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Biomedical subjects

Sung Hoon Kim

Publications and source records attributed to Sung Hoon Kim.

At least 19 recordsLinked to original sources
PubMed2007

Clinical significance of small pulmonary nodules with little or no 18F-FDG uptake on PET/CT images of patients with nonthoracic malignancies.

UNLABELLED: Small pulmonary nodules with little or no perceptible (18)F-FDG uptake are relatively common findings on combined PET/CT images of patients with nonthoracic malignancies. Interpreting such nodules is often a diagnostic challenge, and this study aimed to evaluate the clinical significance of the nodules. METHODS: Patients with pulmonary nodules < or =1 cm in diameter showing no (18)F-FDG uptake or uptake less than the mediastinal background were included. Nodules with clearly benign or metastatic findings on CT were excluded. One hundred twenty-one patients had either tissue confirmation or clinical follow-up with additional chest images. The subjects were studied by 3 variables: (i) solitary versus multiple nodules, (ii) presence of accompanying benign lung lesion versus absence, and (iii) imperceptible (18)F-FDG uptake versus faint (18)F-FDG uptake. The malignancy rates were calculated for each variable. RESULTS: Of the 121 patients, 24 had malignancy, with a strong possibility of pulmonary metastasis (19.8%). Six of the 44 patients with solitary nodules (13.6%) and 18 of the 77 patients with multiple nodules (23.4%) had malignancies, though there was no statistically significant difference in the incidences of malignancy between the solitary and multiple groups. On the other hand, there was a statistically significant difference (P = 0.040) between the accompanying lung lesion present (8.3%) and absent (24.7%) groups. No statistically significant difference was noted between the (18)F-FDG uptake imperceptible group and faint (18)F-FDG uptake group (20.7% vs. 17.2%). CONCLUSION: For patients with incidental lung nodules of indeterminate nature with no (18)F-FDG uptake or uptake less than that of the mediastinum on PET/CT images, >19% of the cases turned out to be malignant. The nodule was more likely to be malignant when no other benign pulmonary lesions could be identified elsewhere in the lung field. Thus, regardless of the number of nodules and (18)F-FDG uptake, tissue confirmation or close imaging follow-up is necessary when small nodules with imperceptible or faint (18)F-FDG activity are present on the PET/CT images, especially in the absence of accompanying benign lung lesions.

Adult↗
PubMed2006

MAPK regulation and caspase activation are required in DMNQ S-52 induced apoptosis in Lewis lung carcinoma cells.

6-(1-Hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) was reported to have cytotoxic activity against L1210 leukemia cells. In the present study, we investigated the apoptotic mechanism of DMNQ S-52 in vitro and in vivo in murine solid cancer cells. DMNQ S-52 exerted cytotoxicity against Lewis lung carcinoma (LLC) cells (IC50=12.3 microM). DMNQ S-52 increased Annexin V positive cell population in a concentration-dependent manner. DMNQ S-52 also induced apoptosis through caspase-mediated pathway, including activation of caspase-3, cleavage of Poly(ADP-ribose) polymerase (PARP) and decreased expression of Bcl-2 in LLC cells in a time and concentration-dependent fashion. DMNQ S-52 activated the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 as well as abrogated the expression of extracellular signal-regulated kinase (ERK) in a time-dependent manner at 10 microM. Similarly, cell proliferation inhibition by DMNQ S-52 was masked by caspase inhibitor Z-Asp-Glu-Val-Asp-fluoromethylketone (Z-VAD-FMK), JNK inhibitor SP600125 and p38 inhibitor SB203580, but not by MEK inhibitor U0126. Furthermore, i.p. administration of DMNQ S-52 at 5 mg/kg resulted in a potent inhibition of the growth of LLC cells implanted on the right flank of C57BL/6 mice compared to untreated control. Immunohistochemical analysis revealed the decreased tumor cell proliferation and increased tumor cell apoptosis in DMNQ S-52 treated tumor sections using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and proliferation cell nuclear antigen (PCNA). Taken together, these findings demonstrate that DMNQ S-52 may exhibit anti-tumor activity by inducing apoptosis via caspases and mitogen activated protein (MAP) kinase-dependent pathways.

Animals↗
PubMed2006

Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity.

