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Biomedical subjects

B K Park

Publications and source records attributed to B K Park.

At least 19 recordsLinked to original sources
PubMed2006

Isolation and phylogenetic analysis of H1N1 swine influenza virus isolated in Korea.

A swine influenza H1N1 virus was isolated from a pig during a severe outbreak of respiratory disease in Korea. All genes of the H1N1 isolate, including hemagglutinin (HA), neuraminidase (NA), matrix (M), nucleoprotein (NP), non-structural (NS), PA, PB1 and PB2, were of swine origin. Also, all these genes showed a close phylogenic relationship with those of H1N1 viruses previously isolated from pigs in the United States. These results suggest that North American swine influenza virus has actually been transmitted to pigs in Korea.

Animals↗
PubMed2006

Oral efficacy of Vero cell attenuated porcine epidemic diarrhea virus DR13 strain.

A Vero cell attenuated porcine epidemic diarrhea virus (PEDV) strain, DR13, was distinguished from wild-type PEDV using restriction enzyme fragment length polymorphism (RFLP). Cell attenuated DR13 was orally or intramuscularly (IM) administered to late-term pregnant sows, and mortality resulting from the highly virulent PEDV challenge was investigated in passively immunized suckling piglets of the two different groups. The mortality rate of the oral group (13%) was lower than that of the IM group (60%). In particular, the concentration of IgA against PEDV was higher in piglets of sows in the oral group, compared to the IM group. The attenuated DR13 virus remained safe, even after three backpassages in piglets. The findings of this study support the theory that the Vero cell attenuated DR13 virus may be applied as an oral vaccine for inducing specific immunity in late-term pregnant sows with a high margin of protection against PEDV infection.

Administration, Oral↗
PubMed2006

Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features.

Although acute exacerbations of idiopathic pulmonary fibrosis are well recognised, there are no studies documenting their prevalence or identifying pre-existing risk factors. This study analysed the clinical, radiological and pathological data of 11 patients who satisfied the criteria for acute exacerbation among 147 patients with biopsy-proven idiopathic pulmonary fibrosis. There were five additional patients who had similar demographics, radiology and surgical lung biopsy pathology, but had clinically less severe disease, and so were not included. The 2-yr frequency of acute exacerbation was 9.6% after the diagnosis. Most exacerbations were idiopathic, although two cases presented after surgical lung biopsy and one after bronchoalveolar lavage. No significant risk factor was found by univariate proportional hazard analysis. Imaging revealed diffuse bilateral ground-glass opacification superimposed on subpleural reticular and honeycombing densities. The biopsies of four patients taken during acute exacerbation exhibited diffuse alveolar damage superimposed upon usual interstitial pneumonia. The findings of this study demonstrate that acute exacerbation of idiopathic pulmonary fibrosis is rather common and this exacerbation is likely to have a spectrum of severity.

Acute Disease↗
PubMed2004

Comparative analysis on the 5'-untranslated region of bovine viral diarrhea virus isolated in Korea.

Samples of 249 bovine abortuses, one intestine, and four diarrheal stools from 254 cows were collected, and bovine viral diarrhea virus (BVDV) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Subsequently, virus isolation was preformed with PCR-positive samples, and then PCR product of 5(')-untranslated region (UTR) of BVDV isolate was sequenced and analyzed. Among the samples collected, 20 (from 17 bovine abortuses, one intestine, and two diarrheal stools) were positive for BVDV RT-PCR; four BVDVs (from two bovine abortuses, one intestine, and one diarrheal stool) were isolated. When the four isolates were biotyped in cell culture, one BVDV isolate from a bovine abortus was cytopathic and the others were non-cytopathic. In addition, three isolates were genotyped as BVDV-1 and one isolate from a diarrheal stool as BVDV-2. In phylogenetic analysis, it suggested that the BVDV-2 isolate in Korea is closer to the North American strains than Asian strains. This is the first report on the identification and isolation of BVDV-2 in Korea.

5' Untranslated Regions↗
PubMed2004

Time course toxicogenomic profiles in CD-1 mice after nontoxic and nonlethal hepatotoxic paracetamol administration.

