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Biomedical subjects

Z Zhen

Publications and source records attributed to Z Zhen.

At least 19 recordsLinked to original sources
PubMed2001

[Progress in proteomics].

Proteomics, the large-scale analysis of proteins, will contribute greatly to our understanding of gene function in the post-genome era. Proteomics uses a combination of sophisticated techniques including two-dimensional(2D) gel electrophoresis, mass spectrometry, yeast two-hybrid system, bioinformatics, etc. to characterize, to quantify, and to analyze cellular proteins in a global way. The application of proteomics provides major opportunities to elucidate disease mechanisms and to identify new therapeutic targets. This review aims to explain the definition of proteomics and then to outline proteomic techniques. Finally, applications to the study of human disease are briefly discussed.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2000

[Biological characteristics and occurrence regularity of Phassus excrescens Bulter].

The biological characterisitics and occurrence regularity of Phassus excrescens were studied from 1997 to 2000 in the eastern part of Heilongjiang Province and Jilin Province. In this area, most of its individuals took two years to finish one generation, and over-wintered two times with eggs and larvae, respectively. At the end of June or the first ten days of July, larvae transferred to damage Fraxinus mandshurica. Feeding with artificial diet indoor, the larvae finished 6 instars before pupation. In artificial Manchurican ash forest, the larva mainly damaged the truck basal(below 20 cm) or truck of 2 to 20 years old Fraxinus mandshurica. The occurrence amount of this species was closely related to the forest age and the stand structure. Usually, pure artificial Fraxinus mandshurica stands and Fraxinus mandshurica-Pinus koraiensis mixed stands were damaged seriously, while Fraxinus mandshurica-Larix mixed forests were damaged lightly.

Animals↗
PubMed1999

Construction of plant vectors with high level expression of B.t. toxin gene and studies on their expression behavior in transgenic tobaccos.

Breeding pest-resistant plants using plant genetic engineering technique is an effective strategy in integrated pest management (IPM). Increasing the expression level of foreign insecticidal protein by using a strong promoter is a useful method. In this work, a plant expression vector, pBinMoBc, was constructed. It contained the CryIA(c) gene under the control of a chimeric OM promoter and the omega factor. As a control, another vector, pBinoBc, was also constructed in this study. pBinoBc carrying CryIA(c) gene was under the control of a CaMV 35S promoter. The vectors were transferred into tobacco plants via Agrobacterium-mediated transformation. ELISA assay showed that the average expression level of the CryIA(c) gene in pBinMoBc transgenic tobacco plants is 2.44-times that in pBinoBc transgenic tobacco plants. The expression of B.t. toxin in individual plant can be up to 0.255% of total soluble proteins. Bioassay showed that pBinMoBc transgenic tobacco plants had more notable insecticidal effects than pBinoBc transgenic tobacco plants. The above results showed that the chimeric OM promoter is a stronger promoter than the CaMV 35S promoter that was widely used in plant genetic engineering. This is very useful in pest-resistant plant genetic engineering.

Animals↗
PubMed1997

A point mutation in the MET oncogene abrogates metastasis without affecting transformation.

The MET oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF), known to stimulate invasive growth of epithelial cells. MET is overexpressed in a significant percentage of human cancers and is amplified during the transition between primary tumors and metastasis. To investigate whether this oncogene is directly responsible for the acquisition of the metastatic phenotype, we exploited a single-hit oncogenic version of MET, able to transform and to confer invasive and metastatic properties to nontumorigenic cells, both in vitro and in nude mice. We mutagenized the signal transducer docking site of Met (Y1349VHVX3Y1356VNV), which has the uncommon property of binding and activating multiple src homology region 2 (SH2)-containing intracellular effectors. Notably, a point mutation (H1351 --> N) increased the transforming ability of the oncogene but abolished its metastatic potential. This mutation duplicates the Grb2 binding site, super-activating the Ras pathway and preventing the binding of the other intracellular transducers. Complementation in trans with another nonmetastatic mutant (N1358 --> H), recruiting all the transducers downstream to Met except Grb2, rescued the invasive-metastatic phenotype. It is concluded that the metastatic potential of the MET oncogene relies on the properties of its multifunctional docking site, and that a single point mutation affecting signal transduction can dissociate neoplastic transformation from metastasis.

