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Biomedical subjects

E H Kang

Publications and source records attributed to E H Kang.

18 recordsLinked to original sources
PubMed2005

Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.

OBJECTIVE: To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). METHODS: We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. RESULTS: Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024). CONCLUSIONS: ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.

Adult↗
PubMed2001

Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.

The mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the possible mechanisms. We attempted to demonstrate the role of mitogen-activated protein (MAP) kinases, generally considered to be important mediators of proliferative and apoptotic signals, in NSAID-induced colon cancer cell apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion method. MAP kinase activation was assessed by Western blot using phosphospecific antibodies to MAP kinases. Kinase assay using activating transcription factor-2 (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole compound (SB203580) was utilized. Caspase-3 activity was measured using the tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis. From these results, we conclude that NSAIDs can induce prolonged activation of MAP kinases in colon cancer cells and that, of these, p38 MAP kinase may play a partial but significant role in indomethacin-induced apoptosis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Effect of preexisting anti-herpes immunity on the efficacy of herpes simplex viral therapy in a murine intraperitoneal tumor model.

HSV-1716, a replicating nonneurovirulent herpes simplex virus type 1, has shown efficacy in treating multiple types of human tumors in immunodeficient mice. Since the majority of the human population has been previously exposed to herpes simplex virus, the efficacy of HSV-based oncolytic therapy was investigated in an immunocompetent animal tumor model. EJ-6-2-Bam-6a, a tumor cell line derived from h-ras-transformed murine fibroblast, exhibit a diffuse growth pattern in the peritoneal cavity of BALB/c mice and replicate HSV-1716 to titers observed in human tumors. An established intraperitoneal (ip) tumor model of EJ-6-2-Bam-6a in naive and HSV-immunized mice was used to evaluate the efficacy of single or multiple ip administrations of HSV-1716 (4 x 10(6) pfu/treatment) or of carrier cells, which are irradiated, ex vivo virally infected EJ-6-2-Bam-6a cells that can amplify the viral load in situ. All treated groups significantly prolonged survival versus media control with an approximately 40% long-term survival rate (cure) in the multiply treated, HSV-naive animals. Prior immunization of the mice with HSV did not significantly decrease the median survival of the single or multiply treated HSV-1716 or the carrier cell-treated groups. These studies support the development of replication-selective herpes virus mutants for use in localized intraperitoneal malignancies.

Animals↗
PubMed2000

Oncolytic herpes simplex virus-1 lacking ICP34.5 induces p53-independent death and is efficacious against chemotherapy-resistant ovarian cancer.

Replication-restricted herpes simplex virus-1 (HSV-1) strains lacking ICP34.5 are emerging as powerful anticancer agents against several solid tumors including epithelial ovarian cancer (EOC). Although chemotherapy-resistant tumors would be likely candidates for treatment with HSV-1 mutants lacking ICP34.5, the efficacy of these mutants on such tumors is unknown. In the present study, we investigated whether chemotherapy resistance affects the response of ovarian cancer cells to HSV-R3616, an ICP34.5-deficient, replication-restricted HSV-1. Primary EOC cultures obtained from patients who varied in their responses to platinum/paclitaxel induction chemotherapy displayed similar sensitivity to HSV-R3616. Similarly, chemotherapy-sensitive ovarian cancer cells A2780 and PA-1, possessing wild-type p53, and their respective chemotherapy-resistant clones A2780/200CP, lacking p53 function, and PA-1/E6, permanently expressing the HPV E6 gene, were equally sensitive to HSV oncolysis. Because wild-type HSV can kill cells by apoptosis and nonapoptotic mechanisms, we investigated the involvement of apoptosis and the role of the p53 tumor suppressor gene in oncolysis induced by HSV-R3616. Infection of ovarian cancer cell lines by HSV-R3616 was followed by cell death via apoptosis or nonapoptotic mechanisms as noted by morphology, cell cycle analysis, and in situ TUNEL assay. p53 protein levels remained unchanged, and Bax protein levels decreased in cells possessing intact p53 and that mainly underwent HSV-induced apoptosis. Loss of p53 function did not affect the frequency or rate of apoptosis or the sensitivity of EOC cells to the oncolytic effect of HSV-R3616. These results suggest that recombinant HSV-1 lacking ICP34.5 is capable of killing ovarian cancer cells that lack p53 function, resist apoptosis, and/or are chemotherapy resistant. These data support the hypothesis that HSV-based oncolytic therapy may be efficacious in chemotherapy-resistant tumors, including tumors that are deficient in p53.

