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Biomedical subjects

D-H Kim

Publications and source records attributed to D-H Kim.

14 recordsLinked to original sources

Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history.

BACKGROUND: To investigate the clinicopathological significance of promoter methylation of the helicase-like transcription factor (HLTF) in primary gastric cancer. PATIENTS AND METHODS: Two-hundred fifty six patients participated in this study. Methylation status of HLTF gene was evaluated in fresh-frozen tissues by the methylation-specific polymerase chain reaction. All statistical analyses were two-sided, with a 5% type I error rate. RESULTS: Aberrant methylation of HLTF was found in 98 (38%) of 256 gastric cancer patients. HLTF methylation was significantly associated with a family history in the early stages of gastric cancer, regardless of histologic types. In intestinal-type cases, HLTF methylation occurred in 15 (56%) of 27 patients with family histories, and in 26 (31%) of 85 patients without family histories (P = 0.02). In diffuse-type cases, patients with family histories were also found to exhibit a higher prevalence of HLTF methylation than those without family histories (61% vs. 34%; P = 0.009). HLTF methylation in both of the histologic types occurred in about 70-90% of the early stage cases in which the patient had a family history and in 15-30% of cases in which the patient did not have a family history. In our multivariate logistic regression analysis, the stage 1-2 cases with family histories were determined to carry a higher risk of HLTF methylation than did the stage 3-4 cases without family histories in both the intestinal-type (OR = 6.01, 95% CI = 1.20-30.01, P = 0.02) and the diffuse-type cancers (OR = 8.25, 95% CI = 1.67-40.86, P = 0.009). CONCLUSIONS: These results suggest that HLTF methylation may play a crucial role in the early stages of gastric carcinogenesis in patients with family histories and may be a valuable susceptible marker for the risk of gastric cancer in individuals with family histories.

Aged↗

Typical and atypical trafficking pathways of Ad5 penton base recombinant protein: implications for gene transfer.

The adenovirus (Ad) penton base protein facilitates viral infection by binding cell surface integrins, triggering receptor-mediated endocytosis and mediating endosomal penetration. Given these multiple functions, recombinant penton base proteins have been utilized as non-viral vehicles for gene transfer by our lab and others. Although we have previously demonstrated that penton base-derived vectors undergo integrin-specific binding and cell entry, less than desirable levels of gene expression have led us to re-evaluate the recombinant penton base as an agent for gene delivery. To do so, we have examined here the intracellular trafficking of an Ad serotype 5 (Ad5) recombinant penton base protein (PB). Here, we not only observed that PB utilizes a similar, typical trafficking pathway of whole Ad, but also found that PB entered HeLa cells through pathways not yet identified as contributing to cell entry by the whole virus. We show by high-resolution confocal microscopy and biochemical methods that binding to alphav-integrins is a requirement for cell entry, but that early internalization stages did not substantially pass through clathrin-positive and early endosomal compartments. Moreover, a subpopulation of internalized protein localized with caveolin-positive compartments and Golgi markers, suggesting that a certain percentage of proteins pass through non-clathrin-mediated pathways. Similar to the virus, trafficking toward the nucleus was affected by disruption of microtubules and dynein. The majority of penton base molecules avoided the lysosome while facilitating early vesicle release of low molecular weight dextran molecules. In further support of a vesicle escape capacity, a subpopulation of internalized penton base appeared to enter the nucleus, as observed by high-resolution confocal microscopy and cell fractionation. As a confirmation of these findings, we demonstrate that a recombinant penton base facilitated cytosolic entry of an siRNA molecule as observed by RNA interference of a marker gene. Based on our findings here, we suggest that whereas soluble penton base proteins may enter cells through clathrin- and non-clathrin-mediated pathways, vesicle escape and nuclear delivery appear to be supported by a clathrin-mediated pathway. As our previous efforts have focused on utilizing recombinant penton base proteins as delivery agents for therapeutics, these findings allow us to evaluate the use of the penton base as a cell entry and intracellular trafficking agent, and may be of interest concerning the development of vectors for efficient delivery of therapeutics to cells.

Capsid Proteins↗

Pathogenicity of Edwardsiella tarda to olive flounder, Paralichthys olivaceus (Temminck & Schlegel).

