Biomedical subjects

Jae Hyun Park

Publications and source records attributed to Jae Hyun Park.

11 recordsLinked to original sources

PubMed2006

Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model.

Using a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD), this study investigated on the neuroprotective effects of acupuncture by examining whether acupuncture contributed to inhibiting microglial activation and inflammatory events. C57BL/6 mice were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. Acupuncture was then applied to acupoints Yanglingquan (GB34) and Taichong (LR3) starting 2 h after the first MPTP administration and then at 48 h intervals until the mice were sacrificed for analyses at 1, 3, and 7 days after the last MPTP injection. These experiments demonstrated that acupuncture inhibited the decreased of the tyrosine hydroxylase (TH) immunoreactivity (IR) and generated a neuroprotective effects in the striatum (ST) and the substantia nigra (SN) on days 1, 3, and 7 post-MPTP injections. Acupuncture attenuated the increase of macrophage antigen complex-1 (MAC-1), a marker of microglial activation, at 1 and 3 days and reduced the increases in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression on days 1, 3, and 7. In MPTP group, striatal dopamine (DA) was measured by 46% at 7 days, whereas DA in the acupuncture group was 78%. On the basis of these results, we suggest that acupuncture could be used as a neuroprotective intervention for the purpose of inhibiting microglial activation and inflammatory events in PD.

Acupuncture↗

PubMed2006

Construction, affinity maturation, and biological characterization of an anti-tumor-associated glycoprotein-72 humanized antibody.

The tumor-associated glycoprotein (TAG)-72 is expressed in the majority of human adenocarcinomas but is rarely expressed in most normal tissues, which makes it a potential target for the diagnosis and therapy of a variety of human cancers. Here we describe the construction, affinity maturation, and biological characterization of an anti-TAG-72 humanized antibody with minimum potential immunogenicity. The humanized antibody was constructed by grafting only the specificity-determining residues (SDRs) within the complementarity-determining regions (CDRs) onto homologous human immunoglobulin germ line segments while retaining two mouse heavy chain framework residues that support the conformation of the CDRs. The resulting humanized antibody (AKA) showed only about 2-fold lower affinity compared with the original murine monoclonal antibody CC49 and 27-fold lower reactivity to patient serum compared with the humanized antibody HuCC49 that was constructed by CDR grafting. The affinity of AKA was improved by random mutagenesis of the heavy chain CDR3 (HCDR3). The highest affinity variant (3E8) showed 22-fold higher affinity compared with AKA and retained the original epitope specificity. Mutational analysis of the HCDR3 residues revealed that the replacement of Asn(97) by isoleucine or valine was critical for the affinity maturation. The 3E8 labeled with (125)I or (131)I showed efficient tumor targeting or therapeutic effects, respectively, in athymic mice with human colon carcinoma xenografts, suggesting that 3E8 may be beneficial for the diagnosis and therapy of tumors expressing TAG-72.

Adenocarcinoma↗

PubMed2006

Modulation of immune response induced by co-administration of DNA vaccine encoding HBV surface antigen and HCV envelope antigen in BALB/c mice.

Plasmid DNA vaccines encoding the hepatitis B virus (HBV) surface and hepatitis C virus (HCV) envelope antigens, respectively, were constructed, and attempt were made to find the possibility of a divalent vaccine against HBV and HCV. The expression of each plasmid in Cos-1 cells was confirmed using immunocytochemistry. To measure the induced immune response by these plasmids in vivo, female BALB/c mice were immunized intramuscularly with 100 microg of either both or just one of the plasmids. Anti-HBV and HCV-specific antibodies and related cytokines were evaluated to investigate the generation of both humoral and cellular immune responses. As a result, specific anti-HBV and anti-HCV serum antibodies from mice immunized with these plasmids were observed using immunoblot. The levels of IL-2 and RANTES showing a Th1 immune response were significantly increased, but there was no change in the level of IL-4 (Th2 immune response) in any of the immunized groups. Compared with each plasmid DNA vaccine, the combined vaccine elicited similar immune responses in both humoral and cell-mediated immunities. These results suggest that the combined DNA vaccine can induce not only comparable immunity experimentally without antigenic interference, but also humoral and Th1 dominant cellular immune responses. Therefore, they could serve as candidates for a simultaneous bivalent vaccine against HBV and HCV infections.

Animals↗

PubMed2006

Psychroserpens mesophilus sp. nov., a mesophilic marine bacterium belonging to the family Flavobacteriaceae isolated from a young biofilm.

