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Y Ko

Publications and source records attributed to Y Ko.

At least 127 records · Page 7Linked to original sources
PubMed1993

High-density lipoprotein reduces epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells.

High concentrations of high-density lipoprotein (HDL) are known to decrease the risk of coronary artery disease. In order to study the underlying cellular mechanisms, the influence of HDL on the epidermal growth factor (EGF)-induced vascular smooth muscle cell (VSMC) proliferation was investigated. Approximately 40% of the EGF-induced increase of the cell DNA synthesis was abolished in the presence of 30 micrograms/ml HDL. The EGF-induced dose-dependent (10 pg/ml to 100 ng/ml) increase in DNA synthesis was blunted by 30 micrograms/ml HDL. In addition HDL (3-300 micrograms/ml) caused a dose-dependent inhibition of EGF (20 ng/ml)-induced DNA synthesis, yielding a half maximal effective dose (ED50) of 30 micrograms/ml. Similar experiments with the HDL-protein and HDL-lipid fraction indicated that the HDL-protein fraction is most probably responsible for the observed inhibiting effects of HDL. This was confirmed by using purified apolipoprotein (apo) A-I and apo A-II. Both induced an approximately 80% inhibition of the EGF-induced DNA synthesis. These results may help to explain the observed beneficial effects of HDL on cardiovascular diseases that are described in many epidemiological studies.

Animals↗
PubMed1993

Long-term insulin treatment of vascular smooth muscle cells from rat aorta attenuates the synergistic effect of insulin on angiotensin II- and epidermal growth factor-induced DNA synthesis.

1. In the present study the effects of acute and chronic insulin treatment on growth factor-induced cell growth were investigated in vascular smooth muscle cells. Cell growth was quantified by the incorporation of [3H]thymidine into cell DNA and by determination of total protein. 2. Insulin in a concentration range of 10(-9)-10(-6) mol/l had no effect on cell DNA synthesis. Insulin-like growth factor-1 in a concentration range of 10(-9)-10(-6) mol/l induced a concentration-dependent increase in total cell protein, whereas no changes in DNA synthesis were observed. 3. Acutely, insulin enhanced the mitogenic effect of epidermal growth factor and angiotensin II. Long-term treatment with 10 and 100 ng/ml insulin over 14 weeks was associated with a time-dependent reduction in this potentiating effect of insulin on growth factor-induced DNA synthesis. To evaluate the mechanism of this effect, receptor binding studies were performed with 125I-labelled insulin-like growth factor-1. No difference in the Kd value (2.1 nmol/l) for insulin-like growth factor-1 was found between untreated and chronically insulin-treated cells, whereas the maximal number of binding sites decreased from 5.9 x 10(4) (untreated cells) to 4.7 x 10(4) (10 ng/ml) and to 4.3 x 10(4) (100 ng/ml) binding sites/cell in chronically insulin-treated cells. 4. We conclude that insulin acutely enhances the mitogenic effect of various growth factors such as epidermal growth factor and angiotensin II on vascular smooth muscle cells. Long-term insulin treatment reduced the number of receptor binding sites for insulin-like growth factor-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Synergistic action of angiotensin II, insulin-like growth factor-I, and transforming growth factor-beta on platelet-derived growth factor-BB, basic fibroblastic growth factor, and epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells.

The effect of angiotensin II (AII), transforming growth factor-beta (TGF-beta), and insulin-like growth factor-I (IGF-I) on platelet-derived growth factor (PDGF)-BB-, basic fibroblastic growth factor (bFGF)-, and epidermal growth factor (EGF)-induced DNA synthesis in vascular smooth muscle cells (VSMCs) was investigated. TGF-beta, AII, IGF-I increased concentration-dependent cell protein. No increase in [3H]thymidine incorporation could be detected. TGF-beta, AII, and IGF-I enhanced PDGF-BB-, bFGF-, and EGF-induced DNA synthesis. Our results suggest that growth factors that possess a weak mitogenic effect on vascular smooth muscle cells such as TGF-beta, AII, and IGF-I may enhance the mitogenicity of PDGF-BB, bFGF, and EGF.