Adverse drug reactions are a major clinical problem. Drug-induced hepatotoxicity constitutes a large percentage of these reactions. A thorough understanding of the genetic events, specifically, the early "decision-making" processes underlying biological changes caused by drugs and metabolites, is required. To assist in the understanding of these events, we have employed the model hepatotoxin, paracetamol (APAP), and GeneChip technology to investigate global genetic events seen after nontoxic and toxic doses in the mouse. Mice were dosed [vehicle, nontoxic APAP (1 mmol/kg), and toxic APAP (3.5 mmol/kg)], and individual hepatic RNA samples were hybridized to separate chips to determine interanimal variation. Statistical analysis detected 175 CD-1 mouse genes that were significantly regulated (P < 4.1 x 10(-6)), and nonsignificant genes were discarded. For clarity, the significantly regulated genes were then binned into categories according to their major function-antioxidant, glutathione, metabolism, transcription, immune, and apoptosis. There was no hepatic stress observed after dosing 1 mmol/kg APAP, when measured by serum alanine aminotransferase levels. Hepatic toxicity was observed at both 4 and 24 h after a 3.5 mmol/kg dose of APAP. Time course expression profiles for selected genes have been created. These results demonstrate that most active gene expression occurs around 4 h after a toxic dose of APAP. Down-regulation of these genes is observed over 24 h, coinciding with the development of overt toxicity. These data provide a deeper understanding of the in vivo time course of physiological responses of the liver to chemical stress and provide a logical step forward for the investigation of new chemical entities demonstrated positive in chemically reactive metabolite screens. The complete data set can be viewed at http://www.ebi.ac.uk/arrayexpress/. The accession number is E-MEXP-82.

Acetaminophen↗
PubMed2003

Differentiation of a Vero cell adapted porcine epidemic diarrhea virus from Korean field strains by restriction fragment length polymorphism analysis of ORF 3.

A porcine epidemic diarrhea virus (PEDV) designated DR13 was isolated in Vero cells and serially passaged by level 100. The virus was titrated at regular intervals of the passage level. Open reading frame (ORF) 3 sequences of the virus at passage levels 20, 40, 60, 80, and 100 were aligned and compared using a computer software program. Suitability of the restriction fragment length polymorphism (RFLP) analysis for differentiating the virus from other Korean field strains was investigated. The DR13 field isolate was successively adapted in Vero cells as observed through polymerase chain reaction (PCR) and titration of the virus. RFLP analysis identified change in cleavage sites of HindIII and Xho II from passage levels 75 and 90, respectively; these RFLP patterns of ORF 3 differentiated the Vero cell-adapted virus from its parent strain, DR13, and 12 other strains of PEDV studied. The cell adapted DR13 was tested for its pathogenicity and immunogenicity in piglets and pregnant sows. The results indicated that cell adapted DR13 revealed reduced pathogenicity and induced protective immune response in pigs. Differentiation between highly Vero cell-adapted virus and wild-type virus could be the marker of adaptation to cell culture and a valuable tool for epidemiologic studies of PEDV infections. The results of this study supported that the cell attenuated virus could be applied as a marker vaccine candidate against PEDV infection.

Animals↗
PubMed2003

Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones.

Administration of carbamazepine (CBZ) causes hypersensitivity reactions clinically characterized by skin involvement, eosinophilia, and systemic symptoms. These reactions have an immune etiology; however, the role of T cells is not well defined. The aim of this study was to characterize the specificity, phenotype, and cytokine profile of CBZ-specific T cells derived from hypersensitive individuals. Proliferation of blood lymphocytes was measured using the lymphocyte transformation test. CBZ-specific T cell clones were generated by serial dilution and characterized in terms of their cluster of differentiation and T cell receptor V beta phenotype. Proliferation, cytotoxicity, and cytokine secretion were measured by [(3)H]thymidine incorporation, (51)Cr release, and enzyme-linked immunosorbent assay, respectively. HLA blocking antibodies were used to study the involvement of antigen-presenting cells. The specificity of the drug T cell receptor interaction was studied using CBZ metabolites and other structurally related compounds. Lymphocytes from hypersensitive patients (stimulation index: 32.1 +/- 24.2 [10 microg ml(-1)]) but not control patients (stimulation index: 1.2 +/- 0.4 [10 microg ml(-1)]) proliferated upon stimulation with CBZ. Of 44 CBZ-specific T cell clones generated, 10 were selected for further analysis. All 10 clones were either CD4+ or CD4+/CD8+, expressed the alpha beta T cell receptor, secreted IFN-gamma, and were cytotoxic. T-cell recognition of CBZ was dependent on the presence of HLA class II (DR/DQ)-matched antigen-presenting cells. The T cell receptor of certain clones could accommodate some CBZ metabolites, but no cross-reactivity was seen with other anticonvulsants or structural analogs. These studies characterize drug-specific T cells in CBZ-hypersensitive patients that are phenotypically different from T cells involved in other serious cutaneous adverse drug reactions.

