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Biomedical subjects

Y S Hong

Publications and source records attributed to Y S Hong.

At least 55 records · Page 3Linked to original sources
PubMed2000

IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis.

OBJECTIVE: To determine the clinical significance of IgG antibodies to type II collagen (CII) and to define any correlation of antibodies to CII with the inflammatory response in patients with rheumatoid arthritis (RA). METHODS: IgG antibodies to native human type II collagen (IgG anti-CII) were measured in sera and synovial fluid (SF) from patients with RA, patients with osteoarthritis (OA), and healthy controls by an improved ELISA. Demographic, clinical, and laboratory data including tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also obtained at the time of sampling in patients with RA. RESULTS: The median level and positivity for circulating IgG anti-CII were higher in patients with RA (n = 297) than patients with OA (n = 34) and healthy controls (n = 50) (p < 0.001). The titers of IgG anti-CII in SF were also higher in RA (n = 45) than in OA (n = 16) (p < 0.001). In paired samples, the levels of IgG anti-CII were significantly higher in SF compared to the sera in patients with RA (n = 45) (p < 0.001), but levels were not different in patients with OA (n = 16). Circulating IgG anti-CII converted from positive to negative in 13 patients (10.7%) and from negative to positive in 18 patients (14.8%) among 122 patients with RA in whom IgG anti-CII were monitored sequentially at a mean interval of 12.2 months. IgG anti-CII positive patients (n = 98) had shorter disease duration (p = 0.04) and less frequent deformity (p = 0.013), and higher median erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p < 0.001) than IgG anti-CII negative patients (n = 120). The levels of IgG anti-CII correlated with CRP (r = 0.270) and ESR (r = 0.253). CRP decreased significantly in patients (n = 13) who converted from IgG anti-CII positive to negative (p = 0.013). IgG anti-CII positive patients (n = 40) had higher levels of TNF-alpha and IL-6 than negative patients (n = 40) (p < 0.001). Levels of IgG anti-CII correlated well with TNF-alpha (r = 0.617) and IL-6 (r = 0.347). CONCLUSION: Increased IgG anti-CII in sera and SF in RA correlated directly with acute phase reactants and the proinflammatory cytokines TNF-alpha and IL-6. Our data suggest that IgG anti-CII could reflect inflammatory activity with a potential to destroy cartilage in the early stages of RA.

Acute-Phase Proteins↗
PubMed1999

INAF, a protein required for transient receptor potential Ca(2+) channel function.

The trp gene of Drosophila encodes a subunit of a class of Ca(2+)-selective light-activated channels that carry the bulk of the phototransduction current. Transient receptor potential (TRP) homologs have been identified throughout animal phylogeny. In vertebrates, TRP-related channels have been suggested to mediate "store-operated Ca(2+) entry," which is important in Ca(2+) homeostasis in a wide variety of cell types. However, the mechanisms of activation and regulation of the TRP channel are not known. Here, we report on the Drosophila inaF gene, which encodes a highly eye-enriched protein, INAF, that appears to be required for TRP channel function. A null mutation in this gene significantly reduces the amount of the TRP protein and, in addition, specifically affects the TRP channel function so as to nearly shut down its activity. The inaF mutation also dramatically suppresses the severe degeneration caused by a constitutively active mutation in the trp gene. Although the reduction in the amount of the TRP protein may contribute to these phenotypes, several lines of evidence support the view that inaF mutations also more directly affect the TRP channel function, suggesting that the INAF protein may have a regulatory role in the channel function.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Site-directed mutagenesis of human dihydrolipoamide dehydrogenase: role of lysine-54 and glutamate-192 in stabilizing the thiolate-FAD intermediate.

