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Biomedical subjects

S S Yoon

Publications and source records attributed to S S Yoon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Oncolysis of diffuse hepatocellular carcinoma by intravascular administration of a replication-competent, genetically engineered herpesvirus.

Herpes simplex virus type 1 (HSV-1) replication within tumors can mediate tumor regression (oncolysis). The genetically engineered, HSV-1 mutant rRp450 does not express viral ribonucleotide reductase and is therefore replication conditional. During the course of infection, rRp450 expresses the cytochrome P450 transgene and HSV-1 thymidine kinase gene, thereby enabling it to bioactivate the prodrugs cyclophosphamide and ganciclovir, respectively. rRp450 replication in hepatocellular carcinoma (HCC) cells is cytotoxic and liberates progeny virion that infect adjacent tumor cells. rRp450-mediated oncolysis is enhanced in the presence of cyclophosphamide, whereas it is inhibited in the presence of ganciclovir. As a consequence of defective viral ribonucleotide reductase expression, the yield of rRp450 progeny virions from infection of HCC cells is 3 to 4 log orders greater than that from infection of normal hepatocytes. This is associated with dramatic tumor reduction of diffuse HCC after a single intravascular administration of rRp450. rRp450 holds the promise of the dual therapeutic benefit of selective oncolysis and P450 transgene delivery.

Animals↗
PubMed2000

Differential activation of MAP kinase family members triggered by CD99 engagement.

The molecular basis for the modulatory properties of CD99 is not well understood. Treatment of human Jurkat T lymphocytes with anti-CD99 antibody led to activation of three mitogen-activated protein kinase (MAPK) members, ERK, JNK, and p38 MAPK, along with homotypic aggregation. While phosphorylation of ERK and JNK was inhibited by the pretreatment of a PKC inhibitor, bisindolylmaleimide I, activation of p38 MAPK was upregulated by the same pretreatment. The signaling pathways to MAPKs by CD99 engagement were independent of PI-3 kinase, distinguishing from those by CD3 engagement. Among MAPKs, ERK pathway was essential for homotypic aggregation together with intracytoplasmic Ca(2+).

Antibodies, Monoclonal↗
PubMed2000

CD44s expression in human colon carcinomas influences growth of liver metastases.

CD44 is a family of cell-surface adhesion molecules which exist in several isoforms arising from mRNA alternative. Malignant transformation of colonic mucosa is associated with alterations in CD44 expression, which result in up-regulation of high-molecular-weight CD44 isoforms and down-regulation of CD44s. We have demonstrated that stable transfection of CD44s into colon-carcinoma cell lines reduces their tumorigenicity. To understand the influence of CD44s expression on the metastatic potential of human colon carcinomas, we measured the ability of several different CD44s-transfected colon carcinomas to establish experimental liver metastases following splenic inoculation in mice. We observed that introduction of CD44s into 2 different human colon carcinoma cell lines, HT29 and KM12C6, resulted in reduced growth of liver metastases by as much as 75%. To explore the relationship between hyaluronate adhesion and metastasis, we transfected HT29 cells with cDNA encoding a mutant CD44s that does not bind to hyaluronate. HT29 transfectants expressing this mutant CD44s demonstrate an 84% reduction in growth of liver metastases, despite minimal binding to hyaluronate by the mutant CD44s. In concert, these results indicate that CD44s down-regulation, which occurs with malignant transformation of colonic mucosa, is associated with enhanced growth of experimental liver metastases. Consequently, the functional consequences of CD44s down-regulation in colon carcinomas may be just as significant as the consequences of up-regulation of other CD44 isoforms.

Alternative Splicing↗
PubMed2000

An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma.