Aberrant expression of cyclooxygenase-2 (COX-2) has been implicated in tumor promotion. Resveratrol, a phytoalexin present in grapes, was reported to inhibit multistage mouse skin carcinogenesis. In the present study, we found that topically applied resveratrol significantly inhibited COX-2 expression induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Resveratrol-suppressed phosphorylation and subsequent degradation of IkappaBalpha, thereby inhibiting activation of nuclear factor-kappaB (NF-kappaB) in TPA-stimulated mouse skin. Pretreatment with resveratrol also suppressed TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Resveratrol blunted TPA-induced phosphorylation of p65 and its interaction with CBP/p300, rendering NF-kappaB transcriptionally inactive. To get further insights into the molecular basis of NF-kappaB inactivation by resveratrol, we examined the role of IkappaB kinase (IKK) in mediating TPA-induced activation of NF-kappaB and COX-2 expression. TPA treatment led to rapid induction of IKK activity in mouse skin, which was abolished either by resveratrol or an IKK inhibitor Bay 11-7082. Topical application of Bay 11-7082 also abrogated TPA-induced NF-kappaB activation and COX-2 expression, supporting the involvement of IKK in TPA-induced COX-2 expression. Taken together, the above findings suggest that resveratrol targets IKK in blocking TPA-induced NF-kappaB activation and COX-2 expression in mouse skin in vivo.

Animals↗
PubMed2006

Alterations in cerebral perfusion in posttraumatic stress disorder patients without re-exposure to accident-related stimuli.

UNLABELLED: Functional neuroimaging studies have shown abnormalities of limbic regions in patients with posttraumatic stress disorder (PTSD) during symptom provocation and cognitive activation. OBJECTIVE: The aim of this study was to determine whether PTSD patients without re-exposure to accident-related stimuli would exhibit alterations in cerebral perfusion compared with age-matched normal subjects. METHODS: Brain perfusion SPECT was measured in medication-free 23 PTSD patients and 64 age-matched healthy subjects under resting conditions and analyzed using statistical parametric mapping to compare between the patient and control groups. RESULTS: We found that PTSD patients exhibited increased cerebral blood perfusion in limbic regions and decreased perfusion in the superior frontal gyrus and parietal and temporal regions in comparison with those of the normal controls. CONCLUSIONS: This result indicates that PTSD patients have alterations in cerebral perfusion of limbic regions and the frontal and temporal cortex without re-exposure to accident-related stimuli. SIGNIFICANCE: This finding supports the hypothesis of the involvement of limbic regions, which might be associated with the regulation of emotion and memory, in the pathophysiology of PTSD.

Adult↗
PubMed2006

A novel frameshift mutation in the 5alpha-reductase type 2 gene in Korean sisters with male pseudohermaphroditism.

OBJECTIVE: To describe two cases of 5alpha-reductase deficiency and the identification of a novel frameshift mutation in this sibling pair. DESIGN: Case report. SETTING: An adolescent clinic at a university hospital. PATIENT(S): A 14-year-old girl and her younger sister, who presented with primary amenorrhea, deepening of the voice, and clitoromegaly. INTERVENTION(S): Deoxyribonucleic acid was extracted from peripheral blood, and 8 exons of the androgen receptor gene and 5 exons of the steroid 5alpha-reductase type 2 gene (encoded by SRD5A2 gene) were amplified by polymerase chain reaction and subjected to sequence analyses. MAIN OUTCOME MEASURE(S): Genetic diagnosis of 5alpha-reductase deficiency. RESULT(S): There was no evidence of a genetic abnormality in the 8 screened exons of the androgen receptor gene, but exon 4 of the SRD5A2 gene showed a novel homozygous deletion of the thymine at nucleotide position c.655 (c.655delT), leading to a frameshift mutation predicted to result in an abnormally long protein with an extended termination signal. CONCLUSION(S): The molecular characterization of the mutation can be a relevant tool for a correct diagnosis of 5alpha-reductase deficiency.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2006

Methylation of p16INK4a is a non-rare event in cervical intraepithelial neoplasia.

