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Biomedical subjects

W Du

Publications and source records attributed to W Du.

At least 109 records · Page 6Linked to original sources
PubMed1997

Regulation of tPA in endothelial cells exposed to cyclic strain: role of CRE, AP-2, and SSRE binding sites.

We have previously reported that exposure of cultured bovine aortic endothelial cells (EC) to 10% average strain resulted in an increase in tissue plasminogen activator (tPA) mRNA, immunoreactive tPA protein, and tPA activity in the medium. The present study was designed to examine the regulation of tPA gene expression in EC by cyclic strain. We performed a functional analysis of the tPA promoter by transfecting bovine aortic EC with a 1.4-kilobase (kb) construct of the human tPA promoter coupled to chloramphenicol acetyltransferase. We found that subjecting the EC to 10% average strain (and not 6% average strain) resulted in a 2.6-fold increase in activity of the 1.4-kb tPA promoter by 4 h. Analysis of deletion mutants of the promoter transfected into EC demonstrated a 60% drop-off in activity between position -145 and -105. Deoxyribonuclease I protection analysis of the segment downstream of position -196 suggested involvement of activator protein-2 (AP-2) and adenosine 3',5'-cyclic monophosphate-responsive element (CRE)-like binding sites, which was confirmed by electrophoretic mobility shift assays. Site-directed mutants of either the AP-2 or CRE-like regions resulted in a 65% decrease in activity compared with the wild type. Double mutations abolished basal transcription and any strain-induced activity. A shear stress responsive element (SSRE) binding site is present at -945, but site-directed mutants did not show any drop in activity compared with wild type by cyclic strain. These studies demonstrate that cyclic strain regulates tPA gene transcription in bovine aortic EC and that this transcriptional activation is dependent on factors that are similar to those activated with phorbol ester.

Animals↗
PubMed1997

Gene regulation by mechanical forces.

Endothelial cells are subjected to various mechanical forces in vivo from the flow of blood across the luminal surface of the blood vessel. The purpose of this review was to examine the data available on how these mechanical forces, in particular cyclic strain, affect the expression and regulation of endothelial cell function. Studies from various investigators using models of cyclic strain in vitro have shown that various vasoactive mediators such as nitric oxide and prostacyclin are induced by the effect of mechanical deformation, and that the expression of these mediators may be regulated at the transcription level by mechanical forces. There also seems to be emerging evidence that endothelial cells may also act as mechanotransducers, whereby the transmission of external forces induces various cytoskeletal changes and second messenger cascades. Furthermore, it seems these forces may act on specific response elements of promoter genes.

Animals↗
PubMed1997

[A study on type I, III and IV collagen production in CCl4 induced rat liver fibrosis].

OBJECTIVE: To study the dynamic changes of alpha 1 (I), alpha 1 (III) and alpha I (IV) procollagen mRNA and collagen-producing cells during CCl4 induced SD rat liver fibrogenesis (20 weeks). METHODS: The investigations were performed using Northern blot analysis, in situ hybridization and immunohistochemical techniques. RESULTS: The increased expression of alpha 1 (III) procollagen mRNA during fibrogenesis by Northern blot analysis was the most predominant among the three mRNAs studied. However, the increase of alpha 1 (IV) procollagen mRNA expression occurred earlier, while the expression of alpha 1 (I) mRNA did not increase until the middle stage of the experiment. Desmin positive and/or smooth muscle actin positive Ito cells and myofibroblasts (MFs) in and around the necrotic areas expressed alpha 1 (I), alpha 1 (III) and alpha 1 (IV) procollagen mRNA signals detected by in situ hybridization during the early stage of the experiment. All the three procollagen mRNAs were mostly localized in fibroblasts (Fbs) and MFs in the septa during the mid and late stages of fibrosis. CONCLUSIONS: Fbs and MFs were considered as important Col I, Col III and Col IV producing cells in liver fibrosis. Sinusoid endothelia were involved in Col IV synthesis in the fibrotic liver.

Animals↗
PubMed1997

[Research on effects of taurine on the transplanted tumor of mice].

