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Biomedical subjects

X F Wang

Publications and source records attributed to X F Wang.

At least 91 records · Page 5Linked to original sources
PubMed1997

Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein.

Members of the Smad family of proteins are thought to play important roles in transforming growth factor beta (TGF-beta)-mediated signal transduction. In response to TGF-beta, specific Smads become inducibly phosphorylated, form heteromers with Smad4, and undergo nuclear accumulation. In addition, overexpression of specific Smad combinations can mimic the transcriptional effect of TGF-beta on both the plasminogen activator inhibitor 1 (PAI-1) promoter and the reporter construct p3TP-Lux. Although these data suggest a role for Smads in regulating transcription, the precise nuclear function of these heteromeric Smad complexes remains largely unknown. Here we show that in Mv1Lu cells Smad3 and Smad4 form a TGF-beta-induced, phosphorylation-dependent, DNA binding complex that specifically recognizes a bipartite binding site within p3TP-Lux. Furthermore, we demonstrate that Smad4 itself is a DNA binding protein which recognizes the same sequence. Interestingly, mutations which eliminate the Smad DNA binding site do not interfere with either TGF-beta-dependent transcriptional activation or activation by Smad3/Smad4 cooverexpression. In contrast, mutation of adjacent AP1 sites within this context eliminates both TGF-beta-dependent transcriptional activation and activation in response to Smad3/Smad4 cooverexpression. Furthermore, concatemerized AP1 sites, in isolation, are activated by Smad3/Smad4 cooverexpression and, to a certain extent, by TGF-beta. Taken together, these data suggest that the Smad3/Smad4 complex has at least two separable nuclear functions: it forms a rapid, yet transient sequence-specific DNA binding complex, and it potentiates AP1-dependent transcriptional activation.

Animals↗
PubMed1997

The viral oncoprotein E1A blocks transforming growth factor beta-mediated induction of p21/WAF1/Cip1 and p15/INK4B.

The adenovirus early gene product E1A is a potent stimulator of cellular proliferation, which when overexpressed can overcome the growth-inhibitory effects of the polypeptide hormone transforming growth factor beta (TGF-beta). The ability of TGF-beta to arrest cell growth in G1 correlates with the transcriptional induction of the cyclin-dependent kinase inhibitors, p15/INK4B and p21/WAF1/Cip1; an inhibition of the G1 cyclin-Cdk complexes; and a maintenance of the retinoblastoma susceptibility gene product, Rb, in a hypophosphorylated state. The ability of E1A to overcome TGF-beta-mediated growth inhibition derives, in part, from its ability to sequester Rb and Rb family members. We report here that E1A also acts upstream of Rb by blocking the TGF-beta-mediated induction of p15 and p21. Consistent with these findings, E1A expression also blocks the ability of TGF-beta to inhibit Cdk2 kinase activity, as well as its ability to hold Rb in a hypophosphorylated state. The effect of E1A on the induction of p15 and p21 is independent of E1A's Rb binding activity. The E1A-mediated decrease in p15 levels is primarily the result of a block at the level of transcriptional activation by TGF-beta. This effect is dependent on E1A's ability to bind p300, one of E1A's target proteins. Thus, the ability of E1A to affect p15 and p21 expression represents an additional possible mechanism by which E1A can circumvent the negative regulation of cell cycle progression.

Adenovirus E1A Proteins↗
PubMed1997

Analysis of social factors and human behavior attributed to family distribution of schistosomiasis japonica cases.

An investigation of family distribution patterns of schistosomiasis japonica was carried out in four pilot villages in Yunnan Province. Family clustering of the disease was present in Bihuayuan Village before and after economic reform (site A); however, such clustering did not occur in Tuanshan and Liantie Villages (sites B and C) in the same periods. Being contrary to the stage prior to economic reform family clustering existed in Zhonghe Village (site D) after the reform. The results obtained from single- and multifactor analysis showed that the main human behavior related to family distribution of schistosomiasis in mountainous regions of Yunnan Province included the frequency of laborer migration, contact with cercariae-infested water in public places or family microenvironments with a high transmission potential, promiscuous defecation and status of cattle grazing. The frequency of laborer migration and human contact with cercariae-infested water in public places in sites B and C without family clustering was higher than that in sites A and D with family clustering. Place for promiscuous defecation and cattle grazing in site A converged compared with that in sites B and C.

