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Biomedical subjects

M H Chung

Publications and source records attributed to M H Chung.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prevention of ultraviolet radiation-induced suppression of contact hypersensitivity by Aloe vera gel components.

We have recently reported that Aloe vera gel contains small molecular weight immunomodulators, G1C2F1, that restore ultraviolet B (UVB)-suppressed accessory cell function of epidermal Langerhans cells (LC) in vitro. In the present study we evaluated the UVB-protective activity of G1C2F1 in vivo. Exposure of the shaved abdominal skin of mice to 2.4 KJ/m2 of UVB radiation resulted in suppression of contact sensitization through the skin to 41.1%, compared to normal unirradiated skin. Topical application of G1C2F1 immediately after irradiation reduced this suppression significantly. The percentage recovery of UVB-suppressed contact hypersensitivity (CHS) response was 52.3, 77.3, and 86.6% when the irradiated skin was treated once with 0.1, 0.5, and 2.5 mg/ml of G1C2F1-containing cream, respectively. G1C2F1 did not show nonspecific stimulatory activity on CHS response. The present study, together with the previous observation, show that Aloe vera gel contains small molecular weight immunomodulators that prevent UVB-induced immune suppression in the skin by restoration of UVB-induced damages on epidermal LC.

Adjuvants, Immunologic↗
PubMed1999

Thermolabile 8-hydroxyguanine DNA glycosylase with low activity in senescence-accelerated mice due to a single-base mutation.

8-hydroxyguanine (8-oxoguanine; oh8Gua) DNA glycosylase (OGG1) repairs oh8Gua, a highly mutagenic oxidative DNA damage. In the present study, we compared two strains of senescence-accelerated mouse (SAM) expressing senescence-prone phenotypes, SAMP1 and SAMP8, with one strain of SAM expressing senescence-resistant phenotype, SAMR1. We found three distinct characteristics of OGG1 in SAMPs: (i) low activity (10-40% of the SAMRI enzyme in all organs and ages observed), (ii) thermolability, and (iii) mutation from Arg (CGG) in SAMR1 to Trp (TGG) at codon 304. There was no difference in the levels of mRNA and protein. As expected, oh8Gua level in tissues was higher in the SAMPs. In contrast, O6-methylguanine-DNA methyltransferase, which repairs alkylated DNA, showed no difference in its activity. The impairment of oh8Gua repair activity caused by the 304 mutation in OGG1 may be one of the factors contributing to the high somatic mutation rate and the accelerated senescence observed in these strains.

Aging↗
PubMed1999

A novel angiogenic factor derived from Aloe vera gel: beta-sitosterol, a plant sterol.

Aloe vera gel has a beneficial effect on wound healing. Because angiogenesis is an essential process in wound healing, we hypothesized that Aloe vera gel might contain potent angiogenic compounds. Here we demonstrate that Aloe vera gel and its extracts are angiogenic on the chorioallantoic membrane (CAM) of chick embryo. Out of the three compounds purified from the final fraction of Aloe vera gel, beta-sitosterol showed a potent angiogenic activity in the CAM assay. In the presence of heparin, beta-sitosterol stimulated neovascularization in the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay. Thus beta-sitosterol is a novel plant-derived angiogenic factor which may have potential pharmaceutical applications for the management of chronic wounds.

Journal Article↗
PubMed1999

Apoptosis of endothelial cell line ECV304 persistently infected with Orientia tsutsugamushi.

Endothelial cells are major targets of Orientia tsutsugamushi. To examine the consequences of the infection of endothelial cells with O. tsutsugamushi, we used human endothelial cell line ECV304. Persistent infection was established and infected cultures could be maintained for over seven months without the addition of normal cells. The heavily infected cells became round and floated in the culture medium, harboring large numbers of organisms inside them. Some of the infected ECV304 cells showed features of apoptotic cells, as determined by the terminal deoxytransferase-mediated dUTP nick end-labeling reaction and DNA fragmentation. We also found that O. tsutsugamushi increased transcription of the mRNAs of proinflammatory cytokines such as IL-6 and IL-8. These results show the first evidence of in vitro-persistent infection by O. tsutsugamushi, which may be related to in vivo persistence reported previously.

