Biomedical subjects

S Chun

Publications and source records attributed to S Chun.

At least 37 records · Page 2Linked to original sources

PubMed2001

Influence of isoproterenol on the accelerated junctional rhythm observed during radiofrequency catheter ablation of atrioventricular nodal slow pathway conduction.

BACKGROUND: Accelerated junctional rhythm (AJR) has been considered as a sensitive but rather nonspecific marker of successful radiofrequency (RF) ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, AJR also occurs commonly during isoproterenol infusion. We therefore investigated the effect of isoproterenol on the significance of AJR while attempting slow pathway ablation. METHODS: Forty patients with AVNRT underwent slow pathway ablation. Sixty-nine RF applications accompanied by AJR were observed and were separated into 2 groups: applications performed without (group I, n = 26) and with (group II, n = 43) isoproterenol infusion. The specificity of AJR for successful ablation for each group was calculated. RESULTS: The specificity of AJR in groups I and II was 73% (19/26) and 49% (21/43), respectively (P <.05). There was no significant difference between the groups in the atrial electrogram width, atrial/ventricular electrogram amplitude ratio, the time from application onset to AJR emergence, or AJR cycle length. The catheter-tip temperature at AJR emergence was significantly lower (47 degrees C +/- 3 degrees C vs 52 degrees C +/- 3 degrees C, P <.001) and the ratio of junctional beats to total heart beats during RF application was significantly greater (46% +/- 24% vs 33% +/- 18%, P <.05) in group II compared with group I. CONCLUSIONS: Isoproterenol lowers the threshold of AJR emergence during RF application and thereby lowers the specificity of AJR for successful ablation. Complete washout of isoproterenol may therefore improve the specificity of AJR during RF ablation in patients with AVNRT.

Adolescent↗

PubMed2001

Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines.

In this study, we examined the effects of murine chemokine DNA, as genetic adjuvants given mucosally, on the systemic and distal mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV) by using the mouse model. The CC chemokines macrophage inflammatory protein 1beta (MIP-1beta) and monocyte chemotactic protein 1 (MCP-1) biased the immunity to the Th2-type pattern as judged by the ratio of immunoglobulin isotypes and interleukin-4 cytokine levels produced by CD4(+) T cells. The CXC chemokine MIP-2 and the CC chemokine MIP-1alpha, however, mounted immune responses of the Th1-type pattern, and such a response rendered recipients more resistant to HSV vaginal infection. In addition, MIP-1alpha appeared to act via the upregulation of antigen-presenting cell (APC) function and the expression of costimulatory molecules (B7-1 and B7-2), whereas MIP-2 enhanced Th1-type CD4(+) T-cell-mediated adaptive immunity by increasing gamma interferon secretion from activated NK cells. Our results emphasize the value of using the mucosal route to administer DNA modulators such as chemokines that function as adjuvants by regulating the activity of innate immunity. Our findings provide new insight into the value of CXC and CC chemokines, which act on different innate cellular components as the linkage signals between innate and adaptive immunity in mucosal DNA vaccination.

Animals↗

PubMed2001

The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation.

Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50-70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic" state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms.

Animals↗

PubMed2001

Apolipoprotein E polymorphism and serum lipoprotein(a) concentrations in a Korean male population.

The purpose of this study was to investigate the effect of apolipoprotein E polymorphism on lipoprotein(a) metabolism by comparing serum lipoprotein(a) concentration with apolipoprotein E genotype in a Korean male population whose high molecular weight (HMW) lipoprotein(a) frequency was 95-98%. Serum lipoprotein(a), total cholesterol, triglyceride and high-density lipoprotein-cholesterol concentrations were measured and the apolipoprotein E genotype determined in 1189 healthy Korean males. The medians of serum lipoprotein(a) concentration in the apo E 2/3 group (0.105 g/L) and the apo E 3/4 group (0-116 g/L) were significantly lower than that in the apo E 3/3 group (0.155 g/L; P < 0.001). The medians of serum triglyceride were 1.497 mmol/L in the apo E 2/3 group, 1.356 mmol/L in the apo E 3/4 group, and 1.452 mmol/L in the apo E 3/3 group (P<0.05). With the significant difference in the serum lipoprotein(a) concentration in Korean males according to apolipoprotein E genotype, and with the negative correlation between serum triglyceride concentration and serum lipoprotein(a) concentration, it is suggested that apolipoprotein E polymorphism and serum triglyceride participate in the metabolism of lipoprotein(a) with HMW.

