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Biomedical subjects

S Y Hong

Publications and source records attributed to S Y Hong.

At least 37 records · Page 2Linked to original sources

The detection of p53 gene mutation using a microdissection technique in primary intracranial germ cell tumors.

Using a microdissection technique, the contribution of the p53 mutation to tumorigenesis and prognosis in each histological subtype of the intracranial germ cell tumors (GCTs) was evaluated. Nineteen patients had primary intracranial GCTs, including 4 germinomas (GEs), 4 teratomas (TEs), 1 mixed tumor of GE and TE, and 10 mixed GCTs containing non-germinomatous malignant germ cell tumors (NG-MGCTs). After microdissection of specific subtypes, genomic DNA was screened for mutations in exons 5-8 of the p53 gene, using the dideoxyfingerprinting (ddF) followed by direct DNA sequencing. The direct sequencing revealed a total of six mutations in PCR products derived from the five cases (26%) which showed mobility shifts in ddF. Among the six mutations detected, four were missense mutations and two were silent. Missense mutations of the p53 gene tended to occur more frequently in the NG-MGCT component than in the GE or TE components (3/15 vs. 1/12 vs. 0/13). The incidence of missense mutations was not different between the survivors (3/13) and the deceased (1/6). This study suggests the possible role of the p53 gene in the tumori-genesis of NG-MGCT. However, p53 gene mutation did not correlate with the prognosis of NG-MGCT.

Adult↗

Reuse of industrial sludge as construction aggregates.

Industrial wastewater sludge and dredged marine clay are high volume wastes that needed enormous space at landfill disposal sites. Due to the limitation of land space, there is an urgent need for alternative disposal methods for these two wastes. This study investigates the possibility of using the industrial sludge in combination with marine clay as construction aggregates. Different proportions of sludge and clay were made into round and angular aggregates. It was found that certain mix proportions could provide aggregates of adequate strength, comparable to that of conventional aggregates. Concrete samples cast from the sludge-clay aggregates yield compressive strengths in the range of 31.0 to 39.0 N/mm2. The results showed that the round aggregates of 100% sludge and the crush aggregates of sludge with up to 20% clay produced concrete of compressive strengths which are superior to that of 38.0 N/mm2 for conventional aggregate. The study indicates that the conversion of high volume wastes into construction materials is a potential option for waste management.

Aluminum Silicates↗

New frontiers in the continuum of dental education.

During the past 150 years, dental education and training have changed from an apprenticeship to a university-based dental school. The future of dental education will be shaped by changing demographics, advances in technology, and a greater integration of science and research into the dental profession. We are entering an age of interdisciplinary practice, where dentistry provides oral health care as an integral part of an individual's overall health care.

Curriculum↗

Associations between laboratory parameters and outcome of paraquat poisoning.

Paraquat, a non-selective herbicide, is a known fatal substance in humans, and intentional ingestion of paraquat is increasing among Korean suicides. In 1999, 147 subjects admitted to the Institute of Pesticide Poisoning, Soonchunhyang Chunan Hospital, Korea ingested paraquat. Initial routine laboratory tests were conducted and the outcome of paraquat poisoning was categorized as survivor and fatality. Mean amount (S.D.) of ingestion was 54.5 (104.9) ml, and the overall fatality rate was 44.2%. Abnormal liver function (GOT and GPT), renal dysfunction (BUN and creatinine), metabolic acidosis (pH and PaCO(2)), and abnormal urine analysis (RBC, WBC, and protein) had significant odds ratios (ORs) for paraquat fatality (P<0.05). In multiple logistic regression, subjects with liver or renal dysfunction or metabolic acidosis had significant risks of the fatality. Our results determined that initial routine laboratory parameters could be used to predict the outcome of paraquat poisoning and recommended that evaluation of acid-base status and renal and liver function should be conducted and evaluated before intensive therapy.