Animals↗
PubMed1999

Exposure to hexavalent chromium does not increase 8-hydroxydeoxyguanosine levels in Korean chromate pigment workers.

This study was performed to determine whether chromium exposure increased 8-hydroxydeoxyguanosine levels in respiratory epithelial and white blood cells of chromate pigment workers. The subjects of this study were 22 chromium pigment workers and 16 controls in a chromate pigments factory. To estimate the level of exposure, hexavalent chromium concentrations in the factory air were measured. Chrominum concentrations of venous blood and spot urine, and 8-hydroxydeoxyguanosine levels in DNA extracted from sputum and white blood cells were determined. Correlation coefficients were calculated between them and their statistical significance was tested. Hexavalent chromium concentration in the factory air ranged from below limit of detection to 0.5150 mg/m3. Chromium levels in blood and 8-hydroxydeoxyguanosine levels in DNA extracted from venous blood and sputum were not statistically different between the two groups. Urine chromium level was significantly higher among workers. Among the correlation coefficients between blood chromium concentration, urine chromium concentration, blood 8-OH-dG level, and sputum 8-OH-dG level, none was statistically significant for workers, controls, and total subjects. Duration of employment did not show any significant correlation with those four variables, either. These results suggest that neither the hydroxyl radical nor 8-hydroxydeoxyguanosine is formed by the reduction of hexavalent chromium, or that one or both of these is formed and then effectively removed by oxygen free radical scavengers or 8-hydroxydeoxyguanosine repair enzymes. Since increased exposure to hexavalent chromium did not result in increased 8-hydroxydeoxyguanosine levels, it is unlikely that hexavalent chromium induces lung cancer through 8-hydroxydeoxyguanosine formation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Identification of familial hypercholesterolemia in Taiwan: report of eleven cases.

BACKGROUND: Familial hypercholesterolemia is associated with a very high risk of premature coronary heart disease. In order to identify cases of familial hypercholesterolemia in Taiwan, we screened the hyperlipidemic patients in our metabolic clinics. METHODS: Hyperlipidemic patients were screened in the metabolic outpatient department and the cases which fulfilled the clinical criteria of definitive or possible familial hypercholesterolemia were further analyzed. Their clinical characteristics, including age, gender, physical findings, past history of coronary heart disease or cerebrovascular accident (CVA), family history, and lipid profiles before and after medical treatment, were reviewed. RESULTS: Eight women and 3 men fulfilled the diagnostic criteria. The mean age at diagnosis was 51.1 +/- 11.9 years old. Tendon xanthomas were found in 5 patients with definitive familial hypercholesterolemia. Coronary heart disease was confirmed in one patient and old CVA was noted in another 2 patients. The mean total cholesterol level was 390.3 +/- 88.9 mg/dl and the mean low density lipoprotein-cholesterol (LDL-cholesterol) level was 309.6 +/- 89.9 mg/dl before treatment. After a mean treatment duration of 45.2 months, the mean total cholesterol level and LDL-cholesterol level were 326.8 +/- 87.8 mg/dl and 249.1 +/- 91.1 mg/dl, respectively. CONCLUSION: Clinically diagnosed familial hypercholesterolemia indeed exists in Taiwan. As compared to other reports, the mean age at diagnosis in our series was older and the majority of patients were women. Most patients were not vigorously treated and the family members were not thoroughly screened. Adequate treatment of patients with familial hypercholesterolemia in clinical practice and screening their family members are crucial in preventing new or recurrent coronary heart disease.

Adult↗
PubMed1998

In vitro angiogenic activity of Aloe vera gel on calf pulmonary artery endothelial (CPAE) cells.