Antineoplastic Agents↗
PubMed1999

Combined therapy with chemotherapeutic agents and herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) in human non-small cell lung cancer.

A replication-selective herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) has shown efficacy both in vitro and in vivo against human non-small cell lung cancer (NSCLC) cell lines but complete eradication of tumor has not been accomplished with a single viral treatment in our murine xenograft models. Therefore, strategies to enhance the efficacy of this treatment were investigated. We determined the oncolytic activity of HSV-1716 in NCI-H460 cells in combination with each of four chemotherapeutic agents: mitomycin C (MMC), cis-platinum II (cis-DDP), methotrexate (MTX), or doxorubicin (ADR). Isobologram analysis was performed to evaluate the interaction between the viral and chemotherapeutic agents. The oncolytic effect of HSV-1716 in combination with MMC was synergistic in two of five NSCLC cell lines. In the other three cell lines, the combined effect appeared additive. No antagonism was observed. The in vivo effect of this combination was then examined in a murine xenograft model. NCI-H460 flank tumors were directly injected with HSV-1716 (4 x 106 PFU) followed by intravenous MMC administration (0.17 mg/kg) 24 hr later. After 3 weeks, the mean tumor weight in the combined treatment group was significantly less than either individual treatment in an additive manner. The synergistic dose of MMC neither augmented nor inhibited viral replication in vitro and HSV-1716 infection did not upregulate DT-diaphorase, which is the primary enzyme responsible for MMC activation. In summary, the combination of HSV-1716 with common chemotherapeutic agents may augment the effect of HSV-based therapy in the treatment of NSCLC.

Animals↗
PubMed1999

A cross-sectional study comparing the nutritional status of peritoneal dialysis and hemodialysis patients in Korea.

OBJECTIVE: This study was performed to compare the nutritional status of peritoneal dialysis (PD) and hemodialysis (HD) patients in Korea and to validate the nutritional assessment method. DESIGN: For nutritional assessment, we used five nutrition-related indicators, including percentage unplanned weight loss, percentage ideal body weight (IBW), serum albumin, appetite and intake, and any gastrointestinal symptoms affecting intake. A 1-month food frequency interview was conducted by clinical dietitians using food models to estimate energy and protein intake. The validity of the nutritional assessment method was tested by objective measures. PATIENTS/SETTING: A cross-sectional study was conducted in our center for 51 PD patients and 169 HD patients who met the study criteria. In the study, HD patients typically underwent dialysis three times per week, and most PD patients performed four 2-L dialysis exchanges every day. RESULTS: Our data showed a higher incidence of malnutrition in PD patients than in HD patients (33% v 18%) and in diabetics than in nondiabetics. Age, height, and dietary energy intake of the two groups were comparable. In PD patients, however, duration of dialysis treatment (23.9 +/- 19.1 months v 41.8 +/- 31.7 months, P < 0.001) and serum albumin (35.2 +/- 5.0 g/L v 39. 7 +/- 3.4 g/L, P < 0.0001) were significantly lower, whereas percentage IBW (108.1% +/- 12.4% v 96.2% +/- 11.6%, P < 0.0001) and dietary protein intake (1.12 +/- 0.34 g/kg IBW v 0.98 +/- 0.31 g/kg IBW, P < 0.05) were significantly higher than in HD patients. In malnourished PD and HD patients, percentage IBW, serum albumin, dietary energy, and protein intake were significantly lower than in well-nourished counterparts. CONCLUSION: A higher incidence of malnutrition was observed in PD patients than in HD patients. Nutritional profile of PD patients was different from that of HD patients. Higher body weight and lower serum albumin in PD patients did not seem to be related to dietary energy and protein intake. The five nutritional indicators can be used as a simple inexpensive and reliable method for the early detection of malnutrition in dialysis patients.