The cell cycle inhibitor, p16INK4a may be a useful surrogate biomarker of cervical intraepithelial neoplasia (CIN); however, there is currently no consensus of p16INK4a genetic alterations throughout the multiple step process of CIN. Our goal was to identify the methylation frequency of p16INK4a in each step of CIN that is associated with human papillomavirus (HPV) infection, using several different detection methods of p16INK4a methylation to correlate the data. The present study included a total of 43 patients, including 38 with CIN, and 5 normal patients. Three different methods were used to detect hypermethylation of CpG islands, methylation-specific PCR (MSP) amplification of different primer sets of M1, M2, and M3, pyrosequencing of each forward primer region, and immunohistochemistry of p16INK4a. Analysis of MSP showed that 20 of the 38 CIN patients (52.6%) revealed hypermethylation in at least 1 primer set of the p16INK4a promoter. A complete loss of p16INK4a protein expression was observed in 11 cases (28.9%). There was no observed association of methylation of the p16INK4a gene with either CIN grading (P=0.0698) or HPV status (P=0.2811): specifically 42.9% (3/7) was found in CIN 1, 57.1% (8/14) in CIN 2, and 52.9% (9/17) in CIN 3. In concordance with immunohistochemistry results, hypermethylation of the p16INK4a promoter was significantly correlated with a lack of p16 protein expression (P=0.0145). All positive peaks from pyrosequencing matched the MSP results, which ranged from 6.3% to 24.5%. In conclusion, p16INK4a gene silencing during CIN was not determined to be a particularly rare event; however, it does not correlate with either HPV status or CIN grading.

Base Sequence↗
PubMed2005

Estrogen dendrimer conjugates that preferentially activate extranuclear, nongenomic versus genomic pathways of estrogen action.

Estrogenic hormones are classically thought to exert their effects by binding to nuclear estrogen receptors and altering target gene transcription, but estrogens can also have nongenomic effects through rapid activation of membrane-initiated kinase cascades. The development of ligands that selectively activate only the nongenomic pathways would provide useful tools to investigate the significance of these pathways. We have prepared large, abiotic, nondegradable poly(amido)amine dendrimer macromolecules that are conjugated to multiple estrogen molecules through chemically robust linkages. Because of their charge and size, these estrogen-dendrimer conjugates (EDCs) remain outside the nucleus. They stimulate ERK, Shc, and Src phosphorylation in MCF-7 breast cancer cells at low concentrations, yet they are very ineffective in stimulating transcription of endogenous estrogen target genes, being approximately 10,000-fold less potent than estradiol in genomic actions. In contrast to estradiol, EDC was not effective in stimulating breast cancer cell proliferation. Because these EDC ligands activate nongenomic activity at concentrations at which they do not alter the transcription of estrogen target genes, they should be useful in studying extranuclear initiated pathways of estrogen action in a variety of target cells.

Adaptor Proteins, Signal Transducing↗
PubMed2005

No association between HLA-DRB1 alleles and susceptibility to advanced stage endometriosis in a Korean population.

BACKGROUND: The aetiological factors of endometriosis still remain poorly understood. While there is growing evidence that genetic and immunological factors play important roles in the pathogenesis of the disease, HLA-DRB1 alleles have been reported to be associated with the risk of endometriosis in Japanese populations. This study was performed to determine whether susceptibility to advanced endometriosis is also associated with HLA-DRB1 alleles in a Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 100 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. HLA-DRB1 genotyping was carried out in two steps. Low to intermediate resolution typing was performed by PCR sequence-specific oligonucleotide hybridization method, followed by high resolution typing utilizing group-specific amplification and PCR-single strand conformation polymorphism method. Distribution of HLA-DRB1 alleles was compared with that of 800 unrelated ethnically matched individuals as well as 108 healthy female subjects. RESULTS: Genotyping revealed that the distribution of HLA-DRB1 alleles in patients with advanced endometriosis was not different from that in the two control groups. CONCLUSIONS: The findings of the present study suggest that susceptibility of advanced endometriosis is not associated with HLA-DRB1 alleles in a Korean population, which is apparently not the case in the Japanese population.

Adult↗
PubMed2005

Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma.