The roles of lysine-54 (K54) and glutamate-192 (E192) of human dihydrolipoamide dehydrogenase (E3) in stabilizing the thiolate-FAD intermediate during electron transfer were investigated by site-directed mutagenesis. Recombinant human E3s, wild-type, K54E, S53K54-K53S54 (SK-KS), and E192Q, were overexpressed, purified, and characterized. Only K54E and SK-KS E3s had about 25% less bound FAD compared to wild-type, implicating that K54 is crucial for the protein-FAD interaction. The specific activities of all mutant E3s were markedly decreased (<5% wild-type). In the case of K54E E3, the Km for lipoamide in the reverse reaction was increased by about twofold. Surprisingly, for both SK-KS and E192Q E3s, the Kms for both dihydrolipoamide (forward reaction) and lipoamide (reverse reaction) were markedly reduced. The catalytic rate constants (kcat/Km) for both reactions for SK-KS E3 were significantly lower than wild-type, indicating that K54 is crucial for the catalytic efficiency of the enzyme. Fluorescence spectral analyses showed that the FAD in E3s were reduced by the addition of dihydrolipoamide, and that its reoxidation by NAD+ in the mutant E3s was slower than wild-type E3. Interestingly, in K54E E3 dihydrolipoamide reduced FAD efficiently only when NAD+ was present, indicating that K54 stabilizes the thiolate-FAD interaction. The lack of the formation of thiolate-FAD intermediate in the absence of NAD+ in K54E E3 was also confirmed by CD spectra. The SK-KS mutation demonstrates that the correct sequence of residues is as critical as the nature of the amino acid residues. These results suggest that K54 plays an important role in stabilizing the thiolate-FAD intermediate during the electron transfer in the reaction, and E192 is involved in maintaining correct orientation of K54 during catalysis.

Base Sequence↗
PubMed1999

The inhibitory effects of lipoic compounds on mammalian pyruvate dehydrogenase complex and its catalytic components.

To examine the stereospecific effects of lipoic compounds on pyruvate metabolism, the effects of R-lipoic acid (R-LA), S-lipoic acid (S-LA) and 1,2-diselenolane-3-pentanoic acid (Se-LA) on the activities of the mammalian pyruvate dehydrogenase complex (PDC) and its catalytic components were investigated. Both S-LA and R-LA markedly inhibited PDC activity; whereas Se-LA displayed inhibition only at higher concentrations. Examination of the effects on the individual catalytic components indicated that Se-LA inhibited the pyruvate dehydrogenase component; whereas R-LA and S-LA inhibited the dihydrolipoamide acetyltransferase component. The three lipoic compounds lowered dihydrolipoamide dehydrogrenase (E3) activity in the forward reaction by about 30 to 45%. The kinetic data of E3 showed that both R-LA and Se-LA are used as substrates by E3 for the reverse reaction. Decarboxylation of [1-14C]pyruvate via PDC by cultured HepG2 cells was not affected by R-LA, but moderately decreased with S-LA and Se-LA. These findings indicate that (i) purified PDC and its catalytic components are affected by lipoic compounds based on their stereoselectivity; and (ii) the oxidation of pyruvate by intact HepG2 cells is not inhibited by R-LA. The later finding with the intact cells is in support of therapeutic role of R-LA as an antioxidant.

Acetyltransferases↗
PubMed1999

Sesquiterpene esters from Celastrus orbiculatus and their structure-activity relationship on the modulation of multidrug resistance.

Six new (1-6) and three known (7-9) sesquiterpene esters were isolated from the roots of Celastrus orbiculatus. The structures of the new compounds were elucidated as 1beta-acetoxy-6alpha-furoyloxy-9alpha-benzoyl oxydihydro-beta-agarofur an (1), 1beta-acetoxy-6alpha-benzoyloxy-9alpha-furoyloxydih ydro-beta-agarofur an (2), 1beta-acetoxy-6alpha, 9alpha-difuroyloxydihydro-beta-agarofuran (3), 1beta, 2beta-diacetoxy-6alpha-furoyloxy-9alpha-benzo yloxydihydro-beta-agarof uran (4), 1beta-acetoxy-2beta, 6alpha-difuroyloxy-9alpha-benzoyloxydihydro-beta -agarofuran (5), and 1beta-acetoxy-2beta,6alpha, 9alpha-tribenzoyloxydihydro-beta-agarofuran (6). Compounds 4, 5, and 7-9 were shown to be more active than verapamil in reversing vinblastine resistance in multidrug-resistant KB-V1 cells.

Cell Survival↗
PubMed1999

Pregnane glycoside multidrug-resistance modulators from Cynanchum wilfordii.