Viruses used for gene therapy are usually genetically modified to deliver therapeutic transgenes and prevent viral replication. In contrast, replication-competent viruses may be used for cancer therapy because replication of some viruses within cancer cells can result in their destruction (oncolysis). Viral ribonucleotide reductase expression is defective in the HSV1 mutant hrR3. Cellular ribonucleotide reductase, which is scarce in normal liver and abundant in liver metastases, can substitute for its viral counterpart to allow hrR3 replication in infected cells. Two or three log orders more of hrR3 virions are produced from infection of colon carcinoma cells than from infection of normal hepatocytes in viral replication assays. This viral replication is oncolytic. A single intravascular administration of hrR3 into immune-competent mice bearing diffuse liver metastases dramatically reduces tumor burden. hrR3-mediated tumor inhibition is equivalent in immune-competent and immune-incompetent mice, suggesting that viral oncolysis and not the host immune response is the primary mechanism of tumor destruction. HSV1-mediated oncolysis of diffuse liver metastases is effective in mice preimmunized against HSV1. These results indicate that replication-competent HSV1 mutants hold significant promise as cancer therapeutic agents. Yoon, S. S., Nakamura, H., Carroll, N. M., Bode, B. P., Chiocca, E. A., Tanabe, K. K. An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma.

Animals↗
PubMed1999

Mouse endostatin inhibits the formation of lung and liver metastases.

Angiogenesis is required for tumor formation. Several studies have demonstrated that tumor angiogenesis is regulated by a balance between proangiogenesis and antiangiogenesis factors and that this balance varies in different organ environments. To investigate whether expression of an angiogenesis inhibitor by cancer cells could alter this balance and prevent tumor formation in different organ environments, we engineered stable transfectants from RenCa mouse renal carcinoma cells and SW620 human colon carcinoma cells to constitutively secrete a mouse endostatin protein with c-myc and polyhistidine (His) tags. Production and secretion of the endostatin-c-myc-His fusion protein by endostatin-transfected cells were confirmed by immunofluorescence staining and Western blot analysis. The endostatin transfectants and control transfectants, stably transfected with a control plasmid, had similar in vitro growth rates compared with their parental cell lines. Conditioned medium from endostatin-transfected cells inhibited human umbilical vein endothelial cell proliferation by 36-51% compared with conditioned medium from control cells. After inoculation into mice, flank tumors from endostatin-transfected cells were 73-91% smaller than flank tumors from control cells after 3 weeks. Inoculation of a cell mixture containing 25% endostatin-transfected cells and 75% control cells resulted in inhibition of flank tumor formation as effective as after inoculation of 100% endostatin-transfected cells. Formation of lung metastases by RenCa endostatin-transfected cells and formation of liver metastases by SW620 endostatin-transfected cells were dramatically inhibited compared with formation of metastases by control cells. These findings demonstrate that endostatin can inhibit tumor formation in different organ environments and that gene delivery of endostatin into even a minority of tumor cells may be an effective strategy to prevent progression of micrometastases to macroscopic disease.

Animals↗
PubMed1999

Partial characterization and cloning of leuconocin J, a bacteriocin produced by Leuconostoc sp. J2 isolated from the Korean fermented vegetable Kimchi.

Leuconostoc sp. J2, isolated from naturally fermented Kimchi, produced a bacteriocin which was named leuconocin J. This bacteriocin exhibited an inhibitory activity against several lactic acid bacteria and some food-borne pathogens. The antimicrobial substance was secreted into the medium during the late log phase. It appears to be proteinaceous since its activity was completely inactivated by a range of proteolytic enzymes, and it was also relatively heat-stable. The bacteriocin was partially purified by ammonium sulphate precipitation, following dialysis. The apparent molecular mass of partially purified bacteriocin, as indicated by activity detection after Tricine-SDS-PAGE, was 2.5-3.5 kDa. Leuconostoc sp. J2 plasmid DNA digested by EcoRI was cloned into pUC118 and transformed into Escherichia coli DH5 alpha. Phenotypic expression of the bacteriocin production was detected in transformants harboring pULBJ5.5. Finally, Southern blotting with the 2.3 kb insert as a probe against plasmid digests of Leuconostoc sp. J2 revealed that the cloned foreign DNA originated from Leuconostoc sp. J2.

