Biomedical subjects

Jong-Hwan Lee

Publications and source records attributed to Jong-Hwan Lee.

10 recordsLinked to original sources

PubMed2006

Accelerated thymic maturation and autoreactive T cells in bronchopulmonary dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns triggered by oxygen and barotrauma, is characterized by arrested alveolarization. Increased levels of bombesin-like peptides shortly after birth mediate lung injury: anti-bombesin antibody 2A11 protects against BPD in two baboon models. The role of adaptive immunity in BPD has not been explored previously. OBJECTIVES: Our goal was to test the hypothesis that thymic architecture and/or T-cell function is altered with BPD, leading to autoimmunity and immunodeficiency. METHODS: Thymic structure was analyzed by histopathology of thymic architecture and immunohistochemistry for thymic maturation markers (terminal deoxynucleotidyl transferase, proliferating cell nuclear antigen, CD4, and CD8). Thymic cortical epithelial cells (nurse cells) were studied using HLA-DR and protein gene product 9.5 as markers. Functional analysis was performed with "mixed lymphocyte reaction" of thymocyte or splenocyte responder cells with autologous lung cells as the stimulators. MEASUREMENTS AND MAIN RESULTS: 2A11 treatment attenuates thymic cortical involution in BPD animals, sustaining terminal deoxynucleotidyl transferase-positive prothymocytes and thymocyte proliferation. BPD animals have increased CD4(+) cells in thymic cortex and lung interstitium, which are reduced by 2A11. Conversely, cortical protein gene product 9.5/HLA-DR-positive thymic nurse cells are depleted in BPD animals, but are preserved by 2A11-treatment. Whereas fetal thymocytes and splenocytes respond to phythemagglutinin/ionomycin and to a lesser extent, to autologous lung, BPD thymocytes and splenocytes are phythemagglutinin/ionomycin-unresponsive, and yet react strongly to autologous lung. The 2A11 normalizes these responses. CONCLUSIONS: These observations suggest that bombesin-like peptides mediate premature thymic maturation and thymic nurse-cell depletion, leading to autoreactive T cells that could contribute to lung injury.

Animals↗

PubMed2006

A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion.

Stromal cells in lymphoid tissues provide microenvironmental fields required for the triggering of efficient immune responses. Fibroblastic reticular cells (FRCs) are one of the integral constituents of such stromal fields; they construct the reticular network and are considered to regulate immune cells' behavior. However, the factors that mediate the interaction between lymphocytes and FRCs are poorly understood. Here we show that a mouse lymph node (LN)-derived FRC cell line, BLS4, expresses a transmembrane chemokine, CXC chemokine ligand (CXCL) 16, in response to tumor necrosis factor alpha (TNFalpha) and IFNgamma. TNFalpha-induced expression of CXCL16 depends on NFkappaB, p38 MAPK and PKA. Matrix metalloproteinase activity is required for producing soluble CXCL16 in the culture supernatant, likely via shedding at the juxtamembrane region of the extracellular domain. IL-12 enhances the expression of CXCR6 in anti-CD3/CD28-stimulated CD8+ T cells and their adhesion to the BLS4 cell surface in a TNFalpha-dependent fashion. The adherence is significantly inhibited in the presence of both anti-CXCL16 and anti-vascular cell adhesion molecule 1 (VCAM-1) antibodies. CXCL16 expression is also detected in the FRCs in LN sections and in gp38+VCAM-1+ FRCs isolated from LNs. Taken together, these findings suggest that CXCL16 is an important mediator of lymphocyte-stromal interaction within lymphoid tissues.

Animals↗

PubMed2006

Ginseng saponins diminish adverse vascular effects associated with chronic methionine-induced hyperhomocysteinemia.

Recent studies have shown that Panax ginseng has a variety of beneficial effects on the cardiovascular systems. Homocysteine (Hcy), which is derived from L-methionine (Met), has been closely associated with the increased risk of cardiovascular diseases. In the present study, we examined whether in vivo long-term administration of ginseng saponins (GS), active ingredients of Panax ginseng, attenuate adverse vascular effects associated with chronic Met-induced hyperhomocysteinemia (H-Hcy). We found that plasma Hcy level, which was measured after 30 and 60 d, in GS (100 mg/kg)+Met co-administration group was significantly reduced when it was compared with Met alone treatment group. We could also observe the alleviation of endothelial damages of aortic artery vessels in GS (100 mg/kg)+Met co-administration group compared with Met alone treatment group. We compared aortic vasocontractile and vasodilatory responses between Met alone and GS (100 mg/kg)+Met co-treatment groups. We found that norepinephrine-induced vasocontractile responses were greatly decreased in GS (100 mg/kg)+Met co-treatment group and that carbachol-induced dilatory responses were greatly enhanced in GS (100 mg/kg)+Met co-administration groups as compared with Met alone treatment group. The present results indicate that in vivo long-term administration of GS attenuates adverse vascular effects associated with chronic Met-induced H-Hcy in rats.

