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Biomedical subjects

Z Qi

Publications and source records attributed to Z Qi.

At least 73 records · Page 4Linked to original sources

[Study of calcitonin gene methylation in chronic myeloid leukemia by using Hpa II-PCR].

To investigate the role of calcitonin(CT) gene hypermethylation in the transformation from the initial chronic phase to blast crisis of chronic myeloid leukemia, 31 CML patients were studied by using Hpa II-PCR. The results showed that the 10.52%(2/19) chronic phase, 71.4%(5/7) accelerated phase and 80.0%(4/5) blast crisis of patients had CT gene hypermethylation and that the increased methylation of the CT gene were related with the disease progression. The reports indicated that the hypermethylation of CT gene might be a useful marker for predicting the evolution of CML and selecting chronic phase patients for BMT.

Adolescent↗

[Discussions with the author of Materia Medica Textual Research on the original plants of the medicinal herbs in Ardisia (comment)].

Objections about the conclusions that six plants of eleven medicinal herbs given by the Materia Medica Textual Research on the Original Plants of the Medicinal Herbs in Ardisia were raised in this paper. It is considered that the eleven herbs recorded in ancient Chinese materia medica books are at least belonging to fourteen species in Ardisia and one species in Solamum.

Ardisia↗

Activation of donor-specific CTL in a tolerant recipient of cardiac allograft.

Permanent graft acceptance was induced with cyclosporine A in a low responder rat strain combination PVG (RT1(c)) to DA (RT1(av1)) of cardiac transplants. Challenge (alloimmunization) with donor and third-party WF (RT1(u)) cells was performed and followed by the analysis of alloreactive cytotoxicity. The cytotoxic T lymphocytes (CTL) from recipients with permanently accepted cardiac grafts manifested cytolytic activity against third-party target cells but not against donor target cells. The findings demonstrated unresponsiveness to be donor-specific, i.e., transplant tolerance was present. This was verified by retransplantation of the DA recipient with either a second PVG heart (which was accepted) or a third-party (WF) heart (which was rejected). Restoration of donor-specific CTL after injection of exogeneous interleukin(IL)-2 concomitant with challenge showed that the donor-specific CTL were not depleted, but unable to be activated as a consequence of IL-2 deficiency. Despite donor-specific CTL activation in vivo the recipients failed to reject their established grafts, implying an ongoing presence of suppression.

Animals↗

Comparison of carcinoembryonic antigen promoter regions isolated from human colorectal carcinoma and normal adjacent mucosa to induce strong tumor-selective gene expression.

To establish in vivo gene therapy against cancer, it is requisite to induce strong, cancer cell-selective expression of a therapeutic gene. Comparison of the promoter activity of 5' flanking regions of the carcinoembryonic antigen (CEA) gene isolated from various origins is therefore of considerable interest. The 5' flanking region of the CEA gene between -135 and +69 bp upstream from the transcriptional start site, which is recognized as the core promoter region, was isolated from CEA-producing human colorectal carcinoma (CRC), normal adjacent mucosa, CEA-producing cell lines and CEA-non-producing cell lines. No mutations were observed by single-strand conformation polymorphism in the CEA promoter regions. Subsequent sequence analysis revealed that there were no mutations in the CEA promoter regions isolated from CEA-producing CRC and normal adjacent mucosa. Furthermore, nuclear extracts prepared from CEA-producing human CRC cells could equally bind to both the CEA promoter fragments isolated from CEA-producing CRC and normal mucosa. Both CEA promoter regions could direct 5- to 20-fold higher expression of a luciferase reporter gene in CEA-producing cells than in CEA-non-producing cells. Therefore, we suggest that the use of either CEA promoter region isolated from CRC or normal mucosa is equally effective to induce strong, CEA-producing cancer-selective expression of a therapeutic gene.

Base Sequence↗

Dynamic properties of individual water molecules in a hydrophobic pore lined with acyl chains: a molecular dynamics study.