Bacteriocins↗
PubMed1999

Cloning and sequencing of beta-1,4-endoglucanase gene (celA) from Pseudomonas sp. YD-15.

A beta-1,4-endoglucanase gene (celA) from Pseudomonas sp. YD-15 was cloned in Escherichia coli DH5 alpha and its nucleotide sequence determined. The open reading frame of celA was 1830 base pairs and the enzyme was composed of 609 amino acids with a molecular weight of 63,617 Da. The deduced amino acid sequence and putative active site of CelA had high amino acid homology with family E cellulases. By dot blot analysis, the induction of celA according to carbon sources was determined. The transcripts hybridizing to the internal fragment of celA were detected in total RNA isolated from Pseudomonas sp. YD-15 cells grown on avicel and glycerol, but not from cells grown on glucose and cellobiose.

Amino Acid Sequence↗
PubMed1999

Surgical treatment and other regional treatments for colorectal cancer liver metastases.

The liver is the most common site of distant metastasis from colorectal cancer. About one-fourth of patients with liver metastases from colorectal cancer have no other sites of metastasis and can be treated with regional therapies directed toward their liver tumors. Surgical resection of colorectal cancer liver metastases can result in a 24%-38% five-year survival, but only a minority of patients are candidates for resection. Other regional therapies such as cryosurgery, radiofrequency ablation, and hepatic intra-arterial chemotherapy may be offered to patients with unresectable but isolated liver metastases. The efficacy of these treatments is still being determined. For most patients with spread of metastatic colorectal cancer beyond the liver, systemic chemotherapy rather than regional therapy is a more appropriate option.

Antineoplastic Agents↗
PubMed1998

Deaths from unintentional carbon monoxide poisoning and potential for prevention with carbon monoxide detectors.

CONTEXT: Unintentional carbon monoxide (CO) poisoning causes approximately 2100 deaths in the United States per year, but the use of CO detectors could potentially prevent many of these deaths. OBJECTIVE: To describe the epidemiology of potentially preventable unintentional CO poisoning deaths in New Mexico. DESIGN: Descriptive analysis. POPULATION STUDIED: A total of 136 deaths from CO poisoning investigated by the New Mexico Office of the Medical Investigator, 1980 through 1995. MAIN OUTCOME MEASURES: Characteristics of deaths from CO poisoning; estimates of the number of deaths potentially preventable with CO detectors. RESULTS: Of 136 people whose deaths were classified as "unintentional carbon monoxide poisoning, not fire related," 49 (36%) most likely were asleep when poisoned. Thirty-nine (49%) of 80 people whose deaths were identified as "residential fatalities" most likely were asleep vs 10 (18%) of 56 of those whose deaths were identified as occurring in or around motor vehicles. A blood-alcohol level greater than 0.01% was present in 56 (42%) of the decedents. Among decedents who had a negative blood-alcohol level (52 in residences and 26 in vehicles), an electronic audible CO detector may have prevented CO poisoning; whereas, among those who had a negative blood-alcohol level and most likely were awake at the time of CO exposure (28 in residences and 23 in vehicles), an electronic detector or a nonaudible, chemical reagent type detector may have prevented CO poisoning. CONCLUSION: Differences exist between deaths due to unintentional CO poisoning that occur in residences and those that occur in or around motor vehicles. Carbon monoxide detectors, whether the electronic or chemical reagent types, may have prevented approximately half of these deaths. The high proportion of decedents with alcohol in their blood indicates that effective public health campaigns must address the role of alcohol in CO poisoning deaths.

Accidents, Home↗
PubMed1998

Cancer gene therapy using a replication-competent herpes simplex virus type 1 vector.