A number of marine bacteria isolated from young biofilms were characterized as belonging to the family Flavobacteriaceae. The taxonomic characterization of strain KOPRI 13649T, which was isolated from an acrylic surface at the seashore at Gangneung, Korea, is reported here. The nearly complete 16S rRNA gene sequence of strain KOPRI 13649T was determined and was found to have a high level of similarity with that of Psychroserpens burtonensis (95.0-95.6 %). In addition, phylogenetic analysis and comparison with closely related strains confirmed that the strain represented a novel member of the genus Psychroserpens. The major respiratory quinone of strain KOPRI 13649T was MK-6 and the DNA G+C content was 29.8 mol%. The dominant fatty acid methyl esters were i-15 : 0, a-15 : 0, i-16 : 0, i-15 : 1omega10, 16 : 1omega7 and 15 : 0. Growth was observed at 10-34 degrees C (optimum 30 degrees C), at pH 6-9 (optimum 6.5-8.0) and with 0.5-4 % NaCl (optimum 1 %). On the basis of the polyphasic taxonomic evidence presented, strain KOPRI 13649T (=KCCM 42261T=JCM 13413T) should be classified as the type strain of a novel species in the genus Psychroserpens, for which the name Psychroserpens mesophilus sp. nov. is proposed.

Bacterial Typing Techniques↗

PubMed2005

Heat shock 70-kDa protein 8 isoform 1 is expressed on the surface of human embryonic stem cells and downregulated upon differentiation.

The cell-surface markers used routinely to define the undifferentiated state and pluripotency of human embryonic stem cells (hESCs) are those used in mouse embryonic stem cells (mESCs) because of a lack of markers directly originated from hESC itself. To identify more hESC-specific cell-surface markers, we generated a panel of monoclonal antibodies (MAbs) by immunizing the irradiated cell clumps of hESC line Miz-hES1, and selected 26 MAbs that were able to bind to Miz-hES1 cells but not to mESCs, mouse embryonic fibroblast cells, and STO cells. Most antibodies did not bind to human neural progenitor cells derived from the Miz-hES1 cells, either. Of these, MAb 20-202S (IgG1, kappa) immunoprecipitated a cell-surface protein of 72-kDa from the lysate of biotin-labeled Miz-hES1 cells, which was identified to be heat shock 70-kDa protein 8 isoform 1 (HSPA8) by quadrupole time-of-flight tandem mass spectrometry. Immunocytochemical analyses proved that the HSPA8 protein was also present on the surface of hESC lines Miz-hES4, Miz-hES6, and HSF6. Two-color flow cytometric analysis of Miz-hES1 and HSF6 showed the coexpression of the HSPA8 protein with other hESC markers such as stage-specific embryonic antigen 3 (SSEA3), SSEA4, TRA-1-60, and TRA-1-81. Flow cytometric and Western blot analyses using various cells showed that MAb 20-202S specifically bound to the HSPA8 protein on the surface of Miz-hES1, contrary to other anti-HSP70 antibodies examined. Furthermore, the surface expression of the HSPA8 protein on Miz-hES1 was markedly downregulated upon differentiation. These data indicate that a novel MAb 20-202S recognizes the HSPA8 protein on the surface of hESCs and suggest that the HSPA8 protein is a putative cell-surface marker for undifferentiated hESCs.

Antibodies, Monoclonal↗

PubMed2004

Evaluation of the potential immunotoxicity of 3-monochloro-1,2-propanediol in Balb/c mice. I. Effect on antibody forming cell, mitogen-stimulated lymphocyte proliferation, splenic subset, and natural killer cell activity.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. However, no previous studies have investigated MCPD-induced alterations in the immune system. In the present study, MCPD was administered by gavage for 14 days at 0, 25, 50, and 100 mg/kg per day to female Balb/c mice. The antibody-mediated immune response to sheep red blood cells (SRBC) was assessed using the antibody-forming cell (AFC) assay, and splenic cell phenotypes were quantified by flow cytometry. Hematological and histopathological changes were assessed. Mitogen-stimulated spleen lymphocyte proliferation and natural killer (NK) cell activity were evaluated. The T-lymphocyte blastogenesis by concanavalin A (Con A) or anti-CD3 and B-lymphocyte blastogenesis by lipopolysaccharide (LPS) were not significantly changed. There were no significant changes in the hematological and histopathological findings of MCPD-treated mice. However, the significant decrease in thymus weight was observed in 100 mg dose group, even though that did not change body weight gain. The cellularities of spleen and thymus were significantly reduced in high-dose group. Exposure to high dose of MCPD decreased the AFC response to SRBC in mice. There was a significant decrease in NK cell activity of mice treated with high dose of MCPD. These results indicate that MCPD could modulate the immune function in Balb/c mice.