Recently, a certain class of synthetic molecules has been shown to form ion channels, the pore of which is lined with hydrophobic acyl chains [M. Sokabe, in: F. Oosawa, H. Hayashi, T. Yoshioka (Eds.), Transmembrane Signaling and Sensation, JSSP/VNU Science Press BV, Tokyo, 1984, p. 119; F. Hayashi, M. Sokabe, M. Takagi, K. Hayashi, U. Kishimoto, Biochim. Biophys. Acta, 510 (1978) 305; M.J. Pregel, L. Jullien, J. Canceill, L. Lacombe, J.M. Lehn, J. Chem. Soc. Perkin Trans., 2 (1995) 417; Y. Tanaka, Y. Kobuke, M. Sokabe, Angew. Chem. Int. Ed. Engl., 34 (1995) 693; M. Sokabe, Z. Qi, K. Donowaki, H. Ishida, K. Okubo, Biophys. J., 70 (1996) A201; H. Ishida, K. Donowaki, Y. Inoue, Z. Qi, M. Sokabe, Chem. Lett. (1997) p. 953]. As an initial step towards understanding the physical mechanisms of ion permeation across such a hydrophobic pore, systematic molecular dynamics simulations were performed to investigate dynamic and energetic properties of water molecules inside the pore using a dimer of alanine-N'-acylated cyclic peptide as a channel model. Dynamic energy profiles for water molecules indicated that the energy barrier at the middle region of the pore is approximately 2-3 kcal/mol higher than that in the cap water region which was defined as a vicinity region of the channel entrance. Energetics analyses demonstrated that the mutual interactions among intrapore water molecules are the major factor to give favorable interaction (negative energy contribution) for themselves. The pore, despite being lined with acyl chains, has a favorable van der Waals interaction with intrapore water molecules. These results may help to explain why water-filled channels can be formed by the hydrophobic helices in natural channels.

Journal Article↗

Effect of heparin on phosphorylation site specificity of neuronal Cdc2-like kinase.

Neuronal Cdc2-like kinase (Nclk) can be stimulated by heparin in a substrate-dependent manner. While phosphorylation of tau is markedly enhanced by heparin, phosphorylation of histone H1 by Nclk is essentially unaffected. A histone H1 peptide, HS(9-18): PKTPKKAKKL, and its substitution analogues were used to examine the basis of the differential heparin effect. In the presence of heparin, the phosphorylation site specificity of Nclk is altered and only proline immediately following the phosphorylation site is still an essential substrate determinant. This change in the site specificity may adequately account for the differential heparin effect on histone H1 and tau phosphorylation.

Anticoagulants↗

Association of neurofilament proteins with neuronal Cdk5 activator.

Cdk5 exists in brain extracts in multiple forms, one of which is a macromolecular protein complex comprising Cdk5, neuron-specific Cdk5 activator p35nck5a and other protein components (Lee, K.-Y., Rosales, J. L., Tang, D., and Wang, J.H. (1996) J. Biol. Chem. 271, 1538-1543). The yeast two-hybrid system was employed to identify p35nck5a-interacting proteins from a human brain cDNA library. One of the isolated clones encodes a fragment of glial fibrillary acidic protein, which is a glial-specific protein. Sequence alignment revealed significant homology between the p35nck5a-binding fragment of glial fibrillary acidic protein and corresponding regions in neurofilaments. The association between p35nck5a and neurofilament medium molecular weight subunit (NF-M) was confirmed by both the yeast two-hybrid assay and direct binding of the bacteria-expressed proteins. The p35nck5a binding site on NF-M was mapped to a carboxyl-terminal region of the rod domain, in close proximity to the putative Cdk5 phosphorylation sites in NF-M. A region immediately amino-terminal to the kinase-activating domain in p35nck5a is required for its binding with NF-M. In in vitro binding assays, NF-M binds both monomeric p35nck5a and the Cdk5/p35nck5a complex. The binding of NF-M has no effect on the kinase activity of Cdk5/p35nck5a.

Amino Acid Sequence↗

Malononitrilamides 715 and 279 prevent accelerated cardiac allograft rejection synergistically with cyclosporin A in presensitized rats.

