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Biomedical subjects

S Ye

Publications and source records attributed to S Ye.

At least 73 records · Page 4Linked to original sources
PubMed2000

Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases.

The matrix metalloproteinases (MMPs) can degrade a range of extracellular matrix proteins and have been implicated in connective tissue destruction and remodelling associated with cancer invasion and metastasis, cartilage destruction in arthritis, atherosclerotic plaque rupture, and the development of aneurysms. Recently, naturally occurring sequence variation has been detected in the promoter of a number of MMP genes. These genetic polymorphisms have been shown to have allele-specific effects on the transcriptional activities of MMP gene promoters, and to be associated with susceptibility to coronary heart disease, aneurysms and cancers. These findings indicate that variation in the MMP genes may contribute to inter-individual differences in susceptibility to these common, complex diseases, likely through effects on the balance between the synthesis and degradation of extracellular matrix proteins.

Disease Susceptibility↗
PubMed2000

Genetic diversity in the matrix metalloproteinase family. Effects on function and disease progression.

Atherosclerosis is an example of a complex trait, where the course of the disease is influenced by a combination of common variation in a constellation of genes and the effect of a wide range of environmental variables. Thus, the underlying disease mechanisms will be modulated by genetic diversity and the effect this diversity has on an individual's response to environmental challenges such as smoking, diet, and exercise. Unlike the consequences of mutations in severe single-gene disorders on protein function, the impact of individual common, functionally important sequence changes in genes contributing to multifactorial diseases is likely to be very small. The challenge is to dissect the contribution that each of these genes makes to the disease process. We have tackled this by identifying common genetic variants, studying their effects on function, and applying them to the analysis of association in appropriately structured and suitably powered studies. Even with our incomplete understanding of the disease, the list of potential candidate genes we could study is vast; but, we do know from pathological studies that a wide spectrum of structural architecture exists in atherosclerotic plaques, suggesting that remodeling of vascular connective tissue is fundamentally important. Matrix remodeling is controlled by a complex network of cell and matrix interactions, the net outcome of which is the product of a balance between synthetic and degradative processes. Our work has focused on the family of enzymes and inhibitors most directly associated with matrix turnover--the matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs, tissue inhibitors of MPs). We specifically searched for functionally relevant genetic variants that might modulate the delicate control of matrix turnover. Using these molecular genetic strategies to investigate the impact of natural genetic variation on vascular matrix remodeling has begun to shed new light on the importance of these genes in atherogenesis.

Arteriosclerosis↗
PubMed2000

Interleukin-1beta and neurogenic control of blood pressure in normal rats and rats with chronic renal failure.

Increased sympathetic nervous system (SNS) activity plays a role in the genesis of hypertension in rats with chronic renal failure (CRF). The rise in central SNS activity is mitigated by increased local expression of neuronal nitric oxide synthase (NOS) mRNA and NO(2)/NO(3) production. Because interleukin (IL)-1beta may activate nitric oxide in the brain, we have tested the hypothesis that IL-1beta may modulate the activity of the SNS via regulation of the local expression of neuronal NOS (nNOS) in the brain of CRF and control rats. To this end, we first found that administration of IL-1beta in the lateral ventricle of control and CRF rats decreased blood pressure and norepinephrine (NE) secretion from the posterior hypothalamus (PH) and increased NOS mRNA expression. Second, we observed that an acute or chronic injection of an IL-1beta-specific antibody in the lateral ventricle raised blood pressure and NE secretion from the PH and decreased NOS mRNA abundance in the PH of control and CRF rats. Finally, we measured the IL-1beta mRNA abundance in the PH, locus coeruleus, and paraventricular nuclei of CRF and control rats by RT-PCR and found it to be greater in CRF rats than in control rats. In conclusion, these studies have shown that IL-1beta modulates the activity of the SNS in the central nervous system and that this modulation is mediated by increased local expression of nNOS mRNA.

Adrenergic alpha-Antagonists↗
PubMed2000

Effects of estrogen on leukocyte adhesion after transient forebrain ischemia.

