattered in the cytoplasm. The number of chloroplasts in the mutant was reduced to 66% compared to that in the wild-type plant. These results suggest that the lyc1 mutation is due to a defect in the biogenesis of chloroplasts. Also, the homozygous lyc1 mutant became lethal in a T2 and F1 progeny analysis, indicating that the mutation is recessive.

Chlorophyll↗