OBJECTIVES: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Korean women remains to be elucidated. In addition, genetic polymorphisms may affect not only cancer development but also cancer progression and, as a result, could influence cancer phenotypes. The purposes of this study were, first, to investigate the presence of BRCA1 and BRCA2 mutations in women with ovarian cancer who were unselected for family history and, second, to evaluate the relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. METHODS: We studied 37 women who were diagnosed with epithelial ovarian cancer and treated at the Yonsei University Hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using a PCR-DHPLC-sequencing method. The relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features was examined. RESULTS: Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer result in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) that led to premature termination. The patient had no family history of breast or ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. CONCLUSION: Our results were consistent with the hypothesis that BRCA1 and BRCA2 mutations have a limited role in sporadic ovarian carcinogenesis in the Korean population. Furthermore, polymorphisms of certain, selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer.

Adolescent↗
PubMed2005

Vascular endothelial growth factor gene +405 C/G polymorphism is associated with susceptibility to advanced stage endometriosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is known to play a pivotal role in the development of endometriosis. This study was performed to investigate whether the VEGF gene 5'-untranslated region polymorphism is associated with susceptibility to advanced stage endometriosis. METHODS: This study comprised 215 women with advanced stage endometriosis, 219 control women without endometriosis, and 70 fertile women. Following extraction of genomic DNA, genotyping of the -460 C/T and +405 C/G polymorphisms of the VEGF gene were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The distribution of genotypes and allele frequencies of the -460 C/T polymorphism in the endometriosis group did not differ from those in the control group and the fertile women group. However, genotype distribution of the +405 C/G polymorphism was significantly different between patients with and without endometriosis (P = 0.01) and between patients with endometriosis and the fertile women (P = 0.02). Patients with endometriosis showed a higher incidence of the +405 CC genotype compared with the controls and the fertile women (P = 0.007 and 0.016 respectively). CONCLUSIONS: These findings suggest that the VEGF +405 C/G polymorphism may be associated with the risk of advanced stage endometriosis in the Korean population.

Alleles↗
PubMed2005

Clinical usefulness of cervicogram as a primary screening test for cervical neoplasia.

The purpose of this study is to evaluate the clinical usefulness of the cervicogram as a primary screening test for cervical neoplasia. A total of 294 women who had undergone a cervicogram and a Pap test between January and July 2003, were selected. The diagnostic accuracy of the Pap test, cervicogram, and the Pap test combined with a cervicogram were compared with the histopathologic diagnosis. Among 294 women, the Pap test was negative in 130 cases and positive in 164 cases. Among patients with positive Pap test, cervicogram were negative in 101 cases (61.6%) and positive in 63 cases (38.4%). The diagnostic accuracy between cervicogram with positive Pap test and histology was as follows; sensitivity 44.9%, specificity 78.3%, positive predictive value 84.1%, negative predictive value 32.7%, false positive rate 15.9%, and false negative rate 67.3%. Although the adjunctive use of cervicogram with the Pap test in the initial screening of cervical neoplasia showed a higher specificity and higher positive predictive value compared to the Pap test alone, consideration in terms of lower sensitivity, lower positive predictive value, higher false positive rate and cost-effectiveness should be given in lieu of clinically applying cervicogram with the pap test as an initial screening test.

Adult↗
PubMed2005

Shiquandabutangjiaweibang inhibits tumor metastasis and angiogenesis via regulation of topoisomerase-1.

Shiquandabutangjiaweibang (SDJ) is a traditional medicine prescription used for increasing body resistance against cancer. In the present study, the effect of SDJ extract on tumor metastasis and angiogenesis was evaluated. SDJ showed cytotoxicity against P388 (leukemia cells) and B16-F10 (murine melanoma cells) to 60% of control at 1 mg. SDJ significantly inhibited lung metastasis and also restored the number of platelets in C57BL/6 mice with thrombocytopenia induced by intravenous injection of B16-F10 cells. SDJ significantly disrupted chick embryonic angiogenesis in the chorioallantoic membrane (CAM). Interestingly, SDJ suppressed DNA topoisomerase I in a concentration-dependent manner. These results suggest that SDJ can be a potent inhibitor of metastasis and angiogenesis, at least in part, via regulation of topoisomerase I.

Animals↗
PubMed2005

Saussurea lappa induces G2-growth arrest and apoptosis in AGS gastric cancer cells.