Apolipoproteins E↗

PubMed2000

On the mechanisms of T cell silencing by IL-10 DNA: direct and indirect inhibition of T cell functions.

Previously we reported that mucosal IL-10 DNA administration resulted in long-term suppression of virus-induced inflammatory responses by silencing Th1-type CD4+ T cell functions. However, the mechanism by which IL-10 silences the activity of CD4+ T cells was not clear. The present report has shown that mucosal IL-10 DNA administration led to the reduction of reactivity of T cells following TCR stimulation. IL-10 DNA also downregulated APC functions to stimulate T cells but the effect was temporary. Bystander suppression, including that of IL-10 producing regulatory cells, appeared not to be directly involved in the inhibition of T cell reactivity because both anti-IL-10 and anti-IL-10R could not block the suppression of T cell functions. This silenced state could be maintained following adoptive transfer to untreated animals. The nature of the silencing appears to be a reversible anergic state since Ag stimulation in the presence of exogenous IL-2 restored T cell reactivity. Furthermore, IL-10-induced silenced T cells could be induced in vitro by culturing the T cells with rIL-10 in the presence or the absence of antigen stimulation. This state persisted in the absence of rIL-10 and persisted for at least 3 days. A more notable effect, however, was observed when the T cells were incubated with IL-10 in the presence of APC and Ag. These results indicate that IL-10 induced a long-term silenced state in T cells by direct and indirect inhibition of T cell functions.

Adjuvants, Immunologic↗

PubMed2000

Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice.

Inducible NO synthase (iNOS) present in human atherosclerotic plaques could contribute to the inflammatory process of plaque development. The role of iNOS in atherosclerosis was tested directly by evaluating the development of lesions in atherosclerosis-susceptible apolipoprotein E (apoE)-/- mice that were also deficient in iNOS. ApoE-/- and iNOS-/- mice were cross-bred to produce apoE-/-/iNOS-/- mice and apoE-/-/iNOS+/+ controls. Males and females were placed on a high fat diet at the time of weaning, and atherosclerosis was evaluated at two time points by different methods. The deficiency in iNOS had no effect on plasma cholesterol, triglyceride, or nitrate levels. Morphometric measurement of lesion area in the aortic root at 16 wk showed a 30-50% reduction in apoE-/-/iNOS-/- mice compared with apoE-/-/iNOS+/+ mice. Although the size of the lesions in apoE-/-/iNOS-/- mice was reduced, the lesions maintained a ratio of fibrotic:foam cell-rich:necrotic areas that was similar to controls. Biochemical measurements of aortic cholesterol in additional groups of mice at 22 wk revealed significant 45-70% reductions in both male and female apoE-/-/iNOS-/- mice compared with control mice. The results indicate that iNOS contributes to the size of atherosclerotic lesions in apoE-deficient mice, perhaps through a direct effect at the site of the lesion.

Animals↗

PubMed2000

Hepatic expression of apolipoprotein E inhibits progression of atherosclerosis without reducing cholesterol levels in LDL receptor-deficient mice.

Apolipoprotein E (apoE) is a multifunctional protein synthesized by the liver and by tissue macrophages. Plasma apoE (derived primarily from the liver) regulates plasma lipoprotein metabolism, but macrophage-derived apoE was shown to slow the progression of atherosclerosis independent of plasma lipid levels. We utilized liver-directed gene transfer to test the hypothesis that hepatic expression of human apoE would inhibit atherogenesis even in a model in which apoE expression has little effect on plasma lipoproteins. LDL receptor-deficient mice fed a western-type diet for 5 weeks were injected with a second-generation recombinant adenovirus encoding human apoE3 or control virus. Plasma cholesterol levels were not significantly different in the two groups of mice after virus injection. Four weeks after injection, atherosclerosis was examined using three independent assays. Expression of apoE was associated with significantly reduced atherosclerosis compared with control mice in both the aortic arch (decreased by 43%) and the aortic root (decreased by 59%). In summary, hepatic overexpression of apoE inhibited progression of atherosclerosis in LDL receptor-deficient mice without reducing plasma cholesterol levels. This finding indicates that liver-derived plasma apoE can influence early atherogenesis through mechanisms other than modulation of lipoprotein metabolism and that liver-directed gene transfer and overexpression of apoE may be a therapeutic approach to atherosclerosis.

Adenoviridae↗

PubMed2000

In vivo antioxidant effect of green tea.

