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Biomedical subjects

H K Chung

Publications and source records attributed to H K Chung.

At least 19 recordsLinked to original sources

Temperature determination using Kalpha spectra from M -shell Ti ions.

The compact multipulse terawatt (COMET) laser facility at LLNL was used to irradiate Al-coated 2-50 microm Ti foils with approximately 10(19) W cm(-2) , 500 fs, 3-6 J laser pulses. Laser-plasma interactions on the front side of the target generate hot electrons with sufficient energy to excite inner-shell electrons in Ti, creating Kalpha emission which has been measured using a focusing spectrometer with spatial resolution aimed at the back surface of the targets. The spatial extent of the emission varies with target thickness. The high spectral resolution (lambda/Deltalambda approximately equal to 3800) is sufficient to measure broadening of the Kalpha emission feature due to the emergence of blueshifted satellites from ionized Ti in a heated region of the target. A self-consistent-field model is used to spectroscopically diagnose thermal electron temperatures up to 40 eV in the strongly coupled Ti plasmas.

Journal Article↗

Complex atomic spectral line shapes in the presence of an external magnetic field.

Both the theoretical basis and the computational approach for extending the capabilities of an established spectral line broadening code are presented. By following standard line broadening theory, the effects of an external magnetic field are incorporated into the plasma average and atomic Hamiltonian. An external magnetic field introduces a preferential axis that destroys the symmetry of the quasistatic electric ion microfield. An external magnetic field also modifies the angular properties of the atomic Hamiltonian-atomic energy levels are perturbed and the spectral emission line is polarized. These extensions have been incorporated in an atomic line shape code for complex atoms and applied to several problems of importance to the understanding of tokamak edge plasmas. Applications fall into two broad categories: (1) determination of local plasma properties, such as the magnetic field strength, from distinct line shape features; and (2) consideration of global plasma phenomenon, such as radiation transport. Observable features of the Zeeman effect make H(alpha) a good line for diagnosing the magnetic field. H(beta) does not make a good electron density diagnostic since the Zeeman effect is comparable to the Stark effect for a majority of tokamak edge plasma conditions. For optically thick lines, the details of the spectral line shapes are shown to significantly influence the transport of radiation throughout the system.

Journal Article↗

Genotypic prevalence of the fimbrial adhesins (F4, F5, F6, F41 and F18) and toxins (LT, STa, STb and STx2e) in Escherichia coli isolated from postweaning pigs with diarrhoea or oedema disease in Korea.

A PCR was used to determine the genotypic prevalence of five fimbrial adhesins (F4, F5, F6, F41 and F18), two heat-stable enterotoxins (STa and STb), the heat-labile enterotoxin (LT), and the shiga toxin 2e (Stx2e) in 230 isolates of Escherichia coli from postweaning pigs with diarrhoea or oedema disease. Ninety-four (40.9 per cent) of the isolates carried genes for at least one of the fimbrial adhesins or toxins. Genes for the F18 fimbrial adhesin were detected in 18.3 per cent, and genes for F4, F6, F5 and F41 were detected in 10.0 per cent, 4.3 per cent, 1.7 per cent and 0.8 per cent of the isolates, respectively. Genes for STa, STb and LT were detected in 25.7 per cent, 15.2 per cent and 8.7 per cent of the isolates, respectively. Genes for Stx2e were detected in 36 (15.6 per cent) of the isolates, and among them 24 also contained the gene for F18ab and four also contained the gene for F18ac.

Adhesins, Escherichia coli↗

Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure: what does it mean?

