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Biomedical subjects

C Y Han

Publications and source records attributed to C Y Han.

At least 19 recordsLinked to original sources
PubMed2001

The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-kappa b in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7.

Small heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated receptor gamma. Furthermore, SHP acted as a transcription coactivator of nuclear factor-kappa B (NF kappa B) and was essential for the previously described NF kappa B transactivation by palmitoyl lysophosphatidylcholine, one of the oxLDL constituents. Accordingly NF kappa B, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF kappa B in oxLDL-treated, resting macrophage cells.

Animals↗
PubMed2001

The angiopoietin-tie2 system in coronary artery endothelium prevents oxidized low-density lipoprotein-induced apoptosis.

OBJECTIVES: A healthy, intact coronary artery endothelium is important because most common coronary artery diseases result from loss of endothelial integrity. In this study, we explored the biological significance of the angiopoietin-Tie2 system in porcine coronary artery. METHODS: Cultured porcine coronary artery endothelial cells and explanted coronary arteries were used. RESULTS: Immunohistochemical analyses indicated that Ang1 is selectively expressed in vascular muscular cells, whereas angiopoietin-2 (Ang2) and Tie2 are selectively expressed in endothelial cells. Accordingly, Ang1 mRNA is mainly expressed in cultured porcine coronary artery vascular smooth muscle cells, whereas Ang2 and Tie2 mRNAs are mainly expressed in cultured porcine coronary artery endothelial cells (PCAECs). Ang1 (200 ng/ml) induced Tie2 phosphorylation, while Ang2 (200 ng/ml) did not produce Tie2 phosphorylation. Ang1 increased the survival of cultured PCAECs during apoptosis induced by oxidized low-density lipoprotein (OxLDL). This survival effect was does-dependent and PI. Furthermore, Ang1 also protected endothelial cells of explanted coronary artery against OxLDL-induced apoptosis artery. CONCLUSION: These results suggest that adult coronary artery contains Ang1-Tie2 components that enhance endothelial cell survival to help maintain the normal integrity of the coronary artery endothelium.

Analysis of Variance↗
PubMed2001

Depletion of mitochondrial DNA alters glucose metabolism in SK-Hep1 cells.

Maternally inherited mitochondrial DNA (mtDNA) has been suggested to be a genetic factor for diabetes. Reports have shown a decrease of mtDNA content in tissues of diabetic patients. We investigated the effects of mtDNA depletion on glucose metabolism by use of rho(0) SK-Hep1 human hepatoma cells, whose mtDNA was depleted by long-term exposure to ethidium bromide. The rho(0) cells failed to hyperpolarize mitochondrial membrane potential in response to glucose stimulation. Intracellular ATP content, glucose-stimulated ATP production, glucose uptake, steady-state mRNA and protein levels of glucose transporters, and cellular activities of glucose-metabolizing enzymes were decreased in rho(0) cells compared with parental rho(+) cells. Our results suggest that the quantitative reduction of mtDNA may suppress the expression of nuclear DNA-encoded glucose transporters and enzymes of glucose metabolism. Thus this may lead to diabetic status, such as decreased ATP production and glucose utilization.

Adenosine Triphosphate↗
PubMed2001

Patient empowerment via 'pushed' delivery of Personalised Healthcare educational content over the internet.

We present an Internet-based Personalised Healthcare Information (PHI) dissemination system. Information personalisation is guided by the individual's current health profile as recorded in his/her EMR. A PHI package is composed by intelligently selecting and synthesizing various topic-specific documents, each corresponding to some health parameter noted in the EMR. To ensure medical consistency, constraint satisfaction techniques are employed during the information selection phase. The resultant PHI package--covering both long-term and immediate health-maintenance requirements--can be pro-actively pushed to the individual via email, thereby ensuring the timely availability of situation-specific health maintenance information. The featured work is in line with the Malaysian Multimedia Super Corridor Telemedicine initiative and can serve as a test-bed to evaluate the effectiveness of PHI, system design and operational considerations for larger-scale deployment.

Health Status↗
PubMed2000

Role of endocytosis in the transactivation of nuclear factor-kappaB by oxidized low-density lipoprotein.