A77 1726 is a malononitrilarnide (MNA) and the active metabolite of leflunomide. Leflunomide has been extensively investigated and shown to be a potent immunosuppressive drug. However, the half-life of A77 1726 is about 15-18 days in humans and the leflunomide is, therefore, currently being evaluated for the treatment of autoimmune disease and not for transplantation. The search for analogues has led to the development of MNA 715 and 279, derivatives of A77 1726. Previous limited experimental experience has shown these MNAs to prevent skin allograft and xenograft rejection and graft-versus-host disease in rodents, and to reverse ongoing allograft rejection. The aim of the present study was to verify the efficacy of these MNAs in a cardiac retransplant model of sensitized rats, concerning prevention of accelerated rejection, inhibition of antibody production and interaction with cyclosporin A (CsA). Heterotopic cardiac transplantation and retransplantation in Dark Agouti (DA) to Piebald Virol Glaxo (PVG) rats was used. Subgroups of rats were given either CsA, MNA 715, MNA 279 or combined CsA/MNA for 10 days starting either day 0 or day -1, as of regrafting or no treatment. Titres of allospecific IgM and IgG were quantitated by flow cytometry. Ten days of MNA 715 or 279 from day -1 prevented accelerated rejection of the retransplant, as did CsA. Neither treatment given from day 0 prevented rejection within 24 h. However, a combination of MNA 715 or 279 and CsA from day 0 effectively prevented accelerated regraft rejection. Production of specific alloantibodies was reduced in all immunosuppressed subgroups, IgG titres at day 7 in MNA-treated subgroups being significantly lower compared with those in the CsA-treated subgroup. In conclusion, MNA 715 and 279 were shown to be potent immunosuppressants with the capacity to prevent accelerated regraft rejection in rat cardiac transplants, most efficiently in combination with CsA, and to suppress specific alloantibody production.

Alkynes↗

Malononitrilamides 715 and 279 prolong rat cardiac allograft survival, reverse ongoing rejection, inhibit allospecific antibody production and interact positively with cyclosporin.

A77 1726 is a malononitrilamide (MNA) and the active metabolite of leflunomide, which has been extensively investigated and shown to be a potent immunosuppressive drug. However, the half-life of A77 1726 is about 15-18 days in humans and leflunomide is therefore currently being developed for the treatment of autoimmune disease and not for transplantation. Search for analogues has led to the discovery of MNA 715 and 279, derivatives of A77 1726. Previous experimental experience of these compounds is still limited. The aim of the present study was to verify the efficacy of these MNAs concerning prevention and reversal of rejection, inhibition of antibody production and interaction with cyclosporin A (CsA). Heterotopic cardiac transplantation in DA to PVG rats was used. Subgroups of rats were given either CsA, MNA 715 or MNA 279 for 10 days, starting at either day 0 or day 4, or received no treatment. Titres of allospecific immunoglobulin M (IgM) and immunoglobulin G (IgG) were quantified by flow cytometry. Ten days of induction with MNA 715 or 279 produced significantly longer graft survival than in controls. Treatment from day 4 onwards, when acute rejection was established, rescued all grafts. Allospecific production of IgM or IgG was absent during MNA induction and was suppressed in animals receiving a rescue course of MNA. The transplant model was potentiated by addition of the immunomodulator quinolone-3-carboxamide (Linomide), which eliminates the effect of CsA and other immunosuppressants. The combined treatment with MNA and CsA was successful in overcoming the challenge of Linomide, demonstrating the additive effects of the two drugs. In conclusion, MNA 715 and 279 were shown to be potent immunosuppressants, preventing and reversing acute allograft rejection, inhibiting and suppressing allospecific antibody production, and the drugs interacted positively with CsA.

Alkynes↗

[Bcl-2 mRNA expression in acute promyelocytic leukemia by RT-PCR].

To check the anti-apoptosis gene bcl-2 mRNA expression in 20 APL patients by PCR, and analyse the relationship between bcl-2 mRNA and the PML-RARa isoform. The result is that the bcl-2 mRNA expression has no significance between the isoforms (P > 0.05). This shows that the PML-RARa transcription type has no influence on the clinical features and prognosis.

Adolescent↗

[Transient and stable expression of human ApoE7 gene in NIH/3T3 cell lines].

OBJECTIVE: To investigate the expressing profile of h-apoE7 gene under the regulation of MT-I promoter in mouse cells. METHODS: The eukaryotic expressing plasmid pME7 was constructed through cloning human apoE7 genomic DNA(6.0 kb) into pMT at the site of Bgl II/Hind III just under the control of the mouse metallothionein-I promoter. Transfection of pME7 plasmid into NIH/3T3 cell lines by Lipo-fectamine was performed. RESULTS: The transient expression of recombinant pME7 in NIH/3T3 cells showed that the expression was not restricted to human cells; The stable expression of pME7 demonstrated that the levels of h-apoE7 mRNA was highly related to the copies of integrated h-apoE7 gene. Whereas the results of ELISA implicated that the exogenous human apoE7 gene was transcribed, processed properly, and eventually translated into functional proteins. Furthermore, heavy metal (ZnSO4) could enhance the expressing level of h-apoE7 gene in transfected cell lines. The level of human apoE7 protein arised 45%-60% while induced. CONCLUSIONS: It was suggested that MT-I promoter could modulate the expression of recombinant h-apoE7 gene correctly. Therefore, cellular studies provided the scientific basis for establishment of h-apoE7 transgenic mouse models.