Animals↗
PubMed1997

Influence of livestock husbandry on schistosomiasis transmission in mountainous regions of Yunnan Province.

An investigation was conducted in the highly endemic areas of schistosomiasis japonica in Weishan and Eryuan counties, Yunnan Province. The results are summarized as follows: 1) the number of domestic animals was increasing annually; 2) the proportion of animal husbandry gains in the total agriculture income had a yearly escalating tendency; 3) the infection rate of inhabitants was upgrading as a result of the development of and the prevalence in domestic animals in the recent decades. Owing to frequent migration of domestic animals, serious spread of infection sources and high prevalence of schistosomiasis japonica occurred. It is suggested that more attention should be paid to the control of schistosomiasis japonica in mountainous endemic regions during the course of economic development, especially in the development of domestic animals.

Agricultural Workers' Diseases↗
PubMed1997

[The effect of chaihu qingxin yin on left cardiac function and T-cell subgroup in peripheral blood in children with viral myocarditis].

OBJECTIVE: To observe the effect of Caihu Qingxin Yin (CHQXY) in treating viral myocarditis. METHODS: CHQXY was used to treat 52 cases of acute viral myocarditis in children, compared with the routine method using energy mixture in 32 patients. RESULTS: (1) The total effective rate of 52 patients using CHQXY was 71.2% which was higher than that of the control group in 32 patients with 53.1%, Ridit analysis, P < 0.01. (2) Functional shortaxial shortening rate (FS) and ejecting fraction (EF) in CHQXY group were superior to those of the control group, P < 0.01. (3) CHQXY might modulate the immune function of T lymphocyte, enabled the CD3 and ratio of CD4/CD8 tended to normalize. CONCLUSION: CHQXY played an important role in the treatment of viral myocarditis with the mechanism of improving the left cardiac function and modulating celluar immune function.

Adolescent↗
PubMed1996

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.

The dwarfin protein family has been genetically implicated in transforming growth factor beta (TGF-beta)-like signaling pathways in Drosophila and Caenorhabditis elegans. To investigate the role of these proteins in mammalian signaling pathways, we have isolated and studied two murine dwarfins, dwarfin-A and dwarfin-C. Using antibodies against dwarfin-A and dwarfin-C, we show that these two dwarfins and an immunogenically related protein, presumably also a dwarfin, are phosphorylated in a time- and dose-dependent manner in response to TGF-beta. Bone morphogenetic protein 2, a TGF-beta superfamily ligand, induces phosphorylation of only the related dwarfin protein. Thus, TGF-beta superfamily members may use overlapping yet distinct dwarfins to mediate their intracellular signals. Furthermore, transient overexpression of either dwarfin-A or dwarfin-C causes growth arrest, implicating the dwarfins in growth regulation. This work provides strong biochemical and preliminary functional evidence that dwarfin-A and dwarfin-C represent prototypic members of a family of mammalian proteins that may serve as mediators of signaling pathways for TGF-beta superfamily members.

Amino Acid Sequence↗
PubMed1996

Four-dimensional echocardiography: methods and clinical application.

4DE (i.e., dynamic three-dimensional) echocardiography is a new developing technique in recent years. In our study, a three-dimensional echo scan computer system was used to acquire and store the two-dimensional information, then to reconstruct the stereoscopic image of the heart according to its space-time continuum. It can yield a better approach, which can help identify the various structures of the heart and great arteries and facilitate understanding of spatial relations and motion. In addition, it can display physiologic information such as the direction, course, size, and shape of the blood flow. We have examined 138 patients by both transthoracic and transesophageal approaches. Our preliminary experience shows that 4DE is of great value in diagnosing congenital heart disease and valvular disease.

Adolescent↗
PubMed1996

Kinetics of neurotensin gene expression in the developing gut.

BACKGROUND: Expression of the gene encoding neurotensin (NT/N) is regulated in a strict temporal- and spatial-specific pattern during gut development; the mechanisms (that is, transcriptional versus posttranscriptional) responsible for this expression pattern are not known. The purpose of this study was to determine whether developmental changes in NT/N expression reflect alternations in gene transcription. METHODS: Sensitive ribonuclease protection assays were performed with a rat NT/N genomic probe containing the entire sequence of both exon 1 and intron 1 hybridized with RNA from fetal (day 19) and postnatal (days 14, 28, and 60) rat jejunum and ileum; signals were quantitated densitometrically. RESULTS: Mature (exon 1) and precursor (exon 1 + intron 1) NT/N RNA, initially low in the fetus, increased dramatically by postnatal day 14 and attained maximal levels by day 28. NT/N RNA levels remained stable in the ileum of the 60-day-old rat but decreased in the jejunum, consistent with the typical expression pattern in the gut. CONCLUSIONS: Concomitant changes in expression of precursor and mature NT/N RNA suggest that NT/N gene regulation occurs at the level of transcription in the gut during development. Identifying the factors that regulate NT/N gene transcription is crucial to our understanding of how neurotensin functions in the gut.