Oxidized low-density lipoprotein (oxLDL) has been shown to modulate transactivation by the peroxisome proliferator-activated receptor (PPAR)-gamma and by nuclear factor-kappaB (NF-kappaB). In the present study, the oxLDL signalling pathways involved in NF-kappaB transactivation were investigated by utilizing a reporter construct driven by three upstream NF-kappaB binding sites, and various pharmacological inhibitors. OxLDL and its constituent lysophophatidylcholine (lysoPC) induced a rapid and transient increase in intracellular calcium and stimulated NF-kappaB transactivation in resting RAW264.7 macrophage cells in an oxidation-dependent manner. NF-kappaB activation by oxLDL or lysoPC was inhibited by inhibitors of protein kinase C or by a chelator of intracellular calcium. Tyrosine kinase or phosphatidylinositol 3-kinase inhibitors did not block NF-kappaB transactivation. Furthermore, oxLDL-induced NF-kappaB activity was abolished by PPAR-gamma ligands. When the endocytosis of oxLDL was blocked by cytochalasin B, NF-kappaB transactivation by oxLDL was synergistically increased, while PPAR transactivation was blocked. These results suggest that oxLDL activates NF-kappaB in resting macrophages via protein kinase C- and/or calcium-dependent pathways, and that this does not involve the endocytic processing of oxLDL. The endocytosis-dependent activation of PPAR-gamma by oxLDL may function as a route of inactivation of the oxLDL-induced NF-kappaB signal.

Animals↗
PubMed1999

Oxidation-dependent effects of oxidized LDL: proliferation or cell death.

Oxidized low-density lipoprotein (oxLDL) induces a wide range of cellular responses to produce atherosclerotic lesion, but key factors determining the response are not understood. In this study, purified LDL was oxidized with copper sulfate, and its physical properties and the related biological responses were investigated. The average hydrodynamic diameter of the lightly oxidized LDL was approximately 25 nm and its Rf value relative to nLDL on agarose gel was between 1.0 and 1.25. The diameter of the extensively oxidized LDL was over 30 nm, the Rf value was over 2.0. A 24 h-exposure of resting RAW264.7 macrophage cells to 100 microg/ml of the lightly oxidized LDL induced proliferation and macrophage activation whereas the extensively oxidized LDL induced cell death at the same concentration. In contrast, 200 microg/ml of oxLDL caused cell death regardless of oxidation degree. Short incubation (4-6 h) of the highly oxidized LDL (100 microg/ml) also resulted in cell proliferation. OxLDL-induced cell death showed mixed characteristics of apoptosis and/or necrosis depending on the strength and duration of the insult. These results suggest that cellular responses induced by oxLDL be dependent on the oxidation degree, the duration of exposure, and the concentration of oxLDL.

Animals↗
PubMed1999

A receptor for advanced glycosylation endproducts (AGEs) is colocalized with neurofilament-bound AGEs and SOD1 in motoneurons of ALS: immunohistochemical study.

Neurofilament (NF)-bound AGEs colocalize immunochemically with SOD1 in the motoneurons of patients with ALS. Among three types of AGE receptors reported in the human brain, AGE-R1 (oligosaccharyltransferase family) and AGE-R2 (substrate of protein kinase C) have been found in neurons, while AGE-R3 is restricted to glia. The present study investigates which of these receptors may be responsible for binding AGEs in the NF conglomerates of motoneurons. Immunostaining of paraffin sections from eight ALS patients (five sporadic and three familial) and three control cases was performed with antibodies directed against R1 and R2, in parallel with those against AGEs and SOD1. The sites of AGE-R1 immunoreactivity (IR) in motoneurons were in conformity to those of NF-associated AGE and SOD1 IRs. By contrast, the IR of R2 was negative in NF conglomerates. Negative R2 IR for NF conglomerates was outlined by surrounding coarse R2 immunopositive granules in the perikaryon. No IR for R1 or R2 was found in hyaline or Bunina inclusions. There was no extraneuronal expression of IR for AGE-R1 or AGEs in microglia or astroglia around the NF accumulation. The colocalization of AGE, AGE-R1, and SOD1 at NF conglomerates in motoneurons supports the notion that AGE-mediated oxidative stress and protein aggregation may be implicated in NF conglomeration and ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗
PubMed1997

[Research on hydrokinetics of self-intermittent vaccum root canal drainage]

A hydrokinetically simulated sucking was made to study the self-intermittent vacuum drainage of the root canal.Results showed that due to the shape difference between diameters at the upper and lower parts of the canal,the high-speed air-flow at the lower-end opening can drain the fluid below the opening out while the lower-speed air-flow at the upper opening is not likely to make the saliva and see page in the oral cavity reenter the root cavity.The above mentioned are in conformity with the Bernoulli's equation.

Journal Article↗
PubMed1995

Acetylation polymorphism and prevalence of colorectal adenomas.