Adult↗

Role of sea surface temperature and soil-moisture feedback in the 1998 Oklahoma-Texas drought.

The drought that affected the US states of Oklahoma and Texas in the summer of 1998 was strong and persistent, with soil moisture reaching levels comparable to those of the 1930s 'dust bowl'. Although other effects of the record-strength 1997-98 El Niño were successfully predicted over much of the United States, the Oklahoma-Texas drought was not. Whereas the response of the tropical atmosphere to strong anomalies in sea surface temperature is quite predictable, the response of the extratropical atmosphere is more variable. Here we present results from mechanistic experiments to clarify the origin and maintenance of this extratropical climate extreme. In addition to global atmospheric models, we use a regional model to isolate regional climate feedbacks. We conclude that during April and May 1998, sea surface temperature anomalies combined with a favourable atmospheric circulation to establish the drought. In June-August, the regional positive feedback associated with lower evaporation and precipitation contributed substantially to the maintenance of the drought. The drought ended in the autumn, when stronger large-scale weather systems were able to penetrate the region and overwhelm the soil-moisture feedback. Our results show the potential for numerical models including appropriate physical processes to make skillful predictions of regional climate.

Journal Article↗

Involvement of two NF-kappa B binding elements in tumor necrosis factor alpha -, CD40-, and epstein-barr virus latent membrane protein 1-mediated induction of the cellular inhibitor of apoptosis protein 2 gene.

The antiapoptotic function of NF-kappaB is believed to be mediated through the induction of antiapoptotic genes. Among the antiapoptotic genes, cellular inhibitor of apoptosis protein 2 (c-IAP2/HIAP-1/MIHC) is originally identified as a molecule recruited to the tumor necrosis factor (TNF) receptor complex, and its expression is preferentially up-regulated by TNF and other stimuli activating NF-kappaB. However, direct evidence of transcriptional regulation of NF-kappaB on the c-IAP2 gene is still missing. Here, we have cloned and characterized the promoter region required for NF-kappaB-dependent transcription of the c-IAP2 gene. Sequencing of a 3.5-kilobase fragment of the 5'-flanking region of the c-IAP2 gene has identified a TATA-like sequence and potential binding sites for nuclear factor of activated T cells, interferon regulatory factor 1, activator protein 1, glucocorticoid response element, and three putative NF-kappaB binding elements. Deletion and mutational analysis of the 5'-flanking region linked to the luciferase gene revealed that transcriptional activation by TNF or interleukin 1 is mediated cooperatively by two NF-kappaB binding sites. Electrophoretic mobility shift assays characterized that the two NF-kappaB sites can be recognized and bound by the NF-kappaB p50/p65 heterodimer. In addition, the transcription of c-IAP2 promoter was strongly up-regulated when CD40 or Epstein-Barr virus latent membrane protein 1 was overexpressed.

Antigens, Viral↗

Identification and characterization of nitric oxide synthase in Salmonella typhimurium.

The presence of the nitric oxide synthase (NOS) enzyme from Salmonella typhimurium (S. typhimurium) was identified by measuring radiolabeled L-[3H]citrulline and NO, and Western blot analysis. NOS was partially purified by both Mono Q ion exchange and Superose 12HR size exclusion column chromatography, sequentially. The molecular weight of NOS was estimated to be 93.3 kDa by Western blot analysis. The enzyme showed a significant dependency on the typical NOS cofactors; an apparent Km for L-arginine of 34.7 mM and maximum activity between 37 degrees C and 43 degrees C. The activity was inhibited by NOS inhibitors such as aminoguanidine and N(G),N(G)-dimethyl-L-arginine. Taken together, partially purified NOS in S. typhimurium is assumed to be a different isoform of mammalian NOSs.

Citrulline↗

An endogenous proteinacious inhibitor in porcine liver for S-adenosyl-L-methionine dependent methylation reactions: identification as oligosaccharide-linked acyl carrier protein.

