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Biomedical subjects

J Y Park

Publications and source records attributed to J Y Park.

At least 19 recordsLinked to original sources
PubMed1999

Transcriptional regulation of the intercellular adhesion molecule-1 gene by proinflammatory cytokines in human astrocytes.

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated by cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-gamma (IFN-gamma) in numerous cell types including the astrocyte, which functions as an immunoregulatory cell within the central nervous system. We investigated the mechanism by which ICAM-1 is transcriptionally regulated by proinflammatory cytokines in human fetal astrocytes. TNF-alpha and IL-1beta enhanced ICAM-1 expression at both the mRNA and protein levels, while IFN-gamma had a modest enhancing effect. However, a synergistic response was noted when IFN-gamma was added with either TNF-alpha or IL-1beta. Using human ICAM-1 deletion constructs and linker scanning mutants, we determined that the NF-kappaB element (-186 bp region) is critical for both TNF-alpha- and IL-1beta-mediated ICAM-1 expression, while the IFN-gamma activation sequence (GAS) element at -75 bp region is important for IFN-gamma stimulation. The synergistic effect between TNF-alpha and IFN-gamma is dependent on both NF-kappaB and GAS elements. Upon TNF-alpha and IL-1beta stimulation, p65 homodimers and p65/p50 heterodimers bind to the NF-kappaB site, and STAT-1alpha homodimers bind to the GAS element upon IFN-gamma stimulation. Transient transfection assays demonstrated that overexpression of the p65 protein transactivated the promoter activity of an ICAM-1 reporter construct, while p50 overexpression inhibited, in a dose-dependent manner, p65-mediated ICAM-1 expression. These data collectively suggest that in human astrocytes, the p65 homodimer is responsible for ICAM-1 upregulation upon TNF-alpha or IL-1beta stimulation, and that IFN-gamma enhancement of ICAM-1 involves activation of STAT-1alpha homodimers.

Astrocytes↗
PubMed1998

Proton exchange kinetics in [d(ACGTATACGT)]2-echinomycin and [d(ACGTTAACGT)]2-echinomycin complexes.

Based on imino proton exchange catalysis, base-pair lifetimes and apparent dissociation constants are reported on the complexes formed by bisintercalation of echinomycin at the CpG steps of the d(ACGTATACGT)2 and d(ACGTTAACGT)2 duplexes. The lifetimes of the four central A x T base pairs between two echinomycin binding sites are much shorter than in the free duplexes. The destabilization of base pairs adjacent to the binding sites is propagated one additional base pair away from the binding site.

Base Composition↗
PubMed1998

Compartmental models of vitamin A and beta-carotene metabolism in women.

We have developed compartmental models of vitamin A and beta-carotene (beta C) metabolism in women living under controlled conditions on diets with known concentrations of vitamins and carotenoids. Fourteen healthy adult women were given either retinyl-d4 acetate, or beta C-d8 before breakfast. Natural and stable-isotopes of retinol and beta C were collected in serum for up to 95 days or 20 days, respectively. Stable isotopes were separated from other components and measured by GC-MS or HPLC-UV. Preformed retinyl-d4 acetate metabolism in all women tested can be accurately described by a simple four-compartment model. However, the model did not fit one women initially, when she had marginal vitamin A status. We tested the hypothesis that dietary changes of beta C intake have important roles on the kinetics of vitamin A metabolism. Dietary changes of beta C intake did not influence the turnover rate of retinol in any compartment. However, it did result in changes in steady-state masses and residence times of retinol in several compartments. A working compartmental model for beta C metabolism was developed. The kinetics of retinol-d4 formed from beta C is more complicated than the pre-formed retinol-d4. Results suggest that beta C-d8 readily converts into retinol-d4 with high inter-individual variability.

Adult↗
PubMed1998

Association of microalbuminuria and atherosclerotic risk factors in non-diabetic subjects in Korea.