Angiotensin II↗
PubMed1993

EXP3174, a metabolite of losartan (MK 954, DuP 753) is more potent than losartan in blocking the angiotensin II-induced responses in vascular smooth muscle cells.

OBJECTIVE: EXP3174 is a metabolite of losartan (previous name DuP753), which is a non-peptide angiotensin II receptor antagonist. DESIGN: The inhibitory potency of these two antagonists on the angiotensin II-induced responses in vascular smooth muscle cells (VSMC) was investigated. METHODS: The effect of angiotensin II on cell growth was determined by [3H]-thymidine incorporation into cell DNA and by cellular protein measurements. Intracellular cytosolic Ca2+ concentration was measured by the fura-2 method. Inositolphosphates were determined by high-performance liquid chromatography after cell labelling with myo-[2-3H]-inositol. The early growth response gene-1 (Egr-1) messenger RNA (mRNA) expression was determined by the Northern blotting method. Binding and displacement studies of the antagonists were performed using [125I]-angiotensin II. RESULTS: An apparent dissociation constant (Kd) of 5.9 nmol/l for [125I]-angiotensin II (maximal binding coefficient 69 fmol/10(6) cells) was found. The specific binding of [125I]-angiotensin II to VSMC was inhibited by losartan, EXP3174 and saralasin with a half-maximal inhibitory concentration (IC50) of 1.0 X 10(-8), 1.1 X 10(-9) and 1.8 X 10(-9) mol/l, respectively. EXP3174 and losartan abolished the angiotensin II-induced formation of inositolphosphates in VSMC. EXP3174 and losartan inhibited the angiotensin II-induced elevation of intracellular cytosolic Ca2+ concentration with an IC50 of 5 X 10(-9) and 5 X 10(-8) mol/l, respectively. EXP3174 was more effective than losartan in blocking the angiotensin II-induced increase in Egr-1 mRNA. EXP3174 and losartan inhibited the angiotensin II-induced cell protein synthesis with an IC50 of 3 X 10(-9) and 4 X 10(-8) mol/l, respectively. CONCLUSIONS: These results indicate that EXP3174 is significantly more potent than losartan in blocking angiotensin II-induced cellular responses.

Angiotensin II↗
PubMed1993

Action of dihydropyridine calcium antagonists on early growth response gene expression and cell growth in vascular smooth muscle cells.

OBJECTIVE: Evidence suggests that calcium antagonists may suppress vascular smooth muscle cell (VSMC) growth and proliferation, which may be a crucial step in the pathogenesis of hypertension and atherosclerosis. DESIGN: The effects of the dihydropyridine calcium antagonists nifedipine, nitrendipine, nisoldipine, nimodipine and isradipine on cell growth induced by platelet-derived growth factor (PDGF)-AB and angiotensin II (Ang II), and expression of the transcription factors c-fos and early-growth response gene 1 (egr-1) were investigated. METHODS: Proliferation of VSMC in culture was measured by [3H]-thymidine incorporation into cell DNA and by cell count. Expression of c-fos and egr-1 messenger RNA (mRNA) was determined by the Northern blot technique. RESULTS: All of the calcium antagonists blunted the PDGF-induced rise in VSMC DNA synthesis. The inhibitory potency of isradipine on PDGF-stimulated DNA synthesis was approximately 10-fold that of the other calcium antagonists used, isradipine having a half-maximal inhibitory concentration (IC50) of (4.2 +/- 0.16) x 10(-7) mol/l. The calcium antagonists investigated also inhibited Ang II-induced DNA synthesis. Isradipine (10(-6) mol/l) completely abolished the PDGF-induced cell proliferation. Both PDGF (50 ng/ml) and Ang II (10(-7) mol/l) induced c-fos and egr-1 mRNA expression, having maximum effect after 30 min. In the case of c-fos, pre-incubation with 5 x 10(-6) mol/l isradipine led to a decrease in both Ang II- and PDGF-induced expression of this immediate-early gene. The expression of egr-1 was not affected by pre-incubation with 5 x 10(-6) mol/l isradipine. CONCLUSIONS: All calcium antagonists investigated in the present study inhibited cell growth. Isradipine was more potent in blocking growth factor-induced cell growth than the other calcium antagonists studied. The inhibitory effect of the dihydropyridine calcium antagonists appears to be dependent on the expression of c-fos.