Aging↗
PubMed1996

Metabotropic glutamate receptors potentiate responses to NMDA and AMPA from layer V cells in rat visual cortex.

1. With the use of whole cell recordings of layer V cells from slices of rat visual cortex, we demonstrate a potentiation of the response to N-methyl-D-aspartate (NMDA) by the metabotropic glutamate agonist (1S,3R)-1-Amino-1,3-cyclopentanedicarboxylic acid. This potentiation occurs within a few seconds and lasts a few minutes. 2. The potentiation is seen with tetrodotoxin in the perfusion solution, but is abolished by guanosine 5'-O-(2-thiodiphosphate) in the pipette solution, showing that it is a postsynaptic phenomenon. The potentiation is also abolished by alpha-methyl-4-carboxyphenylglycine in the bath solution, confirming that it is due to metabotropic glutamate receptors. 3. In 29 of 31 cases tested, the response to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid was also potentiated, and the potentiation remained in the presence of the NMDA antagonist D-2-amino-5-phosphonovalerate.

Animals↗
PubMed1996

[Clinical observation of wenxin decoction in treating 82 patients with spontaneous angina pectoris].

One hundred twenty-two patients with spontaneous angina pectoris (SAP) were randomly divided into treated group (82 cases) and control group (40 cases), and treated with Wenxin decoction and isosorbide dinitrate respectively. Results showed that in treated group the total effective rate of SAP was 95.12% and that of electrocardiographic findings were 74.39%. These results were all superior to those of control group (P < 0.01). Moreover, results of extracorporeal thrombosis test showed after Wenxin decoction treatment, the length of thrombus decreased from 23.56 +/- 5.47 mm to 20.04 +/- 5.17 mm, the wet weight of it decreased from 92.65 +/- 18.45 mg to 76.94 +/- 15.08 mg and the dry weight from 21.76 +/- 7.30 mg to 16.90 +/- 5.35 mg. The submaximal exercise test revealed an increase of exercise time from 474.66 +/- 96.33 seconds to 548.83 +/- 99.93 seconds, increase of acting quantity from 104.16 +/- 19.65 W to 123.61 +/- 24.96 W and a decrease of ST segment depression from 0.183 +/- 0.041 mV to 0.139 +/- 0.038 mV. These results suggested that Wenxin decoction is valuable in treating SAP.

Adult↗
PubMed1995

Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.

The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors that inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-beta on both the levels and activities of the G1 cyclins and their cyclin-dependent kinase partners. The ability of TGF-beta to inhibit the activity of these kinase complexes derives in part from its regulatory effects on the cyclin-dependent kinase inhibitors, p21/WAF1/Cip1, p27Kip1, and p15. Upon treatment of cells with TGF-beta, these three inhibitors bind to and block the activities of specific cyclin-cyclin-dependent kinase complexes to cause cell cycle arrest. Little is known, however, on the mechanism through which TGF-beta activates these cyclin-dependent kinase inhibitors. In the case of p21, TGF-beta treatment leads to an increase in p21 mRNA. This increase in p21 mRNA is partly due to transcriptional activation of the p21 promoter by TGF-beta. To further define the signaling pathways through which TGF-beta induces p21, we have performed a detailed functional analysis on the p21 promoter. Through both deletion and mutation analysis of the p21 promoter, we have defined a 10-base pair sequence that is required for the activation of the p21 promoter by TGF-beta. In addition, this sequence is sufficient to drive TGF-beta-mediated transcription from a previously nonresponsive promoter. Preliminary gel shift assays demonstrate that this TGF-beta responsive element binds specifically to several proteins in vitro. Two of these proteins are the transcription factors Sp-1 and Sp-3. These studies represent the initial steps toward defining the signaling pathways involved in TGF-beta-mediated transcriptional activation of p21.

Base Sequence↗
PubMed1995

Transforming growth factor beta activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site.

