Biomedical subjects

Dae-Yong Kim

Publications and source records attributed to Dae-Yong Kim.

33 records · Page 2Linked to original sources

PubMed2003

Hematein inhibits atherosclerosis by inhibition of reactive oxygen generation and NF-kappaB-dependent inflammatory mediators in hyperlipidemic mice.

Hematein, a natural compound, is a known anti-inflammatory and antiatherogenic agent in the rabbit model. The authors investigated the effects of this compound on atherogenesis and possible mechanisms of the actions in the hyperlipidemic mice. Low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed a high-cholesterol diet alone for 8 weeks developed the fatty streak lesion in the aortic sinus, whereas this lesion was significantly reduced by hematein treatment without a change in plasma lipid levels compared with control mice. Hematein treatment reduced plasma levels of lipid peroxide and superoxide generation in LPS-stimulated peritoneal macrophage. Hematein treatment inhibited NF-kappaB-DNA binding activity in peritoneal macrophages from Ldlr-/- mice and the activation of NF-kappaB in RAW264.7 macrophages. This compound suppressed plasma nitrite/nitrate levels in Ldlr-/- mice and NO production and iNOS expression in LPS+IFNgamma-stimulated peritoneal macrophages. Hematein treatment also suppressed the activity of iNOS promoters in RAW264.7 macrophages, and reduced the plasma levels of TNF-alpha and IL-1beta and the production of these cytokines in LPS+IFNgamma-stimulated peritoneal macrophages. These results suggest that hematein inhibits atherosclerotic lesion formation, possibly by reducing proinflammatory mediators through a decrease in reactive oxygen species generation and NF-kappaB activation.

Animals↗

PubMed2003

Mechanisms of benzene-induced hematotoxicity and leukemogenicity: cDNA microarray analyses using mouse bone marrow tissue.

Although the mechanisms underlying benzene-induced toxicity and leukemogenicity are not yet fully understood, they are likely to be complicated by various pathways, including those of metabolism, growth factor regulation, oxidative stress, DNA damage, cell cycle regulation, and programmed cell death. With this as a background, we performed cDNA microarray analyses on mouse bone marrow tissue during and after a 2-week benzene exposure by inhalation. Our goal was to clarify the mechanisms underlying the hematotoxicity and leukemogenicity induced by benzene at the level of altered multigene expression. Because a few researchers have postulated that the cell cycle regulation mediated by p53 is a critical event for benzene-induced hematotoxicity, the present study was carried out using p53-knockout (KO) mice and C57BL/6 mice. On the basis of the results of large-scale gene expression studies, we conclude the following: (a) Benzene induces DNA damage in cells at any phase of the cell cycle through myeloperoxidase and in the redox cycle, resulting in p53 expression through Raf-1 and cyclin D-interacting myb-like protein 1. (b) For G1/S cell cycle arrest, the p53-mediated pathway through p21 is involved, as well as the pRb gene-mediated pathway. (c) Alteration of cyclin G1 and Wee-1 kinase genes may be related to the G2/M arrest induced by benzene exposure. (d) DNA repair genes such as Rad50 and Rad51 are markedly downregulated in p53-KO mice. (e) p53-mediated caspase 11 activation, aside from p53-mediated Bax gene induction, may be an important pathway for cellular apoptosis after benzene exposure. Our results strongly suggest that the dysfunction of the p53 gene, possibly caused by strong and repeated genetic and epigenetic effects of benzene on candidate leukemia cells, may induce fatal problems such as those of cell cycle checkpoint, apoptosis, and the DNA repair system, finally resulting in hemopoietic malignancies. Our cDNA microarray data provide valuable information for future investigations of the mechanisms underlying the toxicity and leukemogenicity of benzene.

Administration, Inhalation↗

PubMed2003

Clostridium perfringens type A myonecrosis in a horse in Korea.

Acute hemorrhagic myonecrosis accompanied by severe inter- and intrafascicular edema and hemorrhage of the right gluteal area was diagnosed in a 13-year-old male thoroughbred horse. Once the muscular and fascicular changes were subsided, the horse then developed acute respiratory problem. Histologically, the lung had diffuse severe hemorrhage with mild neutrophilic infiltration. The cause of death was acute respiratory failure that is believed to occur secondary to toxaemic event. Alpha and beta2 toxin secreting Clostiridum perfringens type A was isolated from the muscle and lung. The diagnosis was based on the light microscopic examination, bacterial toxinotyping and toxin genotyping from the muscular and pulmonary lesion. Also, susceptibility of the isolates to antimicrobial agents was determined.

Animals↗

PubMed2003

ELISA detection of IgG antibody against a recombinant major surface antigen (Nc-p43) fragment of Neospora caninum in bovine sera.

