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Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 253 records · Page 14Linked to original sources
PubMed2000

Anti-restenotic effect of copper-62 liquid-filled balloon in porcine coronary arteries: novel use of a short half-life positron emitter.

PURPOSE: To determine the efficacy of the use of copper-62, a positron emitter with a half-life of 9.7 minutes, as an intracoronary brachytherapy (IRBT) source in the prevention of neointima formation (NF) following overstretch balloon injury (BI) in the porcine model. METHODS AND MATERIALS: Sixteen swine were treated after BI to their left anterior descending (LAD), left circumflex (LCX), and/or right coronary artery (RCA). Twelve of the injured arteries received placebo and 10 received 25 Gy, delivered to 0.5 mm from the surface of the treatment balloon filled with liquid (62)Cu. Dosimetry was based on Monte Carlo calculations. Two weeks after treatment, the animals were sacrificed, and the treated coronaries were perfusion-fixed and stained. Intimal area (IA) and medial fracture length (FL) were analyzed by computer-aided histomorphometry. RESULTS: The ((62)Zn/(62)Cu) generator, together with a rapid concentration process, was successful in delivering the short-lived (62)Cu at the high concentration required for intravascular brachytherapy (IVBT). The fracture length in the two groups was similar (2.10 +/- 0.57; 2.02 +/- 0.77; p = NS). Arteries studied showed significant reduction in NF (IA: 0.23 +/- 0.47 mm(2) vs. 1.08 +/- 0.57 mm(2); p < 0.01. IA/FL = 0.09 +/- 0.17 mm vs. 0.51 +/- 0.21 mm; p < 0.01). CONCLUSIONS: This study demonstrated that use of liquid (62)Cu as an IVBT source is safe and feasible. All 16 swine tolerated the treatment well with no radiation-induced side effects or symptoms throughout the 2-week period. The isotope delivered the dose necessary to inhibit NF in the porcine coronary BI model.

Animals↗
PubMed2000

Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability.

Many lines of evidence suggest that the retinoblastoma protein interacting zinc finger gene RIZ is a strong candidate for the tumor suppressor locus on 1p36, a region commonly deleted in many human cancers with chromosomal instability. In addition, a role for RIZ in tumors of the microsatellite instability pathway is suggested by frequent frameshift mutations in hereditary non-polyposis colorectal carcinomas. Here we studied RIZ mutations in sporadic cancers with microsatellite instability. Frameshift mutations in the two coding polyadenosine tracks of RIZ were found in 19 (48%) of 40 gastric carcinomas, 6 (33%) of 18 endometrial carcinomas, 14 (26%) of 51 of colorectal carcinomas, and 7 (54%) of 13 cell lines. Eleven tumor tissues showed biallelic inactivation of RIZ. In contrast, no frameshift mutations were found in 70 microsatellite stable tumors. These results suggest an important role for RIZ in sporadic cancers with microsatellite instability.

Alleles↗
PubMed2000

The pharmacology of a new nitric oxide donor: B-NOD.

We describe here a new compound, B-NOD, which, in vitro and in situ, releases nitric oxide (NO). Its activity in situ persists for more than 7 h, it does not cause a fall in blood pressure or an increase in heart rate and can be orally administered. It increases cyclic guanosine monophosphate (cGMP) and prevents platelet aggregation. In vitro, its release of NO is augmented by the presence of living cells (blood platelets). B-NOD may be useful in a number of clinical conditions in which prolonged release of NO without hemodynamic effects are desirable. A combination of aspirin with B-NOD could be formulated in which the individual concentrations of aspirin and B-NOD may be useful in the long-term treatment of coronary artery disease and in clinical situations in which long-term release of NO may be beneficial.

Animals↗
PubMed2000

Spatio-temporal interaction with disease mapping.