Polymorphic N-acetyltransferase (NAT2), an enzyme present in the colon, may effect incidence of colon cancer. Individuals with NAT2 fast acetylator genotypes may have higher colon cancer risks due to faster conversion of certain carcinogens to mutagens. We determined NAT2 genotypes in 447 subjects with distal colon adenomas and in 487 controls. No significant increase in adenoma prevalence among fast acetylators was observed. However, there was a suggestion of ethnic differences in NAT2 effects. For example, white fast acetylators potentially had slightly increased risks for adenomas (odds ratio, 1.29; 95% confidence interval, 0.90-1.84), whereas fast acetylation was potentially protective among blacks (odds ratio, 0.64; 95% confidence interval, 0.32-1.28). The apparent difference between blacks and whites may simply reflect random variation around an overall null effect, or it could represent a real difference. There was preliminary evidence for a possible interaction between NAT2 and the glutathione transferase M1 null genotype. Smokers' adenoma prevalence was 10-fold higher for fast acetylators with the null genotype compared to slow acetylators without the null genotype. Large, multiethnic populations and analysis of combinations of genes for carcinogen metabolism may be needed to further assess the role of NAT2 in colorectal tumorigenesis.

Acetylation↗
PubMed1995

Glutathione transferase (GSTM1) null genotype, smoking, and prevalence of colorectal adenomas.

Colorectal cancer is caused by environmental exposures and genetic predisposition. However, little is known of hereditary factors that influence development of common, non-Mendelian forms of this cancer. Interactions among carcinogen exposure, hereditary variants of enzymes involved in carcinogen metabolism, and other host factors may play a role. Genetic polymorphisms of carcinogen metabolism, such as the glutathione transferase M1 (GSTM1) null genotype, are thus possibly related to cancer risk. The GSTM1 enzyme detoxifies mutagens formed from polycyclic aromatic hydrocarbons which are found in tobacco smoke. We analyzed GSTM1 genotypes and smoking among 488 controls and 446 individuals with a first time diagnosis of colorectal adenomas which are precursors to cancer. Subjects were from two Kaiser Permanente sigmoidoscopy clinics in southern California. We observed no overall effect of the GSTM1 null genotype on the risk for colorectal adenomas (odds ratio, 0.85; 95% confidence interval = 0.65-1.10). The odds ratio for smokers with the null genotype was 2.07 (95% confidence interval = 1.14-3.77) when compared to "never smokers" without the null genotype. Using this same reference group, the odds ratio for smokers without the null genotype was 1.73 (95% confidence interval = 1.03-2.90). These two odds ratios were not significantly different (P = 0.30).

Adenoma↗
PubMed1994

Ethnic distribution of the glutathione transferase Mu 1-1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility.

Polycyclic aromatic hydrocarbons, found in cigarette smoke, food and industrial materials, are potential human carcinogens. Deficiency of detoxifying enzymes, such as glutathione transferases, may affect the metabolic fates of these chemicals and raise cancer risks in exposed individuals. The GSTM1 null genotype is a common form of glutathione transferase deficiency. Because knowledge of its ethnic distribution would be useful in epidemiologic studies, we measured the frequencies of the GSTM1 null genotype among healthy blacks, whites, Asian Indians, Chinese, Japanese, Koreans, Filipinos, Samoans and Hispanics. Rapid genotyping was done by use of a PCR assay, with dried blood spots on blotter paper as DNA templates. The frequency of the null genotype ranged from 0.31 among blacks to 0.88 among Samoans. The PCR assay was also applied to a pilot study of 114 bladder cancer cases from Kaiser Permanente Medical Center, Harbor City, California. DNA for these cases was obtained from paraffin-embedded surgical specimens. The overall odds ratio for bladder cancer with the GSTM1 null genotype was 1.4 (95% confidence interval 0.94-2.1), indicating no statistical difference in null genotype frequencies among bladder cancer patients compared to a healthy population. Large epidemiologic studies, which can be accomplished with dried blood spots or paraffin-embedded tissue specimens, may be useful for further assessment.

Adolescent↗
PubMed1994

Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene.

The acetylation polymorphism may affect rates of activation or detoxification of common carcinogens, thereby influencing cancer risk. Our aim was to define the ethnic distribution of the major slow acetylator mutations in the polymorphic N-acetyltransferase gene, in order to provide background data for epidemiological studies. Our results contain new analyses on 803 individuals, including 365 new specimens and 438 specimens that had been partly characterized in an earlier study. Tests were done to establish the specificity and reproducibility (98%) of our PCR assays. The recognized slow acetylator mutations, 191A, 481T, 590A, and 857A (which correspond to alleles M4 and M4b; M1 and r3; M2/r2; and M3 and S3, respectively), accounted for nearly all slow acetylator alleles among blacks, whites, Asian Indians, Hispanics, Koreans, Japanese, Hong Kong Chinese, Taiwanese, Filipinos and Samoans. The ethnic distribution supports an interpretation that the acetylation polymorphism existed before Paleolithic splitting of human populations from Africa. We identified two additional NAT2 mutations, suggesting that other rare alleles are likely to be found.