OBJECTIVE: The object of this study was to investigate the in vivo antioxidant effect of green tea and dosage effect of green tea on antioxidant effect. DESIGN: We tested 10 healthy subjects (aged 23-25 y, five women and five men) with overnight fasting. The total antioxidant capacity of plasma was measured at baseline and 60 min and 120 min after ingestion of 150 ml green tea. Green tea was prepared by infusing 2.5 g of dried green tea leaves for 2 min at 80 degrees C in 150 ml of water. In the second week, they took 300 ml of tea (5.0 g of green tea leaves) and, in the third week, 450 ml of tea (7.5 g of green tea leaves). The total antioxidant capacities of plasma were determined with a Total Antioxidant Kit (Randox Laboratories Ltd, UK) using a Cobas Mira analyser (Roche Diagnostic Systems Inc., Switzerland). The mean intra-assay coefficient of variation was 1.2%. RESULTS: The total antioxidant capacity of plasma increased by 1.1% at 60 min and 2.1% at 120 min over baseline value in subjects consuming 150 ml of green tea, which was statistically not significant. However, total antioxidant capacity of plasma after consuming 300 ml of green tea showed a significant increase of 7.0% after 60 min and 6.2% after 120 min (P<0.0001), and after consuming 450 ml 12.0% after 60 min and 12.7% after 120 min over baseline value (P<0.0001). CONCLUSIONS: Total antioxidant capacity of plasma was significantly increased after taking green tea in amounts of 300 and 450 ml. A positive increment according to green tea dosage was also observed. SPONSORSHIP: This work was funded by the Pacific Corporation (Korea).

Adult↗

PubMed2000

Distribution of haptoglobin phenotypes in a Korean population, using the semi-automated PhastSystem.

We have established a new phenotyping method for haptoglobin, based on sodium dodecyl sulphate-polyacrylamide gel electrophoresis using the PhastSystem (Pharmacia Biotech, Uppsala, Sweden), followed by immunoblotting for detection. We measured haptoglobin concentrations and determined the haptoglobin phenotypes of 316 healthy Koreans using this method: 31 (9.8%) were of Hp 1-1 type, 140 (44.3%) of Hp 2-1 type and 145 (45.9%) of Hp 2-2 type. The haptoglobin allele frequencies were calculated to be 0.32 for Hp1 and 0.68 for Hp2. We were able to visualize up to 12 bands from the human Hp 2-2 polymeric series, with molecular weights in the range 171.9 x 10(3) to 802.2 x 10(3). The reference range of serum haptoglobin concentrations obtained by the IFCC (International Federation of Clinical Chemistry) standard method was 0.27-2.14 g/L. The serum haptoglobin concentration in Koreans was similar to that of Caucasians, but the Hp1 allele frequency was lower in Koreans. Our method could be used in clinical laboratories as a simple and practical method of haptoglobin phenotyping. In addition, the Hp 2-2 polymeric series could be used as high molecular weight standards.

Alleles↗

PubMed1999

Distribution fate and mechanism of immune modulation following mucosal delivery of plasmid DNA encoding IL-10.

DNA vaccination has been widely studied in several models of vaccination and in the treatment of inflammatory diseases, even though the mechanism involved is still unclear. This report demonstrates that mucosal administration of plasmid DNA leads to rapid and widespread distribution around the body. Dissemination likely occurred via the bloodstream because plasmid DNA was present in blood plasma. The plasmid DNA was also detectable in several tissues including draining lymph nodes, spleen, liver, bone marrow, and even the dermis of ear pinnae. Except for the site of administration, plasmid DNA was no longer detectable in tissues after 3 wk postadministration. RNA and protein expression was also found in the tissues and bloodstream. Animals previously primed by HSV infection and subsequently given IL-10 DNA via the nasal mucosa, showed diminished Ag-induced delayed type hypersensitivity reactions for up to 5 wk posttreatment. The mechanism of modulation involved diminished the Ag-specific proliferation and production of Th1 cytokines. The Ag-specific silencing effects persisted beyond the duration of detectable plasmid encoded protein and was maintained upon adoptive transfer of T cells into a plasmid-free environment. The silenced T cells were not a source of IL-10, and their anergic state was reversible by exposure to Ag in the presence of exogenous IL-2.

Adjuvants, Immunologic↗

PubMed1999

Immune modulation by IL-10 gene transfer via viral vector and plasmid DNA: implication for gene therapy.

