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Biomedical subjects

S H Hong

Publications and source records attributed to S H Hong.

At least 37 records · Page 2Linked to original sources

Fenofibrate lowers abdominal and skeletal adiposity and improves insulin sensitivity in OLETF rats.

The effect of peroxisome proliferator-activated receptor (PPAR)-alpha activators on the liver is well established, but the other effects on muscle and adipose tissue about lipid metabolism and insulin sensitivity are not clear. We investigated whether PPAR-alpha activation affects adiposity of skeletal muscle as well as adipose tissue and improves insulin sensitivity in spontaneous type 2 diabetes model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Thirty-three weeks of aged, 20 male OLETF rats were divided into two groups. Control group (n=10) was fed with chow and treatment group (n=10) with chow contained fenofibrate for 7 weeks. At the age of 40 weeks, all rats were examined with MRI, intravenous glucose tolerance test, and then sacrificed for measurement of fat mass and RNA analyses. The total fat (the sum of subcutaneous, mesenteric, epididymal, and retroperitoneal fat pads) measured by dissection was significantly reduced in treatment group. The signal intensity of muscular adiposity was significantly decreased in treatment group. The mRNA levels of FAT/CD36 and mitochondrial carnitine palmitoyltransferase I (M-CPT I) in liver were remarkably increased. Fasting plasma insulin and leptin levels, insulin response after intravenous glucose loading and homeostasis model assessment insulin resistance (HOMA(IR)) index were lowered in treatment group. Fenofibrate increase mitochondrial fatty acid beta-oxidation in liver but not in skeletal muscle and lower the plasma levels of triglyceride and free fatty acid. It might result in reduction of adiposity of truncal adipose tissue and skeletal muscle. We suggest that reduction of adiposity in trunk and skeletal muscle might improve insulin sensitivity.

Abdomen↗

Isolation and characterization of a new succinic acid-producing bacterium, Mannheimia succiniciproducensMBEL55E, from bovine rumen.

A novel succinic acid-producing bacterium was isolated from bovine rumen. The bacterium is a non-motile, non-spore-forming, mesophilic and capnophilic gram-negative rod or coccobacillus. Phylogenetic analysis based on the 16S rRNA sequence and physiological analysis indicated that the strain belongs to the recently reclassified genus Mannheimia as a novel species, and has been named Mannheimia succiniciproducens MBEL55E. Under 100% CO(2) conditions, it grows well in the pH range of 6.0-7.5 and produces succinic acid, acetic acid and formic acid at a constant ratio of 2:1:1. When M. succiniciproducensMBEL55E was cultured anaerobically in medium containing 20 g l(-1) glucose as carbon source, 13.5 g l(-1) of succinic acid was produced.

Acetic Acid↗

Horizontal and vertical distribution of butyltin compounds in sediments from shipyards in Korea.

Butyltin compounds were quantitatively determined in surface sediment and sediment core samples near shipyards in the south coast of Korea, which is one of the major ship building industries in the world. Tributyltin (TBT) concentrations reached up to 46100 ng Sn/g on a dry-weight basis at the front of the shipyard. Horizontal distribution of butyltin compounds was closely related to dry-docking activities. Butyltin concentrations were relatively low where remote from the sources. The vertical distribution of TBT in sediment cores showed active use of TBT in Korean peninsula for the past decades. The increase of TBT concentrations in sediment core according to estimated sediment age demonstrated a positive correlation with the increase of gross tonnage of ships built in the shipyard for 20 years. High TBT residue levels in sediment core samples raise concerns over persistence of the compound in the marine environment.

Environmental Monitoring↗

Geographical distribution and accumulation features of organochlorine residues in bivalves from coastal areas of South Korea.

As a part of Mussel Watch Program in Korea, the contamination levels and accumulation features of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were assessed for 82 bivalve samples collected from 66 sites along the entire coast of Korea. The dry weight based sigmaPCBs and sigmaOCPs ranged from 4.4 ng g(-1) to 422.0 ng g(-1) (geometric mean = 36.9 ng g(-1)) and from 9.95 ng g(-1) to 131.37 (34.88) ng g(-1), respectively. PCB was predominant in Korean coast, followed by DDTs, HCHs, and Chlordanes. From the observed log normal distribution of PCB and each OCP, low- and high-levels were defined as geometric mean +/- 1 S.D., respectively. The levels at the sites near urban and/or industrial areas often exceeded the high-levels and the spatial distributions of sigmaDDTs and sigmaCHLs were correlated with that of sigmaPCBs, indicating terrestrial input pathways. Even distribution of sigmaHCHs suggested a possibility of atmospheric input pathway of HCHs. The observed isomer ratios of DDTs, HCHs, and CHLs indicated that aging has occurred.