Microalbuminuria in non-diabetic subjects is reportedly associated with increased cardiovascular morbidity and mortality. The prevalence of microalbuminuria in non-diabetic subjects varies widely from 5-6% in the UK and USA to 30-55% in Finland, Mexico, or Australian Aborigines. We studied cross-sectionally 497 clinically healthy, non-diabetic subjects more than 40 years of age who were living in Seoul, Korea for the prevalence of microalbuminuria and various cardiovascular risk factors. Urinary albumin-to-creatinine ratio (UACR) was determined in morning spot urine samples. Subjects were divided into normoalbuminuria (UACR < 2 mg/mmol) and microalbuminuria (UACR > or = 2 mg/mmol) groups. A total of 61 (12.2%) out of 497 subjects were found to have microalbuminuria. Subjects with microalbuminuria had significantly higher values in age, body mass index (BMI), waist-to-hip ratio in women, systolic and diastolic blood pressure, prevalence of hypertension, plasma cholesterol and triglyceride, and fasting plasma insulin. When subjects with microalbuminuria were compared with age-, sex-, and BMI-matched controls without microalbuminuria, systolic and diastolic blood pressure, and fasting plasma insulin concentrations were higher in microalbuminuric subjects. Multiple logistic regression analysis showed that fasting plasma insulin level and systolic blood pressure were independently associated with microalbuminuria. These results indicate that the prevalence of microalbuminuria in Korean non-diabetic subjects is lower than that in Mexico and Finland, but similar to that in Caucasians from the UK and USA, or in Pima Indians. Also, microalbuminuria in Korean non-diabetic subjects is associated with atherosclerotic risk factors such as hyperinsulinemia and hypertension, suggesting that microalbuminuria in these subjects may be a feature of insulin resistance syndrome.

Albuminuria↗
PubMed1998

p53, but not p16 mutations in oral squamous cell carcinomas are associated with specific CYP1A1 and GSTM1 polymorphic genotypes and patient tobacco use.

Inactivation of tumor suppressor genes like p53 and p16 play a key role in tumor progression, with a high incidence of mutations existing for both genes in oral squamous cell carcinomas. Previous studies have demonstrated, (i) a correlation between the prevalence of p53 mutations and tobacco use [Brennan et al. (1995) New Engl. J. Med., 332, 712-717; Lazarus et al. (1996) Carcinogenesis, 17, 733-739], and (ii) a link between genotypes in specific xenobiotic metabolizing enzymes and oral cancer susceptibility [Park et al. (1997) Cancer Epid. Biomarkers Prev., 6, 791-797). In this paper, we present results of our examination of a series of 80 oral squamous cell carcinomas for p53 exons 5-9 and p16 exons 1-2 mutations, and the potential association of these mutations with specific genotyping patterns. p53 mutation prevalence in oral tumors was linked with increased patient tobacco use using several stratification criteria. There was a significantly higher prevalence of p53 mutations in OCSCCs from patients who smoked > 30 pack-years as compared to tumors from patients who smoked < or = 30 pack-years (OR = 2.8; CI = 1.1-7.2). No significant association was observed with patient alcohol consumption. There was a significant association between the prevalence of p53 mutations in oral tumors and CYP1A1 genotyping patterns in these oral cancer patients, with the highest p53 mutation prevalence observed in subjects with the CYP1A1 [val]/GSTM1 [+] genotype (OR = 6.0; CI = 1.2-29.7). A significant association was not observed between the prevalence of p16 mutations in oral tumors and tobacco use, or CYP1A1 [val] or GSTM1 (0/0) genotypes. These data suggest that the induction of mutations in specific tumor suppressor genes or oncogenes in oral tumors may be associated with specific carcinogen exposures, and that this association may be linked to specific polymorphic genotypes in xenobiotic-metabolizing enzyme genes.

Benzo(a)pyrene↗
PubMed1998

Microcystic adnexal carcinoma. First reported case in a black patient.

BACKGROUND: Microcystic adnexal carcinoma is an uncommon malignancy of the skin with a propensity for local aggressive growth and high rates of recurrence. To date, this neoplasm has been described mainly in the Caucasian population. We describe here the first reported case in a black patient. OBJECTIVE: To discuss the successful identification and management of this aggressive neoplasm in the non-Caucasian population. METHODS: Mohs micrographic surgery was performed on this tumor. RESULTS: The tumor was successfully excised without evidence of recurrence at 6 months. CONCLUSIONS: We present the first reported case of microcystic adnexal carcinoma in a black patient. This tumor was identified in its early stages and removed by Mohs micrographic surgery without sequelae.

Adipose Tissue↗
PubMed1998

Effects of FFA on insulin-stimulated glucose fluxes and muscle glycogen synthase activity in rats.