Transforming growth factor beta (TGF-beta) causes growth arrest in the G1 phase in many cell types. One probable pathway for this growth inhibition is through the TGF-beta-mediated up-regulation of the cyclin-dependent kinase (CDK) inhibitor p15INK4B, which specifically inhibits the enzymatic activities of CDK4 and CDK6. An active cyclin D-CDK4/6 complex is required for pRb phosphorylation to allow the cell cycle to progress from G1 to S phase. To study the molecular mechanism of the p15INK4B induction by TGF-beta, we isolated a 780-base pair promoter sequence of the human p15 gene and inserted this fragment upstream of a luciferase reporter gene. When this construct was transiently transfected into HaCaT cells, luciferase activity was induced more than 10-fold upon TGF-beta treatment, indicating that the induction of p15INK4B expression by TGF-beta is partly exerted at the transcription level. Promoter deletion analysis revealed that the sequence from -110 to -40 relative to the transcription start site is capable of conferring the 10-fold induction by TGF-beta. Within this region there are three Sp1 consensus sites. Mutation of one of these sites, GGGGCGGAG, substantially reduced both the induction by TGF-beta and the basal promoter activity, whereas mutations in the other two Sp1 sites and the spacer sequences had little effect. In addition, gel mobility shift assay indicates that the transcription factors Sp1 and Sp3 bind to this Sp1 site. Taken together, these data suggest that a specific Sp1 consensus site is involved in the mediation of TGF-beta induction as well as the basal promoter activity of the p15 gene and that Sp1 and Sp3 transcription factors might be involved in this regulation.

Base Sequence↗
PubMed1995

Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism.

The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors which inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-beta on both the levels and the activities of the G1 cyclins and their kinase partners. The activities of these kinases are negatively regulated by a number of small proteins, p21 (WAF1, Cip1), p27Kip1, p16, and p15INK4B, that physically associate with cyclins, cyclin-dependent kinases, or cyclin-Cdk complexes. p21 has been previously shown to be transcriptionally induced by DNA damage through p53 as a mediator. We demonstrate that TGF-beta also causes a rapid transcriptional induction of p21, suggesting that p21 can respond to both intracellular and extracellular signals for cell cycle arrest. In contrast to DNA damage, however, induction of p21 by TGF-beta is not dependent on wild-type p53. The cell line studied in these experiments, HaCaT, contains two mutant alleles of p53, which are unable to activate transcription from the p21 promoter when overexpressed. In addition, TGF-beta and p53 act through distinct elements in the p21 promoter. Taken together, these findings suggest that TGF-beta can induce p21 through a p53-independent pathway. Previous findings have implicated p27Kip1 and p15INK2B as effectors mediating the TGF-beta growth inhibitory effect. These results demonstrate that a single extracellular antiproliferative signal, TGF-beta, can act through multiple signaling pathways to elicit a growth arrest response.

Amino Acid Sequence↗
PubMed1995

Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression.

Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G1 and is associated with decreased G1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, growth-suppressive state. A variety of recent experiments suggest that a functional target of Rb is the E2F transcription factor. In addition, the growth-suppressive effects of TGF-beta can be overcome by expression of viral oncogene products that dissociate E2F from Rb and Rb-related polypeptides. These results suggest the possibility that control of E2F may be a downstream event of TGF-beta action. Consistent with that possibility is the observation that E2F1 RNA levels are drastically reduced in TGF-beta-treated cells. We have also used a recombinant adenovirus containing the human E2F1 gene to overexpress the E2F1 product in mink lung epithelial cells that were growth arrested with TGF-beta. We find that overexpression of E2F1 can overcome the TGF-beta-mediated effect as measured by the activation of cellular DNA synthesis. These results suggest that a likely downstream target for the cyclin-dependent kinases, which are controlled by TGF-beta, is the activation of E2F.

Adenoviridae↗
PubMed1995

Factors that are critical for plasticity in the visual cortex.

Factors that may be critical for plasticity in the visual cortex are evaluated according to three criteria. (1) Do antagonists to the factor abolish plasticity? (2) Does the concentration or activity of the factor peak with the critical period for plasticity? (3) Does rearing in the dark, which postpones the critical period, affect the factor in a similar fashion? N-methyl-D-aspartate receptors fulfil all three criteria. Metabotropic glutamate receptors fulfil two of them. Most other putative factors do not fulfil more than one.

Animals↗