Amino Acid Sequence↗
PubMed1997

[The developement of a new torque experiment device for biomaterials].

This paper introduces a biomaterial torque experiment apparatus which consists of AST486 computer, photodiode array, code device interface circuit, and magnetoelectric motional coil structure. According to experimental conditions, the computer sends out signal to the coil which under the magnetic field is activated to produce a series of desired torque and bring the sample to deflect. Angular displacement is measured by photodiode array and code device system. The whole system has good dynamics and high precision and could finish a series of torque experiment for biomaterials, and AST486 computer can automatically conduct signals analyzing and data processing.

Biocompatible Materials↗
PubMed1996

Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility.

The biological effects of hepatocyte growth factor/scatter factor are mediated by autophosphorylation of its receptor, the Met tyrosine kinase, on two carboxyl-terminal tyrosines. These phosphotyrosines (Y1349VHVNATY1356VNV) are multifunctional docking sites for several effectors. Grb2, the adaptor for the Ras guanyl-nucleotide exchanger SOS, binds to Tyr1356 in the YVNV motif. By site-directed mutagenesis we either abrogated or duplicated the Grb2 consensus, without interfering with the other effectors. Loss of the link with Grb2 severely impaired transformation. The same mutation, however, had no effect on the "scattering" response, indicating that the level of signal which can be reached by Grb2-independent routes is permissive for motility. Duplication of the Grb2 binding site enhanced transformation and left motility unchanged. Thus, two Met-mediated biological responses, motility and growth, can be dissociated on the basis of their differential requirement for a direct link with Ras.

3T3 Cells↗
PubMed1996

[Sixty years of study on modern Chinese medical history].

This author gives a general description to the study of modern Chinese medical history in the last six decades, which is divided into 3 stages of Initiation, Accumulation and Development, introducing representative works from all stages with emphasis laid on the achievements attained in the last stage.

China↗
PubMed1995

The motogenic and mitogenic responses to HGF are amplified by the Shc adaptor protein.

The receptor of Hepatocyte Growth Factor-Scatter Factor (HGF) is a tyrosine kinase which regulates cell motility and growth. After ligand-induced tyrosine phosphorylation, the HGF receptor associates with the Shc adaptor, via the SH2 domain. Site-directed mutagenesis of the HGF receptor indicates that phosphotyrosines Y1349VHV and Y1356VNV can work as docking sites for Shc. The Kd of this interaction, measured in real time using synthetic phosphopeptides and recombinant Shc on a BIAcore biosensor, is 150 nm for both sites. After stimulation of the HGF receptor, Shc is phosphorylated on Y317VNV, generating an high affinity binding site for Grb2 (Kd = 15 nM). This duplicates the high affinity binding site for Grb2 present on the HGF receptor (Y1356VNV). Thus HGF stimulation can trigger the Ras pathway by recruiting Grb2 both directly through the receptor, and indirectly, through Shc. Overexpression of wild-type Shc, but not of the Y317-->F mutant, enhances cell migration and growth in response to HGF. These data show that Shc is a relevant substrate of the HGF receptor, and works as an 'amplifier' of the motogenic as well as of the mitogenic response.

Adaptor Proteins, Signal Transducing↗
PubMed1995

[Tendency, features and cultural background of modern medicine in China].

The new tendency and features of development of medicine in modern China is discussed on the social and cultural background, which bears a dual character of both advancement and backwardness. By analysing the features of modern Chinese civilization, it is emphasized that modern China's medicine was developed on an extremely complex social and cultural background. It was not only restricted within the cultural framework but also governed by the intrinsic rule of medicine itself. This paper also mentions the five features and three tendencies of medicine based on historical facts, which reflects definitely the objective rules of modern Chinese medicine. It is these rules that links premodern and modern medicine. The work of contemporary China is in line with these rules.

China↗
PubMed1995

[Microthrombi in coronary heart disease].

