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Biomedical subjects

S Y Chung

Publications and source records attributed to S Y Chung.

At least 37 records · Page 2Linked to original sources
PubMed2001

Imaging findings of metastatic disease to the breast.

The purpose of this study was to evaluate imaging findings of metastatic disease to the breast. We analyzed 15 cases that had been previously examined by radiographic study (comprising a total of 11 mammograms, 13 ultrasounds and 3 chest CT). Primary malignancies included the following: 6 breast cancers, 5 stomach cancers, 2 melanomas, 1 cervical cancer, and 1 lung cancer. Radiologic findings were analyzed and the 15 cases were divided into two groups: hematogeneous and lymphangitic metastasis. Eleven cases were classified as lymphangitic metastasis (73.3%) and 4 cases were hematogeneous metastasis (26.7%). Multiple masses were shown in 13 cases (86.7%), and 12 cases displayed unilateral lesions (80%). There was no evidence of calcification. In the 11 cases with available mammogram, 7 cases (63.6%) revealed multiple masses with well-defined (2 cases, 28.6%) or ill-defined margin (5 cases, 71.4%) and 6 cases (54.5%) showed diffuse increased density and skin thickening. Among the 11 cases that revealed mass lesions on ultrasound, 2 cases showed a well-defined margin (18.2%) and 9 cases showed an ill-defined margin (81.8%). Posterior shadowing of the mass was seen in only 1 case. Four cases (36.3%) showed a minimal echogenic boundary around the mass. Eight cases showed diffuse skin thickening (53.3%). Three cases with chest CT showed multiple masses and/or diffuse skin and trabecular thickening of the breast. In conclusion, the characteristic imaging findings of metastatic disease to the breast are multiple ill-defined masses with a lack of desmoplastic reaction and no calcification, as compared to primary breast carcinoma. The diffuse lesions without evidence of breast mass on mammogram and US could be distinguishable from inflammatory carcinoma of breast origin.

Adult↗
PubMed2001

Dose-response assessment by a fuzzy linear-regression method.

Regression analysis has been used to characterize the relationship between an exposure dose and the incidence of an adverse health effect such as cancer. However, the regression rarely describes the true relationship due to uncertainties in dose-response data and relationships. Therefore, a method is developed to perform dose-response assessments by a fuzzy linear regression which explicitly exhibit these uncertainties. This method is applied to define the relationship between a particular nitrate dose to humans and its corresponding cancer risk.

Dose-Response Relationship, Drug↗
PubMed2000

Activation of c-Jun N-terminal kinase 1 (JNK1) in mistletoe lectin II-induced apoptosis of human myeloleukemic U937 cells.

Extracts of mistletoe (Viscum album var. coloratum) have been used for several decades as an anticancer immunomodulating agent in clinical fields. However, the mechanism by which the plant extracts kill tumor cells has remained elusive. We investigated the direct effects of beta-galactoside- and N-acetyl-d-galactosamine-specific mistletoe lectin II in inducing apoptotic death of U937 cells. Three distinct components of mistletoe, including beta-galactoside- and N-acetyl-D-galactosamine-specific lectin II (60 kDa), polysaccharides, and viscotoxin (5 kDa), induced apoptotic cell death, characterized by DNA ladder pattern fragmentation of U937 cells at 12 hr after treatment. Consistent with apoptosis of the cells, mistletoe extracts markedly increased the phosphotransferase activity of c-Jun N-terminal kinase 1 (JNK1)/stress-activated protein kinase (SAPK) in U937 cells. Among the three components, lectin II was the most potent in inducing apoptosis as well as JNK1 activation of U937 cells in a dose- and time-dependent manner. Catalytic activation of JNK1 induced by mistletoe lectin II was inhibited by the addition of peptide aC-DEVD-CHO, but not by aC-YVAD-CHO. In addition, mistletoe lectin II induced apoptosis in a variety of cell types including Jurkat T cells, RAW 264.7 cells, HL-60 cells, DLD-1 cells, and primary acute myelocytic leukemic cells.

Apoptosis↗
PubMed2000

Identification of p53 gene mutations in breast cancers and their effects on transcriptional activation function.