Angiogenic activity of Aloe vera gel was investigated by in vitro assay. We obtained the most active fraction from dichloromethane extract of Aloe vera gel by partitioning between hexane and 90% aqueous methanol. The most active fraction (F3) increased the proliferation of calf pulmonary artery endothelial (CPAE) cells. In addition, F3 fraction induced CPAE cells to invade type 1 collagen gel and form capillary-like tube through in vitro angiogenesis assay, and increased the invasion of CPAE cells into matrigel through in vitro invasion assay. Furthermore, the effect on the mRNA expression of proteolytic enzymes which are key participants in the regulation of extracellular matrix degradation was investigated by northern blot analysis. F3 fraction enhanced mRNA expression of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase-2 (MMP-2), and membrane-type MMP (MT-MMP) in CPAE cells whereas the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA was not changed.

Aloe↗
PubMed1998

Mechanism of regulation of 8-hydroxyguanine endonuclease by oxidative stress: roles of FNR, ArcA, and Fur.

We found previously that 8-hydroxyguanine (oh8Gua) endonuclease in E. coli is induced in response to oxidative stress in a fashion similar to the oxidative response of the Mn-superoxide dismutase (MnSOD). In this study, attempts were made to identify the genes involved in the co-regulation of E. coli endonuclease and MnSOD (sodA). oh8Gua nuclease is induced by molecular oxygen and a superoxide radical generator (paraquat) but not by H2O2, suggesting that the regulation of this endonuclease is dependent on SoxRS but independent of OxyR. This enzyme was induced by paraquat in all of the soxRS mutant strains used (soxR-, soxS- and soxRc), whereas glucose-6-phosphate dehydrogenase (a member of the soxRS regulon) showed the expected responses; therefore, this possibility was excluded. The presence of metal chelators in the growth medium caused the induction of this enzyme, and this induction was suppressed by the addition of Fe++. Consistent with this finding, this enzyme was expressed under anaerobiosis in all of the mutant strains of fnr in particular, as well as fur, arcA, and combinations thereof. These findings suggest that the oxidative regulation of oh8Gua endonuclease is under control of fnr, fur, and arcA, where fnr plays a predominant role. The multiple involvement of regulatory genes as well as co-regulation with antioxidant enzyme will enhance the efficiency of cellular growth and survival in the aerobic environment.

Bacterial Outer Membrane Proteins↗
PubMed1998

Distinctive p53 and mdm2 immunohistochemical expression profiles suggest different pathogenetic pathways in poorly differentiated endometrial carcinoma.

Endometrial serous carcinoma (ESC) and FIGO (International Federation of Gynecology and Obstetrics) grade 3 endometrioid adenocarcinoma (EC) are high-grade endometrial tumors that have different clinical and morphologic attributes. Alteration of p53 tumor suppressor protein function has been implicated in the pathogenesis of both tumors, although the mechanisms may differ. We sought to investigate this difference by comparing immunohistochemical expression of p53 and mdm2. p53 immunoreactivity often correlates with gene mutation, whereas increased mdm2 expression is linked to complex formation with wild-type p53 resulting in its inactivation. Twenty cases of ESC and 21 cases of EC were evaluated and an immunoreactivity score (IRS) was assigned using both the percentage of cells stained and the intensity of staining. The overall IRSs were significantly different in ESCs versus ECs for both p53 and mdm2 (p < 0.001 and p < 0.01, respectively). Strong mean immunoreactivity for p53 was detected in 15 (75%) ESCs as compared to only weak mean immunoreactivity in 17 (81%) ECs. Conversely, for mdm2 expression, 17 (81%) ECs had moderate mean immunoreactivity whereas 9 (45%) ESCs showed only weak mean immunoreactivity. mdm2 expression more closely correlated with p53 expression in ECs than in ESCs. In ECs, mdm2 was detected in 16 of 17 (94%) p53-positive tumors but in only 1 of 3 (33%) p53-negative tumors (p < 0.025). In ESCs, mdm2 was detected in 9 of 15 (60%) p53-positive tumors but in none of the 5 p53-negative tumors (p < 0.10). Overall, our results demonstrate an inverse relationship between the expression of p53 and mdm2 in ESC versus high-grade EC. Specifically, strong p53 immunoreactivity is associated with weak mdm2 expression-in ESC and weak p53 expression is associated with moderate mdm2 expression in EC. These results suggest different pathogenetic pathways resulting in loss of normal p53 function in these two tumors: by p53 gene mutation (strong p53 overexpression) in ESCs, or by mdm2 complex formation and inactivation of p53 in high-grade ECs.