The LD50 and cytotoxic and enzymatic activities of both cells and extracellular products (ECPs) of eight Edwardsiella tarda strains were determined and their bacterial superoxide dismutase gene (sodB) and catalase gene (katB) were sequenced. Strains were also examined for their ability to resist the immune responses of olive flounder, Paralichthys olivaceus. LD50 values of strains (FSW910410, KE1, 2, 3, 4, 5 and 6) in olive flounder ranged between 10(2.5) and 10(5.3) cfu (colony forming units) per fish. Unlike the avirulent strain SU100 (LD50>or=10(7)), all pathogenic strains were able to survive in flounder serum and head kidney leucocytes (except for KE2). The virulent strains possessed type I sodB and katB, whereas SU100 had type II sodB but not katB. However, there was no difference between avirulent and virulent strains in haemolytic and cytotoxic activities. The results of this study demonstrated that the ability of E. tarda to resist complement activity and phagocytosis is conferred by its superoxide dismutase and catalase, which thus play an essential role in the pathogenicity of this bacterium. In addition genotyping of sodB and kat B proved to be a very useful tool to distinguish virulent from avirulent strains.

Animals↗

Ruptured spinal dermoid cyst with disseminated intracranial fat droplets.

Fat droplets in the cerebrospinal fluid (CSF) is a well-known complication of ruptured intracranial dermoid tumours. We report an unusual case of a ruptured spinal dermoid tumour. MR images showed a tethered spinal cord and an intramedullary fat-containing mass. Fat droplets were revealed in the ventricles and the cisternal spaces on brain CT and brain MR. In the English literature, a ruptured spinal dermoid tumour accompanying a tethered spinal cord is extremely rare.

Adult↗

Magnetic microstructures and their dynamics studied by X-ray microscopy.

Full-field soft X-ray microscopy in combination with X-ray magnetic circular dichroism as contrast mechanism is a powerful technique to image with elemental specificity magnetic nanostructures and multilayered thin films at high lateral resolution down to 15nm by using Fresnel zone plates as X-ray optical elements. Magnetization reversal phenomena on a microscopic level are studied by recording the images in varying external magnetic fields. Local spin dynamics at a time resolution below 100ps can be addressed by engaging a stroboscopic pump-and-probe scheme taking into account the time pattern of synchrotron storage rings. Characteristic features of magnetic soft X-ray microscopy are reviewed and an outlook into future perspectives with regard to increased lateral and temporal resolution is given.

Journal Article↗

Genetic variation in Echinacea angustifolia along a climatic gradient.

BACKGROUNDS AND AIMS: Echinacea angustifolia is a widespread species distributed throughout the Great Plains region of North America. Genetic differentiation among populations was investigated along a 1500 km north-south climatic gradient in North America, a region with no major geographical barriers. The objective of the study was to determine if genetic differentiation of populations could be explained by an isolation-by-distance model or by associations with climatic parameters known to affect plant growth and survival. METHODS: Historical climatic data were used to define the nature of the climatic gradient and AFLP markers were used to establish patterns of population genetic differentiation among ten Echinacea populations collected from North Dakota to Oklahoma. A total of 1290 fragments were scored using six EcoRI/MseI and three PstI/MseI primer combinations. Assessment of the correlation between climatic, genetic and geographic distances was assessed by Mantel and partial Mantel tests. KEY RESULTS: PstI/MseI combinations produced significantly fewer fragments, but a larger percentage was unique compared with EcoRI/MseI markers. Using estimates of F(ST), populations in Oklahoma and southern Kansas were identified as the most divergent from the other populations. Both the neighbour-joining tree and principal co-ordinate analysis clustered the populations in a north-south spatial orientation. About 60% of the genetic variation was found within populations, 20% among populations and the remaining 20% was partitioned among groups that were defined by the topology of the neighbour-joining tree. Significant support was found for the isolation-by-distance model independent of the effects of annual mean precipitation, but not from annual mean temperature and freeze-free days. CONCLUSIONS: Echinacea angustifolia populations exhibit genetic divergence along a north-south climatic gradient. The data support an isolation-by-distance restriction in gene flow that is independent of annual mean precipitation.

Adaptation, Physiological↗

Spin-glass phase transition on scale-free networks.