The molecular effects of Saussurea lappa extracts, a traditional medicine in Eastern Asia, on the fate of gastric carcinoma have not been understood. In this study, its cytostatic effects were examined using gastric AGS cancer cells. Its treatment resulted in apoptosis and G2-arrest in a dose- and time-dependent manner. The effects were attributed to the regulation of cyclins and pro-apoptotic molecules and suppression of anti-apoptotic molecules. Therefore, these results suggest that extracts of S. lappa root may be a candidate to deal with gastric cancers either by traditional herbal therapy or by combinational therapy with conventional chemotherapy.

Apoptosis↗
PubMed2005

The clinical value of dacryoscintigraphy in the selection of surgical approach for patients with functional lacrimal duct obstruction.

PURPOSE: Dacryoscintigraphy is widely known to be an effective modality in diagnosing abnormalities of the lacrimal system that cause epiphora (pathological overflow of tear). However, dacryoscintigraphy rarely serves beyond the simple diagnostic use for lacrimal duct obstruction. In our study, dacryoscintigraphy results of patients with functional lacrimal duct obstruction are newly classified into three types, the effects and prognoses of silicone tube intubation are noted according to each type, and the role of dacryoscintigraphy in determining appropriate surgical approaches is evaluated. METHODS: Subjects were 36 eyes of 29 patients complaining of epiphora who had increased tear meniscus, but showed no sign of obstruction on duct syringing. Impression of functional lacrimal duct obstruction was made through dacryoscintigraphy, and silicone tubes were inserted. RESULTS: Patients were classified according to the results of dacryoscintigraphy; those with delayed secretion in the distal nasolacrimal duct were typed as class I; those with delays in the proximal nasolacrimal duct class II; and delayed secretion from the pre-lacrimal sac to the lacrimal sac as class III. All patients had silicone tube intubations together with selective punctoplasty. Symptomatic improvement was observed in all 6 cases of distal nasolacrimal duct obstruction (100%), 14 of 18 proximal obstruction cases (77.8%), and 8 of 12 pre-lacrimal obstructions (66.7%). CONCLUSIONS: Functional lacrimal duct obstruction is easily diagnosed with dacryoscintigraphy. Furthermore, its may be classified by types of obstruction to predict post-operative results of silicone tube insertion. Cases suspicious of pre-lacrimal sac obstructions in particular may achieve better operative results with adjuvant treatments in addition to silicone tube insertion.

Adult↗
PubMed2005

Influence of hydration status in normal subjects: fractional analysis of parameters of Tc-99m DTPA and Tc-99m MAG3 renography.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the influence of hydration status upon renogram patterns and renal physiological parameters and clarify the differences between DTPA and MAG3 studies in normal volunteers. MATERIAL AND METHODS: The study populations were 22 kidneys of 11 volunteers with no history of hypertension or renal disease with normal serum creatinine levels. They were 6 men and 5 women aged from 24 to 48 yrs (mean age: 33.4 yrs). Renal scintigraphies with both 185 MBq (5 mCi) of Tc-99m DTPA and Tc-99m MAG3 were performed after dehydration (urine specific gravity > 1.025) and adequate hydration (urine specific gravity < 1.010) in each subject at least with a 5-7-day interval. Renograms were generated from the whole kidney and cortical ROIs. We analyzed the clearance, renogram pattern, mean transit time, time to maximum activity, time from maximum activity to half activity, and residual cortical activity. Paired t-test and Wilcoxon signed rank test were used as statistical analysis methods. Statistical analysis was considered significant at p < 0.05. RESULTS: In the dehydrated state, with Tc-99m DTPA and whole kidney ROI, parameters such as time to maximum activity, time from maximum activity to half activity, residual cortical activity, and mean transit time were delayed as compared to parameters in the adequately hydrated state, but the clearance was not changed. With the cortical ROI, the changes of parameters due to dehydration were partially offset. There were insignificant differences between most parameters of Tc-99m DTPA and Tc-99m MAG3 with the whole kidney and cortical ROIs. CONCLUSIONS: Dehydration may bring about a false positive curve pattern on renograms which can be prevented or minimized by using the cortical ROI. There were insignificant differences between most parameters of Tc-99m DTPA and Tc-99m MAG3.

Adult↗