Adult↗
PubMed1998

A relapsed case of imported tertian malaria after a standard course of hydroxychloroquine and primaquine therapy.

Resistance of Plasmodium species to antimalarial agents has become increasingly challenging to the management and prevention of malaria. We experienced an imported case of tertian malaria due to Plasmodium vivax relapsed after a seemingly successful treatment with conventional course of hydroxychloroquine and primaquine. A 35-year-old man developed fever three days after return from India and mainland China. After his illness was diagnosed as tertian malaria, he was managed with hydroxychloroquine and then primaquine (primaquine base 15 mg/day for 14 days). Thereafter peripheral blood smears showed no malarial parasites, and there was no relapse of symptom until the 55th post-treatment day, however, six months after the above treatment tertian malaria relapsed. He was managed with the same medications again and malaria did not relapse for 10 months.

Adult↗
PubMed1998

The CD44v6-negative phenotype in high-grade uterine carcinomas correlates with serous histologic subtype.

Uterine serous carcinomas (USCs) and poorly differentiated (International Federation of Gynecology and Obstetrics Grade 3) endometrioid adenocarcinomas (ECs) are two histologic subtypes of high-grade uterine carcinoma that differ in clinical presentation, patterns of dissemination, and biologic aggressiveness. To investigate the mechanisms responsible for this heterogeneity, we studied CD44 and CD44v6 expression in a series of 20 USCs and 21 poorly differentiated ECs. CD44 is a protein involved in cell adhesion and lymphocyte homing, and one of its isoforms, CD44v6, might be related to capillary-lymphatic space invasion and metastasis. Eight (40%) of 20 USCs expressed CD44, compared with 18 (86%) of 21 ECs (P < .005). None of the USCs were reactive with antibodies against CD44v6, whereas 45% of the ECs were immunoreactive (P < .001). CD44v6 expression was observed in the myoinvasive ECs but was not seen in foci of capillary-lymphatic space invasion in either the ECs or the USCs. In summary, the USCs were significantly more likely to demonstrate a CD44- and CD44v6-negative phenotype than were the poorly differentiated ECs.

Adult↗
PubMed1998

Helicobacter pylori infection, oxidative DNA damage, gastric carcinogenesis, and reversibility by rebamipide.

Several epidemiological studies have demonstrated a close association between Helicobacter pylori infection and carcinoma of the mid- or distal stomach. If this can be shown to be a causal association, eradication of the organism may prevent later development of cancer. Several mechanisms have been proposed by which H. pylori infection might lead to predisposition for gastric cancer. Although many potential pathogenic mechanisms, such as increased proliferative gastric epithelial response to H. pylori, lowered gastric ascorbic acid levels, and high occurrences of atrophic gastritis, have been proposed, there is little evidence as to which might be of direct importance to such H. pylori-related disease in vivo. H. pylori-associated inflammation may interact with other causal factors related to gastric carcinogenesis and can result in the intestinal type of gastric cancer and then DNA damage due to oxygen radicals induced by persistent inflammatory cell infiltrations in the gastric mucosa may lead to alterations of the gene and result in the development of diffuse-type carcinoma. In order to know the influence of H. pylori on changes of inflammation-related DNA damage, we measured the sequential changes of 8-hydroxydeoxyguanosine (8-OHdG) contents of DNA and the changes of two biomarkers inducible nitric oxide synthase (iNOS) and apoptosis from human gastric mucosa according to the status of H. pylori. The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS seem to provide the mechanistic links between H. pylori infection and gastric carcinogenesis and rebamipide can abrogate the levels of these hazard factors.

