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Biomedical subjects

N H Park

Publications and source records attributed to N H Park.

At least 19 recordsLinked to original sources
PubMed2006

Polyphenol (-)-epigallocatechin gallate protection from ischemia/reperfusion-induced renal injury in normotensive and hypertensive rats.

INTRODUCTION: The effect of epigallocatechin gallate (EGCG) in an in vivo renal model of ischemia with reperfusion (I/R) was compared between normotensive (WKR) and hypertensive (SHR) rats. METHODS: WKR (groups I, II, III) and SHR groups (groups IV, V, VI) were divided into three types. Groups I and IV were sham-operated animals; groups II and V were subjected to 45 minutes of renal I/R; and groups III and VI received 10 mg/kg EGCG intravenously at the time of reperfusion. Three days after renal I/R, we compared renal function markers, malondialdehyde (MDA), and histologic changes. RESULTS: Following renal I/R, levels of blood urea nitrogen (BUN) and serum creatinine (sCr) were increased and serum creatinine clearance (CrCl) decreased in group V compared to group II (P < .001). Those receiving EGCG treatment (groups III and VI) had decreased BUN and sCr compared to non-EGCG I/R groups (P < .001), but not surprisingly, higher than sham groups. CrCl was lowest in the SHR groups. The MDA was significantly decreased after EGCG treatment (P = .028 in group III, P = .002 in group VI). Following renal I/R, tissue necrosis was more severe among SHR (P < .001). However, the ratio of regeneration to damage significantly increased in SHR after EGCG treatment. CONCLUSIONS: The reperfusion injury was greater among SHR compared with WKR in terms of renal function, lipid peroxidation, and tissue damage. EGCG treatment significantly ameliorated renal impairment and promoted tissue regeneration following renal I/R.

Animals↗
PubMed2006

Chronic hepatitis B in hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a wide geographical variation. Eighty per cent of HCC is attributed to hepatitis B virus (HBV). The predominant carcinogenic mechanism of HBV associated HCC is through the process of liver cirrhosis, but direct oncogenic effects of HBV may also contribute. Prevention of HBV infections as well as effective treatment of chronic hepatitis B is still needed for the global control of HBV associated HCC. Continued investigation of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver.

Apoptosis↗
PubMed2005

Assessing clinical performance of gynecology residents: sonographic evaluation of adnexal masses based on morphological scoring systems.

OBJECTIVE: To assess the performance of inexperienced gynecology residents in the evaluation of adnexal masses using sonographic scoring systems. METHODS: From April 2003 to October 2004, transvaginal sonography was performed preoperatively by junior gynecology residents on 1-month shifts on 123 patients suspected of having adnexal masses. A total of 137 adnexal masses were found and evaluated using two different morphological scoring systems (those of DePriest and Lerner). The diagnostic performance of the sonographic scoring systems was assessed using the McNemar test and receiver-operating characteristics (ROC) curve analysis was used for lesion characterization. The diagnostic accuracy when the results of both scoring systems satisfied malignancy cut-off values was also investigated. RESULTS: Histopathological analysis revealed that, of the 137 lesions, 109 were benign, 23 were malignant and five were borderline. Best clinical cut-off levels were > or = 5 on the DePriest and > or = 3 on the Lerner scores. Both systems achieved good performance for characterizing malignancy. No significant difference was found in terms of the accuracy of the two systems as determined by mean areas under the ROC curves (0.816 and 0.783, P = 0.562). The combined approach using both scoring systems resulted in higher specificity (77.1%, P < 0.05) and positive predictive value without a significant decrease in sensitivity (82.1%) compared with either system alone. Of the 43 histologically confirmed false-positive cases, mature cystic teratoma was most common, with 13/22 (59%) cases being misinterpreted as malignancies. CONCLUSION: Junior residents, inexperienced at sonography, performed fairly in terms of evaluating adnexal masses with the help of morphological scoring systems.

Adnexal Diseases↗
PubMed2005

Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis B.