BACKGROUND AND PURPOSE: Recent findings indicate that estrogen (ie, 17beta-estradiol [E(2)]) provides neuroprotection in models of transient global and focal ischemia. Enhanced postischemic leukocyte adhesion and infiltration have been linked to neuropathology in the brain as well as other tissues. We recently showed that estrogen reduces leukocyte adhesion in the cerebral circulation of female rats during resting conditions. METHODS: We compared leukocyte adhesion in pial venules in vivo in intact, ovariectomized (OVX), and E(2)-treated OVX female rats subjected to transient forebrain ischemia (30-minute right common carotid artery occlusion and hemorrhagic hypotension) and reperfusion. Adherent rhodamine-6G-labeled leukocytes were viewed through a closed cranial window with the use of intravital microscopy. Leukocyte adhesion was measured before ischemia and at different times after reperfusion. RESULTS: Before ischemia, leukocyte adhesion (measured as a percentage of venular area occupied by adherent leukocytes) was 2 to 3 times greater in OVX versus intact or E(2)-treated OVX rats (7.0%, 3.4%, and 2.2%, respectively). This difference disappeared at 120 minutes of reperfusion, when comparable levels of enhanced leukocyte adhesion were observed in all groups. In OVX rats, leukocyte adhesion remained elevated after 4 and 6 hours of reperfusion (11.6% and 12.9%, respectively), while the other 2 groups showed significantly lower levels (5.0% and 5.8% for intact rats and 7.0% and 7.2% for E(2)-treated OVX rats). CONCLUSIONS: Present results demonstrate that estrogen modulates leukocyte adhesion in the cerebral circulation after transient forebrain ischemia. This effect suggests that decreased leukocyte adhesion may be an important mechanism in estrogen-mediated neuroprotection.

Animals↗
PubMed2000

Losartan reduces sympathetic nerve outflow from the brain of rats with chronic renal failure.

Sympathetic nervous system (SNS) activity, measured by norepinephrine (NE) turnover rate, was greater in the posterior hypothalamic (PH) nuclei, the paraventricular nuclei (PVN), and the locus coeruleus (LC) of 5/6 nephrectomised (CRF) rats than of control rats. NE secretion from the PH was also greater in CRF than in control rats. These findings demonstrate that SNS activity plays an important role in the genesis of hypertension associated with CRF. The increase in central SNS activity was mitigated by increased local expression of nitric oxide synthase (NOS)-mRNA and nitric oxide (NOx) production. Because angiotensin II may stimulate the central SNS, we tested the hypothesis that losartan, a specific angiotensin II AT(1)-receptor antagonist, may lower blood pressure (BP), at least in part, by central noradrenergic inhibition. To this end, we studied two groups of CRF rats. One group received losartan (10 mg/kg body weight) in drinking water between the 3rd and 4th week after nephrectomy, the second group received drinking water without losartan. SNS activity was measured by NE secretion from the PH using the microdialysis technique. NOS-mRNA gene expression was also measured by RT-PCR in the PH, PVN, and LC of CRF and control rats. Losartan reduced systolic BP from 184+/-3.7 to 152+/-3.1 mmHg and NE secretion from the PH from 340+/-9.7 to 247+/-4.8 pg/ml. CRF rats treated with losartan manifested a significant (p<0.01) increase in the expression of nNOS-mRNA in the PH (from 84+/-1.2 to 99+/-2.6), the PVN (from 44+/-1.5 to 63+/-2.1), and the LC (from 59+/-6.7 to 76+/-2.1). CRF rats also manifested a significant increase (p<0.01) in the expression of IL-1beta the PH (from 41.6+/-2.8 to 54.3+/-1.4), PVN (from 44+/-1.9 to 54+/-1.5), and LC (from 35.5+/-1.6 to 53.5+/-1.9). In conclusion, these studies suggest that the antihypertensive action of losartan in CRF rats may be mediated, at least in part, by inhibition of central SNS outflow. The studies also suggest that the inhibitory action of losartan on the SNS may be mediated by activation of IL-1beta, which, in turn, stimulates nNOS, an important modulator of central SNS activity.

Angiotensin Receptor Antagonists↗
PubMed2000

[The expression and localization of wild-type p53-GFP fused gene on human high-metastasis hepatocellular carcinoma cell line].