Animals↗

Degradation of IkappaBalpha in activated RAW264.7 cells is blocked by the phosphatidylinositol 3-kinase inhibitor LY294002.

The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated. Activation of nuclear factor kappaB (NF-kappaB) is initiated by the phosphorylation of the inhibitory subunit, IkappaB, which targets IkappaB for degradation and leads to the release of active NF-kappaB. In this study we demonstrate that 2-(4-morpholinyl)-8-phenylchromone (LY294002), which inhibits PI3-kinase, specifically inhibited degradation of IkappaBalpha in RAW264.7 cells stimulated with interferon-gamma (IFN-gamma) plus LPS or IFN-gamma plus PMA. To elucidate the importance of this activity in RAW264.7 cells, we examined tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 production in the activated cells. Pretreatment of the cells with LY294002 resulted in the inhibition of TNF-alpha and IL-6 production in RAW264.7 cells stimulated with IFN-gamma plus LPS or IFN-gamma plus PMA. Furthermore, LY294002 inhibited the production of nitric oxide (NO) in RAW264.7 cells stimulated with IFN-gamma plus LPS or IFN-gamma plus PMA. LY294002 also inhibited inducible NO synthase (iNOS) mRNA expression in the activated RAW264.7 cells. In conclusion, the present results suggest that PI3-kinase is involved in the signal transduction pathway responsible for LPS- or PMA-mediated TNF-alpha and IL-6 production, and that LY294002 inhibits NO generation through blocking the degradation of IkappaBalpha in activated RAW264.7 cells.

Animals↗

Alternative transcriptional initiation and splicing of mouse Lamc2 message.

To investigate the mechanism of two forms of messages (5.1 and 2.4 kb) in mouse Lamc2, a gene encoding for the gamma2 chain of epithelial cell-specific laminin 5, we analyzed approximately 40 kb of genomic DNA containing the sequences from the first intron to the 23rd exon to the 3' untranscribed region. With the 5' rapid amplification of cDNA end (RACE) and primer extension technique using RNA from mouse kidney and thymic epithelial cells, we found that the smaller message starts at the 2895th base of the cDNA within the 19th exon. Upstream sequences of this alternative start site showed the promoter activity in the reporter assay with the secreted form of alkaline phosphatase (SEAP). We also identified a novel alternatively spliced exon (exon 19B) that includes two stop codons. These results revealed two possible additional open reading frame that are different from the previously described alternative human gamma2 peptide. Therefore, the mechanism for generating smaller message and the event of alternative splicing are quite distinct between mouse and human Lamc2, although genomic organization is highly conserved. The significance of the presence of alternative message is discussed.

Alternative Splicing↗

Importance of redox balance on the production of succinic acid by metabolically engineered Escherichia coli.

We had previously shown that succinic acid production in a pfl ldhA double mutant strain of Escherichia coli could be enhanced by amplifying the malic enzyme activity. However, recombinant E. coli NZN111 (F- Apfl::Cam ldhA::Kan) harboring pTrcML, a plasmid containing the E. coli malic enzyme gene, produced a considerable amount of malic acid along with the desired product, succinic acid. To have an insight into the intracellular metabolism, metabolic control analysis was carried out. From the results of a simulation, it was predicted that supplying additional reducing power could enhance succinic acid production. More reduced carbon substrate sorbitol was thus examined for the possibility of matching the potential during succinic acid production. When NZN111 (pTrcML) was cultured in LB medium containing 20 g sorbitol/l under a CO2 atmosphere, 10 g succinic acid/l was produced. The apparent yield of succinic acid was 1.1 g succinic acid/g sorbitol, which is 85% of the maximum theoretical yield. Therefore, it was found that redox balancing was important for the enhanced production of succinic acid in metabolically engineered E. coli.

Carbon Dioxide↗

Effect of hypothermia on bilirubin-induced alterations in brain cell membrane function and energy metabolism in newborn piglets.