The aim of this study was to determine whether the changing patterns of quantitative hepatitis B e antigen (HBeAg) levels by serial monitoring could predict HBeAg seroconversion and viral breakthrough during lamivudine therapy. We retrospectively analysed 340 HBeAg positive naive chronic hepatitis B patients treated with lamivudine. The mean duration of lamivudine therapy was 18.7 (range 6-56) months. The changing patterns and reduction rates of pretreatment HBeAg levels by serial monitoring were categorized into three groups: Decrescendo group (n = 195), Decrescendo-crescendo group (n = 65) and no changing or fluctuating group (n = 80). Of 109 patients who had achieved HBeAg seroconversion, 105 (96.3%) were included in the decrescendo group. The decrescendo group, pretreatment quantitative HBeAg levels, alanine aminotransferase levels, and the duration of lamivudine therapy were independent predictive factors for HBeAg seroconversion. Of 82 patients who had viral breakthrough, 53 (64.6%) were in the decrescendo-crescendo group and 21 (25.6%) were in the no changing or fluctuating group. The only predictive factor for viral breakthrough was the changing patterns of quantitative HBeAg levels, especially, the decrescendo-crescendo group and the no changing or fluctuating group. The mean time of turning points in the decrescendo-crescendo group was 7.1 months earlier than the mean time of viral breakthrough (9.0 months vs 16.5 months). Therefore, the changing patterns of quantitative HBeAg levels by serial monitoring during lamivudine therapy may allow not only the prediction of treatment responses, but also an early recognition of a viral breakthrough.

Adolescent↗
PubMed2005

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B.

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.

Adult↗
PubMed2003

The legacy of the regional research centers for minority oral health.

The Regional Research Centers for Minority Oral Health (RRCMOH) helped to redefine the research and education missions of the participating institutions, and placed new emphasis on early diagnosis, prevention, and conservative interventions in minority-related oral diseases, with an eye toward innovative, cost-effective solutions to long-neglected and underfunded areas of dental and craniofacial research, education, and health promotion programs. This article reviews the legacy of the RRCMOH.

Academies and Institutes↗
PubMed2001

Molecular and enzymatic characterization of a levan fructotransferase from Microbacterium sp. AL-210.

Microbacterium sp. AL-210 producing a novel levan fructotransferase (LFTase) was screened from soil samples. The LFTase was purified to homogeneity by (NH4)2SO4 fractionation, column chromatography on Resource Q, and Superdex 200HR. The molecular weight of the purified enzyme was estimated to be approximately 46 kDa by both SDS-PAGE and gel filtration, and the enzyme's isoelectric point was pH 4.8. The major product produced from the levan hydrolysis by the enzyme reaction was identified by atmospheric pressure ionization mass spectrometry and NMR analysis as di-D-fructose-2,6':6,2'-dianhydride (DFA IV). The optimum pH and temperature for DFA IV production were 7.0 and 40 degrees C, respectively. The enzyme was stable at a pH range 7.0-8.0 and up to 40 degrees C. The enzyme activity was inhibited by FeCl2 and AgNO3. The enzyme converted the levan to DFA IV, with a conversion yield of approximately 44%. A gene encoding the LFTase (lftM) from Microbacterium sp. AL-210 was cloned and sequenced. The nucleotide sequence included an ORF of 1593 nucleotides, which is translated into a protein of 530 amino acid residues. The predicted amino acid sequence of the enzyme shared 79% of the identity and 86% of the homology with that of Arthrobacter nicotinovorans GS-9.

Actinomycetales↗
PubMed2001

Enhanced activity of cloned hamster TERT gene promoter in transformed cells.

