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Biomedical subjects

J H Chung

Publications and source records attributed to J H Chung.

At least 19 recordsLinked to original sources

A biomechanical model of mammographic compressions.

A number of biomechanical models have been proposed to improve nonrigid registration techniques for multimodal breast image alignment. A deformable breast model may also be useful for overcoming difficulties in interpreting 2D X-ray projections (mammograms) of 3D volumes (breast tissues). If a deformable model could accurately predict the shape changes that breasts undergo during mammography, then the model could serve to localize suspicious masses (visible in mammograms) in the unloaded state, or in any other deformed state required for further investigations (such as biopsy or other medical imaging modalities). In this paper, we present a validation study that was conducted in order to develop a biomechanical model based on the well-established theory of continuum mechanics (finite elasticity theory with contact mechanics) and demonstrate its use for this application. Experimental studies using gel phantoms were conducted to test the accuracy in predicting mammographic-like deformations. The material properties of the gel phantom were estimated using a nonlinear optimization process, which minimized the errors between the experimental and the model-predicted surface data by adjusting the parameter associated with the neo-Hookean constitutive relation. Two compressions (the equivalent of cranio-caudal and medio-lateral mammograms) were performed on the phantom, and the corresponding deformations were recorded using a MRI scanner. Finite element simulations were performed to mimic the experiments using the estimated material properties with appropriate boundary conditions. The simulation results matched the experimental recordings of the deformed phantom, with a sub-millimeter root-mean-square error for each compression state. Having now validated our finite element model of breast compression, the next stage is to apply the model to clinical images.

Biomechanical Phenomena↗

Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation.

We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53(-/-) cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53(-/-) cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53(+/+) cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53(+/+) cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.

Apoptosis↗

Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG).

Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs.

Administration, Topical↗

Human T-cell leukemia virus type 1 Tax attenuates gamma-irradiation-induced apoptosis through physical interaction with Chk2.

Checkpoint kinase 2 (Chk2) is known to mediate diverse cellular responses to genotoxic stress. The fundamental role of Chk2 is to regulate the network of genome-surveillance pathways that coordinate cell-cycle progression with DNA repair and cell survival or death. Defects in Chk2 contribute to the development of both hereditary and sporadic human cancers. We now present evidence that the human T-cell leukemia virus type-1 (HTLV-1) Tax protein directly interacts with Chk2 and the kinase activity of Chk2 is inhibited by Tax. The physical interaction of Chk2 and Tax was observed by co-immunoprecipitation assays in HTLV-1-infected T cells (C81) as well as GST pull-down assays using purified proteins. Binding and kinase activity inhibition studies with Tax deletion mutants indicated that at least two domains of Tax mediate the interaction with Chk2. We have analysed the functional consequence of de novo expression of Tax upon the cellular DNA-damage-induced apoptosis, which is mediated by Chk2. Using transient transfection and TUNEL assay, we found that gamma-irradiation-induced apoptosis was decreased in 293T and HCT-116 (p53(-/-)) cells expressing HTLV-1 Tax. Our studies demonstrate an important potential target of Tax in cellular transformation.

Apoptosis↗

Topiramate stimulates glucose transport through AMP-activated protein kinase-mediated pathway in L6 skeletal muscle cells.

The use of topiramate (TPM) in the treatment of binge-eating disorder, bulimia nervosa, and antipsychotic-induced weight gain has recently increased, however, the exact molecular basis for its effects on body weight reduction and improved glucose homeostasis, is yet to be elucidated. Here we investigated the effect and signaling pathway of TPM on glucose uptake in L6 rat skeletal muscle cells, which account for >70% of glucose disposal in the body. Intriguingly, we found that TPM (10 microM) stimulated the rate of glucose uptake up to twofold increase. And TPM-stimulated glucose transport was inhibited with the overexpression of dominant-negative form of AMP-activated protein kinase (AMPK), an important mediator in glucose transport, implicating that AMPK-mediated pathway is involved. The TPM-stimulated glucose transport was blocked by SB203580, a specific inhibitor of AMPK downstream mediator, p38 mitogen-activated protein kinase (MAPK) protein. LY294002, an inhibitor of phosphatidylinositol (PI) 3-kinase, which is another crucial mediator in independent glucose transport pathway, did not inhibit TPM-stimulated glucose transport. We also found that TPM increased the phosphorylation level of AMPK and p38 MAPK, whereas no effect on the activity of PI 3-kinase of TPM, when assessed by PI 3-kinase assay, was observed. These results together suggest that TPM stimulates glucose transport, not via PI 3-kinase mediated, but via AMPK-mediated pathway in skeletal muscle cells, thereby contributing to the body weight regulation and glucose homeostasis.