Markov chain Monte Carlo methods are used to estimate mortality rates under a Bayesian hierarchical model. Spatial correlations are introduced to examine spatial effects relative to both regional and regional changes over time by groups. A special feature of the models is the inclusion of longitudinal variables which will describe temporal trends in mortality or incidences for different population groups. Disease maps are used to illustrate the role of different parameters in the model and pinpointing areas of interesting patterns. The methods are demonstrated by male cancer mortality data from the state of Missouri during 1973-1992. Of special interest will be the geographic variations in the trend of lung cancer mortality over the recent past. Marginal posterior distributions are used to examine effects due to spatial correlations and age difference in temporal trends. Numerical results from the Missouri data show that although spatial correlations exist, they do not have a large effect on the estimated mortality rates.

Aged↗
PubMed2000

Increased expression of p53 and Bax in the spinal cords of rats with experimental autoimmune encephalomyelitis.

The expression of pro-apoptotic molecules p53 and Bax in the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE) was examined. Apoptosis was confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method. TUNEL (+) apoptotic cells were mainly either ED1 (+) macrophages or T-cells in the parenchyma of EAE. Western blot analysis showed that both p53 and Bax expression significantly (P<0. 01) increased in the spinal cords of EAE rats at the peak stage, and thereafter declined. An immunohistochemical study showed that inflammatory cells (notably T cells) in the parenchyma express p53 and Bax, while brain cells, including neurons and glia, were devoid of nuclear staining for these molecules. The nuclear expression of p53 largely matches apoptotic cells in the parenchyma of EAE. These findings suggest that the pro-apoptotic molecules p53 and Bax may play an important role in eliminating T cells in the parenchyma in EAE.

Animals↗
PubMed2000

Cross-coupling of hydroxycinnamyl aldehydes into lignins.

Pathways for hydroxycinnamyl aldehyde incorporation into lignins are revealed by examining transgenic plants deficient in cinnamyl alcohol dehydrogenase, the enzyme that converts hydroxycinnamyl aldehydes to the hydroxycinnamyl alcohol lignin monomers. In such plants the aldehydes incorporate into lignins via radical coupling reactions. As diagnostically revealed by long-range (13)C-(1)H correlative NMR, sinapyl aldehyde (3, 5-dimethoxy-4-hydroxy-cinnamaldehyde) 8-O-4-cross-couples with both guaiacyl (3-methoxy-4-hydroxyphenyl-propanoid) and syringyl (3, 5-dimethoxy-4-hydroxyphenyl-propanoid) units, whereas coniferyl aldehyde cross-couples only with syringyl units.

Alcohol Oxidoreductases↗
PubMed2000

Tissue-specificity, functional characterization and subcellular localization of a rat ubiquitin-specific processing protease, UBP109, whose mRNA expression is developmentally regulated.

A cDNA encoding an ubiquitin-specific processing protease, UBP109, in rat skeletal muscle was cloned and its product was characterized. Northern analysis revealed that UBP109 mRNA is highly expressed in testis and spleen, compared with other tissues. Furthermore, in situ hybridization showed that the level of UBP109 mRNA in liver, spinal cord and brain dramatically changed during embryonic development, indicating that the expression of UBP109 mRNA is developmentally regulated. UBP109 was expressed in Escherichia coli and purified to apparent homogeneity using a (125)I-labelled ubiquitin-peptide fusion as a substrate. The purified enzyme cleaved at the C-terminus of the ubiquitin moiety in natural and engineered fusions irrespective of their sizes. UBP109 also released free ubiquitin from poly-His-tagged penta-ubiquitin. Moreover, it released free ubiquitin from poly-ubiquitinated protein conjugates of rabbit reticulocytes. In addition, UBP109 localized to both the cytoplasm and the nucleus and, among three putative nuclear localization sequences, only the one located near the C-terminus is responsible for nuclear localization. These results suggest that UBP109 may play an important role in generation of free ubiquitin from its precursors and its recycling from poly-ubiquitinated protein conjugates, and hence in regulation of ubiquitin-mediated cellular processes, particularly related to embryonic development.

Amino Acid Sequence↗
PubMed2000

p16 is a major inactivation target in hepatocellular carcinoma.

