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Biomedical subjects

W S Shin

Publications and source records attributed to W S Shin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pre-emptive ganciclovir treatment can play a role in restoration of hematopoiesis after allogeneic bone marrow transplantation.

We performed pre-emptive ganciclovir therapy on two allogeneic bone marrow transplant (BMT) recipients with myelosuppression associated with cytomegalovirus (CMV) antigenemia after successful engraftment. During the hypoplastic phase, the nucleated cells in the bone marrow and peripheral blood were revealed to be of donor origin by DNA fingerprinting. These two patients had CMV antigen in their peripheral leukocytes. Following the pre-emptive ganciclovir treatment, both of them showed gradual recovery of granulocytes and platelets. They are still alive with stable bone marrow function. From these results, we suppose that infection or reactivation of CMV can suppress bone marrow function after bone marrow transplantation, and the pre-emptive ganciclovir therapy based on the CMV antigenemia may be beneficial if bone marrow function deteriorates after engraftment.

Adolescent↗
PubMed1997

Molecular epidemiological analysis of quinolone-resistant Escherichia coli causing bacteremia in neutropenic patients with leukemia in Korea.

We analyzed an outbreak of Escherichia coli bacteremia in eight patients with leukemia in a hematology-oncology unit from July to September 1994. The antibiograms and genotypic patterns of the isolates were different, thus suggesting that the outbreak did not originate from a single clone. However, all the isolates were resistant to quinolones, which led us to examine the microbiological records from 1992 to 1994. The incidence of quinolone-resistant E. coli bacteremia in the hematology-oncology unit ranged from 81.8% to 94.6% during this period. We then analyzed 36 more isolates recovered from late 1994 to 1995. Field inversion gel electrophoresis patterns of these isolates were also different. Analysis of the quinolone resistance determining region in gyrA revealed that all the isolates had a double mutation in gyrA. In conclusion, quinolone-resistant E. coli could be an emerging threat to neutropenic patients with leukemia who receive a quinolone prophylactically, and attention must be paid to this trend of resistance.

4-Quinolones↗
PubMed1997

Seroreactivities of proteinases of Candida albicans, C. tropicalis, and C. parapsilosis in sera from various Candida species-infected mice.

From the culture filtrates of C. albicans, C. tropicalis and C. parapsilosis, proteinases were purified using a series of chromatographic steps consisting of DEAE-Sepharose, Sephacryl S-200 and size-exclusion HPLC which removed contaminating mannoproteins and extraneous proteins. Anti-Candida proteinase antibodies in sera from mice infected with various Candida species were detected using ELISA for serodiagnosis of candidiasis. Three proteinases were blotted by homologous and heterologous anti-proteinase antisera on Western blot analysis. All sera from six Candida species-infected mice were reactive with proteinases of C. albicans, C. tropicalis, and C. parapsilosis, although C. glabrata, C. guilliermondii, and C. krusei did not secrete proteinase. The seroreactivities of proteinase with sera from mice infected with homologous C. albicans and C. tropicalis were higher than those with sera from heterologous Candida species-infected mice. These results suggest that three proteinases have at least one common epitope, but its application for diagnosis of candidiasis should be considered with limits of specificity.

Animals↗
PubMed1997

Role of Y chromosome of hypertensive parent in determination of blood pressure in normotensive offspring.

We investigated whether the sex of hypertensive parents mediates determination of blood pressure in their normotensive offspring. We analyzed medical checkup data from 7279 Japanese university students. Six hundred and forty-one students had one hypertensive parent with or without hypertensive grandparents, and 609 of these were available for the present analysis. Blood pressure levels in the students with one hypertensive parent were within the normotensive range; however, the blood pressure levels were higher than those in students without hypertensive relatives, and lower than those in students with two hypertensive parents. In the students with one hypertensive parent, systolic blood pressure levels were significantly higher in the male than in the female students. However, the sex of the hypertensive parent did not affect the blood pressure values of their offspring. Multivariate analyses revealed that body mass index was an independent predictor of systolic blood pressure solely in male students with a hypertensive father, but not in male students with a hypertensive mother. In female students with one hypertensive parent, body mass index was irrelevant to the determination of blood pressure. These findings suggest that different mechanisms determine blood pressure in the offspring of hypertensive parents, and that blood pressure determination mediated by body mass index in male students is linked to hypertensive Y chromosome.

Adolescent↗
PubMed1996

The role of nitric oxide in the cardiovascular system.