AMP-Activated Protein Kinases↗

Role of patient education level in predicting macrosomia among women with gestational diabetes mellitus.

OBJECTIVE: To evaluate the role of education level in predicting the risk of macrosomia among women with gestational diabetes mellitus. STUDY DESIGN: Women with gestational diabetes, who were referred to the California Diabetes and Pregnancy Sweet Success Program between June 2001 and December 2002, were included in the study. Multiple logistic regression was used estimate the risk of macrosomia, defined as a birth weight >4000 g. RESULTS: Compared to college-educated women, high school- and middle school-educated women were 21% (relative risk (RR), 1.21; 95% confidence intervals (CI), 1.01-1.44) and 35% (RR, 1.35; 95% CI, 1.09-1.70) more likely to deliver a macrosomic infant, respectively. CONCLUSION: Gestational diabetics with a lower level of educational attainment appear to have an increased risk of macrosomia. Future studies are necessary to determine whether this finding reflects a variation in adherence to recommended treatments by education/literacy level, or if it is a surrogate marker for intrinsic, biological differences or differences in lifestyle.

Diabetes Complications↗

Infrared exposure induces an angiogenic switch in human skin that is partially mediated by heat.

BACKGROUND: Angiogenesis plays an important role in physiological and pathological conditions of the skin. Although acute ultraviolet-induced skin angiogenesis has been investigated, little is known about the distinct effects of acute infrared (IR) radiation on angiogenesis in human skin. OBJECTIVES: To elucidate the molecular regulation of the angiogenic switch by acute near-IR radiation or by a single heat treatment in human skin in vivo. METHODS: We subjected 16 healthy volunteers to near-IR irradiation (six minimal heating doses) and 14 healthy volunteers to heat treatment (43 degrees C for 90 min), and skin specimens were obtained by punch biopsy for immunohistochemical, Western blot and reverse transcription-polymerase chain reaction analyses. RESULTS: We observed that CD31-stained vessels in the upper dermis were increased after acute near-IR exposure, and that this was associated with the upregulation of vascular endothelial growth factor (VEGF) and the downregulation of thrombospondin (TSP)-2. During the application of near-IR to buttock skin, skin temperatures immediately increased from 32 degrees C up to 42 degrees C, as measured using a digital thermometer. Moreover, the expression of inducible heat shock protein 70 was increased after near-IR irradiation in human skin. Therefore, we investigated the effects of a single heat treatment on angiogenesis and on the expression of VEGF and TSP-2 in skin, and found that vascularization and VEGF expression were increased, whereas TSP-2 expression was reduced. CONCLUSIONS: Our results suggest that IR radiation plays an important role in skin angiogenesis via regulation of the balance between the angiogenic inducer VEGF and the angiogenic inhibitor TSP-2, and that IR-induced skin angiogenesis might be partially caused by the effects of heat in human skin in vivo.

Adult↗

Clinical features and risk factors for striae distensae in Korean adolescents.