In 7,12-dimethylbenz[a]anthracene-treated hamster pouch epithelial cells, telomerase activity increased within 1 week of treatment and reached a 6-7-fold increase within 3 weeks. To investigate this phenomenon, we have cloned and sequenced the hamster telomerase catalytic subunit (hamTERT) promoter. Transient transfection with different genomic segments upstream of the ATG translation initiation codon linked to the luciferase reporter gene mapped the core promoter within a 250 bp region. Three major transcription initiation sites and several minor sites were found between -42 and -140 bp relative to the ATG site. Like the human and murine TERT promoters, the hamTERT promoter lacks TATA and CAT boxes and all three promoters share similar regulatory factor binding sites. DNase I footprint analysis revealed six protected regions which contain sequences homologous with known transcription factor binding sites. Three protein binding regions (I, II, and III) were essential for the promoter activity. Regions I and III bound to Sp1 and Sp3 transcriptional factors, whereas region II bound to an unknown factor. Transient transfection of a promoter-luciferase plasmid into Drosophila SL2 cells showed that Sp1 and Sp3 regulated the hamster TERT promoter in a concentration-dependent and synergistic manner. Telomerase activity showed a 2-4-fold and 8-10-fold increase in immortalized cells and tumor cells, respectively, but hamTERT expression was only increased 1.7-fold and 2.4-fold, respectively, in the same cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Polymorphism of TP53 codon 72 and the risk of cervical cancer among Korean women.

OBJECTIVE: It has recently been suggested that white women who are homozygous for the allele of the gene for wild-type p53 protein (TP53) that encodes arginine at position 72 are more susceptible to human papillomavirus-associated cervical carcinoma than are women who are heterozygous for this polymorphism and women who are homozygous for the allele that encodes proline at that position. This study was undertaken to analyze whether the TP53 codon 72 single-nucleotide polymorphism might be correlated with the risk of cervical cancer among Korean women. STUDY DESIGN: Peripheral blood samples from patients with invasive cervical carcinoma yielding a positive result for human papillomavirus 16 (n = 100), patients with cervical intraepithelial neoplasia grade III (n = 134), and healthy control subjects (n = 100) were examined. The presence and genotype of human papillomavirus in cancerous cervical tissues were determined by E6, E7-based nested polymerase chain reaction. Germline genomic deoxyribonucleic acid was extracted from peripheral blood leukocytes and examined by polymerase chain reaction amplification of the specific allele assay as described by Storey et al. Deoxyribonucleic acid samples from patients whose TP53 sequences had been determined by direct sequencing were used as positive control preparations. RESULTS: The respective proportions of individuals who are homozygous for the arginine allele, homozygous for the proline allele, and heterozygous for the 2 alleles were 40%, 12%, and 48% among women with invasive cervical carcinoma, 52%, 9%, and 39% among women with cervical intraepithelial neoplasia grade III, and 52%, 11%, and 37% among the control group. No significant differences in the frequency of codon 72 alleles were found among the 3 groups (chi(2) = 4.414; P =.353; degrees of freedom = 4). CONCLUSION: This finding suggests that the risk of cervical cancer may not be increased for Korean women with the allele of TP53 encoding arginine at codon 72.

Antibodies, Viral↗
PubMed2001

Motility and chemotaxis in tissue penetration of oral epithelial cell layers by Treponema denticola.

The ability to penetrate tissue is an important virulence factor for pathogenic spirochetes. Previous studies have recognized the role of motility in allowing pathogenic spirochetes to invade tissues and migrate to sites favorable for bacterial proliferation. However, the nature of the movements, whether they are random or controlled by chemotaxis systems, has yet to be established. In this study, we addressed the role of motility and chemotaxis in tissue penetration by the periodontal disease-associated oral spirochete Treponema denticola using an oral epithelial cell line-based experimental approach. Wild-type T. denticola ATCC 35405 was found to penetrate the tissue layers effectively, whereas a nonmotile mutant was unable to overcome the tissue barrier. Interestingly, the chemotaxis mutants also showed impaired tissue penetration. A cheA mutant that is motile but lacks the central kinase of the chemotaxis pathway showed only about 2 to 3% of the wild-type penetration rate. The two known chemoreceptors of T. denticola, DmcA and DmcB, also appear to be involved in the invasion process. The dmc mutants were actively motile but exhibited reduced tissue penetration of about 30 and 10% of the wild-type behavior, respectively. These data suggest that not only motility but also chemotaxis is involved in the tissue penetration by T. denticola.