Nitric oxide (NO) exerts various pathophysiological effects on the cardiovascular system; inhibition of platelet aggregation or leukocyte adhesion on endothelium and vasorelaxation including lethal hypotension in endotoxic shock. In spite of these significant roles of NO, its direct action on individual cardiovascular cells remains unclarified. Therefore, we have investigated the function of NO on cells which constitute vascular wall and heart, and have found this new evidence. 1) ATP increased intracellular ([Ca2+]i) in vascular endothelial cells (ECs) and decreased [Ca2+]i of adjacently cocultured vascular smooth muscle cells (VSMCs), as detected by 2-D fura-2 image analysis. 2) The [Ca2+]i reduction in cocultured VSMCs with ECs by ATP was attenuated by pretreatment of several types of NO inhibitor, whereas the NO inhibitor potentiated the [Ca2+]i elevation in ECs, suggesting that NO affects VSMCs in a paracrine manner while ECs in an autocrine fashion. 3) Physiological concentration of lysophosphatidylcholine, which is an atherogenic constituent of oxidized LDL, but not native phosphatidylcholine, acted on ECs and VSMCs like a NO inhibitor, indicating that this material attenuates NO effect and disturbs vessel relaxation in the short term. 4) Highly efficient transfection of the ecNOS gene in rat heart showed a toxic effect on individual cardiomyocytes in vivo. In conclusion, NO may exert both beneficial and harmful effects on the cardiovascular system.

Adenosine Triphosphate↗
PubMed1996

Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma. The role of constitutive NF-kappa B activity.

Atherogenesis involves cellular immune responses and altered vascular smooth muscle cell (SMC) function. Cytokines such as interleukin (IL)-1 alpha and interferon-gamma (IFN-gamma) may contribute to this process by activating SMC. To determine whether the anti-atherogenic mediator, nitric oxide (.NO), can modulate cytokine-induced SMC activation, we investigated the effects of various .NO-generating compounds on the expression of intercellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). Induction of ICAM-1 expression by IL-1 alpha and VCAM-1 expression by IFN-gamma was attenuated by .NO donors but not by cGMP analogues. Nuclear run-on assays and transfection studies using various VCAM-1 promoter constructs linked to the chloramphenicol acetyl-transferase reporter gene showed that .NO repressed IFN-gamma-induced VCAM-1 gene transcription, in part, through inhibition of nuclear factor-kappa B (NF-kappa B). Electrophoretic mobility shift assay revealed that SMC possess basal constitutive NF-kappa B activity, which was augmented by treatment with IL-1 alpha. In contrast, IFN-gamma induced and activated interferon regulatory factor (IRF)-1 but had little effect on basal constitutive NF-kappa B activity. .NO donors had no inhibitory effect on IRF-1 activation but did inhibit basal and IL-1 alpha-stimulated NF-kappa B activation. These findings suggest that the induction of ICAM-1 and VCAM-1 expression requires NF-kappa B activation and that .NO attenuates IFN-gamma-induced VCAM-1 expression primarily by inhibiting basal constitutive NF-kappa B activity in SMC.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture.

To elucidate the intracellular Ca2+ (Ca2+i ) transient responsible for nitric oxide (NO) production in endothelial cells (ECs) and the subsequent Ca2+i reduction in vascular smooth muscle cells (VSMCs), we administrated four agonists with different Ca2+i-mobilizing mechanisms for both cells in iso- or coculture. We monitored the Ca2+i of both cells by two-dimensional fura-2 imaging, simultaneously measuring NO production as NO2-. The order of potency of the agonists in terms of the peak Ca2+i in ECs was bradykinin (100 nM) > ATP (10 microM) > ionomycin (50 nM) > thapsigargin (1 microM). In contrast, the order in reference to both the extent of Ca2+i reduction in cocultured VSMCs and the elevation in NO production over the level of basal release in ECs completely matched and was ranked as thapsigargin > ionomycin > ATP > bradykinin. Treatment by NG-monomethyl-L-arginine monoacetate but not indomethacin or glybenclamide restored the Ca2+i response in cocultured VSMCs to the isoculture level. In ECs, when the Ca2+ influx was blocked by Ni2+ or by chelating extracellular Ca2+, all four agonists markedly decreased NO production, the half decay time of the Ca2+i degenerating phase, and the area under the Ca2+i curve. The amount of produced NO hyperbolically correlated to the half decay time and the area under the Ca2+i curve but not to the Ca2+i peak level. Thus, the sustained elevation of Ca2+i in ECs, mainly a result of Ca2+ influx, determines the active NO production and subsequent Ca2+i reduction in adjacent VSMCs. Furthermore, L-arginine but not D-arginine or L-lysine at high dose (5 mM) without agonist enhanced the NO production, weakly reduced the Ca2+i in ECs, and markedly decreased the Ca2+i in VSMCs, demonstrating the autocrine and paracrine effects of NO (Shin, W. S., Sasaki, T., Kato, M., Hara, K., Seko, A., Yang, W. D., Shimamoto, N., Sugimoto, T., and Toyo-oka, T. (1992) J. Biol. Chem. 267, 20377-20382).