With the same forage to the mice, three experiments were done. The control group took water and experimental group took 1% taurine. 1. After the mice were vaccinated with S180 sarcoma, every group was further divided into two groups, one treated with cytoxan (CTX), another one treated with nothing. The survival period, weight of the tumor and the tumor inhibition rate were investigated. The result shows: The survival period of the group fed with taurine was (35.75 +/- 23.7) days longer than that of the control group (18.7 +/- 5.6) days, and the tumor inhibition rate was 42.26%. The mice fed with taurine and treated with CTX survived to 61 days with no death, and no tumor could be seen grossly, so the tumor inhibition rate is 100%. The survival period and weight of the tumor were not different between the CTX treated and control groups. 2. Tumor cell membrane fluidity was observed after the mice were vaccinated with Erlish ascitic tumor. The result shows: in the taurine group, the fluorescence polarization (p) is 0.108 +/- 0.020, the viscosity (eta) is 0.618 +/- 0.140 and in the control group p is 0.139 +/- 0.20, eta is 0.874 +/- 0.150, respectively. Thus the cell membrane fluidity of the taurine group is also obviously better than that of the control group (P < 0.01). 3. The immune functions of the two groups were determined by carbon clearance test and capacity of serum hemolysin. The immune function of the taurine group is also obviously higher than that of control group (P < 0.01). All the results described above show:taurine is functioning for tumor inhibition, and has obvious synergic effect while treated with CTX as chemotherophy. It is considered that the tumor inhibit function of taurine may be related to its effects of immune enhancing and membrane profecting.

Animals↗
PubMed1997

[Effect of processing on reducing the toxicity in sulfur].

The content of arsenic in sulfur before and after processing was determined. The result shows that the content in raw materials is 8-15 times higher than that of the processed product, which implies that the toxicity of sulfur is obviously reduced by processing.

Arsenic↗
PubMed1997

[Serological survey of human T lymphotropic virus type I (HTLV-1) IgG antibody in south region of Xinjiang].

Human T lymphotropic virus type-1 (HTLV-1) is endemic in southwestern Japan, Seychelles Islands, Caribbean basin, Brazil, and Sub Saharan Africa. Recently, the prevalence of HTLV-1 of domestic source has been reported from Beijing, Fujian and so forth. The object of our study is to know whether the prevalence of HTLV-1 is present in Xinjiang. We collected 2642 serm samples of various ages and different nationalities (Uigur, Han and Khalkhas) from south region of Xinjiang and tested for determination of HTLV-1 IgG antibody by IFA. The results showed that the total positive rate of HTLV-1 IgG was 0.34% (9/2642), of which Uigur nationality was 0.74% (8/1082), Khalkhas nationality was 0.21 (1/471), Han nationality was zero (0/1089). This data indicated that there are HTLV-1 infection among the population of Xinjiang and especially in Uigur and Khalkhas. Why did the minority nationalities have relatively high frequency of HTLV-1 infection? This needs to be studied further.

Adolescent↗
PubMed1997

[Synthesis and degradation of type IV collagen in rat experimental liver fibrosis].

OBJECTIVE: To investigate the synthesis and degradation of type IV collagen in CCl4-induced SD rat liver fibrosis. METHODS: Dynamic changes and relationships among the tissue alpha 1 (IV) procollagen mRNA, type IV collagen (Col IV) and serum 7S polypeptide fragment of Col IV in fibrotic livers induced by CCl4 with choline difficiency diet were studied using immunohistochemistry, Northern analysis, in situ hybridization and serum RIA techniques. RESULTS: The transcription of alpha 1 (IV) procollagen mRNA in fibrotic liver and the content of serum 7S polypeptide fragment derived from tissue Col IV degradation was enhanced promptly and obviously in earlier stage of experiment, but not synchronous afterwards. In the early stage of experiment, alpha 1 (IV) procollagen mRNA transcripts was localized in sinusoid Ito cells and endothelial cells. In the mid and late stage, alpha 1 (IV) procollagen mRNA transcripts was localized in myofibroblasts (MFs), fibroblasts (Fbs) and endothelia of small blood vessels in fibrotic septa. CONCLUSIONS: The change of serum 7S polypeptide fragment could reflect the motabolic state of Col IV and the degree of tissue injury in fibrogenesis and might have some clinical significance in identifying the activiation of the liver fibrosis. The "Ito cell-myofibroblast-fibroblast" effective cell system and sinusoid endothelia were the Col IV producing cells during fibrogenesis, in which sinusoid endothelia, as another source of Col IV production, participated in the capillization of liver sinusoids.

Animals↗
PubMed1996

Isolation and sequence of the Drosophila virilis 60 A gene, a transforming growth factor-beta superfamily member related to vertebrate bone morphogenetic proteins.

The complete protein-coding region of the Drosophila virilis 60 A gene, a member of the transforming growth factor-beta superfamily, was isolated and sequenced. The mature domain of the protein-coding region is 99% identical to the Drosophila melanogaster 60 A gene and 73% identical to human bone morphogenetic protein 5. In the pro-domain, a number of large blocks of amino acids are also highly conserved, indicating an important functional role for this portion of the protein as well. In the putative 5' and 3' untranslated regions, several short sequence motifs are conserved between D. virilis and D. melanogaster.

Amino Acid Sequence↗
PubMed1996

Requirements for dE2F function in proliferating cells and in post-mitotic differentiating cells.