The methanol-soluble extracts of the roots of Cynanchum wilfordii showed a significant multidrug-resistance-reversing activity, and four known pregnane glycosides were isolated by bioassay-directed fractionation and separation. Their structures were identified as gagaminin 3-O-beta-D-cymaropyranosyl-(1-->4)-beta-D-oleandropyranosyl- (1-->4)-b eta-D-cymaropyranosyl-(1-->4)-beta-D-cymaropyranoside (1), wilfoside K1N (2), wilfoside C1N (3), and cynauricuoside A (4). In particular, compound 1, at a concentration level of 1 microM, was found to completely reverse the multidrug-resistance of KB-V1 and MCF7/ADR cells to adriamycin, vinblastine, and colchicine.

Antineoplastic Agents↗
PubMed1999

alpha-Glucosidase inhibitors from Commelina communis.

A methanolic extract of Commelina communis showed potent inhibitory activity against alpha-glucosidase. One pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP, 1) and four piperidine alkaloids, 1-deoxymannojirimycin (2), 1-deoxynojirimycin (3), alpha-homonojirimycin (4) and 7-O-beta-D-glucopyranosyl alpha-homonojirimycin (5) were isolated by bioassay-directed fractionation and separation. These compounds have been identified for the first time from Commelina communis, supporting the pharmacological basis of this plant that has been used as a traditional herbal medicine for the treatment of diabetes.

Alkaloids↗
PubMed1999

Indomethacin treatment decreases renal blood flow velocity in human neonates.

This study was designed to evaluate the effect of indomethacin (ID) on renal perfusion in 13 neonates with symptomatic patent ductus arteriosus (PDA). Serial blood flow velocity in the left renal artery was measured just before and at 10, 30, 45, 60, 75 and 90 min after ID administration. Serum creatinine (Cr), sodium (Na), and osmolarity were measured just before, at 12 and 24 h, and at 3 days after ID administration. Timed urine also was collected for measurement of amount, fractional excretion of Na (FE(Na)), and creatinine clearance (C(Cr)). ID decreased end-diastolic flow velocity of renal artery and increased Pourcelot's index, starting at 10 min and lasting for 75 min (p < 0.05). Serum Cr significantly increased at 12 h, and hourly urine output and C(Cr) decreased for 24 h. Serum Na and osmolarity decreased for a period of at least 3 days (p < 0.05). FE(Na) decreased at 12-24 h (p < 0.05). We conclude that ID treatment can induce significant renal dysfunction due to diminution of renal perfusion in human neonates.

Birth Weight↗
PubMed1999

Adult respiratory distress syndrome in systemic lupus erythematosus: causes and prognostic factors: a single center, retrospective study.

OBJECTIVES: To determine the causes and prognostic factors of Adult Respiratory Distress Syndrome (ARDS) in patients with systemic lupus erythematosus (SLE). METHODS: Among 544 Korean SLE patients, who were followed in the Lupus Clinic of the Catholic Medical Center from 1993 to 1997, patients diagnosed as ARDS were examined retrospectively. During the study period, non-SLE patients with ARDS were investigated and then compared to SLE patients with ARDS in terms of clinical variables. RESULTS: Nineteen patients with SLE were revealed to have a history of ARDS (3.5%) and 13 (68.4%) of 19 patients died. Death related to ARDS was found in 34.2% of all deaths (n=38) from SLE during the study period. The frequency and causes of ARDS were as follows; 9 sepsis or bacteremia (47.4%), 2 miliary tuberculosis (10.5%), 2 invasive pulmonary aspergillosis (10. 5%), 2 acute pulmonary alveolar hemorrhage syndrome (10.5%), 1 acute lupus pneumonitis (5.3%), 1 massive hemorrhage due to placenta previa (5.3%), 1 aspiration pneumonitis (5.3%), 1 disseminated intravascular coagulation associated with systemic vasculitis (5.3%). The main organisms in sepsis were gram negative bacilli (61.5%) The median steroid dose administered 1 month before ARDS was significantly higher in patients (n=13) with infectious ARDS compared to those (n=6) with ARDS due to other causes (P=0.038). Comparison of the laboratory and clinical variables between the survivors (n=6) and the deceased (n=13) showed that the survivors had lower SLAM indices at presentation (P=0.004) and APACHE (Acute Physiology, Age, Chronic Health Evaluation) III scores within 24 h after diagnosis of ARDS (P=0.024) than the deceased. The APACHE III scores correlated well with the SLAM indices (r=0.615, P=0.007). Non-SLE patients with ARDS during the study period were selected for comparison to SLE patients with ARDS. Age at the onset of ARDS was younger in SLE (n=19) compared to non-SLE (n=190) (P<0.001). Duration from ARDS onset to death was shorter in SLE patients (P<0. 001). The mortality from ARDS tended to be higher in SLE patients (P=NS). The first-day APACHE III score was significantly higher in deceased SLE patients (n=13) compared to deceased non-SLE patients (n=105) (P=0.001). CONCLUSIONS: ARDS was a common premortem event of SLE and showed a high fatality rate in SLE. The most common cause of ARDS in Korean patients with SLE was sepsis by gram negative bacilli. ARDS in SLE developed at a younger age, and progressed more rapidly compared to ARDS in general. The SLAM index and APACHE III score could be useful to predict the prognosis of ARDS in SLE.