Somatic mutations in the p53 tumor suppressor gene are the most common genetic alterations found in human malignancies. In the present study, we studied 36 primary human breast carcinomas, using a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing analysis of exons 2 through 9 for the presence of p53 gene mutations. Six of 36 (17%) breast cancers contained mutations within the core domain of the p53 protein responsible for sequence-specific DNA binding (codons 102-292); all 5 missense mutations clustered between codons 240 and 291 (codons 240, 243, 250, 285, and 291), whereas one nonsense mutation occurred at codon 199. By using recombinant PCR in vitro mutagenesis, we introduced point mutations at codons 199 from Gly to stop (gly199stop), 240 from Ser to Ile (ser240Ile), 250 from Pro to Ala (pro250ala), 285 from Glu to Lys (glu285lys), and 291 from Lys to Asn (lys291asn), and all the p53 sequences were subcloned into the CMVneoBam vector under the control of the cytomegalovirus (CMV) promoter. To test whether the mutants p53 were functionally wild-type (wt) or mutant, we transfected them to p53-null Saos-2 cells with a reporter plasmid containing a p53-responsive element, and performed chloramphenicol acetyltransferase (CAT) assay. Transient CAT assay for transcriptional activation revealed that one group, including gly199stop, ser240ile, glu285lys, and lys291asn, abolished the transcriptional activity, whereas the other group, including pro250ala, retained stronger transcriptional transactivation activity than that of wt p53.

Adult↗
PubMed2000

Activation of caspase cascades in Korean mistletoe (Viscum album var. coloratum) lectin-II-induced apoptosis of human myeloleukemic U937 cells.

Mistletoe lectins are of high biological activity and exert cytotoxic effects. We have previously shown that Korean mistletoe, Viscum album var. coloratum, lectin-II specifically induces apoptotic cell death in cancer cells, not normal lymphocytes. The destructive mechanism by mistletoe lectins on tumor cells was mediated by activation of c-JUN N-terminal kinase (JNK)/stress-activated protein kinase. Herein, we investigated the involvement of caspase cascade and its proteolytic cleavage effects on biosubstrates of human myeloleukemic U937 cells by D-galactoside and N-acetyl-galactosamine-specific Korean mistletoe lectin-II. Mistletoe lectin-II induced ladder pattern DNA fragmentation and activation of caspase-3, -8, and -9 of U937 cells, but not caspase-1 protease, in a time- and dose-dependent manner. Consistent with catalytic activation of protease, both poly(ADP-ribose) polymerase (PARP) and protein kinase C-delta (PKC-delta) are also cleaved in mistletoe lectin-II-treated U937 cells. An inhibitor of caspase-3-like protease, DEVD-CHO peptide, significantly inhibited mistletoe lectin-II-induced apoptosis, PARP cleavage, and fragmentation of DNA. These results provide the evidence that Korean mistletoe lectin-II induces apoptotic death of U937 cells via activation of caspase cascades.

Adjuvants, Immunologic↗
PubMed2000

The effects of roasting on the allergenic properties of peanut proteins.

BACKGROUND: Because of the widespread use of peanut products, peanut allergenicity is a major health concern in the United States. The effect or effects of thermal processing (roasting) on the allergenic properties of peanut proteins have rarely been addressed. OBJECTIVE: We sought to assess the biochemical effects of roasting on the allergenic properties of peanut proteins. METHODS: Competitive inhibition ELISA was used to compare the IgE-binding properties of roasted and raw peanut extracts. A well-characterized in vitro model was used to test whether the Maillard reaction contributes to the allergenic properties of peanut proteins. The allergic properties were measured by using ELISA, digestion by gastric secretions, and stability of the proteins to heat and degradation. RESULTS: Here we report that roasted peanuts from two different sources bound IgE from patients with peanut allergy at approximately 90-fold higher levels than the raw peanuts from the same peanut cultivars. The purified major allergens Ara h 1 and Ara h 2 were subjected to the Maillard reaction in vitro and compared with corresponding unreacted samples for allergenic properties. Ara h 1 and Ara h 2 bound higher levels of IgE and were more resistant to heat and digestion by gastrointestinal enzymes once they had undergone the Maillard reaction. CONCLUSIONS: The data presented here indicate that thermal processing may play an important role in enhancing the allergenic properties of peanuts and that the protein modifications made by the Maillard reaction contribute to this effect.

Allergens↗
PubMed2000

A nucleoside-nucleotide mixture may reduce memory deterioration in old senescence-accelerated mice.