An ELISA was established to measure bovine IgG directed against the recombinant antigenic determinant of Nc-p43, a major surface antigen of Neospora caninum. In a previous study, two thirds of the C-terminal of the molecule was expressed as a 6 x His tagged protein (Ncp43P) for ELISA using 2/3 of the N-terminal of SAG1 from Toxoplasma gondii as a control (TgSAG1A). Among 852 cattle sera collected from stock farms scattered nation-wide, 103 sera (12.1%) were found to react with Ncp43P positively, but no positive reaction was observed with TgSAG1A. This study shows that Ncp43P could be available as an efficient antigen for the diagnosis of neosporosis in cattle. Furthermore, it together with TgSAG1A, could be useful for the differential diagnosis of N. caninum and T. gondii infections in other mammals.

Animals↗

PubMed2003

Seroprevalence of antibodies to Neospora caninum in dogs and raccoon dogs in Korea.

Neospora caninum is an important cause of abortion in cattle, and dogs are its only known definitive host. Its seroprevalence among domestic urban and rural dogs and feral raccoon dogs (Nyctereutes procyonoides koreensis) in Korea was studied by indirect fluorescent antibody test (IFAT) and by the neospora agglutination test (NAT), respectively. Antibodies to N. caninum were found in 8.3% of urban dogs and in 21.6% of dogs at dairy farms. Antibody titers ranged from 1:50 to 1:400. Antibodies to N. caninum were found in six (23%) of 26 raccoon dogs. However, the potential role of raccoon dogs as a source of horizontal transmission of bovine neosporosis needs further investigation. The results of this study suggest that there is a close relationship between N. caninum infection among dairy farm dogs and cattle in Korea. This study reports for the first time upon the seroprevalence of N. caninum infection in raccoon dogs in Korea.

Animals↗

PubMed2003

Phenotype of peroxisome proliferator-activated receptor-alpha(PPARalpha)deficient mice on mixed background fed high fat diet.

Considerable controversy exists in determining the role of peroxisome proliferator-activated receptor-alpha PPARalpha) on obesity. Previous reports demonstrated that PPARalpha is a critical modulator of lipid homeostasis, but the overt, obese phenotypic characterization in the strain of PPAR deficient (PPARalpha-/-) mice is influenced by other factors, including diet and genetics. Therefore, it is necessary to establish the phenotypic characterization of PPARalpha-/- mice prior to the obesity-related study. In this study, we observed phenotype of PPARalpha-/- mice on mixed genetic background (C57BL/6Nx129/Sv) fed a high fat diet for 16 weeks. PPARalpha-/- mice, regardless of sex, raised body growth rate significantly comparing with wild type and showed male-specific fatty change in the liver. They were shown to lack hepatic induction of PPARalpha target genes encoding enzymes for fatty acid beta-oxidation.

Adipose Tissue↗

PubMed2002

Seroprevalence of Neospora, Toxoplasma gondii and Sarcocystis neurona antibodies in horses from Jeju island, South Korea.

Parasite-specific antibody responses to Neospora spp. and Toxoplasma gondii, antigens were detected using the indirect fluorescent antibody test (IFAT) and immunoblot analysis in a korean equine population located on Jeju island, South Korea (126 degrees 12' E and 33 degrees 34' N). For comparison, a naturally infected Neospora hughesi horse and an experimentally inoculated T. gondii equid (pony) were used. In addition, all samples were tested for antibodies to Sarcocystis neurona by immunoblot analysis. A total of 191 serum samples from clinically normal horses were evaluated. Only 2% (4 out of 191) and 2.6% (5 out of 191) of the samples had showed reactivity at 1:100 using the IFAT for Neospora spp. and T. gondii, respectively. For T. gondii, two samples matched the antigen banding pattern of the positive control by immunoblot analysis. No sample was positive for N. hughesi by immunoblot analysis in this study. Overall, there was a 1% seroprevalence for T. gondii antibodies in the horses tested based on immunoblot analysis. The seroprevalence for S. neurona and N. hughesi antibodies was 0%. We concluded that these horses are either not routinely exposed to these parasites or antibody titers are not sufficiently elevated to be detectable. It is most likely the former explanation since Jeju island equine farms are isolated from the main land, and the horses were all less than 3 years of age. This naïve population of horses could be useful when evaluating S. neurona serodiagnostic tests or evaluating potential S. neurona vaccines since exposure risks to S. neurona and closely related parasites are negligible.

Animals↗

PubMed2002

In vitro antiprotozoal effects of artemisinin on Neospora caninum.