A proteinacious inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent transmethylation reactions was purified to homogeneity from porcine liver by size exclusion chromatography and FPLC. The molecular weight of the inhibitor was 12,222 Da. A 7400 Da polypeptide fragment of the purified inhibitor was sequenced by matrix-associated laser desorption ionization; time-of-flight MS, and was found to be identical with the known sequence of spinach acyl carrier protein (ACP). Although the remainder of the molecule was not clearly defined, 1H and H-H correlation of spectroscopy (COSY) NMR analysis revealed the presence of an oligosaccharide with alpha-glycosidic linkage. The purified oligosaccharide-linked ACP inhibited several AdoMet-dependent transmethylation reactions such as protein methylase I and II. S-farnesylcysteine O-methyltransferase, DNA methyltransferase and phospholipid methyltransferase. Protein methylase II was inhibited with a Ki value of 2.4 x 10(-3) M in a mixed inhibition pattern, whereas a well-known competitive product inhibitor S-adenosyl-L-homocysteine (AdoHcy) had Ki value of 6.3 x 10(-6) M. Commercially available active ACP fragments (65-74) and ACP from Escherichia coli had less inhibitory activity toward S-farnesylcysteine O-methyltransferase than the purified inhibitor. The biological significance of this oligosaccharide-linked ACP which has two seemingly unrelated functions (inhibitor for transmethylation and fatty acid biosynthesis) remains to be elucidated.

Acyl Carrier Protein↗

Effect of D-amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide.

Several diastereomers and an enantiomer of KKVVFKVKFKK, an antimicrobial peptide that acts on the lipid membrane of pathogens were synthesized to investigate the effect of D-amino acid substitution on stability, secondary structure, and activity. The stability of the peptide in serum was improved greatly by the D-amino acid substitutions. D-Amino acid substitutions at the N- and/or C-terminal of the peptide, which had little effect on the alpha-helical structure, and all D-amino acid substitutions that formed a left-handed alpha-helix maintained antimicrobial activity, whereas D-amino acid substitutions in the middle of the amino acid sequence disrupted the alpha-helical structure, resulting in the complete loss of activity. This result confirmed that the peptide did not interact with chiral receptors, enzymes, or any chiral component of the membrane. D-Amino acid substitutions at the termini reduced the inhibition of the activity by heat-inactivated serum, which indicated that local change of chirality or change of secondary structure induced by D-amino acid substitutions might affect the interactions between the peptide and certain components in the serum. The present study suggests that partial D-amino acid substitution is a useful technique to improve the in vivo activity of antimicrobial peptides.

Amino Acid Sequence↗

An endogenous proteinacious inhibitor for S-adenosyl-L-methionine-dependent transmethylation reactions; identification of S-adenosylhomocystein as an integral part.

A proteinacious inhibitor with a molecular weight of 1,600 Da which inhibits S-adenosyl-L-methionine-dependent transmethylation reactions was purified from porcine liver to homogeneity by procedures including boiling, Sephadex G-25 column chromatography and repeated HPLC. Employing both Nuclear Magnetic Resonance (NMR) and Fast Atom Bombardment-Mass (FAB-Mass) spectroscopy, S-adenosylhomocysteine was conclusively identified as an integral part of the inhibitor. The purified S-adenosylhomocysteine was competitive with S-adenosyl-L-methionine with Ki value of 6.3x10(-6) M towards protein methylase II.

Animals↗

Inducible nitric oxide synthase inhibitors from Melia azedarach var. japonica.

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.

Carbolines↗

Influence of 5,10-methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine concentration in patients with end-stage renal disease.