To examine effects of free fatty acids (FFA) on insulin-stimulated glucose fluxes, euglycemic hyperinsulinemic (86 pmol . kg-1 . min-1) clamps were performed for 5 h in conscious rats with (n = 8) or without (n = 8) lipid-heparin infusion. Glucose infusion rate required to maintain euglycemia was not different between the two groups during the first 2 h of clamps but became significantly lower with lipid-heparin infusion in the 3rd h and thereafter. To investigate changes in intracellular glucose metabolism during lipid-heparin infusion, additional clamps (n = 8 each) were performed for 1, 2, 3, or 5 h with an infusion of [3-3H]glucose. Insulin-stimulated whole body glucose utilization (Rd), glycolysis, and glycogen synthesis were estimated on the basis of tracer concentrations in plasma during the final 40 min of each clamp. Similar to changes in glucose infusion rate, Rd was not different between the two groups in the 1st and 2nd h but was significantly lower with lipid-heparin infusion in the 3rd h and thereafter. Whole body glycolysis was significantly lower with lipid-heparin infusion in all time periods, i.e., 1st, 2nd, 3rd, and 5th h of clamps. In contrast, whole body glycogen synthesis was higher with lipid-heparin infusion in the 1st and 2nd h but lower in the 5th h. Similarly, accumulation of [3H]glycogen radioactivity in muscle glycogen was significantly higher with lipid-heparin during the 1st and 2nd h but lower during the 3rd and 5th h. Glucose 6-phosphate (G-6-P) concentrations in gastrocnemius muscles were significantly higher with lipid-heparin infusion throughout the clamps. Muscle glycogen synthase (GS) activity was not altered with lipid-heparin infusion at 1, 2, and 3 h but was significantly lower at 5 h. Thus increased availability of FFA significantly reduced whole body glycolysis, but compensatory increase in skeletal muscle glycogen synthesis in association with accumulation of G-6-P masked this effect, and Rd was not affected in the early phase (within 2 h) of lipid-heparin infusion. Rd was reduced in the later phase (>2 h) of lipid-heparin infusion, when glycogen synthesis was reduced in association with reduced skeletal muscle GS activity.

Analysis of Variance↗
PubMed1998

Development and progression of diabetic retinopathy in Koreans with NIDDM.

OBJECTIVE: To determine the incidence and risk factors for the development and progression of diabetic retinopathy in Korean patients with NIDDM. RESEARCH DESIGN AND METHODS: A total of 186 patients with NIDDM who did not have proliferative diabetic retinopathy (PDR) at baseline were prospectively studied for 5.3 +/- 1.0 years in an outpatient clinic of a university hospital. The incidence and progression of diabetic retinopathy was determined by annual funduscopic examination by an ophthalmologist. RESULTS: Of the 130 patients who were free of diabetic retinopathy at baseline, 30 developed it, giving an incidence of 44.4/1,000 person-years. Age and known duration of diabetes, mean fasting plasma glucose, and HbA1 levels during the follow-up period were higher in the patients who developed diabetic retinopathy. Of the 56 patients who had nonproliferative diabetic retinopathy at baseline, 11 developed PDR, giving an incidence of 37.5/1,000 person-years. The patients who progressed to PDR during follow-up (progressors) had a higher change of BMI and urinary albumin excretion rate at baseline and a higher mean HbA1 during the follow-up period than the nonprogressors. Cox proportional hazards analysis revealed that mean HbA1 was the only independent risk factor for both the development and progression of diabetic retinopathy. CONCLUSIONS: The incidence of PDR in Korean NIDDM patients is comparable to that reported in other populations. Poor glycemic control is the most important risk factor for both the development and progression of diabetic retinopathy in NIDDM patients.

Blood Glucose↗
PubMed1998

High serum lipoprotein(a) levels in Korean type 2 diabetic patients with proliferative diabetic retinopathy.

OBJECTIVE: To examine the possible association between serum lipoprotein(a) [Lp(a)] concentration and proliferative diabetic retinopathy (PDR) in Korean patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 412 Korean outpatients with type 2 diabetes were examined. Diabetic retinopathy was determined by an ophthalmologist using fundoscopic examination. Serum Lp(a) levels were measured by two-site sandwich enzyme-linked immunosorbent assay. RESULTS: The patients with PDR had higher serum Lp(a) levels than those with no diabetic retinopathy or with nonproliferative diabetic retinopathy (NPDR). Multiple logistic regression analysis showed that high serum Lp(a) levels and the presence of diabetic nephropathy were independent variables having a statistically significant association with PDR. CONCLUSIONS: Korean type 2 diabetic patients with PDR had higher serum Lp(a) levels versus those with no diabetic retinopathy or with NPDR. Although these results suggest that Lp(a) might play a role in the occlusion of retinal capillaries leading to PDR, further prospective studies are required to prove the causal relationship.