Adult↗
PubMed1999

Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) remains localized within the peritoneal cavity in a large number of patients, lending itself to i.p. approaches of therapy. In the present study, we investigated the effect of replication-selective herpes simplex virus-1 (HSV-1) used as an oncolytic agent against EOC and the use of human teratocarcinoma PA-1 as carrier cells for i.p. therapy. HSV-1716, a replication-competent attenuated strain lacking ICP34.5, caused a direct dose-dependent oncolytic effect on EOC cells in vitro. A single i.p. administration of 5 x 10(6) plaque-forming units resulted in a significant reduction of tumor volume and tumor spread and an increase in survival in a mouse xenograft model. PA-1 cells supported HSV replication in vitro and bound preferentially to human ovarian carcinoma surfaces compared with mesothelial surfaces in vitro and in vivo. In comparison with the administration of HSV-1716 alone, irradiated PA-1 cells, infected at two multiplicities of infection with HSV-1716 and injected i.p. at 5 x 10(6) cells/animal, led to a significant tumor reduction in the two models tested and the significant prolongation of mean survival in one model. Histological evaluation revealed extensive necrosis in tumor areas infected by HSV-1716. Immunohistochemistry against HSV-1 revealed areas of viral infection within tumor nodules, which persisted for several weeks after treatment. Administration of HSV-infected PA-1 carrier cells resulted in larger areas of tumor infected by the virus. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on EOC, which may be further enhanced by the utilization of a delivery system with carrier cells, based on amplification of the viral load and possibly on preferential binding of carrier cells to tumor surfaces.

Animals↗
PubMed1998

Impact of preexisting and induced humoral and cellular immune responses in an adenovirus-based gene therapy phase I clinical trial for localized mesothelioma.

Little is known about the immune responses induced by recombinant adenoviral (Ad) vectors in humans. The humoral and cellular immune responses were therefore analyzed in 21 patients with localized malignancy (mesothelioma), who received intrapleurally high doses of a replication-defective Ad5 vector carrying a suicide gene. Eight of 21 patients had pretreatment titers of neutralizing antibodies (NAb) to Ad at > or =1:100. Peripheral blood mononuclear cells (PBMCs) proliferated in response to adenoviral 5 structural proteins before treatment in 17 of 21 patients. Preexisting humoral and cellular immunity did not preclude gene transfer. Vector instillation induced high titers of nonneutralizing and neutralizing anti-Ad antibody (4- to 341-fold increase in 18 of 20 patients) in a dose-dependent manner. Three patients generated antibodies to the transgene, herpes simplex virus thymidine kinase. Ad5-specific proliferation of PBMCs increased significantly (>3-fold) after vector administration in 12 of 21 patients in a dose-dependent manner. Thus, replication-defective Ad5 administered intrapleurally induced significant humoral and cellular immune responses that induced no obvious adverse clinical sequelae.

Adenoviridae↗
PubMed1998

In vivo immune evasion mediated by the herpes simplex virus type 1 immunoglobulin G Fc receptor.