BACKGROUND: The p16(INK4A) gene encodes 2 cell cycle regulator proteins, p16 and p14(ARF), by alternative splicing. This genetic locus also contains another cell cycle regulator gene, p15(INK4B), which encodes p15. The inactivation of the p16 protein has been demonstrated in some hepatocellular carcinomas (HCCs); however, the inactivation of the other 2 cell regulator proteins and their inactivation patterns are not well characterized. METHODS: To characterize the role of the above 3 cell cycle regulator proteins in HCCs, the authors examined the genomic status of the p16(INK4A) and p15(INK4B) genes and their RNA products in 20 HCC tissues and 7 human HCC cell lines. Homozygous deletions in each exon of p16(INK4A) and p15(INK4B) were evaluated by comparative multiplex polymerase chain reaction (PCR), and the methylation status of the p16(INK4A) and p15(INK4B) promoter region was analyzed by methylation specific PCR. RESULTS: Homozygous deletions were found in 6 of 20 HCCs (30%) and 2 of 7 HCC cell lines (29%). In 20 HCCs, the frequency of homozygous deletions was 20% in exon 1 of p15(INK4B), 20% in exon 2 of p15(INK4B), 10% in exon 1beta of p16(INK4A), 25% in exon 1alpha of p16(INK4A), 15% in exon 2 of p16(INK4A), and 15% in exon 3 of p16(INK4A). The authors found hypermethylation of the p16(INK4A) promoter region in 7 HCCs (35%) and 3 HCC cell lines (43%). The overall frequency of p16 alterations in HCCs, including hypermethylation and homozygous deletions, was 60% (12 of 20 cases). According to reverse transcriptase-PCR analysis, the absence of RNA expression was most frequent in p16 (11 of 20 cases, 55%) and less frequent in p15 (7 of 20 cases, 35%) and p14(ARF) (5 of 20 cases, 25%). CONCLUSIONS: Among the 3 cell cycle regulator proteins encoded at the 9p21 genetic locus, inactivation of p16 is the most frequent event in HCCs in which promoter hypermethylation and homozygous deletions are the common mechanisms.

Carcinoma, Hepatocellular↗
PubMed2000

The emergence of compartmental organization in olfactory bulb glomeruli during postnatal development.

The olfactory bulb glomerulus is a discrete and heterogeneous neuropil where olfactory receptor cell axons synapse with dendrites of mitral, tufted, and periglomerular neurons. To understand better the maturation of glomeruli and the spatiotemporal interactions that occur during postnatal development, we employed confocal microscopy and markers for immature and mature olfactory receptor cell axons in parallel with a marker for synaptic structure in maturing glomeruli. Sprague-Dawley rats at postnatal days 1, 6, 12, and 18 were processed for single- and double-label immunocytochemistry for olfactory marker protein (OMP), growth-associated protein (GAP-43), and synaptophysin. Mature or adult-like subcompartmental organization within the glomerulus emerged by postnatal day 12. Earlier in development immature axons entered the core of the glomerulus and moved to the periphery as they matured. However, beginning around 12 days postnatal, immature axons distributed in the periphery and moved toward the core as they matured. This change in the trajectories of axons into glomeruli suggests that different rules may be followed in establishing versus maintaining glomeruli. Double labeling with OMP and synaptophysin demonstrated strong colocalization compared with GAP-43 and synaptophysin, which showed much less colocalization, consistent with the notion that OMP is associated with more mature axons.

Age Factors↗
PubMed2000

Molecular cloning of neuronally expressed mouse betaPix isoforms.

Pix, a Pak-interacting exchange factor, is known to be involved in the regulation of Cdc42/Rac GTPases and Pak kinase activity. In this study, we cloned the cDNAs encoding two betaPix isoforms from mouse brain cDNA library. Both of the cloned genes, designated betaPix-b and betaPix-c (GenBank Accession Nos. AF247654 and AF247655, respectively), have a novel insert region consisting of 59 amino acid residues. In betaPix-c, 75 amino acid residues are deleted in the proline-rich region at the carboxyl-terminus of betaPix. In situ hybridization studies with insert region-specific probe in rat embryo show that insert region-containing isoforms are expressed mainly in the central nervous system. Moreover, temporal expression pattern of isoforms is correlated with the active neurogenesis period in the cerebral cortex and cerebellum. These results strongly suggest that betaPix isoforms may play important roles in the cellular events required for brain development such as neuronal migration.