In the present report, we have evaluated and compared the modulatory effect of the cytokine interleukin (IL)-10 expressed via viral vector or plasmid DNA on viral antigen-induced cutaneous inflammatory lesions. Our data demonstrate the superior potency of both recombinant vaccinia virus and herpes simplex virus IL-10 expression vectors after single intramuscular administration, but the effects were only short term and only functioned in animals lacking immunity to the viral vectors used for modulation. In contrast, modulatory effects achieved by plasmid DNA expressing IL-10 were delayed in onset and milder in effect but were far more persistent than those achieved by viral vectors. Moreover, plasmid DNA expressing IL-10 provided effective modulation when given repeatedly to animals. Our data also showed that IL-10 gene delivery resulted in a systemic and durable modulatory effect while the effect caused by a single IL-10 protein treatment was transient and confined to the injected site. Our results imply that the viral vector system is superior for obtaining short-term effects, whereas the plasmid DNA approach represents a better strategy to achieve gene therapy to modulate chronic inflammatory lesions.

Animals↗

PubMed1999

Resistance to herpetic stromal keratitis in immunized B-cell-deficient mice.

This study evaluates the role of antibody as an indicator of immunity to ocular challenge with herpes simplex virus (HSV). Two genotypes of mice, BALB/c or BALB/c with mu-chain knockout (muK/O; which lack functional B cells), were immunized systemically either with nonvirulent infectious virus or with a eukaryotic expression plasmid encoding glycoprotein B (gB). Whereas naive muK/O mice were 10- to 100-fold more susceptible to HSV infection than BALB/c mice, following immunization both groups showed similar levels of resistance to ocular challenge. Thus both HSV-immunized groups cleared virus within 3 days and showed no signs of ocular lesions. gB DNA-immunized mice cleared virus less rapidly (5 days), and the incidence of lesions was 10 and 25% in BALB/c and muK/O mice, respectively. Since muK/O mice failed to produce detectable anti-HSV antibody, the mechanism of rapid viral removal was assumed to have a T cell basis. However, T cells would likely not mediate any protection directly since such cells were absent in infected corneas during clearance. A likely mechanism of immunity could involve innate defenses, perhaps enhanced by the action of cytokines released from antigen-reactive CD4+ cells in vascularized tissue adjacent to the cornea. Thus an abrupt inflammatory response consisting principally of neutrophils occurred in the corneal stroma in immune mice, and this subsided when virus disappeared. These data reveal that even though the deficiency in generating antibody renders mice more susceptible to HSV infection, once primed, resistance to disease expression is mediated solely by the cellular components and their products.

Animals↗

PubMed1999

No relationship between serum lipoprotein(a) and albumin concentrations in patients with acute phase response.

The aim of this study was to investigate the relationship between lipoprotein(a) [Lp(a)] and albumin concentrations in the serum of patients with acute phase response (APR). We have compared the Lp(a) concentrations and apolipoprotein [apo(a)] phenotypes of 40 controls with those of 40 APR patients with normoalbuminaemia and 40 APR patients with hypoalbuminaemia. We have also compared concentrations of haptoglobin (Hp) and alpha 1-antitrypsin (AAT) containing a high sialic acid content, similar to Lp(a). The mean serum Lp(a) concentration (SD) of the 40 controls was 0.190 (0.142) g/L. The mean serum Lp(a) concentration was 0.358 (0.257) g/L (P < 0.001) in 80 APR patients. However, there was no difference in serum Lp(a) concentrations between the APR patients with hypoalbuminaemia [0.353 (0.268) g/L] and the APR patients with normoalbuminaemia [0.362 (0.249) g/L]. No significant difference was found in the distributions of apo(a) phenotypes between the controls, the APR patients with hypoalbuminaemia, and the APR patients with normoalbuminaemia (P = 0.183). In the APR patients, the serum concentrations of AAT and Hp were respectively 2.709 (0.822) g/L and 2.631 (1.340) g/L, whereas those of normal controls were respectively 1.422 (0.219) g/L (P < 0.001) and 0.956 (0.442) g/L (P < 0.001). In conclusion, the Lp(a) is one of the acute phase reactants whose synthesis concurrently increases with other APRs, especially those with a high sialic acid content. The increase of the serum Lp(a) concentrations in the APR patients is not related to serum albumin concentration.

Acute-Phase Reaction↗

PubMed1999

The risk groups for coronary heart disease in Koreans. Assessment by distribution of serum lipid concentrations.