Manganese (Mn) exposure can cause parkinsonism. Pathological changes occur mostly in the pallidum and striatum. Two patients with a long history of occupational Mn exposure presented with Mn-induced parkinsonism. In one patient, magnetic resonance imaging (MRI) showed findings consistent with Mn exposure, and Mn concentration was increased in the blood and urine. However, this patient's clinical features were typical of idiopathic Parkinson disease (PD). Previous pathological and positron emission tomography studies indicate that striatal dopamine transporter density is normal in Mn-induced parkinsonism, whereas it is decreased in PD. Therefore, we performed [(123)I]-(1r)-2 beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) single-photon emission computed tomography. Severe reduction of striatal beta-CIT binding was indicated, which is consistent with PD. We propose three interpretations: (1) the patients have PD, and Mn exposure is incidental; (2) Mn induces selective degeneration of presynaptic dopaminergic nerve terminals, thereby causing parkinsonism; or (3) Mn exposure acts as a risk of PD in these patients. Our results and careful review of previous studies indicate that the axiom that Mn causes parkinsonism by pallidal lesion may be over-simplified; Mn exposure and parkinsonism may be more complex than previously thought. Further studies are required to elucidate the relationship between Mn and various forms of parkinsonism.

Causality↗

Anti-microbial susceptibility for east1 + Escherichia coli isolated from diarrheic pigs in Korea.

The in vitro susceptibilities of 128 isolates of east1 + Escherichia coli from pre-weaned and post-weaned pigs with diarrhoea were tested with nine commonly used anti-microbial agents by an agar dilution minimal inhibitory concentration (MIC) procedure according to National Committee for Clinical Laboratory Standards guidelines. For the isolates from preweaned and post-weaned pigs, most of them were susceptible to low concentrations (MIC90) of tetracycline (4 and 2 microg/ml), ceftiofur (2 and 2 microg/ml), and colistin (4 and 2 microg/ml). Marked resistance was found in others.

Animals↗

A divalent recombinant immunotoxin formed by a disulfide bond between the extension peptide chains.

Recombinant immunotoxin for the treatment of cancer was made by connecting toxins to 'carcinoma-specific' antibodies that selectively bind to cancer cells, then kills them without harming the normal cells. The divalent recombinant immunotoxin, [B3(Fab)-ext-PE38]2, is a derivative of B3(Fab)-PE38. B3(Fab)-PE38 was made by fusing the Fab domain of the monoclonal antibody (MAb) B3 to PE38, a truncated mutant form of Pseudomonas exotoxin (PE). In this study, B3(Fab)-ext-PE38 was constructed, which has the hinge region of the B3(Fab)-PE38 extended with the peptide extension, G4C(G4S)2, and connected to the C3 connector. The Cys residue of the extension peptide chain makes the disulfide bond between the two Fab domains. The extension sequence (ext) makes the dimerization of B3(Fab)-ext-PE38 easier to form the divalent immunotoxin, because it decreases the steric hindrance between the two PE38s. The constructed genes were expressed in E. coli as inclusion bodies. Polypeptides that were obtained from the inclusion body were refolded, and the active forms were purified. The ID50 values of the divalent molecule, [B3(Fab)-ext-PE38]2, were about 4 ng/ml on A431 cell lines, about 1 ng/ml on CRL1739 cell lines, and 5 ng/ml on MCF-7 cell lines. The [B3(Fab)-ext-PE38]2 showed about a 12-fold higher cytotoxicity on CRL1739 cell lines than B3(scFv)-PE40 did.

Antibodies, Monoclonal↗

Dairy-cattle health in Gyeongnam, Korea.

An animal-health monitoring system in the Gyeongnam area was started in 1997 to develop statistically valid data for use in estimating disease frequencies in dairy cattle, and the associated costs. The objectives of this study were to: (1) describe what was done to implement and maintain the system in Gyeongnam; (2) present selected disease frequencies; (3) discuss the epidemiological consideration of what was done and implications for results obtained. Veterinary medical officers (VMOs), comprising professors and graduate students from Gyeongsang National University, faculty of Gyeongnam Livestock Promotion Institute and clinic veterinarians, served as data collectors. After training on current disease and management problems of dairy cattle, interview techniques, sampling methods and data-collection instruments, the VMOs participated in selection of the sample herds and data gathering. Forty (n=40) of 167 dairy herds were selected randomly using a computer-generated list of random numbers and the VMOs visited farms once in a month for 12 months to collect data about management, disease, inventory, production, preventive treatment, financial and other relevant data. Strict data-quality control devices were used. Specific feed-back was developed for the producers and data collectors. The six disorders found most frequently in cows (from the highest to the lowest) were breeding problems, clinical mastitis, birth problems, gastrointestinal problems, metabolic problems and lameness. In young stock, respiratory, multiple system, breeding and gastrointestinal problems were predominant, whereas in calves, gastrointestinal, respiratory and integumental problems predominated.