3T3 Cells↗

[Effect of space environment on germination and vegetation growth in Carthamus tinctorius L].

OBJECTIVE: To substantiate the effects of space condition on medicinal plants. METHOD: The seeds of medicinal plant Carthamus tinctorius were carried on board a retrievable satellite during 3-18 July, 1994. After returing to earth, the seedling rate, state of growth and development were observed. RESULT: The seeding rates, plant heights and branch quantities of weightless seeds and the seeds which were penetrated once and less than once by the heavy ion rays were higher than those of the seeds which were kept on earth, but these indexes of the seeds which were penetrated 2-3 times by the heavy ion rays were higher than those of the ground controlled seeds. CONCLUSION: Weightlessness and little penetration promote the growth and development of Carthamus tinctorius, but much penetration functions the other way round.

Carthamus tinctorius↗

[Evaluation on the anti-hepatitis C virus enzyme-linked immunosorbent diagnostic kits].

Ten different anti-HCV ELISA kits, four manufactured from abroad (ABBOTT, Innogenetics, Murex, Monolisa) and six in China, were evaluated by China national anti-HCV panel(100 positive, 98 negative) and Boston Biomedical Inc. (BBI) anti-HCV mixted titer performance panel(23 positive and 2 negative). The detective rates in 100 China national anti-HCV positive panel were 98% by ABBOTT EIA 2.0, 96% by BHY, SKH and XWK, 95% by BBS and HHM, 97% by SCJ, and that in 23 BBI anti-HCV positive panel were 100% by ABBOTT EIA2.0, but 91% by Murex, 87% by Innogenetics and Monolisa, 74% by BHY, 87% by SKH, 83% by XWK and HHM, 70% by BBS, 91% by SCJ. The specificity for all negative panels were similar in all kits. According to the results of HCV RIBA test (Ortho HCV RIBA 2.0), the structural antigens contained in all kits were almost the same, but the antigenicity of HCV nonstructural proteins were different, in the kits made in China they were lower than that made from abroad.

Antibodies, Viral↗

[Study on quality of China made NS3 antigen].

Using anti-HCV antibody screening assay to control the quality for blood is the main measure for preventing transmission of HCV in China. This study is to evaluate the quality of NS3 antigen because of their positive rate to anti NS3 antibody in HCV infected patients and to all kinds of anti-HCV antibody detecting kits, that need NS3 antigen. We collected four China genetically engineered NS3 antigens and other two NS3 antigens came from abroad. The first step is to confirm that the antibody reactivity with coated NS3 antigen is true. The second step is to compare the quality of China made NS3 antigens with NS3 antigens abroad. The results showed that coated NS3 antigen kits have high sensitivity in identifying the positivity of sera from second generation panel, among them that were RIBA-2 indeterminate or negative. Some negative or false positive results by coated Chinese NS3 antigens indicate that manufacturer should make more efforts to ensure the best condition terms for using these antigens.

Antigens, Viral↗

Double mutagenesis of a positive charge cluster in the ligand-binding site of the ferric enterobactin receptor, FepA.

Siderophores and colicins enter bacterial cells through TonB-dependent outer membrane proteins. Using site-directed substitution mutagenesis, we studied ligand recognition by a prototypic Escherichia coli siderophore receptor, FepA, that binds the iron chelate ferric enterobactin and colicins B and D. These genetic experiments identified a common binding site for two of the three ligands, containing multiple positive charges, within cell surface residues of FepA. Elimination of single residues in this region did not impair the adsorption or transport of ferric enterobactin, but double mutagenesis in the charge cluster identified amino acids (Arg-286 and Arg-316) that participate in siderophore binding and function in FepA-mediated killing by colicins B and D. Ferric enterobactin binding, furthermore, prevented covalent modification of FepA within this domain by either a fluorescent probe or an arginine-specific reagent, corroborating the involvement of this site in ligand recognition. These results identify, for the first time, residues in a TonB-dependent outer membrane protein that participate in ligand binding. They also explain the competition between ferric enterobactin and the colicins on the bacterial cell surface: all three ligands interact with the same arginine residues within FepA during their penetration through the outer membrane.

Amino Acid Sequence↗