Alternative Splicing↗
PubMed2000

Role of peroxiredoxins in regulating intracellular hydrogen peroxide and hydrogen peroxide-induced apoptosis in thyroid cells.

Peroxiredoxins (Prxs) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. One mechanism for this action involves modulation of hydrogen peroxide (H(2)O(2))-mediated cellular responses. This report examines the expression of Prx I and Prx II in thyroid cells and their roles in eliminating H(2)O(2) produced in response to thyrotropin (TSH). Prx I and Prx II are constitutively expressed in FRTL-5 thyroid cells. Prx I expression, but not Prx II expression, is stimulated by exposure to TSH and H(2)O(2). In addition, methimazole induces a high level of Prx I mRNA and protein in these cells. Overexpression of Prx I and Prx II enhances the elimination of H(2)O(2) produced by TSH in FRTL-5 cells. Treatment with 500 micrometer H(2)O(2) causes apoptosis in FRTL-5 cells as evidenced by standard assays of apoptosis (i.e. terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end labeling, BAX expression, and poly(ADP-ribose) polymerase cleavage. Overexpression of Prx I and Prx II reduces the amount of H(2)O(2)-induced apoptosis measured by these assays. These results suggest that Prx I and Prx II are involved in the removal of H(2)O(2) in thyroid cells and can protect these cells from undergoing apoptosis. These proteins are likely to be involved in the normal physiological response to TSH-induced production of H(2)O(2) in thyroid cells.

Animals↗
PubMed2000

Identification of transacting factors responsible for the tissue-specific expression of human glucose transporter type 2 isoform gene. Cooperative role of hepatocyte nuclear factors 1alpha and 3beta.

We investigated transacting factors binding to the cis-element important in tissue-specific expression of the human glucose transporter type 2 isoform (GLUT2) gene. By transient transfection assay, we determined that the 227-base pair fragment upstream of the ATG start site contained promoter activity and that the region from +87 to +132 (site C) was responsible for tissue-specific expression. DNase I footprinting and electrophoretic mobility shift assay indicated that site C contained one binding site for hepatocyte nuclear factor 1 (HNF1) and two binding sites for HNF3. The mutations at positions +101 and +103, which are considered to be critical in binding HNF1 and HNF3, resulted in a 53% decrease in promoter activity, whereas the mutation of the proximal HNF3 binding site (+115 and +117) reduced promoter activity by 28%. The mutations of these four sites resulted in marked decrease (70%) in promoter activity as well as diminished bindings of HNF1 and HNF3. A to G mutation, which causes conversion of the HNF1 and HNF3 binding sequence to the NF-Y binding site, resulted in a 22% decrease in promoter activity. We identified that both HNF1 and HNF3 function as transcriptional activators in GLUT2 gene expression. Coexpression of the pGL+74 (+74 to +301) construct with the HNF1alpha and HNF3beta expression vectors in NIH 3T3 cells showed the synergistic effect on GLUT2 promoter activity compared with the expression of HNF1alpha, HNF3beta, or a combination of HNF1beta and HNF3beta. These data suggest that HNF1alpha and HNF3beta may be the most important players in the tissue-specific expression of the human GLUT2 gene.

Base Sequence↗
PubMed2000

TSH regulates a gene expression encoding ERp29, an endoplasmic reticulum stress protein, in the thyrocytes of FRTL-5 cells.

This experiment was performed to evaluate the effect of thyroid-stimulating hormone (TSH) on the endoplasmic reticulum resident 29 kDa protein (ERp29) gene expression in the thyrocytes of FRTL-5 cells. Although ERp29 mRNA was constantly expressed, its expression began to increase remarkably from 10(-9) M TSH. On the other hand, the effect of TSH on the abundance of ERp29 mRNA started within 6 h and peaked at 8 h. Actinomycin D strongly blocked this effect while cycloheximide did not. The half-life of ERp29 mRNA was about 4-4.5 h in the presence or absence of TSH that was not affected by the stability of ERp29 mRNA. The effect of TSH on the ERp29 gene expression was specific, while other growth factors (transferrin, insulin and hydrocortisone) did not alter its expression. Our data indicate for the first time that the expression of ERp29 is regulated transcriptionally by TSH in thyrocytes.