The transcription factor E2F is a target of the retinoblastoma tumor suppressor protein (pRB) and may mediate pRB regulation of S phase entry in mammalian cells. The recent identification of mutant alleles of the Drosophila E2F gene (dE2F) has shown that dE2F is required for embryogenesis. dE2F-mutant embryos lack a co-ordinated program of gene expression which accompanies S phase entry and DNA synthesis declines to levels that are barely detectable. We have investigated the role of the dE2F gene at later stages of development. dE2F is expressed in several larval tissues and is required for cell proliferation in the eye imaginal disc. Surprisingly, dE2F expression persists in post-mitotic cells of the eye disc of third-instar larvae. The loss of dE2F function in these cells causes a novel phenotype, characterized by loss of photoreceptors and abnormal rhabdomere cell morphology. These results show that dE2F is required at multiple stages of development and suggest that E2F may have an important function in post-mitotic cells in addition to its role during cell proliferation.

Animals↗
PubMed1996

Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye.

The deregulation of E2F activity is thought to contribute to the uncontrolled proliferation of many tumor cells. While the effects of overexpressing E2F genes have been studied extensively in tissue culture, the consequences of elevating E2F activity in vivo are unknown. To address this issue, transgenic lines of Drosophila were studied in which ectopic expression of dE2F and dDP was targeted to the developing eye. The co-expression of dDP or dE2F disrupted normal eye development, resulting in abnormal patterns of bristles, cone cells and photoreceptors. dE2F/dDP expression caused ectopic S phases in post-mitotic cells of the eye imaginal disc but did not disrupt the onset of neuronal differentiation. Most S phases were seen in uncommitted cells, although some cells that had initiated photo-receptor differentiation were also driven into the cell cycle. Elevated expression of dE2F and dDP caused apoptosis in the eye disc. The co-expression of baculovirus p35 protein, an inhibitor of cell death, strongly enhanced the dE2F/dDP-dependent phenotype. These results show that, in this in vivo system, the elevation of E2F activity caused post-mitotic cells to enter the cell cycle. However, these cells failed to proliferate unless rescued from apoptosis.

Animals↗
PubMed1996

RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila.

Genetic studies have shown that cyclin E and dE2F are critical regulators of S-phase entry during Drosophila embryogenesis. Whereas the ectopic expression of cyclin E activates dE2F-dependent transcription, it has been proposed that cyclin E does not act directly on dE2F but targets a negative regulator of E2F activity. Such a regulator might be analogous to the family of RB-related proteins (pRB, p107, and p130) that associate with E2F in humans; however, extensive efforts have failed to find such homologs in Drosophila. We have developed a two-hybrid approach that allows transcription activators to be used as bait for interacting proteins. From a screen using Drosophila E2F (dE2F and dDP) as bait, we identified a novel gene, RBF. RBF combines several of the structural features of pRB, p107, and p130, suggesting that it may have evolved from a common ancestor to the three human genes. RBF associates with dE2F and dDP in vivo and is a stoichiometric component of E2F DNA-binding complexes. RBF specifically repressed E2F-dependent transcription and suppressed the phenotype generated by ectopic expression of dE2F and dDP in the developing Drosophila eye. RBF was phosphorylated by a cyclin E-associated kinase in vitro, and loss-of-function cyclin E mutations enhanced an RBF overexpression phenotype, consistent with the idea that the biological activity of RBF is negatively regulated by endogenous cyclin E. The properties of RBF suggest that it is the intermediary factor that was proposed to allow cyclin E induction of E2F activity. These findings indicate that RBF plays a critical role in the regulation of cell proliferation in Drosophila and show that analogous pathways regulate S-phase entry in a diverse range of species.

Amino Acid Sequence↗
PubMed1996

Variations in the management of acute myocardial infarction. Importance of clinical measures of disease severity.

OBJECTIVE: To determine the extent to which resource use for patients hospitalized with acute myocardial infarction varies with clinical status, and to see if an observed difference in resource use between two states can be explained by clinically detailed risk adjustment. DESIGN: Retrospective review of the clinical characteristics and resource use of 342 patients hospitalised in two states with acute myocardial infarction. DATA SOURCES: Merged data from three sources: a large, existing research database used in developing the Medicare Mortality Predictor Score, clinical data abstracted from medical charts specifically for this study, and Medicare Parts A and B claims records. PATIENTS: A probability sample of Medicare patients hospitalized in 1986 with a diagnosis of acute myocardial infarction and residing in either Wisconsin or Washington state; patients dying within 30 days are oversampled. MEASUREMENTS AND MAIN RESULTS: Although patients were clinically similar in the two states, there were systematic differences in resource use. Patients in Wisconsin spent more than one extra day in the intensive care unit (ICU) (2.8 vs 1.7) as well as more than one extra non-ICU day in the hospital (8.0 vs 6.5) than patients in Washington. Patients in Wisconsin were also more likely to receive an echocardiogram (35.6% vs 15.8%), nuclear ventriculogram (12.8% vs 4.1%), exercise tolerance test (21.5% vs 3.4), and Holter monitoring (5.4% vs 0%). (All p < .01.) Differences in utilization were greater for patients at lower risk of dying. The average cost of care was 20.8% higher in Wisconsin (p = .01); risk adjustment for clinical and other factors reduced this difference to 11.8%, but did not eliminate it (p = .04). CONCLUSIONS: Patients with acute myocardial infarction vary in resource use as a function of clinical factors present at admission and occurring during the hospital stay; comparisons that do not take account of these factors may not discriminate well between providers who care for sicker patients and those who are inefficient. The greater use of resources for patients in Wisconsin is at least partially explained by differences in clinical characteristics that are not presently captured in administrative data.