Anaerobiosis↗
PubMed2001

Cariogenic actinomyces identified with a beta-glucosidase-dependent green color reaction to Gardenia jasminoides extract.

The oral bacteria Actinomyces naeslundii and Actinomyces viscosus are known to contribute to the initiation and progression of human dental caries, especially root caries. We report that both A. naeslundii and A. viscosus react with a component in the Gardenia jasminoides extract to produce a distinct green product. This green color reaction was found to be dependent on the bacterial beta-glucosidase. The reaction is specific for cariogenic actinomyces, and it can detect as few as 10(4) cells of A. naeslundii and A. viscosus per ml.

Actinomyces↗
PubMed2001

Conversion of normal to malignant phenotype: telomere shortening, telomerase activation, and genomic instability during immortalization of human oral keratinocytes.

Normal somatic cells terminate their replicative life span through a pathway leading to cellular senescence, which is triggered by activation of p53 and/or pRb in response to critically shortened telomere DNA. Potentially neoplastic cells must first overcome the senescence checkpoint mechanisms and subsequently activate telomerase to propagate indefinitely. Although telomerase activation is closely associated with cellular immortality, telomerase alone is not sufficient to warrant tumorigenicity. Environmental factors, including chemical carcinogens and viral infection, often contribute to aberrant changes leading to tumorigenic conversion of normal cells. Of particular importance in oral cancer development are tobacco-related chemical carcinogens and human papillomavirus (HPV) infection. To describe the molecular mechanisms by which these environmental factors facilitate the genesis of oral cancer, we first established an in vitro multistep oral carcinogenesis model by sequential exposure of normal human oral keratinocytes (NHOK) to "high risk" HPV and chemical carcinogens. Upon introduction of the HPV genome, the cells bypassed the senescence checkpoint and entered into an extended, but not immortal, life span during which telomere DNA continued to shorten. In a few immortal clones surviving beyond the crisis, we found a marked elevation of telomerase activity and stabilization of telomere length. Furthermore, the E6 and E7 oncoproteins of "high risk" HPV disrupted the cell cycle control and DNA repair in immortalized HOK, and enhanced mutation frequency resulting from genomic instability. However, HPV infection alone failed to give rise to a tumorigenic cell population, which required further exposure to chemical carcinogens in addition to HPV infection. Analysis of the data presented suggests that oral carcinogenesis is a series of discrete genetic alterations that result from a continued genotoxic challenge by environmental risk factors. Our in vitro model may be useful for investigators with interest in furthering our understanding of oral carcinogenesis.

Alcohol Drinking↗
PubMed2001

Cloning and expression of hamster telomerase catalytic subunit cDNA.

Topical application of 7,12-dimethylbenz(alpha)-anthracene induces tumors in the hamster cheek pouch. Telomerase activity is increased in the cancer tissues if compared to normal adjacent tissues in both human and hamster oral cancer. In order to achieve a probe and to investigate the putative role of telomerase in oral carcinogenesis using the hamster cheek pouch model, we have cloned the cDNA encoding the hamster telomerase catalytic subunit (hamTERT). The hamster TERT cDNA encoded 1128 amino acids and shared 64% amino acid identity with human TERT and 80% with murine TERT. As noted with human TERT which express several alternatively spliced mRNAs, we have also detected one alternatively spliced hamTERT mRNA in hamster cancer cells. Transient transfection of hamTERT cDNA in a retroviral expression vector reconstituted telomerase activity in the telomerase negative human lung fibroblast IMR90 cells.

Alternative Splicing↗
PubMed2001

c-Myc and Sp1/3 are required for transactivation of hamster telomerase catalytic subunit gene promoter.