APACHE↗
PubMed1999

Macroamylasemia in a patient with acute appendicitis: a case report.

Macroamylasemia is a condition of persistent, elevated serum amylase activity with no apparent clinical symptoms of a pancreatic disorder. In Korea, however, no such case has been reported to date. We report a case of a 17-year-old female diagnosed with macroamylasemia and acute appendicitis. One day earlier, she developed epigastric and right lower quadrant abdominal pain. She was characterized by high level of serum amylase, but normal lipase. Amylase isoenzyme analysis demonstrated increased fraction of salivary type and follow-up amylase level was persistently increased. Immunofixation disclosed the macroamylase binding with an immunoglobulin, consisting of IgA and kappa chain. The patient was treated by appendectomy, and the abdominal pain subsided.

Adolescent↗
PubMed1999

Hyperimmunoglobulin E-recurrent infection syndrome in a patient with juvenile dermatomyositis.

A 13-year-old girl presented with multiple skin abscesses. She was diagnosed as having juvenile dermatomyositis (DM) at the age of 7 years. She had suffered from recurrent skin infections, atypical pruritic dermatitis and pneumonia since the age of 8 years. Bacteriologic and fungal cultures for skin abscesses and oral mucosa were positive S. aureus and C. albicans, respectively. Chemotactic defect in peripheral blood neutrophils was observed. The level of serum IgE was markedly elevated, and anti-S.aureus specific IgE was found. A diagnosis of hyperimmunoglobulin E-recurrent infection syndrome (HIE) was made and she was successfully treated with surgical drainage and antibiotics. To our knowledge, this is the first case report of HIE in a patient with juvenile dermatomyositis.

Adolescent↗
PubMed1999

Nasal angiocentric lymphoma with hemophagocytic syndrome.

OBJECTIVES: Hemophagocytic syndrome (HS) is a fatal complication of nasal angiocentric lymphoma (AL) and difficult to distinguish from malignant histiocyosis. Epstein-Barr virus (EBV)-associated HS is frequently observed in lymphoma of T-cell lineage and EBV is highly associated with nasal AL. Clinicopathologic features of 10 nasal ALs with HS were reviewed to determine the clinical significance and the pathogenetic association with EBV. METHODS: Ten patients of HS were identified from a retrospective analysis of 42 nasal ALs diagnosed from 1987 to 1996. Immunohistochemical study and in situ hybridization were performed on the paraffin-embedded tumor specimens obtained from 10 patients. Serologic study of EBV-Ab was performed in 3 available patients. RESULTS: Five patients had HS as initial manifestation, 3 at the time of relapse and 2 during the clinical remission of AL. Four patients were treated by combination chemotherapy (CHOP) and others had only supportive care. The median survival of all patients with HS was 4.1 months (range 2 days-36.5 months) and all had fatal outcome regardless of the treatment-modality. All cases were positive for UCHL1 (CD45RO) and EBV by EBER in situ hybridization. The data of serologic tests indicated the active EBV infection. CONCLUSIONS: HS is a fatal complication of nasal AL and has a high association with EBV. Reactivation of EBV may contribute to HS and further investigation of predictive factors and effective treatment of HS should be pursued in the future.

Adult↗
PubMed1998

Polymorphism of the CYP1A1 and glutathione-S-transferase gene in Korean lung cancer patients.