Coronary heart disease is the most severe form of disease caused by atherosclerosis; and there is a strong relationship between serum lipid concentrations and atherosclerosis. By decade of life, means, standard deviations and selected percentiles were calculated according to sex for serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride in 69,563 Koreans. The prevalence of dyslipoproteinemias which were related to high risk of coronary heart disease were assessed. The mean concentrations of serum total cholesterol and LDL-C in the Korean population were 5.02 mmol/l and 3.00 mmol/l. The 75th and 90th percentile concentrations of total cholesterol were 5.59 mmol/l and 6.24 mmol/l. The mean concentrations of serum triglyceride and HDL-C were 1.58 mmol/l and 1.30 mmol/l. The hyperlipoproteinemia type IV (4.8%) was the most frequent, followed by Type IIa (4.6%), hypoalphalipoproteinemia (3.3%), and type IIb (0.2%). According to the National Cholesterol Education Program Adult Treatment Panel II, 4.1% of Korean adults needed the initial drug therapy and 10.8% the initial dietary therapy for hypercholesterolemia. The age and sex-specific treatment guidelines for hypercholesterolemia would make it possible that early intervention could be applied to atherosclerosis in Korean adults.

Adolescent↗

PubMed1999

Management of farm-related injuries to the upper extremity.

This article familiarizes physicians with common farm equipment that can cause devastating hand injuries. The focus is on farm-related injuries to the hand and stresses the degree of soft tissue injuries, discusses avulsion injuries, and acute management principles. Types of injuries, their pathophysiology, case reports, and treatments also are reviewed. This article also stresses how these injuries differ from the urban trauma patient.

Accidents, Occupational↗

PubMed1998

Effect of infusion of vasoactive intestinal peptide (VIP)-antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus on the hyperglycemia caused by intracranial injection of 2-deoxy-D-glucose in rats.

We examined the effect of the infusion of a vasoactive intestinal peptide (VIP) antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus (SCN) using osmotic minipump for 3 days (0.2 nmol/ml per h) on the hyperglycemic response to intracerebroventricular injection of 2-deoxy-D-glucose (2DG) (80 micromol) in rats. After the infusion of the VIP antisense the inhibition of VIP expression in the SCN was observed in association with suppressions of the hyperglycemia, hyperglucagonemia and relative hypoinsulinemia due to the 2DG injection. Furthermore, additional intracranial injection of VIP (4 nmol) restored these responses to the 2DG injection in rats treated with the VIP antisense. These findings suggest that VIP neurons in the SCN are involved in the regulation of glucose metabolism.

Animals↗

PubMed1998

Immunomodulation by mucosal gene transfer using TGF-beta DNA.

This report evaluates the efficacy of DNA encoding TGF-beta administered mucosally to suppress immunity and modulate the immunoinflammatory response to herpes simplex virus (HSV) infection. A single intranasal administration of an eukaryotic expression vector encoding TGF-beta1 led to expression in the lung and lymphoid tissue. T cell-mediated immune responses to HSV infection were suppressed with this effect persisting as measured by the delayed-type hypersensitivity reaction for at least 7 wk. Treated animals were more susceptible to systemic infection with HSV. Multiple prophylactic mucosal administrations of TGF-beta DNA also suppressed the severity of ocular lesions caused by HSV infection, although no effects on this immunoinflammatory response were evident after therapeutic treatment with TGF-beta DNA. Our results demonstrate that the direct mucosal gene transfer of immunomodulatory cytokines provides a convenient means of modulating immunity and influencing the expression of inflammatory disorders.

Administration, Intranasal↗

PubMed1998

Role of mucosal immunity in herpes simplex virus infection.

This study evaluates whether the vaginal mucosal surface of immunized mice can prevent invasion by herpes simplex virus (HSV) and aims to identify immune components that affect immunity after challenge at the vaginal mucosa. Despite the induction of both IgA and IgG vaginal Ab following immunization with recombinant vaccinia virus vectors expressing either glycoproteins B or D, viral infection occurred in most animals even after minimal viral dose challenge. Challenged immune animals, including those genetically unable to generate anti-HSV Ab, survived and showed few if any clinical signs of infection. Experiments with T cell subtype knockout animals and depletion with T cell subset-specific MAb indicated that immunity following vaginal challenge was principally dependent on the function of CD4+ T cells. Our results indicate that anti-HSV vaccines may not provide barrier immunity at the vaginal mucosal site but may be adequate to minimize clinical expression of disease.

Administration, Intranasal↗