BACKGROUND: Despite the high prevalence of striae distensae, clinical studies are few in number, and their pathophysiology still obscure. OBJECTIVES: To determine the prevalence and clinical characteristics of striae distensae that occur in Korean adolescents, and to correlate their clinical features with family history, other dermatological conditions, and body measurements. METHODS: One hundred and fifty-seven healthy Korean students, aged 15 to 17, were studied. A questionnaire and physical examination were employed to assess the subjects' past and family history, and the distribution, clinical features and severity of striae distensae. RESULTS: Striae distensae were present in 131 subjects (83.4%). Ninety-four (88.2%) of 109 male and 37 (77.1%) of 48 female subjects were affected. The striae were white in colour in 69.5% and asymptomatic in most of the subjects. They developed at an average age of 13.8 years. Family history was present in 18 subjects (11.5%). Seborrhoea of the face was positively correlated (P < 0.035) with striae distensae, and atopic dermatitis negatively correlated (P < 0.001). In both sexes, the buttock was the most prevalent area of striae development, followed by the lower back and knee in boys and by the thigh and calf in girls. Striae were significantly more common on the thigh of girls and on the knee of boys. CONCLUSIONS: Our results indicate that striae distensae are a common skin condition that occurs early in puberty regardless of gender, and that they have a different anatomical distribution and relationship with body measurements in each gender.

Adolescent↗

The effect of erythrodiol-3-acetate on the expressions of matrix metalloproteinase-1 and type-1 procollagen caused by ultraviolet irradiated cultured primary old aged human skin fibroblasts.

Methanol and aqueous extracts of Styrax japonica used traditionally for the treatments of skin elastic materials were screened in vitro for the matrix metalloproteinase (MMP)-1 inhibitor actions. The methylene chloride soluble fraction of methanol extract from the stems of S. japonica showed significant MMP-1 inhibition in primary old aged human skin fibroblasts caused by ultraviolet (UV) irradiation. Main triterpenoids were isolated by repeated column chromatography. Among them, the triterpenoid erythrodiol-3-acetate reduced the expression of MMP-1 and induced the expression of type-1 procollagen at the protein levels in a dose-dependent manner caused by UV irradiated cultured old aged human skin fibroblasts. Taken together, our results suggest that erythrodiol-3-acetate plays an important role in the skin aging process caused by UV irradiation.

Aged↗

Quantitation of niflumic acid in human plasma by high-performance liquid chromatography with ultraviolet absorbance detection and its application to a bioequivalence study of talniflumate tablets.

A rapid and simple HPLC method with UV detection (288 nm) was developed and validated for quantitation of niflumic acid in human plasma, the active metabolite of talniflumate. After precipitation with 100% methanol containing the internal standard, indomethacin, the analysis of the niflumic acid level in the plasma samples was carried out using a reverse phase C18 CAPCELL PAK (5 microm, 4.6 mm x 250 mm) column. The chromatographic separation was accomplished with an isocratic mobile phase consisting of a mixture of 0.1M sodium acetate in water and acetonitrile (37:63, v/v), adjusted to pH 6.4. This HPLC method was validated by examining its precision and accuracy for inter- and intra-day runs in a linear concentration range of 0.02-5.00 microg/mL. Stability of niflumic acid in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method was successfully applied to the bioequivalence study of talniflunate in healthy volunteers.

Adult↗

Coptis japonica root extract induces apoptosis through caspase3 activation in SNU-668 human gastric cancer cells.

Apoptosis-modulating approaches offer an attractive opportunity for therapeutic use for many tumors. We investigated the effects of the roots of Coptis japonica var. dissecta (Ranunculaceae) on human gastric cancer cells, SNU-668. The cytotoxicity of Coptis japonica at 100 microg/ml (methanol extract) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was 13.89 +/- 1.91% of control value. Considering the features by 4,6-diamidino-2-phenylindole (DAPI) staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, it was confirmed that the death of SNU-668 cells was due to apoptosis. In the apoptosis-regulating genes, BCL2 expression was diminished out, whereas BAX and CASP3 expressions were increased, compared with control. Furthermore, the activity of caspase3 was significantly increased by Coptis japonica treatment. These results suggest that Coptis japonica could induce apoptotic anticancer effect through caspase3 activation on SNU-668 human gastric cancer cells.

Antineoplastic Agents, Phytogenic↗

Teratogen risk counselling by internet: a prospective cohort study.