Blood Glucose↗
PubMed1998

Incidence and determinants of microalbuminuria in Koreans with type 2 diabetes.

OBJECTIVE: The incidence of diabetic nephropathy in type 2 diabetes differs widely by race. Although clinical proteinuria is reportedly more common in East Asian type 2 diabetic patients than in their Caucasian counterparts, data on the incidence of microalbuminuria are not available. This study was undertaken to investigate the incidence and the determinants of microalbuminuria in Korean type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 188 Korean type 2 diabetic patients with initial normoalbuminuria were followed prospectively for 5.5 +/- 0.9 years in an outpatient clinic of a university hospital. The incidence of elevated urinary albumin excretion (UAE) (> 20 micrograms/min) and its relationship with baseline characteristics and follow-up data were determined. RESULTS: Of the 146 patients who finished the study, 37 showed persistently elevated UAE during follow-up, giving an incidence of 52/1,000 person-years. Age, duration of diabetes, and baseline UAE were significantly higher in the progressors than in the nonprogressors. More patients in the progressor group had retinopathy at baseline and at the end of follow-up. The mean values of fasting plasma glucose, HbA1, and systolic and diastolic blood pressure during the follow-up period were significantly higher in the progressors than in the nonprogressors. Cox proportional hazards analysis revealed that presence of retinopathy, duration of diabetes, mean fasting plasma glucose, and mean systolic blood pressure during follow-up are independent variables that have a statistically significant influence on the development of microalbuminuria. CONCLUSIONS: The incidence of microalbuminuria in Korean type 2 diabetic patients is lower than that reported in Pima Indians with type 2 diabetes but is as high as that in Caucasians with type 1 diabetes. Presence of diabetic retinopathy, poor glycemic control, and high blood pressure are risk factors for development of microalbuminuria in Koreans with type 2 diabetes.

Aged↗
PubMed1998

Chemokines, osteopontin, ICAM-1 gene expression in cultured rat mesangial cells.

To investigate whether MCP-1, CINC, RANTES, osteopontin and ICAM-1 mRNA could be induced in cultured rat mesangial cells by interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), and whether MCP-1 and CINC gene expression could be modulated by dexamethasone, Northern blot assays were performed. IL-1beta induced MCP-1, CINC, RANTES and ICAM-1 gene expression in a time dependent manner. IL-1beta-induced MCP-1, CINC and ICAM-1 mRNA amount were maximal at 3 hours exposure around 14.5, 15.7, 2.2 folds increase and IL-1beta-induced RANTES mRNA at 24 hours around 2.0 folds. TNF-alpha and LPS also induced MCP-1 and ICAM-1 gene expression. TNF-alpha also induced RANTES gene expression but LPS did not. On the other hand, IL-1beta, TNF-alpha and LPS had little effect on osteopontin gene expression but fetal calf serum could increase osteopontin mRNA. Dexamethasone suppressed the IL-1beta-induced MCP-1 and CINC mRNA. These results suggest that, through these gene expressions, mesangial cells are able to communicate directly or indirectly with macrophages or neutrophils, which may lead to glomerulosclerosis.

Animals↗
PubMed1998

Fanconi anemia screening by diepoxybutane and mitomicin C tests in Korean children with bone marrow failure syndromes.

Fanconi anemia (FA) is an autosomal recessive disorder of progressive bone marrow failure in patients with congenital malformations. FA is different from acquired aplastic anemia (AA) in terms of the natural course and treatment options. As the frequency of FA is unknown in Korea, we conducted screening tests using DNA clastogenic agents, diepoxybutane (DEB) and mitomicin C (MMC) in southwestern Korea. Forty-three children with AA or other bone marrow failure syndromes and siblings of known FA were evaluated. Six patients with AA (6/24=25.0%) and a 2-month-old patient with myelodysplastic syndrome were found to have increased chromosomal breakage to both DEB and MMC, confirming the diagnosis of FA. No overlap in chromosomal breakage to both agents was found between the FA group and non-FA group. The frequency of FA in this study, much higher than those of previous studies in Korea which did not incorporate the above tests, was similar to that of other countries. DEB and MMC tests were readily feasible and useful in screening FA in patients with AA as well as other bone marrow failure syndromes. A nation-wide screening and registry for FA should be initiated since FA requires different therapeutic and management options from idiopathic AA.

Adolescent↗
PubMed1998

Religious affiliation, religious involvement, and alcohol use in Korea.