Neospora caninum is an intracellular apicomplexan parasite that infects a wide range of mammals and has been associated with abortion in cattle worldwide. Artemisinin is an effective antimalarial compound derived from a traditional Chinese herbal remedy, qinghao or Artemisia annua L. In the study reported, the cultured host cells (vero cells or mouse peritoneal macrophages) infected with N. caninum tachyzoites were incubated with alpha-MEM (minimal essential medium) 10%HS supplemented with various concentration or artemisinin (20, 10, 1, 0.1 and 0.01 microg/ml) to examine the efficacy of artemisinin against N. caninum tachyzoites intracellular multiplication. In long-term studies, at 20 or 10 microg/ml for 11 days, artemisinin reduced N. caninum and completely eliminated all microscopic foci of N. caninum. At 1 microg/ml for 14 days, artemisinin reduced N. caninum and completely achieved elimination of all microscopic foci of N. caninum. There was no apparent toxicity to host cells in long-term studies. In short-term studies, at > or = 0.1microg/ml, artemisinin reduced N. caninum tachyzoites intracellular multiplication, significantly (P < 0.05) and appeared to depend on the artemisinin concentrations. Pretreatment of host cells or N. caninum tachyzoites with artemisinin had no effect on N. caninum tachyzoites intracellular multiplication. These results demonstrate that artemisinin inhibited N. caninum tachyzoites intracellular multiplication.

Animals↗

PubMed2002

Helicobacter pylori infection promotes gastric carcinogenesis in a mice model.

BACKGROUND AND AIM: Debate that Helicobacter pylori might play a causative role in gastric carcinogenesis still exists in spite of the World Health Organization's definition of H. pylori as a class I carcinogen. In order to define the exact role of H. pylori infection in gastric carcinogenesis, we established a mice model of H. pylori infection. METHODS: One hundred and forty-four female C57BL/6 mice were divided into nine groups according to N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. All mice were killed at the 50th or 80th week after treatment, and their histopathological changes were evaluated according to group. RESULTS: The incidence of gastric adenocarcinoma at the 50th week was 80% in mice treated with both MNU 240 microg/L and H. pylori infection, whereas the incidence was only 27% in mice treated with only MNU 240 microg/L. Although H. pylori caused marked expansion of the proliferative zone at the surface epithelium, H. pylori infection alone caused only chronic atrophic gastritis without any evidence of carcinomas until 80 weeks. The combination of MNU and H. pylori infection also resulted in a significantly higher incidence of gastric adenoma and adenocarcinoma. Significantly higher expressions of proliferating cell nuclear antigen were noted in the gastric mucosa infected with H. pylori compared to controls. CONCLUSIONS: These results clearly demonstrated the role of H. pylori infection, rather than direct carcinogens, in promoting gastric carcinogenesis in a mice model.

Adenocarcinoma↗

PubMed2002

Aryl hydrocarbon receptor mediates benzene-induced hematotoxicity.

Benzene can induce hematotoxicity and leukemia in humans and mice. Since a review of the literature shows that the CYP2E1 knockout mouse is not known to possess any benzene toxicity, the metabolism of benzene by CYP2E1 in the liver is regarded to be prerequisite for its cytotoxicity and genotoxicity, although the mechanism is not fully understood yet. Because it was found some years ago that benzene was also a substrate for CYP1A1, we investigated the involvement of the aryl hydrocarbon receptor (AhR) in benzene hematotoxicity using AhR wild-type (AhR(+/+)), heterozygous (AhR(+/-)), and homozygous (AhR(-/-)) male mice. Interestingly, following a 2-week inhalation of 300 ppm benzene (a potent dose for leukemogenicity), no hematotoxicity was induced in AhR(-/-) mice. Further, there were no changes in cellularity of peripheral blood and bone marrow (BM), nor in levels of granulocyte-macrophage colony-forming units in BM. This lack of hematotoxicity was associated with the lack of p21 overexpression, which was regularly seen in the wild-type mice following benzene inhalation. Combined treatment with two major benzene metabolites, phenol and hydroquinone, induced hemopoietic toxicity, although it was not known whether this happened due to a surprising lack of expression of CYP2E1 by AhR knockout, or due to a lack of other AhR-mediated CYP enzymes, including 1A1 (i.e., a possible alternative pathway of benzene metabolism). The former possibility, evaluated in the present study, failed to show a significant relationship between AhR and the expression of CYP2E1. Furthermore, a subsequent evaluation of AhR expression after benzene inhalation tended to show higher but less significant expression in the liver, and none in the BM, compared with sham control. Although this study failed to identify the more likely of the above-mentioned two possibilities, the study using AhR knockout mice on benzene inhalation presents the unique possibility that the benzene toxicity may be regulated by AhR signaling.

Administration, Inhalation↗

PubMed2002

Overexpression of urokinase-type plasminogen activator in human gastric cancer cell line (AGS) induces tumorigenicity in severe combined immunodeficient mice.