Adult↗
PubMed2003

Idiopathic presacral retroperitoneal fibrosis: report of two cases.

Retroperitoneal fibrosis is characteristic plaques of dense fibrous tissue, typically extending from the level of the kidney down to the sacral promontory. Involvement of the presacral space is extremely rare in retroperitoneal fibrosis. We report two cases of idiopathic retroperitoneal fibrosis manifested by a presacral mass.

Adult↗
PubMed2002

Encephalomyelitis associated with akabane virus infection in adult cows.

Between August and September 2000, five 2-7-year-old cows in Korea exhibited neurologic signs and were diagnosed as infected with Akabane virus based on the results of histopathology, immunohistochemistry, serology, and reverse transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemistry and RT-PCR were equally effective and sensitive for diagnosing Akabane virus infection during the early stage of infection. Typical lymphohistiocytic inflammation characterized by perivascular mononuclear cell infiltration, gliosis, neuronophagia, and neuronal loss was noted in the brain and the ventral horn gray matter of the spinal cord. The lesions in the brain were most prominent in the pons and medulla oblongata. Akabane virus antigen was detected in the brain and spinal cord, mainly in degenerating neurons and glial cells. RT-PCR analysis revealed a target band of expected size in four cows. This is the first report on an outbreak of natural Akabane virus infection in adult cattle.

Animals↗
PubMed2002

Are chemically reactive metabolites responsible for adverse reactions to drugs?

Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into short-lived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.

Animals↗
PubMed2001

Implication of co-measured platelet factor 4 in the reliability of the results of the plasma transforming growth factor-beta 1 measurement.

We examined the possible alteration of circulating transforming growth factor-beta1 (TGF-beta1) concentrations in a time-dependent fashion in human plasma. Plasma TGF-beta1 was measured three times at 2 week-intervals from each of 12 healthy participants. Platelet factor 4 (PF4) was measured in parallel with TGF-beta1 to estimate the degree of platelet degranulation. TGF-beta1 levels of the second and third plasma samples, in which PF4s were measured as < approximately 1000 IU/ml, were relatively low and fell in a narrow range. However, TGF-beta1 levels of the first samples, in most of which PF4s were > approximately 1000 IU/ml, appeared much higher and more variable than those of the second or third samples. These results indicate that the platelet degranulation accounted for the higher TGF-beta1 levels in the first samples, and thus did not support our initial assumption. We, nevertheless, could propose a useful guidance in the assessment of TGF-beta1 levels in plasma. When the PF4 level is measured as < approximately 1000 IU/ml under our assay conditions, the TGF-beta1 level in a given plasma sample might be accepted as a reliable value considering the effect of platelet degranulation on TGF-beta1 level.

Adult↗
PubMed2001

Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells.

The roles of the protein-serine/threonine kinase, Akt1, in signaling pathways associated with cell motility and extracellular matrix invasion were examined in the immortalized mouse mammary epithelial cell line, COMMA-1D. COMMA-1D cells were engineered to express the avian leukosis subtype A receptor, tv-a, to permit infection by recombinant avian leukosis virus produced by the replication-competent avian splice vector, RCAS. COMMA-1D/tv-a cells transduced with RCAS/v-akt, but not RCAS/Akt1, formed anchorage-independent colonies in soft agar; however, cells overexpressing either v-akt or Akt1 became highly invasive when grown on the ECM, Matrigel. Zymography of extracellular protease activity shed into the medium by COMMA-1D/Akt1 or COMMA-1D/v-akt cells revealed elevated gelatinase activity that was confirmed to be matrix metalloproteinase-2 (MMP-2; gelatinase A) by Western blotting and immunoprecipitation-zymography. The MMP inhibitor, BB-94, blocked MMP-2 activity and invasion associated with Akt1- and v-akt-expressing cells. The proteasome inhibitor, lactacystin, markedly increased MMP-2 levels and invasion in control cells but not in Akt1- and v-akt-expressing cells. These results suggest that the invasive behavior of mammary epithelial cells induced by Akt1 is associated with increased MMP-2 expression that may result from inhibition of MMP-2 degradation by the proteasome pathway.

Animals↗
PubMed2001

Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix.