Alanine↗
PubMed1997

Cyclic AMP and cyclic GMP relax phorbol ester-induced contractions of rat aorta by different mechanisms.

This study was designed to test the hypothesis that 8-Br-cAMP and 8-Br-cGMP dependent relaxation of phorbol dibutyrate stimulated contractions of intact rat aorta are independent of changes in the level of myosin light chain phosphorylation. Phorbol dibutyrate stimulated contraction with a concomitant increase in myosin light chain phosphorylation in normal tissues and without an increase in myosin light chain phosphorylation in calcium-depleted tissues. Phorbol dibutyrate stimulated contractions in normal CaCl2-containing physiological salt solution were relaxed in a concentration-dependent manner by 8-Br-cAMP and 8-Br-cGMP. Phorbol dibutyrate-induced contractions in the absence of Ca2+ were only relaxed by 8-Br-cGMP; 8-Br-cAMP had no effect. The relaxation induced by 8-Br-cGMP was associated with a decrease in myosin light chain phosphorylation suggesting that cGMP-dependent protein kinase may alter the activity of either the myosin light chain kinase or phosphatase. The relaxation induced by 8-Br-cAMP was not associated with a decrease in phosphorylation suggesting that cAMP-dependent protein kinase may uncouple myosin light chain phosphorylation from force.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Prevention of ultraviolet radiation-induced suppression of accessory cell function of Langerhans cells by Aloe vera gel components.

The active components of Aloe vera gel that can prevent ultraviolet B (UVB)-induced suppression of accessory cell function of Langerhans cells (LC) were purified by activity-guided sequential fractionation followed by in vitro functional assay. The functional assay was based on the fact that exposure of freshly isolated murine epidermal cells (EC) to UVB radiation resulted in impairment of accessory cell function of LC, as measured by their ability to support anti-CD3 monoclonal antibody (mAb)-primed T-cell mitogenesis. This UVB-suppressed LC accessory cell function was prevented by addition of partially purified Aloe gel components to cultures of UVB-irradiated EC. The Aloe gel components appeared to prevent events occurring within the first 24 h after UVB irradiation that lead to the impairment of accessory cell function. The Aloe gel components did not cause proliferation of anti-CD3 mAb-primed T-cells, nor did induce proliferation of normal EC. The activity-guided final purification of Aloe gel components resulted in the isolation of two components. Both of the components were small molecular weight (MW) substances with an apparent MW of less than 1,000 Da but different from each other in net charge characteristics at pH 7.4. These results suggest that Aloe vera gel contains at least two small molecular weight immunomodulators that may prevent UVB-induced immune suppression in the skin.

Adjuvants, Immunologic↗
PubMed1997

Aloesin up-regulates cyclin E/CDK2 kinase activity via inducing the protein levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells.

In the present study, we show that aloesin, which is a low molecular weight ingredients present in Aloe vera, stimulates the proliferation of cultured human hepatoma SK-HEP-1 cells. The incorporation of [3H] thymidine into DNA in the cell cultures was significantly increased at a dose of 10 microM aloesin. The aloesin-induced DNA synthesis appears to require newly synthesized proteins because cycloheximide treatment blocked the DNA synthesis evoked by this compound. We then examined whether this compound increases the intracellular levels of cell cycle regulators by immunoblotting. The data showed that aloesin increased the levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells. In addition, immuno-complex kinase assays showed that aloesin up-regulated the enzyme activity of cyclin E/CDK2 kinase in a dose-dependent manner. Collectively, these results suggest that aloesin stimulates the proliferation of SK-HEP-1 cells by inducing the intracellular levels of cyclin E/CDK2 kinase complex and CDC25A, which, together, result in the up-regulation of cyclin E-dependent kinase activity.

CDC2-CDC28 Kinases↗