Animal Husbandry↗

1,4-dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor receptor kinase.

The 4-anilinoquinazoline PD 153035 (1) is a potential antitumor agent which acts by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR) via competitive binding at the ATP site of enzyme. A series of cyclic analogues of PD 153035 bearing the 1,4-dioxane ring was prepared by reaction of 6-chloro derivative 5 with several aniline nucleophiles. These were evaluated for their ability to inhibit the EGFR kinase and the growth of primary human tumor cell cultures. All of the new 4-anilinoquinazolines exhibited less potency than PD 153035 against EGFR kinase. However, compounds 2b, 2c, 2e, 2g, and 2h showed higher inhibitory activities than PD 153035 against the growth of A431 tumor cell line. The compound 2b containing 3-chloroaniline ring was as potent as PD 153035 against EGFR kinase and showed about 5.4-fold better potency than PD153035 in the inhibition of growth of A431 cell line with good selectivity.

Antineoplastic Agents↗

A novel tumor-associated mucin of gastrointestinal carcinoma.

PURPOSE: To identify a new tumor-associated antigen, a monoclonal antibody, SC142, was produced by immunizing mice with a stomach cancer cell line. The tumor specificity of mAb SC142 was studied by immunohistochemical staining, and the biochemical characteristics of this new gastrointestinal tumor-associated antigen were also studied. METHODS: The expression of SC142-reactive antigen was investigated in various cancers by immunohistochemical staining. The SC142-reactive antigen was characterized by immunoblotting, sodium metaperiodate treatment assay, O-glycanase digestion assay, and lectin binding assay. RESULTS: The SC142-reactive antigen was highly expressed in 78% of gastric cancers (29/37) and 87% of colon cancers (27/31). No normal colon or stomach tissues remote from the tumor were positive for the antigen. The antibody also reacted with other tumors of epithelial origin such as lung squamous cell cancer (2/4), breast ductal cancer (2/20), bladder transitional cell carcinoma (4/6), and uterine cancer (3/16). Western blot analysis of the antigen revealed glycoprotein(s) which migrated as a smear ranging from the origin of the gel to about the 80 kDa region. The reactivity of this antigen with SC142 was reduced by sodium metaperiodate treatment or O-glycanase digestion, but not by N-glycanase, suggesting that the epitope is an O-glycan. In lectin-binding assay, this antigen reacted only with wheat germ agglutinin but not with Ricinus communis agglutinin, Datura stramonium agglutinin, and Sambucus nigra agglutinin. CONCLUSIONS: Our findings indicate that the antigen defined by SC142 is a tumor-associated antigen that could differentiate the gastrointestinal cancer cells from the normal cells. Therefore, SC142 may become a valuable tool for the immunohistochemical diagnosis and tumor immunoscintigraphy of the gastrointestinal cancer patients.

Animals↗

Neonatal intensive care unit outbreak caused by a strain of Klebsiella oxytoca resistant to aztreonam due to overproduction of chromosomal beta-lactamase.

Klebsiella oxytoca strains resistant to both aztreonam and ceftriaxone were isolated from six neonates in a neonatal intensive care unit and water reservoirs of two humidifiers attached to the neonatal incubators. These isolates were assumed to be of the same clone because they were characterized by the same antimicrobial susceptibility and pulsed field gel electrophoresis patterns. It was established that the drug resistance was attributed to overproduction of chromosomally encoded Kl beta-lactamase. It was determined that an isolate (K. oxytoca H1) contained a high enzyme concentration (27microg/100microg of protein in enzyme extracts), at least 27 times higher than the control K. oxytoca N1. It was also demonstrated that isolates had a point mutation in the - 35 concensus region of the promotor gene of bla(OXY-2)leading to enzyme overproduction. Outbreaks caused by K1 hyperproducers have not previously been described.