Although the internet may play a role in providing proper teratogen-risk counselling for pregnant women, the experience with this type of service has not been reported. We aimed to compare the pregnancy outcome of women counselled by the internet to women that received typically in-clinic teratogen risk counselling in the clinic. In a prospective cohort design, 1,011 patients were counselled in the clinic and 235 patients were counselled via the internet. Teratogen risk counselling was provided according with the information obtained from medical literature and specialised software. Information about pregnancy outcome (delivery, spontaneous abortion, or termination of pregnancy and major malformations) was obtained from 903 (89.3%) patients from the clinic group and 141 (60%) from the internet group. The amount of alcohol, cigarettes smoked, and millirads of X-ray were greater ( p < 0.05) in patients counselled by internet than in clinic. The rate of deliveries, ongoing pregnancies, pregnancy terminations, and spontaneous abortions were similar between clinic and internet (chi2 = 1.32; p = 0.7). Of 498 babies born to mothers counselled in the clinic, major malformations were identified in 3.6%. Of 67 babies born to mothers counselled by internet, major malformations were present in 1.5% ( p = 0.6). Teratogen-risk counselling by internet and clinic seems to have a similar efficacy in pregnancy outcome.

Abnormalities, Drug-Induced↗

Arabidopsis thaliana expresses multiple Golgi-localised nucleotide-sugar transporters related to GONST1.

Transport of nucleotide-sugars across the Golgi membrane is required for the lumenal synthesis of a variety of essential cell surface components, and is mediated by nucleotide sugar transporters (NSTs) which are members of the large drug/metabolite superfamily of transporters. Despite the importance of these proteins in plants, so far only two have been described, GONST1 and AtUTr1 from Arabidopsis thaliana. In this work, our aim was to identify further Golgi nucleotide-sugar transporters from Arabidopsis. On the basis of their sequence similarity to GONST1, we found four additional proteins, which we named GONST2, 3, 4 and 5. These putative NSTs were grouped into three clades: GONST2 with GONST1; GONST3 with GONST4; and GONST5 with six further uncharacterized proteins. Transient expression in tobacco cells of a member of each clade, fused to the Green Fluorescent Protein (GFP), suggested that all these putative NSTs are localised in the Golgi. To obtain evidence for nucleotide sugar transport activity, we expressed these proteins, together with the previously characterised GONST1, in a GDP-mannose transport-defective yeast mutant (vrg4-2). We tested the transformants for rescue of two phenotypes associated with this mutation: sensitivity to hygromycin B and reduced glycosylation of extracellular chitinase. GONST1 and GONST2 complemented both phenotypes, indicating that GONST2, like the previously characterized GONST1, is a GDP-mannose transporter. GONST3, 4 and 5 also rescued the antibiotic sensitivity, but not the chitinase glycosylation defect, suggesting that they can also transport GDP-mannose across the yeast Golgi membrane but with a lower efficiency. RT-PCR and analysis of Affymetrix data revealed partially overlapping patterns of expression of GONST1-5 in a variety of organs. Because of the differences in ability to rescue the vrg4 - 2 phenotype, and the different expression patterns in plant organs, we speculate that GONST1 and GONST2 are both GDP-mannose transporters, whereas GONST3, GONST4 and GONST5 may transport other nucleotide-sugars in planta.

Amino Acid Sequence↗

Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients.

The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. We tested the genetic association between schizophrenia and lung cancer by analyzing polymorphic sites in the p53 gene. Genotype and allele frequencies at two polymorphic sites in the p53 gene (BstUI and MspI restriction sites in exon 4 and intron 6, respectively) were studied in Korean schizophrenia (n=179) and lung cancer patients (n=104). Comparisons of the genotype and allele frequencies of the MspI polymorphism revealed significant differences between schizophrenia and lung cancer patients. The results suggest that the p53 polymorphism specifically found in schizophrenia patients may be associated with reduced vulnerability to lung cancer.

Adult↗

Effects of Paeonia lactiflora root extracts on the secretions of monocyte chemotactic protein-1 and -3 in human nasal fibroblasts.