Animals↗
PubMed1996

Toxic action of nitric oxide on myocardial cells: direct evidence from gene transfer in vivo.

To examine whether nitric oxide (NO) has a protective effect against Ca2+ overdose or a beneficial action on myocardial cells, we employed direct gene-transfer of endothelial (type III) nitric oxide synthase (eNOS), using HVJ (Sendai virus) coated liposomes and beta-galactosidase (lac-z) as a marker for the transfection. The transfection efficiency of the lac-z gene was comparable with adenovirus as a vector, though the subsequent inflammation was much improved. The lac-z gene transfection was restricted to myoplasm between two intercalated discs, indicating that the transfected gene dose not permeate the disc. Co-transfection with human eNOS gene revealed degraded myoplasm of not only transfected cells but adjacent myocytes, fibrotic changes and infiltration of mononuclear cells seven days after the transfection. Electron microscopy of the lesions revealed a huge accumulation of mitochondria and loss of myofilaments, though fragmentation of nucleus or cytoplasm was not obvious. We conclude that an expression of human eNOS gene in cardiomyocytes causes a degenerative process, incompatible with typical apoptosis.

Animals↗
PubMed1996

Epstein-Barr virus-associated gastric adenocarcinomas among Koreans.

Epstein-Barr virus (EBV)-associated gastric carcinomas have been reported from various regions of the world. Epstein-Barr virus appears to be pathogenetically related to some gastric carcinomas. To determine the incidence of EBV association with gastric carcinomas among Koreans, the authors have studied EBV genome expression in 89 consecutive patients with gastric carcinomas diagnosed at the Catholic University Hospitals in Seoul, Korea, using in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs), and immunohistochemistry for EBV latent membrane proteins (LMP) and CD21 antigen on paraffin sections. Thirty-seven gastric specimens with benign ulcer disease were used controls. EBV-encoded small RNAs were expressed in tumor cell nuclei in 12 patients (13.5%). None of the controls or benign portions of the cases were positive. In the positive cases, all tumor cell nuclei were uniformly stained and the staining intensity was strong. Immunohistochemistry for LMP was positive in 3 of 12 EBERs positive patients and none of EBERs negative patients. EBV latent membrane proteins was localized only in the lymphoid cells infiltrating the tumor in two patients, and tumor cells as well as infiltrating lymphoid cells in one patient. These results indicate that the rate of EBV association with gastric carcinomas in Koreans is relatively high and comparable to other Far Eastern Asian regions. The expression pattern in EBV-associated gastric carcinomas is similar to those of nasopharyngeal carcinomas in which clonality analysis using specific probes to the tandem repeat region of EBV yielded single episomal bands suggesting that EBV infection in EBV-associated gastric carcinomas are also clonal and pathogenetically related to the neoplasm. However, the mechanism of tumorigenesis remains to be elucidated.

Adenocarcinoma↗
PubMed1996

In-vitro effects of cefodizime on leucocyte functions and colony formation from granulocyte-monocyte progenitors.

Infections in immunocompromised patients are often difficult to treat, even with currently available antimicrobial agents. An understanding of the effects of antibiotic therapy on the host's immune response is therefore important when deciding on the clinical management of such patients. Antimicrobial agents which lack immunodepressive effects and/or potentiate the immune response are the goal of current research into the treatment of infections in immunocompromised patients. The effects of cefodizime (1-250 micrograms/mL) in vitro on some functional activities of leucocytes and on colony formation by granulocyte monocyte progenitors were studied to investigate the effects of the antibiotic on the host's immune response. A marked enhancement in the lymphocyte transformation reaction was observed in cells exposed to cefodizime. This effect was dose-dependent. Cefodizime had no significant effect on antibody-dependent cell cytotoxicity or on natural killer cell-mediated cytotoxicity. The chemotactic activity of neutrophils was not influenced by the presence of cefodizime (P > 0.05). The phagocytic activity of neutrophils was significantly increased by cefodizime (P > 0.01). Cefodizime significantly stimulated, in a dose-dependent manner, colony formation by granulocyte-monocyte progenitors (P < 0.01). Results suggest that cefodizime has certain stimulatory effects on immunocompetent cells such as enhancing the transformation reaction of lymphocytes, neutrophil phagocytosis and colony formation by granulocyte-monocyte progenitors. Further studies are required to clarify the mechanisms responsible for these effects.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1995

Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase.