Of 180 patients with coronary heart disease (CHD) 43 (23.9%) showed in microthrombi conjunctival microcirculation. We compared the healthy subjects with the patients with microthrombi and thrombi-free as well as with the patients with microthrombi pre- and post-treatment of heparin or salvia miltiorrhizae. The formation and the number of microthrombi in the CHD patients were closely related to symptoms, ECGS, plasma TXB2, 6-kero-PGF1a and other indexes on hemodynamics. Follow-up of the patients with microthrombi revealed that their death rate was higher than that of CHD patients without microthrombi, especially in the sudden deaths. We consider that microthrombi may be regarded as an important index of the state, therapeutic efficacy, and prognosis of the CHD patients. The use of heparin may certainly be based on the condition of the microthrombi in the microcirculation of CHD patients.

Adult↗
PubMed1994

A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family.

Signaling by tyrosine kinase receptors is mediated by selective interactions between individual Src homology 2 (SH2) domains of cytoplasmic effectors and specific phosphotyrosine residues in the activated receptor. Here, we report the existence in the hepatocyte growth factor/scatter factor (HGF/SF) receptor of a multifunctional docking site made of the tandemly arranged degenerate sequence YVH/NV. Phosphorylation of this site mediates intermediate- to high-affinity interactions with multiple SH2-containing signal transducers, including phosphatidylinositol 3-kinase, phospholipase C gamma, pp60c-src, and the GRB-2-Sos complex. Mutation of the two tyrosines results in loss of biological function, as shown by abrogation of the transforming activity in the oncogenic counterpart of the receptor. The same bidentate motif is conserved in the evolutionarily related receptors Sea and Ron, suggesting that in all members of the HGF/SF receptor family, signal transduction is channeled through a multifunctional binding site.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Structural and functional domains critical for constitutive activation of the HGF-receptor (Met).

The MET gene, encoding the tyrosine kinase receptor for Hepatocyte Growth Factor, is a potentially harmful oncogene overexpressed in a significant fraction of human cancers. To study the molecular mechanisms responsible for oncogenic activation, the biochemical and biological properties of a number of MET constructs were analysed. The native heterodimeric receptor (alpha beta), the beta chain alone, as well as a kinase defective mutant did not transform rodent fibroblasts upon transfection. The cytoplasmic domain, truncated immediately below the transmembrane region, acquired constitutive tyrosine kinase activity in vivo, produced foci of transformation, and was tumorigenic in nude mice. Removal of the first 39 amino acids of the juxtamembrane domain resulted in loss of constitutive activation in vivo and transforming potential, without impairment of the in vitro kinase activity. Replacement of the juxtamembrane domain with 5' TPR sequences restored constitutive kinase activation and transforming properties. Site-directed mutagenesis of either of the two tyrosine residues involved in the positive regulation of the catalytic activity upon phosphorylation (Y1234 or Y1235 in the kinase domain of the HGF receptor), strongly impaired TRP-MET transforming potential. These data show that: (1) the truncated cytoplasmic HGF receptor has constitutive kinase activity and is oncogenic; (2) the first 39 amino acids of the juxtamembrane domain and (3) the regulatory tyrosines in the catalytic domain are required to unleash its transforming potential.

3T3 Cells↗
PubMed1993

Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene.

The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.

3T3 Cells↗
PubMed1991

[Small-airway lesions induced by inhalation of asbestos dust in dogs--pathological and aetiological studies].

This paper presents the pathological changes of the small airways of dogs inhaling asbestos dust in the workshop of Xin Kong Asbestos Mine for 1 to 3 years. Dogs of the experimental group showed that variable degrees of dust deposition and fibrous tissue reaction were found in all the three types of the small airways-respiratory bronchioles, alveolar ducts and membranous bronchioles of both lungs. The lesions in the lung increased with the duration of exposure. These changes in the canine small airways resulting from asbestos dust were very much similar to those of the humans. In addition, deposited dust collected from the workshop of the asbestos mine, and 50 dust particles selected randomly in foci were identified in situ by energy dispersive X-ray analysis. Findings demonstrated that the majority of the dust particles in the foci was principally mixed silicate dust. Among them asbestos dust predominated absolutely, and there were more amphiboles than chrysotiles. Therefore, it is concluded that the small airway lesions induced in the dogs are mainly due to mixed asbestos dust, and that there appears to exist a dose-response relationship.

Animals↗