The levels of expressions and catalytic activities of cytochrome P450 (CYP1A1) and glutathione-S-transferase class mu (GSTM1) enzymes in lungs and their metabolic balance may be an important determinant host factor underlying lung cancer. Genetic differences in metabolism, MspI restriction sites, Ile-Val polymorphism of CYP1A1 gene, and the null genotype of GSTM1 have been reported to be associated with susceptibility to lung cancer. The present studies were undertaken to establish frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Koreans, and to evaluate linkage disequilibrium of the genotypes associated with higher lung cancer risks among Koreans. GSTM1(-) genotype was found in 52% of control subjects, whereas it was found in 55% of lung cancer patients. The allelic variants in CYP1A1 were distributed differently in lung cancer patients and controls. The heterozygous genotype frequency of the MspI site in lung cancer patients (53%) was higher than in controls (49%). The frequency of Ile/Val genotype of CYP1A1 was low in lung cancer patients, which are mostly squamous cell carcinoma.

Adenocarcinoma↗
PubMed1998

Genomic structure of the regulatory region of the voltage-gated calcium channel alpha 1D.

In excitable and endocrine organs, calcium influxes through the L-type voltage-gated calcium channel (VGCC) which is composed of four (alpha 1, alpha 2, beta, and gamma) subunits. Temporal and spatial expression of calcium channel activity is regulated by the transcription of alpha 1 subunit. To elucidate the genomic organization of the VGCC alpha 1D subunit gene, a genomic clone was isolated from the human genomic library and its sequence was analyzed. A 12 kb genomic clone contained the 5'-flanking regulatory region and first two exons was selected and the initiation site for alpha 1D mRNA synthesis was examined by primer extension analysis. The major initiation site was found at the -523 NT position in the translation initiation site. The TATA box could not be found above the transcription initiation site. The CAT vector construct containing the 2.5 kb upstream region had high CAT activity on transfection to NG108-15 and PC12 cells, which confers the neuronal expression of the alpha 1D gene.

Amino Acid Sequence↗
PubMed1998

Mode of action of torilin in multidrug-resistant cancer cell lines.

The mechanism of action of multidrug-resistance reversing activity of torilin was studied. In vitro experiments for the accumulation and efflux of vinblastine clearly indicated that MDR reversing effects of torilin would directly be associated with the increase of the intracellular accumulation of anticancer drugs by blocking the drug efflux. Furthermore, torilin increased the membrane ATPase activity from KB-V1 cells, suggesting that torilin might function by inhibiting drug transport mediated by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC).

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.

Adult↗
PubMed1998

Inhibitory effect of calyculin A, a Ser/Thr protein phosphatase type I inhibitor, on renin secretion.

We have recently shown that several putative selective inhibitors of Ca2+-calmodulin-dependent myosin light chain kinase (MLCK), such as ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine], reversibly stimulate renin secretion [C. S. Park, S.-H. Chang, H. S. Lee, S.-H. Kim, J. W. Chang, and C. D. Hong. Am. J. Physiol. 271 (Cell Physiol. 40): C242-C247, 1996]. We hypothesized that Ca2+ inhibits renin secretion, via phosphorylation of 20-kDa myosin light chain (MLC20), by activating MLCK. In the present studies, we have investigated the types of protein phosphatase (PP) involved in the control of renin secretion through inhibition of MLC dephosphorylation using inhibitors of various types of serine/threonine-specific protein phosphatases. Cyclosporin A, a putative inhibitor of PP type 2 (calcineurin), was without effect. Calyculin A and okadaic acid, putative selective inhibitors of both PP type 1 (PP1) and type 2A (PP2A), significantly inhibited renin secretion under control conditions. Calyculin A had inhibitory effects at least 10-fold more potent than okadaic acid, suggesting that PP1, rather than PP2A, is involved in the control of renin secretion. Furthermore, calyculin A blocked the reversal of renin secretion preinhibited by raised intracellular Ca2+ concentrations in a concentration-dependent manner. Calyculin A (10(-6) M) significantly inhibited renin secretion stimulated by lowering intracellular Ca2+ concentrations and blocked the stimulatory effect of ML-9 on renin secretion. Taking all of these results into consideration, we hypothesize that dephosphorylation of MLC20 by Ca2+-independent PP1 stimulates renin secretion, whereas phosphorylation of MLC20 by Ca2+-calmodulin-dependent MLCK inhibits it. This hypothesized regulatory model of renin secretion predicts that the rate of renin secretion at a given time is determined by the ratio of phosphorylated to dephosphorylated MLC20, which is, in turn, determined by the dynamic balance between activity of MLCK and MLC phosphatase.

Animals↗