The aim of this study was to evaluate the effects of hypothermia on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the developing brain. Thirty-seven newborn piglets were divided randomly into four groups: normothermic control (NC, n=9); hypothermic control (HC, n=7); normothermic bilirubin infusion (NB, n=11); and hypothermic bilirubin infusion (HB, n=10) groups. In bilirubin infusion groups (NB and HB), a loading dose of bilirubin (35 mg/kg) was given over 5 min, followed by a continuous infusion (25 mg/kg/h) for 4 h. The control groups (NC, HC) received a bilirubin-free buffer solution. Sulfadimethoxine was administered to animals in all experimental groups. Rectal temperature was maintained between 38.0 and 39.0 degrees C in normothermic groups, and between 34.0 and 35.0 degrees C in hypothermic groups for 4 h after the start of bilirubin infusion. The final blood and brain bilirubin concentrations in the bilirubin infusion groups (NB and HB) were not significantly different. Decreased cerebral cortical cell membrane Na(+),K(+)-ATPase activity and increased lipid peroxidation products observed in the NB group, indicative of bilirubin-induced brain damage, were significantly attenuated in the HB group. Hypothermia also significantly improved the bilirubin-induced reduction in brain ATP and phosphocreatine levels and increase in blood and brain lactate levels. In summary, hypothermia significantly attenuated the bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglet. These findings suggest the possibility that hypothermia could be a good neuroprotective therapeutic modality in neonatal bilirubin encephalopathy.

Adenosine Triphosphate↗

Metabolic flux analysis for succinic acid production by recombinant Escherichia coli with amplified malic enzyme activity.

A pfl ldhA double mutant Escherichia coli strain NZN111 was used to produce succinic acid by overexpressing the E. coli malic enzyme. Escherichia coli strain NZN111 harboring pTrcML produced 6 and 8 g/L of succinic acid from 20 g/L of glucose in flask culture at 37 degrees C and 30 degrees C, respectively. When NZN111(pTrcML) was cultured at 30 degrees C with intermittent glucose feeding the final succinic acid concentration obtained was 9.5 g/L and the ratio of succinic acid to acetic acid was 13:1. This system could not be analyzed by conventional metabolic flux analysis techniques, since some pyruvate and succinic acid were accumulated intracellularly. Therefore, a new flux analysis method was proposed by introducing intracellular pyruvate and succinic acid pools. By this new method the concentrations of intracellular metabolites were successfully predicted and the differences between the measured and calculated reaction rates could be considerably reduced.

Acetyltransferases↗

Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid interactions.

Many arachidonic acid metabolites function in growth signaling for epithelial cells, and we previously reported the expression of the major arachidonic acid enzymes in human breast cancer cell lines. To evaluate the role of the 5-lipoxygenase (5-LO) pathway on breast cancer growth regulation, we exposed cells to insulinlike growth factor-1 or transferrin, which increased the levels of the 5-LO metabolite, 5(S)-hydrooxyeicosa-6E,8C,11Z,14Z-tetraenoic acid (5-HETE), by radioimmunoassay and high-performance liquid chromatography. Addition of 5-HETE to breast cancer cells resulted in growth stimulation, whereas selective biochemical inhibitors of 5-LO reduced the levels of 5-HETE and related metabolites. Application of 5-LO or 5-LO activating protein-directed inhibitors, but not a cyclooxygenase inhibitor, reduced growth, increased apoptosis, down-regulated bcl-2, up-regulated bax, and increased G1 arrest. Exposure of breast cancer cells to a 5-LO inhibitor up-regulated peroxisome proliferator-activated receptor (PPAR)a and PPARg expression, and these same cells were growth inhibited when exposed to relevant PPAR agonists. These results suggest that disruption of the 5-LO signaling pathway mediates growth arrest and apoptosis in breast cancer cells. Additional experiments suggest that this involves the interplay of several factors, including the loss of growth stimulation by 5-LO products, the induction of PPARg, and the potential activation of PPARg by interactions with shunted endoperoxides.

Apoptosis↗

Novel findings in inhibition of mast cell-dependent immediate-type cutaneous reactions by Gahmi-Shini-San.

This report describes an inhibitory effect of Gahmi-Shini-San (GSS) on mast cell-mediated immediate-type allergic reactions. GSS is an Oriental herbal medication, which has been successfully used in Korea for the treatment of allergic disorders, mainly skin anaphylactic diseases. GSS inhibited the ear swelling response induced by intradermal injection of compound 48/80 in a mouse model on a concentration-dependent basis. The mast cells in mouse ear tissue were stained by alcian blue/nuclear fast red. GSS significantly inhibited the compound 48/80-induced degranulation from mast cells in ear tissue. GSS dose-dependently inhibited the histamine release from the rat peritoneal mast cells by compound 48/80. We also studied the effect of GSS on mast cell-dependent passive cutaneous anaphylaxis activated by dinitrophenyl IgE antibody. GSS showed inhibition of passive cutaneous anaphylaxis following oral administration. These results indicated that GSS has inhibitory effect on mast cell-dependent immediate type cutaneous reactions.