Animals↗

PubMed2005

Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats.

The precise cause of neuronal cell death in Huntington's disease (HD) is not known. Systemic administration of 3-nitropropionic acid (3-NP), an irreversible succinate dehydrogenase inhibitor, not only induces a cellular ATP depletions but also causes a selective striatal degeneration similar to that seen in HD. Recent accumulating reports have shown that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, we examined in vitro and in vivo effects of GTS on striatal neurotoxicity induced by repeated treatment of 3-NP in rats. Here, we report that systemic administration of GTS produced significant protections against systemic 3-NP- and intrastriatal malonate-induced lesions in rat striatum with dose-dependent manner. GTS also improved significantly 3-NP-caused behavioral impairment and extended survival. However, GTS itself had no effect on 3-NP-induced inhibition of succinate dehydrogenase activity. To explain the mechanisms underlying in vivo protective effects of GTS against 3-NP-induced striatal degeneration, we examined in vitro effect of GTS against 3-NP-caused cytotoxicity using cultured rat striatal neurons. We found that GTS inhibited 3-NP-induced intracellular Ca(2+) elevations. GTS restored 3-NP-caused mitochondrial transmembrane potential reduction in cultured rat striatal neurons. GTS also prevented 3-NP-induced striatal neuronal cell deaths with dose-dependent manner. The EC(50) was 12.6 +/- 0. 7microg/ml. These results suggest that in vivo protective effects of GTS against 3-NP-induced rat striatal degeneration might be achieved via in vitro inhibition of 3-NP-induced intracellular Ca(2+) elevations and cytotoxicity of striatal neurons.

Analysis of Variance↗

PubMed2005

The influence of endotracheal tube tip design on nasal trauma during nasotracheal intubation: magill-tip versus murphy-tip.

UNLABELLED: We performed this study to assess the influence of endotracheal tube (ETT) tip design (Murphy-tip versus Magill-tip) on nasal trauma during nasotracheal intubation with a conventional polyvinyl chloride ETT. Patients were randomly allocated to one of four groups (n = 25 each): Magill-tipped ETT and Murphy-tipped ETT with or without thermosoftening. After preparation with a vasoconstrictor, the selected, well-lubricated ETT was advanced blindly into the nasopharynx, and intubation was completed under direct laryngoscopy. The severity of epistaxis was estimated based on the distance that blood had traveled up the suction catheter and tubing. Without thermosoftening, the Murphy-tipped ETT produced more severe epistaxis than the Magill-tipped ETT (P < 0.05). Thermosoftening effectively reduced the severity of epistaxis for both conventional types of ETT (P < 0.05). However, there was no difference in the severity of epistaxis and the incidence of nasal injury and pain between the Magill-tipped, non-thermosoftened ETT and Murphy-tipped, thermosoftened ETT. Thermosoftening is recommended because it decreases the trauma during nasotracheal intubation. However, if one chooses to use a normal ETT, the Magill-tipped ETT will cause fewer traumas than the Murphy-tipped ETT. IMPLICATIONS: During nasotracheal intubation with conventional endotracheal tubes, Magill-tipped, non-thermosoftened tubes seem to be comparable to Murphy-tipped, thermosoftened tubes with regard to trauma on the nasal mucosa.

Adult↗

PubMed2005

Role of apoptosis in the pathogenesis of Asian and South American foot-and-mouth disease viruses in swine.

In this study, we performed experiments to evaluate the extend of the process of apoptotic cell death by foot-and-mouth disease virus (FMDV). Apoptosis can also occur in some virus-infected cells, and ability of viruses to either inhibit or promote apoptosis may influence the pathologic outcome of infection. In this study, to determine if apoptosis plays a role in the outcome of FMDV infection in swine, we evaluated apoptosis in diseased tissues collected from pigs inoculated with two different stains of FMDV (O1 Campos and O Taiwan). And host cell DNA fragmentation in diseased tissue from animals which were infected with either virus was evaluated by occurrence of a laddering pattern characteristic of apoptosis. Infection of cultured keratinocytes from swine tongue failed to demonstrate apoptosis in the first few hours of infection, suggesting that cell-to-cell correlation between viral antigen and apoptotic changes, e.g. cytokine secretions by immune system cells, could be critical to initiating apoptosis. Consistent with this finding, we were able to detect the pro-inflammatory cytokine TNF-alpha in diseased tissues. A clear difference in the pathogenicity of the two different FMDV isolates to pigs was not demonstrated in our study.