Animals↗

PubMed2004

Novel method for determining pyrene biodegradation using synchronous fluorimetry.

To study the biodegradation rate of pyrene dissolved in liquid medium supplemented with mineral salts, a synchronous fluorimetry (SF) method was established. The limit of detection for pyrene dissolved in mineral salts medium (MSM) was determined as 0.19 ng/ml with a relative standard deviation of less than 1.3% (n = 9). The pyrene degrading rates of four bacterial strains were investigated using this method under the same experimental conditions. The degradation rates of the three active strains ranged from 76% to 87% after a 14-h incubation. The results were confirmed by the gas chromatography with a flame ionized detector (GC/FID) method. This implies that pyrene degradation can be directly monitored by the SF method without the solvent extraction of samples. The advantages of SF are that it is less laborious, faster, and less expensive than the GC/FID determination method with solvent extraction. The SF method provides a new tool for studying the degradation of polynuclear aromatic hydrocarbons (PAHs) in the natural environment and under experimental conditions.

Bacteria↗

PubMed2004

Immunomodulatory effect of caffeic acid phenethyl ester in Balb/c mice.

Caffeic acid phenethyl ester (CAPE), an the active component of propolis, is known to have anticarcinogenic, antiviral and various biological activities; however, the effect of CAPE on the immunomodulatory activity in vivo remains unknown. We have investigated the effect of CAPE on the immune system in female Balb/c mice. CAPE (0, 5, 10, 20 mg/kg) was given to mice orally for 14 days. Immunomodulatory activity was evaluated by assessment of body and organ weight, lymphocyte blastogenesis, plaque-forming cell (PFC) assay, lymphocyte subpopulation by flow cytometry and cytokine production. Even though the change of body weight was not observed in CAPE-administered group, thymus weight and/or cellularity of thymus and spleen are decreased at the all dose groups of CAPE (5, 10, 20 mg/kg). On the other hand, CAPE had no effect on B lymphocyte proliferation induced by lipopolysaccharide (LPS) but increased T lymphocyte blastogenesis induced by concanavalin A (Con A) at the dose of 20 mg/kg. In the case of lymphocyte subpopulation, the population of T and B cells was not changed but CD4(+) T cell subsets are significantly increased in exposure to CAPE. The antibody responses to T lymphocyte dependent antigen, sheep red blood cell and keyhole limpet hemocyanin (KLH) were increased more than 10 mg/kg in CAPE-treated group. Likewise, the cytokine, IL-2, IL-4 and IFN-gamma were significantly increased at the dose of 20 mg/kg CAPE group. These results suggest that CAPE could have immunomodulatory effects in vivo.

Adjuvants, Immunologic↗

PubMed2003

Pyrrolidine dithiocarbamate-induced neuronal cell death is mediated by Akt, casein kinase 2, c-Jun N-terminal kinase, and IkappaB kinase in embryonic hippocampal progenitor cells.

Pyrrolidine dithiocarbamate (PDTC) is known to induce cell death by the stimulation of intracellular zinc transport and subsequent modulation of nuclear factor-kappaB (NF-kappaB) activity. Zinc is a signaling messenger that is released by neuronal activity at many central excitatory synapses. Excessive synaptic release of zinc followed by entry into vulnerable neurons contributes to severe neuronal cell death. In the present study, we explored how PDTC modulates intracellular signal transduction pathways, leading to neuronal cell death. The exposure of immortalized embryonic hippocampal cells (H19-7) to PDTC within the range of 1-100 microM caused cell death in a dose-dependent manner. During the cell death, NF-kappaB activity increased in response to PDTC, and this activity corresponded well with the increase of intracellular free zinc levels, implying that the activation of NF-kappaB transmits the cell death signals of PDTC. Furthermore, PDTC caused the activation of IkappaB kinase (IKK), casein kinase 2 (CK2), phosphatidylinositol 3-kinase (PI-3K), and Akt, as well as mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 kinase. The blockade of PI-3K, JNK, and CK2 pathways resulted in a remarkable suppression of PDTC-induced cell death and also the activation of IKK, which subsequently led to a decrease of IkappaB phosphorylation. Although the overexpression of dominant-negative SEK in a transient manner did not inhibit the activation of Akt by PDTC, the transfection of kinase-inactive Akt mutants did cause a remarkable blockade of JNK activation, implying that Akt is present upstream of JNK in the PDTC-signaling pathways. Moreover, whereas selective CK2 inhibitors suppressed PDTC-induced JNK activation, the inhibition of JNK did not affect CK2 activity, suggesting that CK2 is directly related to the regulation of cell viability by PDTC and that the CK2-JNK pathway could be a downstream target of PDTC. Taken together, our results suggest that PDTC-mediated accumulation of intracellular zinc ions may affect cell viability by modulating several intracellular signaling pathways in neuronal hippocampal progenitor cells.