This article is the first study of religious commitment and involvement of homeland Koreans as related to alcohol use. Religious affiliation and involvement are predictive of abstemiousness, but chiefly for women, who are at low risk for alcohol abuse and dependency, and not for men, who are at high risk. The frequent abstemiousness of Buddhist women results chiefly from data having to do with mothers and probably is a consequence of the women's traditional lifestyles, being both Buddhist and abstemious. Among the probably more Westernized Christians, religious involvement is most clearly associated with abstemiousness among daughters, a group at a relatively low but increasing risk for alcohol use.

Adult↗
PubMed1998

Therapy planning as constraint satisfaction: a computer-based antiretroviral therapy advisor for the management of HIV.

We applied the Protégé methodology for building knowledge-based systems to the domain of antiretroviral therapy. We modeled the task of prescribing drug therapy for HIV, abstracting the essential characteristics of the problem solving. We mapped our model of the antiretroviral-therapy domain to the class of constraint-satisfaction problems, and reused the propose-and-revise problem-solving method, from the Protégé library of methods, to build an antiretroviral therapy advisor, ART Critic. Careful modeling and using Protégé allowed us to build a useful and extensible knowledge-based application rapidly.

Anti-HIV Agents↗
PubMed1997

Identification of three regions essential for interaction between a sigma-like factor and core RNA polymerase.

The cyclic interactions that occur between the subunits of the yeast mitochondrial RNA polymerase can serve as a simple model for the more complex enzymes in prokaryotes and the eukaryotic nucleus. We have used two-hybrid and fusion protein constructs to analyze the requirements for interaction between the single subunit core polymerase (Rpo41p), and the sigma-like promoter specificity factor (Mtf1p). We were unable to define any protein truncations that retained the ability to interact, indicating that multiple regions encompassing the entire length of the proteins are involved in interactions. We found that 9 of 15 nonfunctional (petite) point mutations in Mtf1p isolated in a plasmid shuffle strategy had lost the ability to interact. Some of the noninteracting mutations are temperature-sensitive petite (ts petite); this phenotype correlates with a precipitous drop in mitochondrial transcript abundance when cells are shifted to the nonpermissive temperature. One temperature-sensitive mutant demonstrated a striking pH dependence for core binding in vitro, consistent with the physical properties of the amino acid substitution. The noninteracting mutations fall into three widely spaced clusters of amino acids. Two of the clusters are in regions with amino acid sequence similarity to conserved regions 2 and 3 of sigma factors and related proteins; these regions have been implicated in core binding by both prokaryotic and eukaryotic sigma-like factors. By modeling the location of the mutations using the partial structure of Escherichia coli sigma70, we find that two of the clusters are potentially juxtaposed in the three-dimensional structure. Our results demonstrate that interactions between sigma-like specificity factors and core RNA polymerases require multiple regions from both components of the holoenzymes.

Amino Acid Sequence↗
PubMed1997

Opposite effect of intracellular Ca2+ and protein kinase C on the expression of inwardly rectifying K+ channel 1 in mouse skeletal muscle.

The level of inwardly rectifying K+ channel 1 (IRK1) mRNA decreased upon denervation and increased during muscle differentiation in mouse skeletal muscle. To identify the mechanism(s) underlying the regulation of IRK1 mRNA expression, we examined its expression using the well differentiated C2C12 mouse skeletal muscle cell line as a model system. Since nerve-induced muscle activity results in contraction, it was questioned whether the changes in IRK1 expression might be relevant to the increased intracellular calcium that functions as a cytoplasmic messenger in excitation-contraction coupling. Indeed, activation of either L-type calcium channels or ryanodine receptors increased the level of IRK1 mRNA. More directly, ionomycin activated the IRK1 expression in time- and dose-dependent manners, which was abolished by treatment with EGTA. Genistein, a tyrosine kinase inhibitor, also abolished the stimulating effect of ionomycin. Meanwhile, activation of protein kinase C by 12-O-tetradecanoylphorbol acetate (TPA) markedly decreased the level of IRK1 mRNA, which required ongoing protein synthesis. Actinomycin D experiments revealed that ionomycin increased the half-life of IRK1 mRNA from 0.86 to 1.97 h, but TPA decreased it to 0.38 h. However, neither ionomycin nor TPA appreciably altered the rate of IRK1 gene transcription. Based on these observations, we conclude that intracellular calcium and protein kinase C are oppositely involved in the muscle activity-dependent regulation of IRK1 gene expression and that both act at the level of mRNA stability.

Animals↗