Acetylation↗
PubMed1993

Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology.

Our aim was to determine the population frequencies of the major slow acetylator alleles of the polymorphic N-acetyltransferase (NAT2) gene, whose locus maps to chromosome 8. We used allele-specific PCR amplification on 786 dried blood spots obtained from Hong Kong Chinese, U.S. Koreans, U.S. blacks, U.S. Hispanics, Germans, and U.S. whites. Our results show that four slow acetylator alleles can be detected as mutations at positions 481, 590, and 857 in the NAT2 gene. Recognized base substitutions at positions 341 and 803 need not be determined, because they were almost always associated with the 481T mutation. The known mutation at position 282 was strongly associated with the 590A mutation. The 481T, 590A, and 857A mutations accounted for virtually all of the slow acetylator alleles in Asian and white populations. The 857A mutation proved to be an Asiatic allele. The results will be useful in large-scale epidemiologic studies of cancer and other conditions potentially associated with the acetylator polymorphism.

Acetylation↗
PubMed1992

Functional profile of the human fetal gamma-globin gene upstream promoter region.

We performed a systematic functional analysis of the human gamma-globin promoter to identify its activator domains. We used a panel of truncation and scanning mutants as well as transfection in human K562 fetal erythroid cells. The various mutations produced relatively small changes in promoter function in both transient and stable transfection assays. The CACCC region and the region containing the binding sites for protein GATA-1 behaved as activator domains. We also obtained evidence for a minor activator site in the - 200 to - 190 region. The results are consistent with the interpretation that gamma-globin gene regulation may occur in part through multiple small effects of promoter elements.

Base Sequence↗
PubMed1991

Up-promoter mutations in the trpBA operon of Pseudomonas aeruginosa.

In Pseudomonas aeruginosa, the operon encoding tryptophan synthase (trpBA) is positively regulated by the TrpI protein and an intermediate in tryptophan biosynthesis, indoleglycerol phosphate (InGP). A gene fusion in which the trpBA promoter directs expression of the Pseudomonas putida xylE gene was constructed. By using a P. putida F1 todE mutant carrying this fusion on a plasmid, three cis-acting mutations that increased xylE expression enough to allow the todE strain to grow on toluene were isolated. The level of xylE transcript from the trpBA promoter was increased in all three mutants. All three mutations are base substitutions located in the -10 region of the trpBA promoter; two of these mutations make the promoter sequence more like the Escherichia coli RNA polymerase sigma 70 promoter consensus sequence. The activities of the wild-type and mutant trpBA promoters, as monitored by xylE expression, were assayed in P. putida PpG1 and in E. coli. The up-regulatory phenotypes of the mutants were maintained in the heterologous backgrounds, as was trpI and InGP dependence. These results indicate that the P. aeruginosa trpBA promoter has the key characteristics of a typical E. coli positively regulated promoter. The results also show that the P. aeruginosa and P. putida trpI activator gene products are functionally interchangeable.

Bacterial Proteins↗
PubMed1991

Nucleotide sequence and analysis of a gene encoding anthranilate synthase component I in Spirochaeta aurantia.

A Spirochaeta aurantia DNA fragment containing the trpE gene and flanking chromosomal DNA was cloned, and the sequence of the trpE structural gene plus 870 bp upstream and 1,257 bp downstream of trpE was determined. The S. aurantia trpE gene codes for a polypeptide of 482 amino acid residues with a predicted molecular weight of 53,629 that showed sequence similarity to TrpE proteins from other organisms. The S. aurantia TrpE polypeptide is not more closely related to the other published spirochete TrpE sequence (that of Leptospira biflexa) than to TrpE polypeptides of other bacteria. Two additional complete open reading frames and one partial open reading frame were identified in the sequenced DNA. One of the complete open reading frames and the partial open reading frame are upstream of trpE and are encoded on the DNA strand opposite that containing trpE. The other open reading frame is downstream of trpE and on the same DNA strand as trpE. On the basis of the results of a protein sequence data base search, it appears that trpE is the only tryptophan biosynthesis gene in the sequenced DNA. This is in contrast to L. biflexa, in which trpE is separated from trpG by only 64 bp.

Amino Acid Sequence↗