We study the Ising spin-glass model on scale-free networks generated by the static model using the replica method. Based on the replica-symmetric solution, we derive the phase diagram consisting of the paramagnetic (P), ferromagnetic (F), and spin glass (SG) phases as well as the Almeida-Thouless line as functions of the degree exponent lambda, the mean degree K, and the fraction of ferromagnetic interactions r. To reflect the inhomogeneity of vertices, we modify the magnetization m and the spin-glass order parameter q with vertex- weights. The transition temperature T(c) (T(g)) between the P-F (P-SG) phases and the critical behaviors of the order parameters are found analytically. When 2 1/2, while it is in the SG phase at r=1/2. m and q decay as power-laws with increasing temperature with different lambda-dependent exponents. When lambda>3, the T(c) and T(g) are finite and related to the percolation threshold. The critical exponents associated with m and q depend on lambda for 3<lambda<5 (3<lambda<4) at the P-F (P-SG) boundary.

Journal Article↗

Characterization of the Phase II metabolites of rutaecarpine in rat by liquid chromatography-electrospray ionization-tandem mass spectrometry.

From the authors' previous studies on the Phase I metabolism of rutaecarpine, nine metabolites formed were identified as products of hydroxylation on the aromatic rings in rat liver microsomes. In order to determine the possible metabolic fate of rutaecarpine, the Phase II metabolites of rutaecarpine were characterized in the present study by using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS). When male Sprague-Dawley rats were treated intravenously with 4 mg kg(-1) rutaecarpine, 16 different Phase I and II metabolites were identified in urine including four sulfate and four glucuronide conjugates. Phase I metabolites of rutaecarpine were identified as four mono-hydroxylated metabolites (M2-5) and four isobaric di-hydroxylated metabolites (M6-9). These metabolites were identical to the in vitro metabolites except one, which was hydroxylated in the aliphatic moiety. In addition, Phase II metabolites were identified as conjugated with sulfate (S1-4) and glucuronide (G1-4). In faeces, 11 different metabolites were identified. The metabolites M8 and glucuronide conjugated (G1-4) were not detected. Structures of all metabolites were confirmed with CID fragmentation spectra of MS(2), MS(3) and retention times by LC/ESI-MS.

Alkaloids↗

Estimated daily intakes of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ) antioxidants in Korea.

The study was conducted to establish the estimated daily intake (EDI) of antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ) in Korea. The EDIs were obtained from two sources. One of the estimations was based on the analytical determination of BHA, BHT and TBHQ in 12 food categories (ten food categories for TBHQ) and on individual dietary intake data obtained from the National Health and Nutrition Survey in 1998 (n=11 525, age > 1 year). The other EDIs of BHA, BHT and TBHQ were based on the maximum permitted levels specified in national food standards in Korea and on individual dietary intake data obtained from the National Health and Nutrition Survey in 1998 (n=11 525, age > 1 year). To establish the EDIs based on the analytical determination and on individual dietary intake data, 133 food samples in 12 food categories were selected from the foods considered to be representative sources of BHA, BHT and TBHQ in the Korean diet. Selected samples were analysed by GC with FID. BHA was not detected in any of the samples analysed. BHT and TBHQ were detected in the samples, but the levels were significantly lower than their maximum limits. The EDIs1 of BHT, and TBHQ for average consumers were 0.0156(-3), and 0.0012(-3) mg kg(-1) body weight bw day(-1) and as a proportion of the ADI were 0.0052 and 0.0002%, respectively. For 95th percentile consumers, the EDIs of BHT and TBHQ were 0.0080 and 0.0006 mg kg(-1) bw day(-1), and as a proportion of the ADI were 2.67 and 0.09%, respectively. EDIs for BHA, BHT and TBHQ based on the maximum permitted levels and on individual dietary intake data were 0.04, 0.04 and 0.04 mg kg(-1) bw day(-1), respectively. The EDIs of BHA, BHT and TBHQ for average consumers ranged from 6.00 to 14.42% of the ADI of each antioxidant. According to these results, the EDIs of BHA, BHT and TBHQ in Korea were significantly lower than ADI of these antioxidants established by the JECFA.

Antioxidants↗

Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis B.