The hamster and human TERT promoters share common critical protein binding sites, such as the GC-box or E-box, which is known to be a binding site for Sp1/Sp3 transcriptional factors and c-Myc, respectively. Our previous data demonstrated that Sp1/Sp3 synergistically transactivate the hamster TERT (hamTERT) promoter. In this study, we determined the role of c-Myc in the regulation of hamTERT, and analyzed the relative significance of GC-boxes and the E-box for transcriptional activation of hamster TERT. Wild-type, mutated E-box or mutated GC-box hamTERT core promoter reporter was introduced into 293T cells in combination with murine or human Myc expression vectors. The promoter activity was determined using the luciferase assay, and the transfection efficiency was normalized with CAT activity. The electrophoretic mobility shift assay (EMSA) was done to prove the nuclear protein binding activity of the GC-box (region II) or E-box. Overexpression of murine or human Myc transactivated hamTERT core promoter activity. Inversion mutation in the E-box or substitution mutation in the GC-boxes abrogated endogenous or Myc induced hamTERT transactivation. Region II is the single most important Sp1/3 binding site in transcriptional activation, and multiple combined mutations in the GC-boxes abolished the hamTERT promoter activity. These results indicate that c-Myc and Sp1/3 are the major regulatory determinants of the hamTERT transcriptional activation. The mechanism of TERT gene activation during immortalization and carcinogenesis may be conserved among species.

Animals↗
PubMed2001

Bacterial biofilm and dentistry.

Bacterial biofilms are ubiquitous in nature. Recent studies have demonstrated many unique qualities previously unknown to bacteria and have yielded new insights into relevant dental issues.

Bacterial Physiological Phenomena↗
PubMed2001

Elevated expression of hTERT is associated with dysplastic cell transformation during human oral carcinogenesis in situ.

PURPOSE: Telomerase is a ribonucleoprotein complex composed of the catalytic protein subunit (human telomerase reverse transcriptase or hTERT) and the RNA template. This enzyme activity is a necessary and rate-limiting step of cellular immortalization and could provide a unique marker of aberrant cells, which may selectively be targeted. The current study was undertaken to quantitatively determine the degree of telomerase activation during multistage oral carcinogenesis using paraffin-embedded tissue samples. EXPERIMENTAL DESIGN: hTERT expression level was quantitatively compared between normal and cancerous oral tissues by real-time reverse-transcription-PCR (RT-PCR). Also, the presence of hTERT transcript in individual cells was surveyed in the biopsy specimens with varying degrees of histopathology by in situ RT-PCR. RESULTS: Low level of hTERT amplification was detected by real-time RT-PCR in most (11/13) normal human oral mucosa. hTERT expression was also detected in the majority (11/12) of squamous cell carcinoma tissues, and the level was significantly (P < 0.05) elevated, on the average, by a factor >6.9. By in situ RT-PCR, hTERT expression was not noted in normal epithelium (0/10) nor in mild dysplasia (0/7) but was detected in moderate dysplasia (4/5) and in those tissues with a higher grade of histopathology: severe dysplasia (3/3) and invasive carcinoma (4/4). CONCLUSIONS: These results indicate that enhanced expression of telomerase activity occurs early during human oral carcinogenesis and support the critical role of telomerase in the development of human oral cancer.

Adult↗
PubMed2001

Anticancer effect of a lentiviral vector capable of expressing HIV-1 Vpr.

A lentiviral vector capable of expressing the HIV-1 vpr gene (Vpr lentiviral vector) was constructed, and its in vivo anticancer effect was determined against cutaneous tumors derived from the AT-84 oral cancer cells in immunocompetent mice. A single intratumoral injection of the Vpr lentiviral vector not only significantly reduced the primary tumor volume but also completely regressed tumors in >40% of animals. More interestingly, the mice of which the primary tumors were completely regressed by the Vpr lentiviral vector were additionally protected from a secondary challenge of AT-84 cells. These data suggest that the Vpr lentiviral vector elicits its anticancer activity in part by the activation of the immune system. The above suggestion is additionally supported by the failure of the lentiviral vector to demonstrate anticancer activity in immunocompromised nude or SCID mice. The Vpr lentiviral vector offers a powerful new strategy for cancer gene therapy and may be useful for the control of solid tumors, such as human oral squamous cell carcinomas.

Animals↗