Animals↗
PubMed1992

Angiotensin II induces formation of the early growth response gene-1 protein in rat vascular smooth muscle cells.

The effect of angiotensin II (Ang II) on the early growth response gene-1 (Egr-1) mRNA, on the Egr-1 protein and on the phosphoinositide PI turnover signalling system was investigated in the presence and absence of EXP3174, a potent non-peptide Ang II receptor antagonist. Ang II induced an accumulation of 3.4 kb Egr-1 mRNA and the 80 kDa Egr-1 protein, with a maximum at 30 min and 60 min, respectively. EXP3174 blocked the Ang II-induced increase of inositol phosphates, Egr-1 mRNA and the Egr-1 protein, suggesting the involvement of the PI signalling system by the expression of the Egr-1 gene.

Angiotensin II↗
PubMed1992

Losartan inhibits the angiotensin II-induced stimulation of the phosphoinositide signalling system in vascular smooth muscle cells.

2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole, potassium salt (Losartan) (previous name, DuP 753 or MK 954) is a nonpeptide angiotensin II receptor antagonist. This study was performed to investigate the ability of Losartan to inhibit the angiotensin II-induced stimulation of the phospoinositide signalling system and the angiotensin II-induced hypertrophy in aortic vascular smooth muscle cells of normotensive Wistar-Kyoto rats. 10(-7) M Losartan abolished the angiotensin II-induced formation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. 10(-6) M Losartan completely abolished the angiotensin II-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i). 10(-6) M Losartan lacked effects on the [Arg8]vasopressin-induced elevation of [Ca2+]i. In addition, 10(-6) M completely inhibited the angiotensin II-induced stimulation of Na+/H+ exchange in the vascular smooth muscle cells. 10(-10) to 10(-6) M Losartan inhibited the angiotensin II-induced cell protein synthesis in a concentration-dependent manner, yielding to an effective concentration (ED50) of 6.2 +/- 1.8 x 10(-8) M (n = 4). Losartan did not affect the platelet-derived growth factor-BB-induced increase in cell protein. These results show that Losartan is a highly specific angiotensin II receptor antagonist which inhibits angiotensin II-induced cell growth and thus may have beneficial effects on the development and regression of vascular hypertrophy.

Angiotensin II↗
PubMed1992

A sensitive enzyme-linked immunosorbent assay for human interleukin-8.

In order to quantify human interleukin-8 (IL-8), which is chemotactic for T cells and basophils as well as neutrophils, we developed an enzyme-linked immunosorbent assay (ELISA). Since binding inhibition tests indicated that three monoclonal antibodies (mAbs; BS-1, WS-4, WS-6) blocked the binding of 125I-labelled IL-8 to neutrophils, we tested an ELISA using these mAbs as primary antibodies, rabbit anti-IL-8 Ab as the secondary antibody, and alkaline phosphatase-labelled goat anti-rabbit Ab as the conjugate. Among the three mAbs tested, WS-4 was the most sensitive with a detection limit of 16 pg/ml. Several other cytokines, including monocyte chemotactic and activating factor (MCAF), which is structurally related to IL-8, showed no cross-reactivity in this system, indicating that this ELISA is specific for IL-8. The coefficients of variation for the intra- and interassays were below 10%. Furthermore, this ELISA also detected natural IL-8 (including both 72 and 77 amino acid forms) produced by cultured human cells and cell lines stimulated with IL-1, suggesting that this system will be useful in the detection of natural IL-8 in various body fluids.