OBJECTIVE: To study the normal expression and location of wt-p53 protein on human high-metastasis hepatocellular carcinoma (HCC) cell line. METHODS: According to the sequence of human wild-type p53, the mp53 cDNA in which stopped codon TGA was mutated to TGG, was amplified by PCR, ligated to EGFP gene, of pEGFP-N1. The recombinant plasmid was transfected into MHCC97, in which p53 gene was mutated. The expression of human p53 protein was observed by fluorescence microscopy. RESULTS: There was a p53 mutation on 249 codon in human high-metastasis hepatocellular carcinoma cell line MHCC97, but no mutation in low-metastasis HCC cells LD20. The two genes of wt-p53 and GFP were fused in codon frame by DNA sequencing. The fluorescence microscopy showed that fluorescence light was spread in all of MHCC97 cells transfected with pEGFP-N1, but fluorescence light was focused on the nucleus of MHCC97 cells transfected with pEGFP-53. CONCLUSION: The p53 mutation on 249 codon may be related to the character of metastasis of HCC cells. The human wild-type p53-GFP fusion protein is expressed in MHCC97 cell line and located in cell nucleus, which is similar to the expression of wt-p53 protein.

Artificial Gene Fusion↗
PubMed2000

Mutagenicity of methyl tertiary butyl ether.

Methyl tertiary butyl ether (MTBE), the main component of oxygenated gasoline, is added to gasoline as an octane enhancer to reduce automotive emissions. We evaluated the mutagenicity of domestic MTBE using the Ames test, unscheduled DNA synthesis (UDS) assay, and NIH/3T3 cell micronucleus test. MTBE did not show any mutagenic potential in the Ames assay (TA98, TA100 strains) with or without rat liver-derived metabolic activation system (S-9). In rat primary hepatocyte UDS assay, a dose-response relationship was observed, which meant that MTBE might damage normal DNA and induce unscheduled DNA synthesis. MTBE did not show positive results in the NIH/3T3 cell micronucleus test. It could be concluded that MTBE has some degree of mutagenicity.

3T3 Cells↗
PubMed2000

Effect of leaded and unleaded gasoline on the mutagenicity of vehicle exhaust particulate matter.

With the removal of lead from gasoline and the use of new technologies, there have been some changes in vehicle emissions. In order to find out if the unleaded gasoline has the ability to reduce the emission of pollutants, leaded and unleaded gasoline were tested on a Santana engine dynamometer under a standard test cycle. The concentrations of hydrocarbons (HC) and carbon monoxide (CO) in emission were analyzed. The extracts of total exhaust particles were also collected and the components were detected by gas chromatography/mass spectrometry (GC/MS). A series of different end point genotoxicity tests, including the Ames test, the single cell gel electrophoresis (SCGE) assay, and micronucleus induction assay, were performed to investigate the mutagenicity in the two kinds of gasoline. We found that unleaded gasoline could reduce the emission of CO and HC and significantly decrease the quantity of vehicle exhaust particulate matter by 60%. As for the component analysis, only 23 kinds of organic substances adsorbed onto the particles were identified in the unleaded gasoline, while 32 kinds of compounds were detected in the leaded gasoline. The genotoxicity tests indicated that both types of gasoline could enhance the number of histidine-independent colonies in the Ames test, cause DNA damage, and increase the frequency of induced micronucleus in the Chinese hamster lung (CHL) cells. For the same particle weight, no difference was found between their mutagenicity. Because of the decrease in the emission of CO, HC, and particles in unleaded gasoline, this gasoline has some benefits for the environment and human health.

Animals↗
PubMed2000

[The role of membrane-type 1 matrix metalloproteinase in the invasion and metastasis of hepatocellular carcinoma].

OBJECTIVE: To study the role of membrane-type 1 matrix metalloproteinase (MT(1)-MMP) in the invasion and metastasis of hepatocellular carcinoma (HCC), and find a method to judge the invasion and metastasis of HCC through MT(1)-MMP. METHODS: RT-PCR was used to study the expression of MT(1)-MMP mRNA in the HCC and in HCC nude mice model with higher metastasis potential (LCI-D20) and lower metastasis potential (LCI-35), and statistical methods were used to analyse the association between the expression of MT(1)-MMP mRNA and the pathological indexes of HCC. RESULTS: MT(1)-MMP mRNA was expressed by all the normal liver tissue (1.12 +/- 0.73), HCC (3.51 +/- 0.97), surrounding liver parenchyma (1.19 +/- 0.57), tumor embolus, and HCC nude mice model with LCI-D20, LCI-D35. The overexpression of MT(1)-MMP mRNA in HCC, embolus, LCI-D20 was related to the invasion and metastasis of HCC. The expression of MT(1)-MMP mRNA in HCC being higher than that in surrounding liver parenchyma was an important index to judge the invasion and metastasis of the HCC. CONCLUSION: MT(1)-MMP is related to the invasion and metastasis of HCC. The expression of MT(1)-MMP mRNA in HCC being higher than that in surrounding liver parenchyma could be acted as an important index to judge the invasion and metastasis of HCC.