The significance of urokinase-type plasminogen activator (uPA) expression in gastric cancer development was tested by using a human uPA cDNA transfection approach and an in vivo severe combined immunodeficient (SCID) mouse model. The AGS gastric cancer cell line, which has urokinase-type plasminogen-activator receptor (uPAR) but lacks uPA, was transfected with a plasmid containing human uPA cDNA and injected into the backs of SCID mice. Compared with the parent AGS cells, uPA protein secretion in AGS-2-, AGS-4-, and AGS-8-transfected cells increased by 26.1-, 34.6-, and 4.8-fold, respectively (P < 0.05). mRNA expression levels of uPA in the AGS-4 clone were much stronger than those in AGS-2 and AGS-8 clones. After the cancer cells (2 x 10(6)) were injected s.c. into the SCID mice, a palpable mass was observed at the injection site at around 140 days post-injection, followed by accelerated growth of the xenograft up to 180 days post-injection only in the high uPA-producing clone (AGS-4). These results suggest that continuous and high production of uPA by tumor cells is one of the important factors reflecting the malignancy of gastric cancer cells.

Animals↗

PubMed2002

Juvenile malignant mesothelioma in a dog.

An 11-month-old male mixed breed dog was euthanized due to two months history of vomiting and anorexia. At necropsy, numerous, multifocal or coalescing, firm, protruding nodules, 5 to 40 mm in diameter were scattered throughout the mesentery and omentum. Histologically and immunohistochemically, the nodules were diagnosed as malignant mesothelioma. Metastasis to the regional mesenteric, mediastinal and tracheobronchial lymph nodes were observed.

Abdominal Neoplasms↗

PubMed2002

A case of chronic wasting disease in an elk imported to Korea from Canada.

A seven-year-old male elk (Cervus elaphus nelsoni) was euthanized and necropsied after having a 3-week history of body weight loss, emaciation, excessive salivation, teeth grinding, fever, anorexia, and respiratory distress. The elk was imported into Korea from Canada on March 9, 1997. Gross pathologic findings were restricted to a diffuse fibrinous pneumonia. Microscopic lesions included mild neuronal vacuolation and spongiform change in the neuropil of selected brain stem nuclei and generalized astrocytosis. Immunohistochemistry for protease-resistant prion protein (PrP(res)) was positive in all brain sections but more pronounced in the section of the obex of the medulla. And the PrP(res) was also detected by western immunoblotting in the brain and spinal cord. All the remaining elk and deer that had been in contact with this elk were destroyed and negative for chronic wasting disease (CWD). To our knowledge, this is the first case of CWD occurring outside of the U.S.A. and Canada.

Animals↗

PubMed2002

Prevalence of antibodies to Neospora caninum in Korean native beef cattle.

A total of 438 sera from Korean native beef cattle in 9 provinces were tested for Neospora caninum antibodies using an immunofluorescent antibody test (IFAT). Eighteen (4.1%) cattle were positive by IFAT. The titers ranged from 1:200 (10 animals), 1:400 (5 animals), 1:800 (2 animals) to 1:1,600 (1 animal). Although the seroprevalence was slightly higher in Chungnam (8.9%), this was not significantly different from those noted in Kyunggi, Kangwon, Kyungbuk, Kyungnam, and Cheju provinces. Sera obtained from beef cattle in the provinces of Chungbuk, Jeonbuk and Jeonnam were all negative. Neospora positive sera were also tested for anti-Toxoplasma gondii antibodies using a commercial latex agglutination test (LAT). Antibody to T. gondii was detected in only 1 (5.6%) of 18 N. caninum positive sera. These results indicate that N. caninum and T. gondii infection are present at a low level in the Korean native beef cattle.

Animals↗

PubMedDate not supplied

Measurement of oxidative damage at individual gene levels by quantitative PCR using 8-hydroxyguanine glycosylase (OGG1).

In this study, an attempt was made to develop a method to estimate oxidative damage of individual genes for assessing chemopreventive potential of dietary or medicinal plants. Oxidative damage was investigated on the two genes in gastric mucosal tissue infected with Helicobacter pylori, which were genes of glyceraldehydes-3-phosphate dehydrogenase (GAPDH), a house-keeping gene, and gene of insulin-like growth factor II receptor (IGFIIR), a gene known to be mutated frequently in gastric carcinoma. The oxidative damage in genomic DNA in the above tissue was confirmed by immunohistochemical study using monoclonal antibody to 8-hydroxyguanine (oh(8)G), which showed much higher degree of staining in their nuclei. Using the method we developed, it was demonstrated that the number of oh(8)G (indicated by 8-hydroxyguanine glycosylase (OGG1) sensitive sites) in GAPDH was almost not changed in H. pylori-infected tissue but in IGFIIR, it increased significantly. These results indicate that this method is valid for the estimate of oxidative damage of individual genes and also showed that the susceptibility of genomic DNA to attack of reactive oxygen species is not homogeneous but different depending upon the region of DNA. We expect to use this method in studies of carcinogenic mechanism and chemoprevention since it can provide more specific information pertaining to individual genes we are interested in.

Adult↗