Alcian Blue↗

8-Cl-cAMP induces cell cycle-specific apoptosis in human cancer cells.

8-Cl-cyclic adenosine monophosphate (8-Cl-cAMP) has been known to induce growth inhibition and differentiation in a variety of cancer cells by differential modulation of protein kinase A isozymes. To understand the anticancer activity of 8-Cl-cAMP further, we investigated the effect of 8-Cl-cAMP on apoptosis in human cancer cells. Most of the tested human cancer cells exhibited apoptosis upon treatment with 8-Cl-cAMP, albeit with different sensitivity. Among them, SH-SY5Y neuroblastoma cells and HL60 leukemic cells showed the most extensive apoptosis. The effect of 8-Cl-cAMP was not reproduced by other cAMP analogues or cAMP-elevating agents, showing that the effect of 8-Cl-cAMP was not caused by simple activation of protein kinase A (PKA). However, competition experiments showed that the binding of 8-Cl-cAMP to the cAMP receptor was essential for the induction of apoptosis. After the treatment of 8-Cl-cAMP, cells initially accumulated at the S and G2/M phases of the cell cycle and then apoptosis began to occur among the population of cells at the S/G2/M cell cycle phases, indicating that the 8-Cl-cAMP-induced apoptosis is closely related to cell cycle control. In support of this assumption, 8-Cl-cAMP-induced apoptosis was blocked by concomitant treatment with mimosine, which blocks the cell cycle at early S phase. Interestingly, 8-Cl-cAMP did not induce apoptosis in primary cultured normal cells and non-transformed cell lines, showing that 8-Cl-cAMP-induced apoptosis is specific to transformed cells. Taken together, our results show that the induction of apoptosis is one of the mechanisms through which 8-Cl-cAMP exerts anticancer activity.

3T3 Cells↗

Changes in external ear resonance after ventilation tube (Grommet) insertion in children with otitis media with effusion.

OBJECTIVE: As otitis media with effusion is common in children, the effects of a ventilation tube should be taken into account in the prescription of hearing aids for children. In ears with a ventilation tube, the external auditory canal communicates directly with the middle ear space, and so the impedance of the middle ear may change. Consequently, this will affect external-ear resonance. The aim of this study is to observe the effects of the tympanic membrane perforations caused by the ventilation tube on external-ear resonance. We selected 30 ears with otitis media with effusion to measure external-ear resonance before and after ventilation tube insertion. We compared the external-ear resonance of a control group with that of the otitis media with the effusion group and two types of ventilation-tube groups, respectively. In the subjects who have otitis media with effusion, the average gain of the peak resonance was larger than that in the control group. After ventilation-tube insertion, the amplitude of the gain decreased to the same level as the control group, but a characteristic negative gain appeared around 1000 Hz in about half of all cases. This negative gain was observed more frequently in the ventilation tube with a larger diameter. The raised peak resonance gain in the otitis media with effusion group decreased to a level roughly the same as that of the control group after ventilation-tube insertion. Provision of an additional gain in the low frequencies around 1000 Hz should be considered for patients with a ventilation tube when prescribing hearing aids.

Acoustic Stimulation↗

Caspase-mediated Cdk2 activation is a critical step to execute transforming growth factor-beta1-induced apoptosis in human gastric cancer cells.