Wogonin (5,7-dihydroxy-8-methoxyflavone), isolated from Scutellaria radix, was previously reported to inhibit the expression and activity of the enzyme cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated cells of a mouse macrophage cell line, RAW 264.7. Here, in order to find in vivo effects, inhibition by wogonin of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxygenase-2 expression and anti-inflammatory activity in vivo were investigated. When applied topically to the dorsal skin of mice, wogonin at doses of 50-200 microg/site/treatment (total of five treatments in 3 days) inhibited cyclooxygenase-2 expression and prostaglandin E2 production induced by multiple treatments with TPA. At 200 microg/site/treatment, wogonin caused a 55.3% reduction of prostaglandin E2 production on the dorsal skin compared with an increased production in the TPA-treated control group. The same compound significantly inhibited mouse ear edema induced by TPA in both preventive (58.1% inhibition) as well as curative treatment (31.3% inhibition) schedules at 200 microg/ear/treatment. Inhibition of neutrophil infiltration was also observed. Therefore, wogonin may be beneficial for cyclooxygenase-2-related skin disorders.

Animals↗
PubMed2001

TNFalpha promoter region gene polymorphisms in carbamazepine-hypersensitive patients.

OBJECTIVE: To evaluate whether the major histocompatibility complex contains susceptibility genes for carbamazepine hypersensitivity. Carbamazepine hypersensitivity is immune-mediated, although factors determining its occurrence and severity are unknown. METHODS: Using PCR in 60 carbamazepine-hypersensitive patients, 37 with nonserious (Group I) and 23 with serious (Group II) reactions, and 313 control subjects (63 patients on carbamazepine without adverse effects and 250 healthy volunteers), the association with polymorphisms in the promoter region of the tumor necrosis factor alpha (TNFalpha) gene (positions -308 and -238), and with HLA-DR3 and -DQ2 was determined. RESULTS: The frequency of the variant allele (TNF2) at the -308 position was increased in Group II but not Group I carbamazepine-hypersensitive patients compared with all control subjects (p = 0.01; OR = 2.4), as was the frequency of HLA-DR3 (p = 0.01; OR = 3.3), HLA-DQ2 (p = 0.04; OR = 2.7), and the TNF2-DR3-DQ2 haplotypes (p = 0.02; OR = 3.2). None of the alleles were independently associated with serious carbamazepine hypersensitivity. For the -238 polymorphism, there was a difference in the genotype, but not in the allelic, frequencies between Group II hypersensitive patients and all control subjects. CONCLUSIONS: The TNF2 allele was associated with severe, but not nonserious, carbamazepine hypersensitivity reactions, suggesting that hypersecretion of tumor necrosis factor alpha may be a determinant of the severity of tissue damage. However, the association of the TNF2 allele with carbamazepine hypersensitivity was not independent of HLA-DR3 and -DQ2, and therefore the possibility that it constitutes a passive component of the TNF2-DR3-DQ2 haplotype cannot be excluded.

Adolescent↗
PubMed2001

Toxicogenetics in drug development.

The major progress made in the understanding of the genetic basis of inter-individual variation in drug response, alongside the rapid advances in technology, provides major new opportunities to ensure the safe introduction of a new chemical entity into clinical practice. In essence, the aim is to get the right drug into the right patient using knowledge of factors that influence both benefit and risk. The stage of the drug development process at which genetic analysis needs to be undertaken is dependent on the frequency of the event, and the availability of clinical samples. Thus, common adverse events, or assessment of efficacy, will be feasible for testing in phases I-III. However, when a rare event is being studied, for example idiosyncratic toxicity, prospective analysis becomes impossible. Thus, retrospective studies using available drugs is important as it may provide paradigms for future drug development. Additionally, prospective collection of samples will be important so that rare adverse events identified during phase IV can then be analysed using toxicogenetic approaches. Ultimately, information obtained from toxicogenetics must be included in the Specific Product Characteristics (SPC) and thus formally translated into clinical practice in order to contraindicate the drug in specific patients with a genetically determined susceptibility to drug toxicity.

Carbamazepine↗
PubMed2001

Observation of polarization in bottomonium production at square root of s = 38.8 GeV.

We present a measurement of the polarization observed for bottomonium states produced in p-Cu collisions at square root of s = 38.8 GeV. The angular distribution of the decay dimuons of the Upsilon(1S) state shows no polarization at small values of the fractional longitudinal momentum x(F) and transverse momentum p(T) but significant positive transverse production polarization for either p(T)>1.8 GeV/c or for x(F)>0.35. The Upsilon(2S+3S) (unresolved) states show a large transverse production polarization at all values of x(F) and p(T) measured. These observations challenge NRQCD calculations of the polarization expected in the hadronic production of bottomonium states.

Journal Article↗