We investigated the effects of a mixture of dietary nucleosides and nucleotides (NS + NT) on memory in 1- and 7-mo-old senescence-accelerated mice (SAM). Memory retention was studied with passive avoidance (step-through) and active avoidance (shuttle) tests. For 14 wk, mice in the control groups were fed a 20 g of casein/100 g diet, whereas the NS + NT groups were fed this diet supplemented with a 0.5 g of NS + NT mixture/100 g. All mice were killed at wk 14, and we studied the brain histopathology. Lipofuscin, monovacuoles and multiple vacuoles of various brain regions were measured. Body weight, food intake and ambulatory activity did not differ between the control and NS + NT groups. In old mice, the time of passive avoidance was significantly higher in the NS + NT group than in the control group at d 1 and 7 (P: < 0.05). However, such an effect of NS + NT was not observed in young mice. In the active avoidance test, the incidence of successful avoidance in old mice was higher in the NS + NT group than in the control group at d 1 and 2 (P: < 0.05). The percentages of specific brain cells containing lipofuscin were lower in NS + NT groups than in the control groups in both young and old mice (P: < 0.05). The number of monovacuoles and multiple vacuoles in specific brain regions tended to be lower (P: = 0.1-0.25) in NS + NT than in control groups, with significant differences in the microvacuoles of the middle cortex of young mice and in the multiple vacuoles in the hind cortex of old mice (P: < 0. 05). These results suggest that increased dietary NS + NT may be associated with decreases in the age-induced deterioration of brain morphology and certain memory tasks.

Age Factors↗
PubMed2000

Marked hippocampal neuronal damage without motor deficits after mild concussive-like brain injury in apolipoprotein E-deficient mice.

Of various biological factors, only allele epsilon 4 of apolipoprotein E (apoE, protein; APOE4, gene) has been thus far suggested as a major determinant of genetic risk for sporadic and late-onset familial Alzheimer's disease (AD). Environmental influences such as lack of education, traumatic brain injury, oxidative stress, environmental toxins, hormonal imbalances, and alterations in immune or inflammatory responses may also contribute to the pathogenesis of AD. Thus genetic susceptibility and environmental risk factors may have synergistic effects on the development of AD. The purpose of present report was to assess whether the gene (APOE) and the environmental risk factor (traumatic brain injury) could interact in hippocampal neuronal degeneration. We investigated the histopathological changes of hipoccampal regions after mild concussive-like brain injury without motor deficits in apoE-deficient mice using the recently described novel weight-drop device. Control mice revealed minimal neurodegenerative changes limited to CA2 and CA3, while apoE-deficient mice showed widespread neuronal degeneration throughout hippocampal subfields and part of dentate gyrus. We also observed widespread glial fibrillary acidic protein (GFAP) immunoreactivity throughout the hippocampus, which was more intense in apoE-deficient mice. The results of this study indicate that even very mild traumatic brain injury could result in widespread hippocampal damage in apoE-deficient mice. This again supports the hypothesis that apoE might play a neurotrophic or neuroprotective function in the central nervous system.

Alzheimer Disease↗
PubMed2000

Correlation of aging and smoking with air trapping at thin-section CT of the lung in asymptomatic subjects.

PURPOSE: To assess the frequency and degree of air trapping at thin-section computed tomography (CT) of the lung in relation to age and smoking history in asymptomatic subjects. MATERIALS AND METHODS: Thin-section CT of the lung was performed prospectively at end inspiration and end expiration in 82 subjects (27 smokers, 55 nonsmokers) without any history of pulmonary diseases and without present pulmonary symptoms. The frequency and degree of air trapping were evaluated according to age and smoking status. RESULTS: The overall frequency of air trapping was 52% (43 of 82 subjects, kappa = 0.72). Air trapping was found in three of 13 (23%), seven of 17 (41%), nine of 18 (50%), 11 of 17 (65%), and 13 of 17 (76%) subjects aged 21-30, 31-40, 41-50, 51-60, and greater than or equal to 61 years, respectively. The frequency of air trapping increased with age (P < .05). The degree of air trapping had a significant correlation with age (r = 0.523, P < .001) and was higher in smokers with a smoking history of more than 10 pack-years (P < .05). CONCLUSION: Air trapping was found in approximately 50% of asymptomatic subjects. The frequency of air trapping increased with age, and its severity increased with age and smoking.