Animals↗
PubMed2000

[Antitumor activities in vivo of interleukin-12 gene modified dendritic cells in murine models].

OBJECTIVE: To study the antitumor activities of the mIL-12 transfected and acid-eluted peptide sensitized dendritic cells (DC) in murine H22 liver cancer model. METHODS: The murine bone marrow derived DC were transfected with the recombinant adenovirus (Ad mIL-12) containing the mIL-12 gene and control virus AdBGFP. The peptides on the surface of the murine H22 cell line were eluted with mild acid buffer and then sensitized the transfected DC. The experimental animals were immunized with the differently disposed DC and the state of tumorgenesis and tumor growth was observed. RESULTS: The tumor growth and weight in the group immunized with mIL-12 transfected and acid-eluted peptide sensitized DC were significantly lower than those of control group (P<0.05). CONCLUSION: The mIL-12 transfected and acid-eluted peptide sensitized DC can induce obvious antitumor activities in the murine liver cancer models and may suggest new strategies for constructing new type of DC vaccine for liver cancer.

Animals↗
PubMed2000

[Application of monocyte strains (THP-1 cells) in study on silicosis in vitro].

OBJECTIVE: To explore the application of human blood monocyte strain (THP-1 cells) with properties of pulmonary alveolar macrophage in study on pathogenesis of silicosis in vitro. METHODS: Effects of cell culture supernatant of THP-1 stimulated by silica or induced and differentiated by phorbol ester (PMA) on proliferation of fibroblast (CHL), formation of Ag-NORs granule, migration of pulmonary alveolar epithelium (CCL-64) and occurrence of silicosis-like pathological changes were observed in rats. Chemo-illuminescence stimulated by silica in PMA-primed THP-1 cells was studied, as compared with that by PMA. RESULTS: Supernatant of silica-stimulated THP-1 cell culture could effectively enhance proliferation of CHL cells and increase the mean number of Ag-NORs granule and their dispersion, with a good dose-response relationship, which correlated highly with cytotoxicity index, pulmonary alveolar macrophage (PAM), caused by silica. And, they could also inhibit the migration of CCL-64 and the repair of epithelial damage. The supernatants from silica-stimulated PAM and THP-1 cell culture could cause early silicotic nodule-like lesions in rats. Chemo-illuminescence response in PMA-primed THP-1 cells and PAM was enhanced by stimulation with silica in a dose-dependent pattern. CONCLUSION: PMA-primed THP-1 cells may have a prospect of wide application in study on pathogenesis of silicosis and production of silicosis-related cytokine and oxygen free radicals in vitro.

Animals↗
PubMed2000

[Effects of methyl tertiary butyl ether on cell cycle and cell apoptosis].

OBJECTIVE: To explore the effects of the new gasoline additive, methyl tertiary butyl ether (MTBE) on cell cycle and cell apoptosis. METHODS: Flow cytometry was used to evaluate the effect of MTBE (1, 2, 4 microl/ml, 24 h) on NIH/3T3 cell cycles; and the effect of MTBE on Hela cell apoptosis was evaluated by detecting cell survival using crystal violet staining. RESULTS: Flow cytometry showed that MTBE could change NIH/3T3 cell cycles, decrease the number of cells in S stage, and arrest cells at G(2) + M stage. The results suggested that MTBE could affect NIH/3T3 cell cycles and induce cell proliferation. This situation existed 48 hours after the treatment, and cell cycles came back normal 96 hours after the treatment. By detecting cell survival using crystal violet staining, we found that MTBE could inhibit the apoptosis of Hela cells which was induced by tumor necrosis factor (TNF)alpha and cycloheximide. CONCLUSION: MTBE's carcinogenicity to animals may relate to induction of cell proliferation and inhibition of cell apoptosis.