Cell Line↗
PubMed2000

Loss of p16 and p27 is associated with progression of human gastric cancer.

We performed the immunohistochemical staining for six G1 check point cell cycle proteins to study their expression patterns and roles in the gastric carcinogenesis. We studied 76 cases of paraffin blocks that included the sections of 18 tubular adenomas (TA), 38 early gastric carcinomas (EGC) (20 cases of mucosal type, nine cases of submucosal type with no nodal metastasis, nine cases of submucosal type with nodal metastasis), 20 advanced gastric carcinomas (AGC) (ten cases with no nodal metastasis, ten cases with nodal metastasis). We found that abnormal expression of p16 and p27 increased with the progression of tubular adenomas to advanced gastric cancers. Inverse relationship between pRb and p16 proteins was found in a small portion of the gastric tumors. Expressions of pRb and cdk4 were consistently high in benign and malignant gastric tumors. Expression of cyclin D1 and cyclin E rather decreased with the tumor progression. In conclusion, losses of p16 and p27 seem to play a significant role during the gastric carcinogenesis, and the G1 checkpoint cell cycle proteins such as pRb, cdk4, cyclin D1, and cyclin E variably participate in the gastric carcinogenesis and metastasis by the mechanisms which are yet unknown; thus, further studies need to be performed to elucidate the mechanisms.

Biomarkers, Tumor↗
PubMed2000

Structure of III-Sb(001) growth surfaces: the role of heterodimers

We have determined the structure of AlSb and GaSb (001) surfaces prepared by molecular beam epitaxy under typical Sb-rich device growth conditions. Within the range of flux and temperature where the diffraction pattern is nominally (1x3), we find that there are actually three distinct, stable (4x3) surface reconstructions. The three structures differ from any previously proposed for these growth conditions, with two of the reconstructions incorporating mixed III-V dimers within the Sb surface layer. These heterodimers appear to play an important role in island nucleation and growth.

Journal Article↗
PubMed2000

Selenium deficiency potentiates methamphetamine-induced nigral neuronal loss; comparison with MPTP model.

The present study was designed to understand the role of an antioxidant, selenium (Se) on methamphetamine (MA)-induced dopaminergic cell damage in the substantia nigra (SN). Male C57BL/6J mice were fed either selenium-deficient (<0.01 ppm Se) or selenium-replete (0.2 ppm Se) diet for 90 days. Se-deficiency potentiates MA-induced reductions of tyrosine hydroxylase-like immunoreactivity (TH-IR), dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in the SN. These dopaminergic toxicities were comparable to that induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). By contrast, Se-repletion significantly blocked dopaminergic toxicity after MA treatments. These results suggest that Se-deficient MA-treated mouse is a relevant model of Parkinsonism, and that optimal level of Se plays a crucial role in preventing nigral dopaminergic toxicity induced by MA. However, different mechanisms in the thermoregulation mediated by MA or MPTP remain to be further determined.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Lipopolysaccharide activates matrix metalloproteinase-2 in endothelial cells through an NF-kappaB-dependent pathway.

Vascular endothelial cells release proteinases that degrade the extracellular matrix, thus enabling cell migration during angiogenesis and vasculogenesis. Endothelial cells secrete mainly the proform of matrix metalloproteinase-2 (proMMP-2). In this report, we examined several growth factors, cytokines, and other molecules for activation of MMP-2 by human umbilical vein endothelial cells. Of these factors, we found that lipopolysaccharide (LPS) is the strongest activator of MMP-2. LPS induced MMP-2 activation in a time- and dose-dependent manner. While pretreatment with zinc chelators or nuclear factor kappaB (NF-kappaB) inhibitors suppressed LPS-induced MMP-2 activation, pretreatment with phosphatidylinositol 3'-kinase inhibitors had no effect. These results indicate that, in endothelial cells, LPS can directly enhance angiogenesis by inducing MMP-2 activation mediated through an NF-kappaB pathway.

Cells, Cultured↗