Adult↗
PubMed2000

LPS induces direct death of IFN-gamma primed murine embryonic hepatocyte, BNL CL2 cells in a TNF-alpha independent manner.

Although it has been well known that the role of LPS on liver damage is mediated through TNF-alpha, the mechanism by which LPS modulates the cytotoxicity of IFN-gamma on hepatocytes has not yet been clearly demonstrated. Here, we demonstrate that IFN-gamma mediated apoptosis in murine embryonic hepatocyte BNL CL2 cells is potentiated by the addition of LPS (0.5 microg/ml). Consistently, LPS markedly increases the catalytic activity of caspase 3-like protease but not caspase 1-like protease in IFN-gamma treated cells. In addition, TNF-alpha alone does not affect cell viability but rather it potentiates the cytotoxic effect of IFN-gamma on BNL CL2 cells. However, the cell viability of IFN-gamma/LPS treated cells is affected by the addition of polymyxin B but not by TNF binding protein I (TNF-BPI). These data suggest that the lipid moiety of LPS may mediate direct cytotoxicity of BNL CL2 cells in a TNF-alpha independent manner.

Animals↗
PubMed1999

The methanol extract of Spiraea prunifolia var. simpliciflora root inhibits the generation of nitric oxide and superoxide in RAW 264.7 cells.

It is well established that nitric oxide (NO) and superoxide radicals play pivotal roles in the pathogenesis of inflammatory diseases and fever. This study is undertaken to address whether the methanol extract of Spiraea prunifolia var. simpliciflora root, a traditional medicine as an antipyretic, modulates the generation of NO and superoxide in IFN-gamma primed or polymyristic acetate (PMA) stimulated RAW 264.7 cells, respectively. The generation of NO as well as the expression of inducible nitric oxide synthase (iNOS) protein from IFN-gamma primed RAW 264.7 cells is markedly decreased by the methanol extract in a dose dependent manner. However, the methanol extract does not affect the viability of RAW 264.7 cells, as assessed by methylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. In addition, the methanol extract suppresses the generation of superoxide in PMA-stimulated RAW 264.7 cells in a dose and a time dependent manner. Taken together, anti-pyretic effects of Spiraea prunifolia var. simpliciflora root extract could result from direct suppression of NO and decreased superoxide generation.

Analgesics, Non-Narcotic↗
PubMed1999

Validation of NMR side-chain conformations by packing calculations.

The precision and accuracy of protein structures determined by nuclear magnetic resonance (NMR) spectroscopy depend on the completeness of input experimental data set. Typically, rather than a single structure, an ensemble of up to 20 equally representative conformers is generated and routinely deposited in the Protein Database. There are substantially more experimentally derived restraints available to define the main-chain coordinates than those of the side chains. Consequently, the side-chain conformations among the conformers are more variable and less well defined than those of the backbone. Even when a side chain is determined with high precision and is found to adopt very similar orientations among all the conformers in the ensemble, it is possible that its orientation might still be incorrect. Thus, it would be helpful if there were a method to assess independently the side-chain orientations determined by NMR. Recently, homology modeling by side-chain packing algorithms has been shown to be successful in predicting the side-chain conformations of the buried residues for a protein when the main-chain coordinates and sequence information are given. Since the main-chain coordinates determined by NMR are consistently more reliable than those of the side-chains, we have applied the side-chain packing algorithms to predict side-chain conformations that are compatible with the NMR-derived backbone. Using four test cases where the NMR solution structures and the X-ray crystal structure of the same protein are available, we demonstrate that the side-chain packing method can provide independent validation for the side-chain conformations of NMR structures. Comparison of the side-chain conformations derived by side-chain packing prediction and by NMR spectroscopy demonstrates that when there is agreement between the NMR model and the predicted model, on average 78% of the time the X-ray structure also concurs. While the side-chain packing method can confirm the reliable residue conformations in NMR models, more importantly, it can also identify the questionable residue conformations with an accuracy of 60%. This validation method can serve to increase the confidence level for potential users of structural models determined by NMR.

Animals↗
PubMed1999

Identification of two important heme site residues (cysteine 75 and histidine 77) in CooA, the CO-sensing transcription factor of Rhodospirillum rubrum.