In the field of Oriental medicine, the root of Paeonia lactiflora (Paeoniae Radix) has been prescribed usually to treat the common cold, and it was thought to alleviate upper respiratory infection or nasal inflammation. Monocyte chemotactic proteins (MCP)-1 and MCP-3 are known as the most potent chemokines to mediate allergic inflammation. The object of the study was to investigate the effect of Paeoniae Radix on the release of the chemokines such as MCP-1 and MCP-3. To detect the secretion of MCPs, an enzyme-linked immunosorbent assay was performed for human nasal mucosal fibroblasts after stimulation with several cytokines such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-1beta (IL-1beta). The secretion of MCP-1 was increased after stimulation with TNF-alpha or IL-1beta treatment. Co-treatment of TNF-alpha and IFN-gamma, or IL-1beta and IFN-gamma increased the secretion of MCP-1 and MCP-3. Paeoniae Radix was tested with inflammatory cytokines, and the results showed that the Paeoniae Radix significantly decreased the secretion of MCP-1 and MCP-3. In our study, Paeoniae Radix may play an important role in nasal inflammation with a modulation of MCP-1 and MCP-3.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of Jaoga-Yukmiwon(R), a Korean herbal medicine, on chondrocyte proliferation and longitudinal bone growth in adolescent male rats.

Externally visible growth of the body is the result of proliferation of chondrocytes and longitudinal bone growth. The effects of the Korean herbal medicine, Jaoga-Yukmiwon((R)), on the growth of adolescent rats were investigated in the present study. The proliferation ratio of chondrocytes was calculated from 5-bromo-2'-deoxyuridine incorporation during DNA synthesis. The 5-bromo-2'-deoxyuridine incorporation ratio of the control group was 21.1 +/- 3.5%, and Jaoga-Yukmiwon((R)) administration markedly increased the ratio to 34.5 +/- 4.6% (p < 0.05). The bone formation rate of longitudinal bone was estimated by labelling with tetracycline, which binds to newly formed bone. The bone formation rate in the tibia of Jaoga-Yukmiwon((R))-administered rats was increased to 405.1 +/- 4.3 micro m (p < 0.05) from 292.2 +/- 11.8 micrometer (control value). The height of the growth plate in the administrated rats was increased to 614.6 +/- 10.0 micro m (p < 0.05) from 552.3 +/- 17.1 micro m. The bone morphogenetic protein-2 immunostaining in the growth plate was also increased. These results suggest that Jaoga-Yukmiwon((R)) may promote longitudinal bone growth during the developmental period.

Animals↗

Treadmill exercise increases cell proliferation in hippocampal dentate gyrus in alcohol-intoxicated rats.

AIM: Effect of treadmill exercise on hippocampal cell proliferation under normal conditions has been well documented; however, this effect under alcohol intoxication conditions is not clarified, yet. In the present study, the effect of treadmill exercise on cell proliferation in the dentate gyrus in alcohol-intoxicated rats was investigated. METHODS EXPERIMENTAL DESIGN: comparative investigation on number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus 8 days after commencement. SETTING: animal laboratory. PARTICIPANTS: male Sprague-Dawley rats of 5 weeks in age weighing 150+/-10 g. INTERVENTION: animals were divided into 4 groups: the control-rest group, the control-exercise group, the alcohol-treated-rest group, and the alcohol-treated-exercise group. Animals of the alcohol-treated groups were injected intraperitoneally with alcohol (2 g/kg) once a day for 3 days. All animals were injected BrdU (50 mg/kg) intraperitoneally, and rats of exercise groups were made to run on treadmill for 30 min each day for 5 days following alcohol administration. MEASURES: mean number of BrdU-positive cells in dentate gyrus was observed via immunohistochemistry. RESULTS: Treadmill exercise significantly increased the number of BrdU-positive cells in the dentate gyrus. Also, treatment with alcohol for 3 days inhibited cell proliferation and treadmill exercise alleviated alcohol-induced inhibition of new cell formation. CONCLUSION: These results suggest the possibility that treadmill exercise may help in improvement following alcohol-induced brain damage.

Alcoholic Intoxication↗