OBJECTIVE: The authors investigate the efficacy of hrR3, a viral vector derived from herpes simplex virus type 1 (HSV 1), in destroying colon carcinoma cells in vitro and in vivo. The effect of adding the prodrug ganciclovir in combination with hrR3 infection also is assessed. SUMMARY BACKGROUND DATA: Most cancer gene therapy strategies use viral vectors that are incapable of replication. The HSV 1 vector hrR3 is capable of replication, and its replication is cytotoxic to cells. hrR3 also possesses the HSV-thymidine kinase gene, which converts ganciclovir into a toxic metabolite. Thus, the addition of ganciclovir to hrR3-infected cells may enhance the ability of hrR3 to destroy tumor cells. To increase specificity for tumor cells, hrR3 has a mutated ribonucleotide reductase gene and replicates selectively in cells with high levels of endogenous rbonucleotide reductase. Actively dividing cells such as tumor cells have high levels of endogenous ribonucleotide reductase for synthesis of DNA precursors. The authors are interested in the use of HSV 1 vectors to treat liver metastases from colorectal cancer. METHODS: Ribonucleotide reductase expression in several colon carcinoma cell lines and in primary cultures of human hepatocytes was determined by Western blot analysis. hrR3-mediated cytotoxicity in the colon carcinoma cell lines was determined using an in vitro assay. The human colon carcinoma cell line HT29 was injected into the flanks of nude mice followed by intratumoral injection of hrR3. Tumor growth rate was assessed with and without the addition of intraperitoneal ganciclovir. RESULTS: Ribonucleotide reductase levels in colon carcinoma cell lines are much higher than in primary cultures of human hepatocytes. hrR3 efficiently destroys colon carcinoma cell lines in vitro. A single intratumoral injection of hrR3 into HT29 flank tumors significantly reduces tumor growth rate, and the administration of ganciclovir has no additive effect. CONCLUSIONS: The inherent cytotoxicity of hrR3 replication effectively destroys colon carcinoma cells in vitro and in vivo. This cytotoxicity is not enhanced in vivo by the addition of ganciclovir. In the future, more efficacious and selective HSV 1 vectors may be useful in the treatment of cancer.

Animals↗
PubMed1998

Type A behavior and stroke: high tenseness dimension may be a risk factor for cerebral infarction.

Although type A behavior (TAB) has been shown to be related to coronary heart disease, the relationship between TAB and stroke was rarely investigated. We studied TAB in stroke patients with the use of the questionnaire developed by Eysenck and Fulker that has 4 subdimensions: Tenseness, Ambition, Activity, and Unrepressed. The questionnaire was administered to 224 patients with acute stroke and 100 controls. The patients were further classified as having cerebral infarction (large vessel infarction and small vessel infarction), and intracerebral hemorrhage. We found that, among the 4 subdimensions, only the Tenseness score was significantly higher in patients with cerebral infarction but not in those with intracerebral hemorrhage compared to the controls. On subgroup analysis, Tenseness score was higher in patients with large vessel infarction but not in those with small vessel infarction than in those with intracerebral hemorrhage or controls. The association of high Tenseness score with cerebral infarction (and large vessel infarction) remained significant after multiple logistic analysis adjusting various risk factors such as hypertension, diabetes mellitus, cigarette smoking and habitual alcohol drinking. Our data suggest that a high Tenseness dimension of TAB may be an independent risk factor for ischemic stroke, probably associated with atherogenesis.

Cerebral Infarction↗
PubMed1998

Indoleamine-accumulating cell death and endogenous glial cell reaction induced by 5,7-dihydroxytryptamine in the cat retina.