The CO-sensing mechanism of the transcription factor CooA from Rhodospirillum rubrum was studied through a systematic mutational analysis of potential heme ligands. Previous electron paramagnetic resonance (EPR) spectroscopic studies on wild-type CooA suggested that oxidized (FeIII) CooA contains a low-spin heme with a thiolate ligand, presumably a cysteine, bound to its heme iron. In the present report, electronic absorption and EPR analysis of various substitutions at Cys residues establish that Cys75 is a heme ligand in FeIII CooA. However, characterization of heme stability and electronic properties of purified C75S CooA suggest that Cys75 is not a ligand in FeII CooA. Mutational analysis of all CooA His residues showed that His77 is critical for CO-stimulated transcription. On the basis of findings that H77Y CooA is perturbed in its FeII electronic properties and is unable to bind DNA in a site-specific manner in response to CO, His77 appears to be an axial ligand to FeII CooA. These results imply a ligand switch from Cys75 to His77 upon reduction of CooA. In addition, an interaction has been identified between Cys75 and His77 in FeIII CooA that may be involved in the CO-sensing mechanism. Finally, His77 is necessary for the proper conformational change of CooA upon CO binding.

Amino Acid Substitution↗
PubMed1999

Kleisli: a new tool for data integration in biology.

One of the central problems in bioinformatics is data retrieval and integration. The existing biological databases are geographically distributed across the Internet, complex and heterogeneous in data types and data structures, and constantly changing. With the current rapid growth of biomedical data, the challenge is how large volumes of data retrieved from multiple databases can be transformed and integrated automatically and flexibly. This article describes a powerful new tool, the Kleisli system, for complex queries across multiple databases and data integration.

Computational Biology↗
PubMed1999

Allergenicity of Maillard reaction products from peanut proteins.

It is known that peanut allergy is caused by peanut proteins. However, little is known about the impact of roasting on the allergenicity of peanuts. During roasting, proteins react with sugars to form Maillard reaction products, which could affect allergenicity. To determine if the Maillard reaction could convert a nonallergenic peanut protein into a potentially allergenic product, nonallergenic lectin was reacted with glucose or fructose at 50 degrees C for 28 days. Browning products from heat-treated peanuts were also examined. The products were analyzed in immunoblot and competitive assays, using a pooled serum (i.e., IgE antibodies) from patients with peanut anaphylaxis. Results showed that the products were recognized by IgE and had an inhibitory effect on IgE binding to a peanut allergen. Thus, the findings suggest that these Maillard reaction products are potentially allergenic and indicate the need to verify whether the Maillard reaction products formed in peanuts during roasting increase their allergenicity.

Arachis↗
PubMed1999

Pharmacokinetics of a new proton-pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with streptozotocin-induced diabetes mellitus.

Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, were investigated after intravenous and oral administration of the drug (50 mg kg(-1)) to control rats and to rats with streptozotocin-induced diabetes mellitus (SIDM). After intravenous administration of YJA-20379-8 to SIDM rats, plasma concentrations of the drug were significantly higher and this resulted in a significantly greater AUC (area under the concentration-time curve; 2520 +/- 366 compared with 1870+/-272 microg min mL(-1)). This was because of significantly slower clearance (CL; 19.5+/-2.88 compared with 27.2+/-3.93 mL min(-1) kg(-1)) in SIDM rats. The significantly slower metabolism of YJA-20379-8 in SIDM rats was confirmed by an in-vitro tissue metabolism study; the amounts of YJA-20379-8 remaining in the liver (27.1+/-5.19 compared with 18.9+/-8.24 microg(g tissue)(-1)) were significantly greater after 30-min incubation of the drug (50 microg) with supernatant fractions obtained from the tissues by centrifugation at 9000 g. After oral administration of YJA-20379-8 to SIDM rats the plasma concentrations of the drug were significantly lower and this resulted in significantly smaller AUC (128+/-31.0 compared with 219+/-45.6 microg min mL(-1)). This was because of reduced gastrointestinal absorption of YJA-20379-8 in SIDM rats; the amounts of the oral dose recovered as unchanged drug from the entire gastrointestinal tract after 24h were significantly greater (32.9 compared with 19.2%) in SIDM rats. The tissue distribution of YJA-20379-8 was not affected by SIDM.

Administration, Oral↗