The purpose of this study is to observe the influence of the methylenetetrahydrofolate reductase (MTHFR) gene (677C-->T substitution) on plasma homocysteine levels in end-stage renal disease (ESRD) patients who received a relatively large amount of folate (2 mg/d) and are undergoing hemodialysis. A cross-sectional study of plasma homocysteine, vitamin B(12), and folate was performed in patients with ESRD. The study population for the MTHFR gene study included 312 healthy subjects and 106 patients with ESRD undergoing hemodialysis. The C677T transition in the MTHFR gene was detected by HinF 1 restriction enzyme analysis and subsequent electrophoresis in a 3% agarose gel. The genotype of the MTHFR gene in 106 patients with ESRD was homozygous C677T mutation (VV) in 17 patients (16.1%) and heterozygous (AV) in 63 patients (58.4%); 26 patients (24.5%) did not carry this mutation (AA). The mean levels of homocysteine, vitamin B(12), and folate in the patients with ESRD were 23.3 +/- 14.0 mmol/L, 620.2 +/- 98.5 pmol/L, and 138.6 +/- 55.6 nmol/L, respectively. There was no significant difference in homocysteine levels among the three genotypes: 28.2 +/- 19.4 mmol/L for VV, 22.7 +/- 14.9 mmol/L for AV, and 23.4 +/- 11.1 mmol/L for AA genotype (P > 0.05). There was no difference in genotype distribution between the patient groups of less than 25th and greater than 75th percentiles, classified according to plasma homocysteine levels (P = 0.47). In conclusion, with high-dose folate supplementation, the hyperhomocysteinemia in patients with ESRD does not seem to be caused by the 677C-->T mutation in the MTHFR gene.

Cross-Sectional Studies↗

The comparison of characteristics between membrane-active antifungal peptide and its pseudopeptides.

By the introduction of various amide surrogates, novel pseudopeptides corresponding to a membrane active depsipeptide were synthesized and their native characteristics compared with that of the peptide. The pseudopeptides had more resistance to serum proteases than the peptide and similar antimicrobial activities to that of the peptide without hemolytic activity. The pseudopeptides like the peptide were active against current drug resistant fungi and pathogenic fungi isolated from patients, and also had a strong synergism with current antifungal drugs against Candida albicans. The leakage assay suggested that the pseudopeptides also acted on the lipid membrane of pathogenic cells. These results indicated that the novel pseudopeptides had advantages over the peptide as a candidate for a novel antifungal drug and backbone modifications can be a tool in the development of a novel antifungal agent from membrane-active peptides isolated from natural sources or chemically synthesized.

Antifungal Agents↗

Design, synthesis and characterization of antimicrobial pseudopeptides corresponding to membrane-active peptide.

To obtain active and metabolically stable analogues, peptide backbone modifications have been incorporated into many biologically active peptides. In this study, we designed and synthesized pseudopeptides corresponding to the antimicrobial peptide that acted on the lipid membrane of the pathogen. Most pseudopeptides exhibited a longer half-life than the peptide in the presence of serum as well as a considerable activity against test bacteria and fungi. Circular dichroism spectra and retention times of the pseudopeptides helped us to elucidate the effect of the incorporation of backbone modifications on the structural parameters necessary for the activity, indicating that alpha-helical structure was the most important factor for the activity and hydrophobicity had a considerable effect on the activity. Backbone modifications employed in this study can be a useful tool for structure-activity relationship studies and the development of therapeutic agents from membrane-active antimicrobial peptides.

Amino Acid Sequence↗

Life stress, mood disturbance, and elevated interleukin-6 in healthy older women.