We investigated the patterns of degenerative changes of indoleamine-accumulating cells (IACs) induced by 5,7-dihydroxytryptamine (5,7-DHT, 100 microg), and the glial reaction to the neurodegenerative changes of IACs in the cat retina by using light-and electron-microscopy. The neurons accumulating 5,7-DHT in the cat retina were a few ganglion cells and displaced amacrine cells located in the ganglion cell layer (GCL), and some amacrine cells in the inner nuclear layer (INL). The cell density (per unit area, 1 mm2) of the 5,7-DHT accumulating cells in the GCL and INL was 910 and 134 cells, respectively. Most 5,7-DHT accumulating cells showed dark degeneration characterized by widening of the cellular organelles at early stage, and by darkening of the cytoplasm at a late stage. In addition, amacrine cells, showing a typical filamentous degeneration, were observed in a few cases. The degenerated neurons were phagocytosed by microglial cells and astrocytes. The immunoreactivity for glial fibrillary acidic protein (GFAP) in Muller cells was increased at early stage, but thereafter abruptly decreased. In a few cases, severe degenerative changes were observed in Miller cells. These results indicate that 5,7-DHT induces severe dark degeneration of IACs, and most degenerated cells could be eliminated by microglial cells and astrocytes in the cat retina.

5,7-Dihydroxytryptamine↗
PubMed1998

Superior sagittal sinus thrombosis and transient ischemic attacks: possible mechanism.

Clinical manifestations of superior sagittal sinus (SSS) thrombosis are nonspecific but characterized by headache, papilledema, seizures, focal deficits, progressive coma and death. Recurrent transient focal neurologic deficit is an extremely rare manifestation in superior sagittal sinus thrombosis and the mechanism is unknown. A 45-year-old man presented with headache for two weeks and four episodes of transient (5-10 minutes) right or left hemiparesis for two days. Magnetic resonance image and transfemoral cerebral angiography revealed superior sagittal sinus thrombosis with numerous prominent collateral venous channels. There was no parenchymal lesion. After four days of heparinization, no further transient focal neurologic deficits developed. Follow-up angiography showed partial recanalization of the SSS. Possible mechanism of transient ischemic attacks in this patient is thought to be a transient functional disturbance due to a temporal reduction of tissue perfusion in the process of operating fully-enough collateral channels.

Cerebral Angiography↗
PubMed1997

Sampling designs for xerophthalmia prevalence surveys.

BACKGROUND: The purpose of this study was to estimate the bias and design effects associated with the Expanded Program on Immunization's (EPI) sampling design when estimating xerophthalmia prevalence, and to estimate the savings associated with EPI in terms of distance travelled within selected clusters. METHODS: Computer simulation of the EPI sampling strategy was done using maps from a xerophthalmia survey of 40 wards in Sarlahi district, Nepal. Samples of fixed cluster sizes of 7, 10, 15, 20 and 25 were compared. The estimated prevalence using the EPI design was compared with the true prevalence in the 40 wards to estimate the bias. The design effect was estimated by taking the ratio of the variance under EPI sampling to that of stratified random sampling (SRS) with fixed cluster sizes. The EPI was also modified by increasing the distance between selected houses from nearest neighbour to skipping 1-4 houses between selected ones. The difference between the distance travelled within clusters using SRS compared with EPI was weighed against the bias and increased variance. RESULTS: The prevalence of xerophthalmia was 2.8%. The EPI design overestimated xerophthalmia prevalence by between 0.27% and 1.16%. The design effects of EPI cluster sampling within wards varied between 0.73 and 1.35. Neither the bias nor the design effect was related to distance between households or cluster size. Distance travelled within wards was always less for EPI designs with cluster sizes of 7 or 10. There was no saving in terms of distance travelled for designs with cluster sizes from 15 to 25 if there were two or more houses between selected ones. For fixed cluster sizes of 15 or fewer, the EPI sampling design using nearest or next nearest neighbours is a better choice than SRS in terms of minimizing the distance travelled and the mean square error. CONCLUSIONS: The choice of an optimum method would need to account for the density of clusters and difficulty of travel between clusters, as well as the costs of travel within clusters. Based on certain assumptions, EPI with 15 children per cluster would be favoured over examining all children in selected wards unless the travel time between wards was more than 2 days.