Animals↗

PubMed2004

Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.

Front-rear asymmetry in motile cells is crucial for efficient directional movement. The uropod in migrating lymphocytes is a posterior protrusion in which several proteins, including CD44 and ezrin/radixin/moesin (ERM), are concentrated. In EL4.G8 T-lymphoma cells, Thr567 phosphorylation in the COOH-terminal domain of ezrin regulates the selective localization of ezrin in the uropod. Overexpression of the phosphorylation-mimetic T567D ezrin enhances uropod size and cell migration. T567D ezrin also induces construction of the CD44-associated polar cap, which covers the posterior cytoplasm in staurosporine-treated, uropod-disrupted EL4.G8 cells or in naturally unpolarized X63.653 myeloma cells in an actin cytoskeleton-dependent manner. Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor Y-27632 disrupts the uropod but not the polar cap, indicating that Rho-ROCK signaling is required for posterior protrusion but not for ERM phosphorylation. Phosphorylated ezrin associates with Dbl through its NH2-terminal domain and causes Rho activation. Moreover, constitutively active Q63L RhoA is selectively localized in the rear part of the cells. Thus, phosphorylated ERM has a potential function in establishing plasma membrane "posteriority" in the induction of the uropod in T lymphocytes.

Actins↗

PubMed2004

A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells.

For efficient adaptive immunity, the lymph nodes (LNs) are equipped with a strategically organized microarchitecture, which is largely supported by the reticular network (RN). The RN can be clearly visualized by fluorescence immunohistochemistry coupled with confocal imaging using a monoclonal antibody, ER-TR7, and can be subdivided into four structurally distinct regions, each of which correlates well with the location of distinct immune cell subsets. In addition, we noticed a characteristic reticular structure designated the 'cortical ridge' at the boundary of the T and B zone, in which dendritic cells are preferentially accumulated. In vitro adhesion assays of frozen sections demonstrated a preference of dendritic cells for the cortical ridge rather than the deeper cortex. Adoptive transfer experiments also demonstrated that antigen-bearing dendritic cells migrated to this region from peripheral tissues, especially in the vicinity of the high endothelial venules, and were anchored on the reticular fibers waiting to interact with the antigen-specific T cells. Taken together, the findings obtained in this study provide new insights into how the LN stromal reticulum works as a specialized 'immuno-platform' for tissue compartmentalization and the immune response.

Animals↗

PubMed2002

Differential activation of caspase-3 at two maturational stages during okadaic acid-induced rat neuronal death.

Okadaic acid (OA), a protein phosphatase inhibitor, is used as a research model of Alzheimer's disease to induce tau phosphorylation and neuronal death. We reported previously that OA induces neuronal apoptosis of immature neurons (in vitro days (IVD) 3-5), which is inhibited by cycloheximide (CHX). In this study, we demonstrate that CHX fails to prevent OA-induced neuronal death in mature neurons (IVD 14-15). Upon comparison of both types of dying cells, the immature neurons displayed characteristic features of apoptosis, such as nuclear fragmentation, phosphatidylserine externalization and prominent caspase-3 activation, while the mature neurons showed few characteristic features of apoptosis. Lack of the beneficial effects of CHX and the lesser activation of caspase-3 in the mature neurons argue against typical apoptotic neuronal death in the OA-induced neurodegeneration model.

Animals↗

PubMed2002

Protective effect of ginsenosides, active ingredients of Panax ginseng, on kainic acid-induced neurotoxicity in rat hippocampus.

Ginsenosides are known to attenuate glutamate-induced cell injuries in vitro. We investigated the in vivo effect of ginsenosides on kainic acid (KA)-induced neurotoxicity in rat hippocampus using the methods of acid fuchsin (AF) staining and heat-shock protein-70 (HSP-70) immunoreactivity to detect neuronal death and stress, respectively. Pretreatment of ginsenosides (50 or 100 mg/kg for 7 days) via intraperitoneal (i.p.) administration significantly attenuated KA (10 mg/kg i.p.)-induced cell death by decreasing AF-positive neurons in both CA1 and CA3 regions of rat hippocampus compared with KA treatment alone. Pretreatment of ginsenosides (50 or 100 mg/kg for 7 days) via i.p. administration also significantly suppressed KA-induced induction of HSP-70 in both regions of rat hippocampus. These results show that ginsenosides are effective in protecting hippocampal CA1 and CA3 cells against KA-induced neurotoxicity.

Animals↗