Herpes simplex virus (HSV) glycoproteins gE and gI form an immunoglobulin G (IgG) Fc receptor (FcgammaR) that binds the Fc domain of human anti-HSV IgG and inhibits Fc-mediated immune functions in vitro. gE or gI deletion mutant viruses are avirulent, probably because gE and gI are also involved in cell-to-cell spread. In an effort to modify FcgammaR activity without affecting other gE functions, we constructed a mutant virus, NS-gE339, that has four amino acids inserted into gE within the domain homologous to mammalian IgG FcgammaRs. NS-gE339 expresses gE and gI, is FcgammaR-, and does not participate in antibody bipolar bridging since it does not block activities mediated by the Fc domain of anti-HSV IgG. In vivo studies were performed with mice because the HSV-1 FcgammaR does not bind murine IgG; therefore, the absence of an FcgammaR should not affect virulence in mice. NS-gE339 causes disease at the skin inoculation site comparably to wild-type and rescued viruses, indicating that the FcgammaR- mutant virus is pathogenic in animals. Mice were passively immunized with human anti-HSV IgG and then infected with mutant or wild-type virus. We postulated that the HSV-1 FcgammaR should protect wild-type virus from antibody attack. Human anti-HSV IgG greatly reduced viral titers and disease severity in NS-gE339-infected animals while having little effect on wild-type or rescued virus. We conclude that the HSV-1 FcgammaR enables the virus to evade antibody attack in vivo, which likely explains why antibodies are relatively ineffective against HSV infection.

Animals↗
PubMed1996

Prevalence of red marrow around the knee joint in adults as demonstrated on magnetic resonance imaging.

RATIONALE AND OBJECTIVES: We determined the prevalence of red marrow around the knee joint in adults and evaluated variations with age, gender, and other variables. METHODS: One hundred ninety-nine adult patients presenting for routine knee magnetic resonance (MR) imaging completed a questionnaire that covered age, gender, menstrual history, past pregnancies, smoking history, and medications. The presence or absence of visible red marrow in the distal femur and proximal tibia on both coronal and sagittal MR images was recorded for each patient. Associations between the presence of red marrow and the other recorded variables then were evaluated. RESULTS: Red marrow was present in more than half of the women and less than one sixth of the men, a statistically significant difference. The age distribution of red marrow in men and women also was different. Red marrow was the most common in women aged 30-60 years. In men, there was no clear-cut age trend. Red marrow also was more likely to be present in obese individuals and smokers. No association was found between the presence of red marrow and any of the other recorded variables. CONCLUSION: There are clear gender, age, obesity, and smoking-related differences in the prevalence of red marrow around the knee joint in adults. Red marrow is relatively common in this site in all age groups, and its presence should not be a cause for clinical concern.

Adolescent↗
PubMed1991

Laparoscopic cholecystectomy: evaluation with sonography.

To determine the normal postoperative appearance of gallstones in the common duct at ultrasound (US) examination, the significance of fluid collections after surgery, and the usefulness of routine postoperative scanning, US of the right upper quadrant was performed in 106 consecutive patients 24 hours after laparoscopic cholecystectomy. The location, volume, and appearance of fluid collections were recorded. The maximum diameter of the common duct was measured in all patients and compared with preoperative measurements in 58 patients. Small fluid collections were identified in the gallbladder fossa in 56 patients (53.0%). Fluid collections did not correlate with fever or white blood cell count. In 15 of 58 patients, the diameter of the common duct had increased on the postoperative scan. This did not correlate with alkaline phosphatase or bilirubin levels. One hundred one patients (95.3%) were discharged the day after surgery. Routine US performed the day after surgery did not alter management; the authors conclude that it is unwarranted in their group of patients.

Adult↗
PubMed1986

Fatty acid metabolism and mitochondrial proteins in the C57BL/6J-dy2Jdy2J dystrophic mice.

Measurements of [1-14C]oleoyl CoA oxidation in homogenates and isolated mitochondria of skeletal muscles, hearts and livers from dystrophic C57BL/6J mice and unaffected litter-mates indicate that rates are lower in dystrophic mitochondria, but are comparable in whole homogenates. These findings are not due to differences in the endogenous concentrations of the fatty CoA esters. Qualitative and quantitative differences in the molecular weight distribution of the proteins in the mitochondria and post-mitochondrial supernatants are found in the skeletal muscles with increases in the post-mitochondrial supernatant and decreases in the mitochondria in dystrophic samples. We suggest that these results are due to increased leakiness of the mitochondrial membranes in dystrophic muscles. Such differences were not observed in preparations from normal animals.

Animals↗