The atherogenic effects of low-density lipoprotein (LDL) may be mediated, in part, by its effect(s) on endothelial-derived nitric oxide (NO). To determine whether LDL can modulate NO production by changing NO synthase expression, we treated human saphenous vein endothelial cells with increasing concentrations of native or oxidized LDL (0-100 micrograms/ml) for various durations (0-72 h). Oxidized, but not native LDL caused a time-dependent decrease in steady-state NO synthase mRNA levels. This coincided with a maximal 56% decrease in NOS activity was determined by [3H]arginine to [3H]citrulline conversion. In the presence of actinomycin D, treatment with oxidized LDL reduced the half-life of NO synthase mRNA from 36 to 10 h. This decrease in NO synthase mRNA correlated with the degree of LDL oxidation and was attenuated by pretreatment with cycloheximide. Nuclear run-off studies showed a biphasic transcriptional pattern of NO synthase gene with an initial 25% decrease during the first 6 h followed by a maximal 2.2-fold increase over baseline during the subsequent 18 h. These results indicate that oxidized LDL regulates endothelial NOS expression through a combination of early transcriptional inhibition and post-transcriptional mRNA destabilization.

Amino Acid Oxidoreductases↗
PubMed1995

Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.

To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall.

Base Sequence↗
PubMed1995

Immunogenicity of Vi capsular polysaccharide vaccine evaluated for three years in Korea.

The immunogenicity of a single dose of Salmonella typhi(S.typhi) Vi capsular polysaccharide(CPS) vaccine was evaluated before, and at 1, 3, 12, and 36 months after vaccination. Eighty-five adults(20-28 years of age) and sixty-four children(8-16 years of age) received a single dose of 25 micrograms Vi CPS vaccine intramuscularly, and antibody titers to Vi CPS were measured by passive hemagglutination. Of 149 vaccinees, 138(92.6%) showed seroconversion at 1 month after vaccination, and then 138 out of 141(97.9%) did at 3 months. Of 137 vaccinees, 116(84.7%) maintained a persistent rise in Vi antibody titer 12 months after vaccination, and 55 out of 100(55.0%) had a 4-fold or greater rise at 36 months. No significant adverse reactions were observed. Booster injection may be needed 3-5 years after vaccination.

Adolescent↗
PubMed1994

Multiple effects of haemin binding on protease susceptibility of bovine serum albumin and a novel isolation procedure for its large fragment.

The effects of ligand binding on the proteolytic susceptibility of BSA were investigated. The rate for proteolytic digestion with either trypsin or chymotrypsin decreased in the presence of bilirubin and fatty acids, suggesting that overall albumin conformation is stabilized by these ligands. In contrast, haemin showed multiple effects on a proteolytic digestion pattern: the rate for the degradation of intact albumin greatly increased, but a large 45 kDa fragment accumulated during proteolytic digestion in the presence of this ligand. This unique fragmentation pattern allowed us to isolate the 45 kDa fragment at a high yield (about 30% on a molar basis) by one-step purification. Sequence analyses indicated that this fragment lies between residues Thr190 and Ala583, which constitutes domains II and III of the albumin molecule. Far-u.v. c.d. spectra strongly suggested that the secondary structure in the intact albumin is almost retained in the 45 kDa fragment. The isolated 45 kDa fragment showed haemin-binding ability, as evaluated by spectroscopic titration; upon re-digestion of the 45 kDa fragment, haemin showed strong protective effects. These results were consistent with the idea that haemin binding to BSA induces an increased protease susceptibility in the loop region between domains I and II, but in the overall conformation of domains II and III, a protease-resistant property.

Animals↗
PubMed1994

Epstein-Barr virus associated posttransplant malignant lymphoma in renal allograft recipients.

We report two cases of posttransplant malignant lymphoma(PTML) of B cell origin associated with Epstein-Barr virus(EBV) infection. They were a 52-year-old male and a 37 year-old-female, in whom intermediate-grade diffuse malignant lymphomas of large cell type developed in the submandibular area and jejunum, respectively. DNA and RNA in situ hybridization revealed the presence of EBV-specific DNA and RNA sequences in the tumor cells.

Adult↗