The aim of this study was to determine whether the changing patterns of quantitative hepatitis B e antigen (HBeAg) levels by serial monitoring could predict HBeAg seroconversion and viral breakthrough during lamivudine therapy. We retrospectively analysed 340 HBeAg positive naive chronic hepatitis B patients treated with lamivudine. The mean duration of lamivudine therapy was 18.7 (range 6-56) months. The changing patterns and reduction rates of pretreatment HBeAg levels by serial monitoring were categorized into three groups: Decrescendo group (n = 195), Decrescendo-crescendo group (n = 65) and no changing or fluctuating group (n = 80). Of 109 patients who had achieved HBeAg seroconversion, 105 (96.3%) were included in the decrescendo group. The decrescendo group, pretreatment quantitative HBeAg levels, alanine aminotransferase levels, and the duration of lamivudine therapy were independent predictive factors for HBeAg seroconversion. Of 82 patients who had viral breakthrough, 53 (64.6%) were in the decrescendo-crescendo group and 21 (25.6%) were in the no changing or fluctuating group. The only predictive factor for viral breakthrough was the changing patterns of quantitative HBeAg levels, especially, the decrescendo-crescendo group and the no changing or fluctuating group. The mean time of turning points in the decrescendo-crescendo group was 7.1 months earlier than the mean time of viral breakthrough (9.0 months vs 16.5 months). Therefore, the changing patterns of quantitative HBeAg levels by serial monitoring during lamivudine therapy may allow not only the prediction of treatment responses, but also an early recognition of a viral breakthrough.

Adolescent↗

Bacterial enteritis and the development of the larval digestive tract in olive flounder, Paralichthys olivaceus (Temminck & Schlegel).

Three bacterial isolates obtained from diseased olive flounder larvae, Paralichthys olivaceus, were identified as Vibrio ichthyoenteri based on the results of phenotypic characterization and 16S rRNA gene sequencing studies. Bacterial enteritis was reproduced in 16 and 22 days post-hatch (dph) larvae by administering brine shrimp nauplii, Artemia salina, dosed with the environmental isolates and reference strains of V. ichthyoenteri. To investigate the effect of the disease on development of the stomach, a pepsin activity assay and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression of the pepsinogen gene were performed. Expression of olive flounder pepsinogen was detected from 30-dph larvae and the increased level of pepsin activity coincided with reduced susceptibility to the disease. Growth rates of V. ichthyoenteri, V. anguillarum and Edwardsiella tarda were tested in artificial stomach conditions using HCl and porcine pepsin. All the strains of V. ichthyoenteri were inhibited by low pH conditions which corresponded with an increase in pepsin levels. This suggests that differentiation of the stomach in olive flounder larvae and juveniles, an essential physiological development, also provides the host with a non-immunological defence mechanism.

Amino Acid Sequence↗

Genetic diversity of Echinacea species based upon amplified fragment length polymorphism markers.

The taxonomy of Echinacea is based on morphological characters and has varied depending on the monographer. The genus consists of either nine species and four varieties or four species and eight varieties. We have used amplified fragment length polymorphisms (AFLP) to assess genetic diversity and phenetic relationships among nine species and three varieties of Echinacea (sensu McGregor). A total of 1086 fragments, of which approximately 90% were polymorphic among Echinacea taxa, were generated from six primer combinations. Nei and Li's genetic distance coefficient and the neighbor-joining algorithm were employed to construct a phenetic tree. Genetic distance results indicate that all Echinacea species are closely related, and the average pairwise distance between populations was approximately three times the intrapopulation distances. The topology of the neighbor-joining tree strongly supports two major clades, one containing Echinacea purpurea, Echinacea sanguinea, and Echinacea simulata and the other containing the remainder of the Echinacea taxa (sensu McGregor). The species composition within the clades differs between our AFLP data and the morphometric treatment offered by Binns and colleagues. We also discuss the suitability of AFLP in determining phylogenetic relationships.

Cluster Analysis↗

Ferromagnetism induced by clustered Co in Co-doped anatase TiO2 thin films.

We investigated ferromagnetism of a newly discovered ferromagnetic semiconductor Co-doped anatase TiO2 thin film, using the magnetic circular dichroism (MCD) at the Co L(2,3) absorption edges. The magnetic moment was observed to be approximately 0.1 micro(B)/Co in the measurements, but the MCD spectral line shape is nearly identical to that of Co metal, showing that the ferromagnetism is induced by a small amount of clustered Co. With thermal treatments at approximately 400 degrees C, the MCD signal increases, and the moment reaches up to approximately 1.55 micro(B)/Co, which is approximately 90% of the moment in Co metal. In the latter case, the cluster size was observed to be 20-60 nm.

Journal Article↗