Aztreonam↗

Inhibition of tumor growth and metastasis by Korean mistletoe lectin is associated with apoptosis and antiangiogenesis.

The mistletoe lectins are major active components in the extract of European mistletoes that have been widely used in adjuvant chemotherapy of cancer. This study was performed to investigate the mechanism of anticancer and antimetastatic activity of the purified Korean mistletoe lectin (Viscum album L. coloratum agglutinin, VCA). C57BL6 mice inoculated with B16-BL6 melanoma cells and treated with VCA were assessed for survival and metastasis. The induction of apoptosis of B16-BL6 cells by VCA was investigated by morphological changes, DNA fragmentation characteristics, and cell cycle analysis. The antiangiogenic activity of VCA was also measured by the CAM (choriallantoic membrane) assay. Length of survival of mice was increased and lung metastasis was inhibited by VCA. Treatment of cells with VCA resulted in growth suppression, nuclear morphological changes, DNA fragmentation, and an increased fraction of cells in sub-G1 consistent with apoptosis. Antiangiogenesis of VCA was assessed by CAM assay, where vessel growth induced by fat emulsion was decreased. These results suggest that VCA inhibits tumor growth and metastasis by increasing apoptosis and inhibiting angiogenesis.

Allantois↗

Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes.

To investigate the disease process of pneumoconiosis induced by welding-fume exposure, a lung fibrosis model was established by building a stainless steel arc welding fume generation system and exposing male Sprague-Dawley rats for 90 days. The rats were exposed to welding fumes with concentrations of 57-67 mg/m3 (low dose) and 105-118 mg/m3 (high dose) total suspended particulates for 2 h per day in an inhalation chamber for 90 days. The concentrations of the main metals, Fe, Mn, Cr, and Ni, were measured in the welding fumes, plus the gaseous compounds, including nitrous gases and ozone, were monitored. During the exposure period, the animals were sacrificed after the initial 2-h exposure and after 15, 30, 60, and 90 days. Histopathological examinations were conducted on the animals' upper respiratory tract, including the nasal pathway and conducting airway, plus the gas exchange region, including the alveolar ducts, alveolar sacs, and alveoli. When compared to the control group, the lung weights did not increase significantly in the low-dose group, yet in the high-dose group there was a significant increase from day 15 to day 90. The histopathological examination combined with fibrosis-specific staining (Masson's trichrome) indicated that the lungs in the low-dose group did not exhibit any progressive fibrotic changes. Whereas, the lungs in the high-dose group exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Accordingly, it would appear that a significant dose of welding-fume exposure was required to induce lung fibrosis.

Administration, Inhalation↗

Effects of local anesthetics on the contractility of rat bladders.

PURPOSE: We investigated the effect of local anesthetic agents on the detrusor muscle in rats. MATERIALS AND METHODS: In vitro isometric contraction of rat detrusor strips was measured. We investigated the effects of tetracaine, bupivacaine and lidocaine on baseline spontaneous contractions and contractions induced by various stimuli, including 60 mM. KCl, carbachol and electricalal field stimulation with a pulse duration of 0.8 or 100 milliseconds. RESULTS: Local anesthetic agents have complex effects on baseline spontaneous contractility that depend on the type of agent used and its concentration. These agents inhibited nerve mediated contraction resulting from electricalal field stimulation with a pulse duration of 0.8 milliseconds in a concentration dependent manner and also inhibited nonnerve mediated detrusor contractions induced by KCl, carbachol or electricalal field stimulation with a pulse duration of 100 milliseconds Higher concentrations of local anesthetic agents were needed to inhibit nonnerve than nerve mediated contractions. In rat detrusor muscle carbachol induced a sustained tonic contraction even after the depletion of internal and external Ca2+ sources, which was also inhibited by local anesthetic agents. CONCLUSIONS: These results show that local anesthetic agents have a wide spectrum of inhibitory effects on the contraction of bladder smooth muscle induced by various stimulants at different concentrations, which may be potentially useful for treating overactive bladder.

Anesthetics, Local↗

Methimazole as an antioxidant and immunomodulator in thyroid cells: mechanisms involving interferon-gamma signaling and H(2)O(2) scavenging.