Animals↗

PubMed2002

Middle cerebral artery stenosis is a major clinical determinant in striatocapsular small, deep infarction.

BACKGROUND: The significance of the stenotic lesions of the middle cerebral artery (MCA) in Asian patients with striatocapsular small, deep infarctions (SSDIs) remains undetermined. OBJECTIVES: To investigate the frequency of stenotic lesions of the MCA in patients with SSDIs and to evaluate clinical and radiological features in those same patients. SETTING: Acute stroke registry of a university hospital. PATIENTS AND METHODS: One hundred two Korean patients with acute symptomatic SSDIs underwent cerebral angiography or magnetic resonance angiography and echocardiography. We divided these patients into 2 groups-patients with and without MCA occlusive lesions. The clinical and magnetic resonance image features were compared between these 2 groups. RESULTS: Thirty-seven patients (36%) had an ipsilateral proximal MCA lesion, whereas 65 patients (64%) showed no MCA abnormality on cerebral angiography or magnetic resonance angiography. Among 65 patients without an MCA lesion, 18 had an embolic source; the remaining 37 patients had no demonstrable embolic source. There were significant differences in the temporal profile and magnetic resonance imaging findings between the groups. Although the type of lacunar syndrome and the volume of infarcts did not differ between the groups, the unstable temporal profile and magnetic resonance imaging findings of multiple small infarcts in the symptomatic hemisphere were frequently observed in patients with MCA lesions. CONCLUSIONS: The proximal MCA lesion was a common cause of SSDIs in Korean patients. Depending on the existence of an MCA lesion, the clinical course and magnetic resonance imaging feature of the patients with SSDIs were different.

Acute Disease↗

PubMedDate not supplied

A nonradioisotopic endpoint for measurement of lymph node cell proliferation in a murine allergic contact dermatitis model, using bromodeoxyuridine immunohistochemistry.

INTRODUCTION: The murine local lymph node assay (LLNA) was developed as an alternative to guinea pig models for the assessment of the xenobiotic contact sensitization potential. However, it would be advantageous to have an alternative endpoint to the usual radioisotopic-dependent measures. In the present study, we investigated the development of a nonradioisotopic endpoint for LLNA using immunohistochemistry. METHODS: Female Balb/c mice were treated by the topical application of strong sensitizers, 2,4-dinitrochlorobenzene (DNCB) and toluene diisocyanate (TDI), and a strong irritant, sodium lauryl sulfate (SLS), on the dorsum of both ears once daily for three consecutive days. The proliferation of cells in the auricular lymph node and ears was analyzed by means of the labeling index (LI) of bromodeoxyuridine (BrdU) incorporation into cells. RESULTS: Skin reactions, consisting of increased ear thickness and the presence of inflammatory cell infiltrates, were observed in mice treated with DNCB and TDI. The cell number and the weight of the lymph nodes in the mice treated with the allergens, DNCB and TDI, were increased compared to vehicle control. We observed an increase in the areas of the B220(+) cells in the lymph nodes of mice treated with allergens, as determined by immunohistochemistry. There was an increase in the percentage of B220(+) cells in mice treated with DNCB and TDI compared to the vehicle control, but not in those treated with SLS. Because we observed an increase in the percentage of B cells in the allergen-treated group, we measured the stimulation index (SI) in the cortex and medulla (C+M) of the lymph node. The SI values of the C+M in the lymph nodes of the mice treated with DNCB and TDI were increased more than threefold compared with that of the control. However, the SI of the C+M in the lymph nodes of the mice exposed to 25% SLS was not significantly increased compared to the vehicle control, although the lymph node weight of the SLS group was significantly increased. DISCUSSION: In Balb/c mice, BrdU immunohistochemistry showed its potential use for the identification and differentiation of chemicals with the capacity to induce irritation and sensitization. The results suggest that the measurement of the SI in the cortex and medulla of the lymph node using BrdU immunohistochemistry could provide a useful method to screen irritants and allergens.

Allergens↗