Although TGF-beta1, a growth inhibitor, is known to also induce apoptosis, the molecular mechanism of this apoptosis is largely undefined. Here, we identify the mechanism of TGF-beta1-induced apoptosis in SNU-16 human gastric cancer cells. Cell cycle and TUNEL analysis showed that, upon TGF-beta1 treatment, cells were initially arrested at the G1 phase and then driven into apoptosis. Of note, caspase-3 was activated in accordance with TGF-beta1-induced G1 arrest. Activated caspase-3 is targeted to cleave p21(cip1), p27(kip1), and Rb, which play important roles in TGF-beta-induced G1 arrest, into inactive fragments. Subsequently, Cdk2 was aberrantly activated due to the cleavage of p21 and p27. We found that the inhibition of Cdk2 activity efficiently blocks TGF-beta1-induced apoptosis, whereas it did not prevent caspase-3 activation or the subsequent cleavage of target proteins. In contrast, the suppression of caspase-3 activity inhibited the cleavage of target proteins, the activation of Cdk2, and the induction of apoptosis. Taken together, our results suggest that activation of caspase-3 by TGF-beta1 may initiate the conversion from G1 cell cycle arrest to apoptosis via the cleavage of p21, p27 and Rb, which in turn causes Cdk2 activation and, most significantly, Cdk2 activation as a downstream effector of caspase is a critical step for the execution of TGF-beta1-induced apoptosis.

Annexin A5↗

Genetic variation of the methylenetetrahydrofolate reductase and cystathionine beta-synthase genes in Korean patients with coronary artery disease and a new polymorphism in intron 7.

We investigated polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes in Korean patients with coronary artery disease (CAD) and identified a new polymorphism (c-->t) in intron 7 of the CBS gene using the single-strand conformation polymorphism method. No significant differences were found in allele frequencies for either gene between the CAD and normal groups although the frequency of the so-called thermolabile MTHFR polymorphism, a proposed risk factor for CAD, was higher in Koreans than in other populations studied. The relatively low incidence of CAD in Korea suggests that this MTHFR polymorphism is not causative in this population.

Coronary Disease↗

Low tibial osteotomy for moderate ankle arthritis.

Low tibial osteotomy is one of the significant advances of ankle reconstruction techniques that has been made recently in an effort to halt arthritis in its early stages and leave fusion as the last, not the only, alternative treatment of ankle arthritis. From 1989 to 1995, we performed 18 low tibial osteotomies which included 6 cases of post-traumatic arthritis and 12 cases of degenerative arthritis. The ages of the 7 male and 11 female patients ranged from 18 to 78 years with an average of 41.9 years. The follow-up period lasted a mean of 47.7 months, ranging from 25 to 82 months. The average functional score changed from 49.6 pre-operatively to 88.5 at the last follow up, and showed yearly improvement. Complications included one case of late infection and two cases of implant failure, none of which led to nonunion. The indication for low tibial osteotomy is the intermediate stage of moderate ankle arthritis with a medial joint lesion and intact lateral facet. Using pressure redistribution on the joint surface, this procedure is an alternative treatment for ankle arthritis which may save an arthritic ankle from the fate of fusion or at least postpone fusion surgery.

Adolescent↗

Genetic variations of the paraoxonase gene in patients with coronary artery disease.

OBJECTIVES: Paraoxonase (PON) plays an important role in preventing low density lipoprotein (LDL) oxidation and thus may be involved in protection against atherosclerosis. Several studies have suggested that genetic variations of the PON gene are associated with plasma HDL levels and coronary artery disease (CAD). This study was conducted to elucidate the association between three polymorphisms of the PON1 and PON2 genes and Korean patients with CAD. DESIGN AND METHODS: One hundred ninety-one patients with CAD and 113 age-matched normal controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for PON polymorphisms by restriction enzyme digestion. RESULTS: There was linkage disequilibria between each polymorphism pair in the CAD and control groups. The Hsp92II polymorphism at codon 54 of the PON1 gene was positively associated with HDL-cholesterol levels in the control group (p = 0.02). An association between the AlwI polymorphism and HDL-cholesterol level appeared statistically significant in women of the normal group (p = 0.04). In addition, the DdeI and AlwI polymorphisms were positively associated with HDL (p = 0.02) and LDL (p = 0.03) levels in men of the CAD group, respectively. CONCLUSIONS: Our study suggested a gene-gene interaction between the PON1 and PON2 polymorphisms for CAD risk. However, we could not exclude the possibility that these polymorphisms may have linkage disequilibrium with a tightly linked PON3 locus or significant atherosclerotic alleles of nearby genes. Family studies may, therefore, help to confirm the role of the PON polymorphism for CAD risk.

Adult↗

MR findings of tuberculous dactylitis: case report.

A case of tuberculous dactylitis in an immunocompetent patient is presented and the radiographic findings and differential diagnosis discussed. MR image, although nonspecific, was helpful for differential diagnosis and evaluating the extent of the lesion. Although this is a rare condition, the diagnosis should be considered when dealing with an unusual destructive bony lesion.

Adolescent↗