Bias↗
PubMed1997

Intratumoral heterogeneity for and epigenetic modulation of mdr-1 expression in murine melanoma.

We determined whether tumour size in vivo and cell density in vitro modulate the expression of the mdr-1 gene in B16 melanoma cells. Cells were injected subcutaneously into syngeneic mice. Small (5 mm in diameter) and large (15-20 mm in diameter) tumours were harvested. Tumour cells from small subcutaneous tumours exhibited higher levels of mdr-1 mRNA (measured using Northern blot and in situ hybridization) and P-glycoprotein (P-gp) (measured using immunohistochemistry and fluorescent activated cell sorter analysis), as well as greater. In vitro resistance to doxorubicin (DXR) than cells from large subcutaneous tumours. immunohistochemical studies using an antibody against proliferating cell nuclear antigen revealed that the small subcutaneous tumours contained a larger fraction of proliferating cells than the large tumours. To determine whether cell proliferation correlated with expression of mdr-1, we plated B16-F10 cells to yield sparse and confluent monolayer cultures. The levels of mdr-1 mRNA and P-gp and resistance to DXR and phosphotyrosine activity were higher in the sparse cultures than in the confluent cultures. These results demonstrate an intratumoral heterogeneity for the expression of mdr-1 that directly correlates with intratumoral heterogeneity for cell division.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Perspectives of stroke in persons living in Seoul, South Korea. A survey of 1000 subjects.

BACKGROUND AND PURPOSE: The aim of the present study was to investigate the perspectives of stroke in persons who live in Seoul, South Korea, a country which is unique in that the social and political status of traditional (herbal) medicine is equal to that of western (modern) medicine. METHODS: We randomly selected 1000 persons living in Seoul, South Korea, and performed open-ended telephone interviews regarding stroke risk factors, symptoms, and the choice of treatment for stroke. We also asked whether the subjects would prefer to visit western-medicine doctors or traditional-medicine doctors if they developed stroke. RESULTS: Twenty-nine percent of the interviewees responded correctly that the most important risk factor for stroke is hypertension. However, other major factors, such as cigarette smoking, diabetes mellitus, and heart disease, were greatly underappreciated, while less important risk factors such as hyperlipidemia/obesity, stress, and exposure to coldness were overappreciated. Also, although 65% of the subjects correctly identified paresis as the most important symptom of stroke, tremor was indicated incorrectly as an important symptom of stroke. Regarding the choice of treatment, only 46% responded that visiting a hospital is the most important method of treatment, whereas a significant percentage of the subjects responded that they would prefer herbal medicine and other traditional methods of treatment. Generally, the older and less educated the subjects, the more they prefer to depend on traditional medicine. CONCLUSIONS: These data show that perspectives of stroke are heavily influenced by the presence of traditional medicine in Korea, especially in older and less educated persons. This perspective significantly deviates from the scientific concept regarding the etiology, symptoms, and treatment of stroke. Current science-based health education is urgently needed in this country.

Adult↗
PubMed1997

Efficiency of EPI cluster sampling for assessing diarrhoea and dysentery prevalence.

This study examines the efficiency of EPI cluster sampling in assessing the prevalence of diarrhoea and dysentery. A computer was used to simulate fieldwork carried out by a survey taker. The bias and variance of prevalence estimates obtained using EPI cluster sampling were compared with those obtained using simple random sampling and cluster (stratified random) sampling. Efficiency ratios, calculated as the mean square error divided by total distance travelled, were used to compare EPI cluster sampling to simple random sampling and standard cluster sampling. EPI cluster sampling may be an appropriate low-cost tool for monitoring trends in the prevalence of diarrhoea and dysentery over time. However, it should be used with caution when estimating the prevalence of diarrhoea at a single point in time because of the bias associated with this cluster sampling method.

Age Factors↗