BACKGROUND: Although adverse effects of severe chronic stress on immunocompetence and physical well-being in older adults have been reported, the immune response to less severe life stress among healthy older adults, particularly among women, is not well understood. Interleukin-6 (IL-6) has been considered a good overall indicator of immune functioning in older adults because of its contribution to the pathogenesis of several age-related conditions such as osteoporosis. Regulation of IL-6 is impaired in elderly adults, and levels of IL-6 increase with stress and depression. This research cross-sectionally examined levels of IL-6 in three groups of healthy older women with varying levels of life stress and mood disturbance and a healthy group of young women. METHODS: Subjects included 18 caregivers of Alzheimer's patients, 17 older women assessed one month before relocation of their residence, 15 nonmoving and noncaregiving older women, and 20 younger women. Subjects completed the Profile of Mood States (POMS) and had early morning blood draws. RESULTS: Alzheimer's caregivers reported significantly greater distress than women of all other groups. IL-6 levels in caregivers were significantly higher than those of all other women. The older women had significantly higher IL-6 than young controls, but there were no significant differences in IL-6 between movers and older controls. Among all women, greater depression and distress were related to higher levels of IL-6. CONCLUSIONS: These findings suggest that in older women, chronic stressors are associated with significant elevations in IL-6 over and above the elevations associated with normal aging, but that moderate stressors may not be related to appreciable elevations in IL-6.

Aged↗

Structure-activity relationship study: short antimicrobial peptides.

Many short antimicrobial peptides (< 18mer) have been identified for the development of therapeutic agents. However, Structure-activity relationship (SAR) studies about short antimicrobial peptides have not been extensively performed. To investigate the relationship between activity and structural parameters such as an alpha-helical structure, a net positive charge and a hydrophobicity, we synthesized and characterized diastereomers, scramble peptides and substituted peptides of the short antimicrobial peptide identified by combinatorial libraries. Circular dichroism (CD) spectra and in vitro activity indicated that an alpha-helical structure correlated with the antimicrobial activity and a beta-sheet structure also satisfied a structural requirement for antimicrobial activity. Most peptides consisting of L-amino acids lost antifungal activity in the presence of heat-inactivated serum, while active diastereomers and a scramble peptide with the beta-sheet structure retained antifungal activity in the same condition.

Anti-Bacterial Agents↗

In vitro antifungal activity and cytotoxicity of a novel membrane-active peptide.

In the present study, we investigated the antifungal activity and cytotoxicity of a novel membrane-active peptide, KKVVFKVKFKK (MP). MP inhibited the growth of various pathogenic fungi isolated from patients and of fluconazole-resistant fungi at concentrations of 2 to 32 microg/ml. MP had potent fungicidal activity; the minimal fungicidal concentrations of the peptide were no more than fourfold greater than the MICs. Time course experiments of MP-induced killing of Candida albicans ATCC 36232 showed that the rate of killing was rapid and depended on the concentration of MP. MP had a strong synergism with other antifungal drugs; the fractional inhibitory concentration index values of MP with amphotericin B and fluconazole for C. albicans were 0.16 and 0.02, respectively. The 50% inhibitory concentrations of MP for NIH 3T3 and Jurkat cells were approximately 100 times higher than the MIC for C. albicans ATCC 36232, indicating that MP had high selectivity between the fungal and mammalian cells. These results suggest that MP has great advantages in the development of antifungal agents.

3T3 Cells↗

Synthesis and structure-function study about tenecin 1, an antibacterial protein from larvae of Tenebrio molitor.

Tenecin 1, an inducible antibacterial protein secreted in the larvae of Tenebrio molitor, has a long N-terminal loop and common structural feature of insect defensin family corresponding to cysteine stabilized alpha/beta motif. To study the function of the N-terminal loop and disulfide bridges, N-terminal loop deleted tenecin 1, reduced tenecin 1 and tenecin 1 were chemically synthesized and their activities were measured. N-terminal loop deleted tenecin and reduced tenecin 1 did not show antibacterial activity. Circular dichroism (CD) spectroscopy data revealed that the alpha-helical content of tenecin 1 and the other proteins increased in the presence of 50% (v/v) trifluoroethanol (TFE) and the alpha-helical content of tenecin 1 was much higher than that of the other proteins in buffer with or without 50% (v/v) TFE. These results suggest that disulfide bridges are necessary for the activity structure and the N-terminal loop plays an important role in the increase of alpha-helix in the membrane mimetic environment and the activity.

Amino Acid Sequence↗