Antibodies, Monoclonal↗
PubMed1992

The effect of angiotensin II on DNA synthesis varies considerably in vascular smooth muscle cells from different Wistar-Kyoto rats.

OBJECTIVE: It is well established that angiotensin II induces vascular smooth muscle cell (VSMC) growth but conflicting data exist concerning whether angiotensin II induces cell hypertrophy and/or DNA synthesis from Wistar-Kyoto (WKY) rats. DESIGN: In this study we examined the effect of 10(-7) mol/l angiotensin II on cell protein and DNA synthesis in VSMC (passages 5-30) derived from eight different WKY rats. METHODS: The mitogenic and hypertrophic effect of angiotensin II was determined by 3H-thymidine incorporation into cell DNA and by total cellular protein measurements. RESULTS: In cells derived from two cell lines, angiotensin II induced a potent mitogenic effect. In cells derived from two other cell lines it induced a weak mitogenic effect. No significant effects on DNA synthesis were observed in cells derived from the four remaining cell lines. Cells from all cell lines reacted to angiotensin II with a 30-40% increase in cell protein. The observed mitogenic effect of angiotensin II was inhibited by losartan, a non-peptide angiotensin II receptor antagonist, proving that the angiotensin II-induced mitogenic effect is directly triggered via the angiotensin II subtype AT1 receptor. The hypertrophic effect of angiotensin II was also illustrated by morphological studies showing that angiotensin II increases the cell size in all cell lines used. CONCLUSIONS: Our study shows that angiotensin II not only is a hypertrophic agent, but may also be a potent mitogenic agent for VSMC from WKY rats.

Angiotensin II↗
PubMed1992

Action of metoprolol, enalapril, diltiazem, verapamil, and nifedipine on cell growth of vascular smooth muscle cells.

The influence of nifedipine, verapamil, diltiazem, metoprolol, and enalapril on the basal and angiotensin II (Ang II)-induced elevation of [3H]thymidine incorporation into vascular smooth muscle cell (VSMC) DNA was examined. Our results from four independent experiments, each performed in triplicate, are summarized by calculating the half-maximal inhibitory concentration (IC50) of the drugs. Nifedipine, verapamil, and diltiazem had IC50 values of 2.3 +/- 0.7 x 10(-6), 3.5 +/- 0.3 x 10(-6), and 6.6 +/- 2.8 x 10(-6) M, respectively. Metoprolol had an IC50 value of 49 +/- 16 x 10(-6) M, whereas enalapril was completely ineffective. All drugs used had no influence on the basal cell [3H]thymidine incorporation. This in vitro study allows one to conclude that the calcium-entry blockers can inhibit the Ang II-induced cell growth and thus may have beneficial effects on the development and regression of vascular growth, which is associated with the pathogenesis of cardiovascular diseases.

Animals↗
PubMed1992

Spinal meningeal melanocytoma.

A case of spinal meningeal melanocytoma is reported along with clinicopathologic, immunohistochemical and ultrastructural studies. This patient presented clinically with paraparesis, tingling sensation and numbness of both lower extremities of 4 months duration. No mucocutaneous pigmented nevi were found. On operation, scattered coal-black pigmented lesions were found in the meninges between T3 and T4-5 interspace level. Nearly total removal was carried out. The tumor was composed of spindle and epithelioid cells with heavy brown-black pigmentation. There was no pleomorphism, mitosis, hemorrhage, necrosis or invasion to the underlying cord tissue. In Korea, this case appears to be the first example of this disease. Neurologic deficit improved after surgical excision.

Adult↗
PubMed1992

Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line.