The antithyroid drug, methimazole (MMI) is used to treat patients with Graves' hyperthyroidism. The major action of MMI is to inhibit synthesis of thyroid hormone in the thyroid gland. However, MMI also has antioxidant and immunomodulatory effects on thyrocytes and/or immune cells. This study identifies novel antioxidant and immunomodulatory effects of MMI involving the interferon-gamma (IFN-gamma) signaling pathway in thyroid cells. MMI inhibits transcription of the intercellular adhesion molecule-1 (ICAM-1) gene by modulating the function of transcription factor STAT1 (signal transducer and activator of transcription 1), which binds to the IFN-gamma activated site of the ICAM-1 promoter. Furthermore, MMI rapidly eliminates H(2)O(2) produced by IFN-gamma treatment in thyroid cells and thus inhibits the H(2)O(2)-mediated phosphorylation of tyrosine 701 in STAT1. MMI also eliminates H(2)O(2) in vitro. MMI facilitates electron transfer from NADPH to H(2)O(2) using thioredoxin or glutathione, fulfilling a role similar to peroxiredoxin or glutathione peroxidase, respectively. MMI prevents the IFN-gamma and H(2)O(2)-mediated reversible inactivation of phosphatases. These effects inhibit full activation of the IFN-gamma-induced Janus kinase(JAK)/STAT signaling pathway in FRTL-5 thyroid cells. These results may in part explain the antioxidant and immunomodulatory effects of MMI in thyroid cells of Graves' disease patients.

Adjuvants, Immunologic↗

Pretreatment of whole blood for use in immunochromatographic assays for hepatitis B virus surface antigen.

Immunochromatographic assays (ICAs) are also referred to as rapid tests, since they are simple and the results can be obtained within minutes after manually loading a few drops of a sample into each sample well of the test device. However, whole blood cannot be tested with ICA kits due to the visual hindrance caused by the color of red blood cells (RBCs), unless a cell-removing device such as a filter is mounted on the kits. Thus, when testing with blood, the advantage of the ICA kit is lost because of the additional time and machines required to coagulate and separate whole blood before preparing the serum. To overcome this limitation, whole-blood samples were added to a pretreatment solution to decolor the RBCs; the resulting mixtures were then loaded into the sample wells of the test device. The pretreating solution was composed of hydrogen peroxide (H(2)O(2)) to decolor the RBCs, Sag 471 (Osi Specialties) to restrain the mixture from vigorous foaming, sodium azide (NaN(3)) to inhibit the enzyme, which generates excessive foam at the beginning of decolorization, and EDTA as a chelating agent. As a result of this pretreatment, whole blood could be used with the ICA kit without reducing its simplicity and rapidity.

Anticoagulants↗

Thyroid-stimulating hormone transcriptionally regulates the thiol-specific antioxidant gene.

Thiol-specific antioxidant (TSA) plays an important role in regulating cell differentiation and proliferation by modulating the hydrogen peroxide (H2O2) mediated responses in a variety of mammalian cells. Thyroid cells are constantly exposed to the actions of reactive oxygen species (ROS), because they produce high levels of H2O2 in response to the physiological action of TSH (thyroid-stimulating hormone). Thyrocytes have several defense mechanisms against ROS, including TSA and SOD (superoxide anion dismutase). Using Northern blot hybridization, we tested the effects of TSH on TSA gene expression in FRTL-5 cells derived from rat thyroids. TSA mRNA expression increased following treatment of cells with TSH at concentrations greater than 10(-9) M. This effect was observed within 6 hours following treatment, and peaked at 8 hours. The effect was blocked by actinomycin D, but not by cycloheximide. The half-life of TSA mRNA was approximately 5.5 hours in the presence or absence of TSH, and that was not affected by TSA mRNA stability. The effects on TSA gene expression were specific to TSH. Other growth factors (e.g., insulin, transferrin and hydrocortisone) did not alter TSA expression. Our results are the first indication that TSH regulates the expression of TSA transcriptionally in thyrocytes.

Animals↗