Aged↗
PubMed1996

The nitric oxide synthesis inhibitor L-NAME facilitates associative learning.

1. Nitric oxide has been suggested to play an important role in synaptic plasticity and in learning. 2. The authors examined the effects of NW-nitro-L-arginine methyl ester, a competitive and enantiomeric specific inhibitor of nitric oxide synthase, on classical conditioning of the rabbit's nictitating membrane response. 3. It was found that L-NAME significantly enhanced the acquisition of conditioned responses. 4. The enhanced conditioned responses were not due to a sensitization of the conditioned and unconditioned reflexes or to changes in baseline levels of responding. 5. The dose and route of administration of L-NAME employed in this study had no effect on blood pressure. 6. These results suggest that nitric oxide normally functions as a tonic inhibitory modulator of associative learning and that procedures aimed at decreasing its production may provide a novel approach for improving learning.

Animals↗
PubMed1995

Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE binding protein and NF-kB, in endothelial cells: species and vascular bed diversity.

Recent studies demonstrate that cyclic strain stimulates protein kinase C in bovine aortic endothelial cells (BAEC) as well as the induction of immediate early genes and the transcription factor activator protein-1 (AP-1) in human umbilical vein endothelial cells (HUVEC). The objective of this study was to determine whether transcriptional factor induction in endothelial cells (EC) exposed to strain is the same with regard to the species and vascular bed they are derived from. Evidence for a heterogeneous response for growth, orientation and prostacyclin secretion has been obtained for a variety of EC exposed to cyclic strain. In this study, we investigated cyclic strain mediated induction of transcription factors, AP-1, cAMP response element binding protein (CRE) and nuclear factor kB (NF-kB) in cultured EC from HUVEC, human aorta (HAEC), and BAEC. EC were exposed to 10% average strain at 60 cpm for up to 24 h. At varying time points, nuclear protein was extracted and analyzed for production of AP-1, CRE and NF-kB by electromobility shift assay. The results demonstrate that EC exposure to cyclic strain leads to a significant induction of AP-1, CRE and NF-kB in HAEC and HUVEC, but not in BAEC. Furthermore, these findings are in marked contrast to the previously described shear stress induced activation of AP-1 and NF-kB in BAEC. There was also a temporal difference in their response such that stretch-induced activation of AP-1 and NF-kB peaked at 4 h, whereas CRE increased in a biphasic manner at 15 min and 24 h. These results may partially explain the divergent effects of cyclic strain on EC gene expression and phenotype in EC from different vascular beds and species and underscore the difference in EC response to cyclic strain and shear stress.

Activating Transcription Factor 2↗
PubMed1995

Hypotensive stress retards associative learning in rabbits.

This study examined the effects of hypotensive stress on classical conditioning of the rabbit's nictitating membrane response. Hypotension, consisting of an approximately 45% decrease in blood pressure, was maintained for 30 min by the i.v. infusion of sodium nitroprusside. Twenty minutes later animals were exposed to a conditioning session consisting of 60 pairings of a 200 ms tone conditioned stimulus with a 100 ms airpuff unconditioned stimulus directed at the cornea. This procedure was repeated for four consecutive days. Animals exposed to the hypotensive stress demonstrated a significantly retarded acquisition of conditioned responses as measured by their frequency and onset latency as well as by an increase in the number of trials required to reach acquisition criteria of five and 10 consecutive conditioned responses as compared with controls. A separate group of animals received a nitroprusside infusion one day after the acquisition of conditioned responses to the tone conditioned stimulus. These animals demonstrated a normal retention of conditioned responses and a normal response to varying intensities of the conditioned stimulus. Hypotensive stress also had no effect on the frequency and topography of the unconditioned response. It was concluded that a decrease in blood pressure can serve as a physiological stressor. One of the reactions to this stress consists of a retardation in the formation of associations during a learning task, without any decrease in the ability to retrieve previously learned material.

Analysis of Variance↗