In order to analyse the effects of glucocorticoids on interleukin-8 (IL-8) production more precisely, we examined the effects of dexamethasone on IL-8 production at the molecular level in a human fibrosarcoma cell line, 8387, which IL-1 induces to express IL-8 messenger RNA (mRNA) and to secrete IL-8. Over a wide dose range, dexamethasone inhibited IL-8 production induced by IL-1 alpha stimulation. Northern blotting analysis showed that dexamethasone also inhibited the IL-8 mRNA accumulation in a similar dose-related manner. Nuclear run-off assay revealed that dexamethasone decreased the transcription of the IL-8 gene and the degree of inhibition of transcription correlated well with the inhibition of IL-8 production, suggesting that the action of glucocorticoids is mainly at the transcriptional level. Furthermore, transfection with chloramphenicol acetyl transferase (CAT) expression vectors inserted with the 5'-deleted IL-8 gene demonstrated that the 5'-flanking region which contains the glucocorticoid response element (GRE) was mainly involved in the dexamethasone-induced repression of the IL-8 gene. These data suggest that the inhibition of the IL-8 gene transcription by glucocorticoids occurs through the interaction of the glucocorticoid receptor complex with GRE in the 5'-flanking region of the IL-8 gene.

Blotting, Northern↗
PubMed1991

Demonstration of two distinct subsets of gastric varices. Observations during a seven-year study of endoscopic sclerotherapy.

Over a seven-year period, assessment of gastric varices was made on 225 patients receiving endoscopic sclerotherapy for variceal hemorrhage. Of 170 patients with complete data, gastric varices were observed in 26 (15.3%). Importantly, two distinct subsets of gastric varices were identified: varices distal to the gastroesophageal junction without extension into the fundus, termed "junctional varices," occurred in 11.2%, and varices that were confined only to the fundus, termed "fundal varices," occurred less frequently in 4.1%. Although rebleeding was increased in both subsets of gastric varices, junctional varices were more amenable to sclerotherapy. Patients with fundal varices (N = 7) had a significantly higher rebleeding rate, increased complications with sclerotherapy, and significantly decreased survival (P less than 0.005) when compared to patients with esophageal varices alone (N = 87) who were followed for more than three months. Cumulative survival was not significantly different (P less than 0.08) in patients with junctional varices (N = 19) when compared with patients with esophageal varices alone. We conclude that not all patients with gastric varices have a poor result with sclerotherapy. Recognition of these subsets may improve treatment strategies in patients with gastric varices.

Esophageal and Gastric Varices↗
PubMed1991

Insulin-like growth factors in sheep uterine fluids: concentrations and relationship to ovine trophoblast protein-1 production during early pregnancy.

Uterine luminal fluids (ULFs) from Days 10, 12, 14, and 16 cyclic (C) and pregnant (Px) ewes were analyzed for presence of insulin-like growth factors (IGF-I, IGF-II) and other mitogenic factor(s). IGF content and non-IGF mitogenic activity were measured by IGF RIAs after removal of IGF binding proteins and by stimulatory effects on DNA synthesis of density arrested AKR-2B cells, respectively. ULF IGF-I content was not different between days, but differences in IGF-I between C and Px groups at Day 16 (C greater than Px) were found (p less than 0.05). ULF IGF-II content was not different between C and Px ewes; however, differences among days (p less than 0.01) were apparent. In both C and Px ewes, Day 14 ULF had highest IGF-II content (C: 4.60 +/- 0.98 ng/ml, Px: 5.39 +/- 1.38 ng/ml). In Day 12 and Day 14 (C and Px) ULF, IGF-II concentration was about 10-fold greater than that of IGF-I. AKR-2B mitogenic activity in ULF differed among days (p less than 0.01), but not between C and Px ewes. Highest activity was observed for Day 14 and Px ULF, whereas lowest activity was for Day 10 C and Day 16 Px ULF. Sephadex G-200 gel-filtration chromatography of ULF from Day 14 Px ewes demonstrated mitogenic activity in the column void volume fractions and in the 30-kDa size range of eluted proteins. Day 13 conceptuses were cultured in serum-free medium to define the effect of exogenous IGFs on ovine trophoblast protein-1 (oTP-1) secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