3T3 Cells↗
PubMed2000

[Detection of soluble endothelial protein C receptor (sEPCR) in patients with CHD, DM and SLE].

OBJECTIVE: To evaluate the clinical significance of plasma soluble endothelial protein C receptor (sEPCR) level in patients with coronary heart disease (CHD), diabetes mellitus (DM) and systemic lupus erythematosus (SLE). METHODS: ELISA of antibody-sandwiched principle was used to detect sEPCR in 34 patients with CHD, 42 with DM-II, 63 with SLE and 20 normal controls (NC). RESULTS: The plasma level of sEPCR in patients with DM was higher than that in NC group (P < 0.05). The sEPCR level in SLE patients with thrombosis and non-thrombosis are higher than that in NC group (P < 0.005 and P < 0.001, respectively). There is no significant difference between the two groups of SLE (P > 0.05), and between the CHD and NC groups. CONCLUSION: sEPCR level increased in DM and SLE, it seems related to the process of inflammatory reaction and damage of endothelial cell.

Adolescent↗
PubMed2000

[Stage-dependent expression of androgen binding protein mRNA in sertoli cell of rat testis].

OBJECTIVE: To investigate the variation of rat androgen binding protein (ABP) mRNA in sertoli cell of rat testis during spermatogenesis. METHODS: In situ hybridization was performed with digoxin-labeled rat ABP cDNA probe on frozen testis tissue sections from SD rats. The expression of ABP mRNA was quantified by using laser density scanning system. RESULTS: It was shown that ABP mRNA levels were low from stage I to stage VI, increased to the peak level at the stages VII-VIII, and then declined rapidly at stages IX-XI. Thereafter, ABP mRNA levels increased again at stages XII-XIV, and then decreased to the lowest level at stages I-VI. CONCLUSIONS: ABP mRNA level was stage-dependent during the spermatogenic cycle.

Androgen-Binding Protein↗
PubMed1999

Human stromelysin gene promoter activity is modulated by transcription factor ZBP-89.

Matrix metalloproteinase expression is under strict regulation in physiological conditions. Disruption of the regulatory mechanisms can lead to tissue destruction and is associated with tumour invasion and metastasis. Using the one-hybrid assay technique with a cis-element in the promoter region of the stromelysin (matrix metalloproteinase-3) gene, a cDNA encoding a transcription factor termed ZBP-89 was obtained. The interaction between ZBP-89 and the stromelysin promoter element was confirmed by electrophoretic mobility shift assays with a recombinant ZBP-89. Reporter gene expression under the control of the stromelysin promoter in transiently transfected cells was significantly increased when the cells were cotransfected with a ZBP-89 expression construct. These results indicate that ZBP-89 interacts with the stromelysin promoter and upregulates its activity. As ZBP-89 expression is known to be increased in gastric carcinoma cells, induction of stromelysin expression may be a significant factor in tumour metastasis.

DNA-Binding Proteins↗
PubMed1999

Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis.

BACKGROUND: Gelatinase B, a matrix metalloproteinase that has proteolytic activity against connective tissue proteins, has been suggested to be important in the connective tissue remodeling processes associated with atherogenesis and plaque rupture. This study tested the hypothesis that sequence variation in the promoter region of the gelatinase B gene influences its expression, predisposing individuals carrying certain genetic variants to more severe atherosclerosis. METHODS AND RESULTS: Single-strand conformation polymorphism analysis was carried out to search the promoter region of the gene encoding gelatinase B for naturally occurring genetic variation. As a result, an unreported common polymorphism was detected, which arose from a cytosine (C) to thymidine (T) transition at position -1562 relative to the start of transcription. Transient transfection experiments and DNA-protein interaction assays indicated that the T allele had a higher promoter activity than the C allele, which appeared to be due to preferential binding of a putative transcription repressor protein to the C allelic promoter. A sample of 584 male patients with myocardial infarction and 645 age-matched male healthy control subjects were genotyped. The allele frequencies were not significantly different between the cases and control subjects. However, in 374 patients with available angiographic data, 26% of those carrying 1 or 2 copies of the T allele had >50% stenosis in 3 coronary arteries, whereas only 15% of C/C homozygotes had triple-vessel disease. CONCLUSIONS: These data suggest that this functional genetic variation influences gelatinase B gene promoter activity in an allele-specific manner and has an effect on atherosclerotic phenotype.

Adult↗