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Biomedical subjects

X Mao

Publications and source records attributed to X Mao.

118 records · Page 7Linked to original sources
PubMed1993

The NFAT-1 DNA binding complex in activated T cells contains Fra-1 and JunB.

Activation of T cells induces transcription of the interleukin-2 (IL-2) gene. IL-2 expression is regulated through the binding of transcription factors to multiple sites within the IL-2 enhancer. One such cis-acting element within the IL-2 enhancer is the NFAT-1 (nuclear factor of activated T cells) binding site. NFAT-1 binding activity is absent in resting cells but is induced upon T-cell activation. The induction of NFAT-1 binding activity can be inhibited by cyclosporin A, potentially accounting for the ability of cyclosporin A to inhibit IL-2 production by T cells. We have previously reported that the NFAT-1 binding complex is composed of at least two proteins and that the 5' portion of the NFAT-1 sequence acts as a binding site for one or more proteins from the Ets family of transcription factors. We now report that the 3' portion of the NFAT-1 sequence contains a variant AP-1 binding site. NFAT-1 binding can be specifically inhibited by oligonucleotides containing a consensus AP-1 site. Moreover, mutation of the AP-1 site at the 3' end of the NFAT-1 sequence inhibits both NFAT-1 binding and the ability of the NFAT-1 binding site to activate expression from a reporter plasmid upon T-cell activation. Since AP-1 sites bind dimeric protein complexes composed of individual members of the Fos and Jun families of transcription factors, we used antibodies specific for individual Fos and Jun family members to determine whether they are present in the NFAT-1 binding complex. These experiments demonstrated that the NFAT-1 binding complex contains JunB and Fra-1 proteins. Northern (RNA) blot analyses demonstrate that both fra-1 and junB mRNAs are induced upon T-cell activation, although fra-1 mRNA is present even in quiescent T cells. Of interest, junB is not expressed in quiescent T cells, and it is induced with kinetics that are similar to those for the induction of IL-2 mRNA expression. Taken together, these results suggested that the JunB-Fra-1 heterodimer is the inducible nuclear component of the NFAT-1 binding activity and that JunB expression regulates the formation of the heterodimer. In addition, these data indicated that specific heterodimers of Fos and Jun family members may have selective roles in the induction of transcription during cellular activation.

Enhancer Elements, Genetic↗
PubMed1993

N-(phosphonacetyl)-L-aspartate synergistically enhances the cytotoxicity of 5-fluorouracil/interferon-alpha-2a against human colon cancer cell lines.

Recombinant interferon-alpha (IFN) enhances the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), against two human colon cancer cell lines. The aspartate transcarbamylase (ATCase) inhibitor, N-(phosphonacetyl)-L-aspartate (PALA), was studied in combination with 5FU/IFN to determine whether further anti-pyrimidine effects would result in greater cytotoxicity. By median effects analysis PALA synergistically augmented the cytotoxic effects of 5FU/IFN against both human colon cancer cell lines. This occurred in the absence of any effects of 5FU/IFN on ATCase and without further potentiation of the PALA-mediated inhibition of ATCase. To explore the mechanism by which this interaction occurred, detailed studies of pools of dNTPs were performed. Both 5FU/IFN and PALA/5FU/IFN treatments resulted in early (2-8 hr) depletion of pools of dTTP, but no effects on pools of dCTP. PALA had no effect on dTTP pools either alone or in the combination. In contrast, both PALA and PALA/5FU/IFN treatments resulted in later (12-24 hr) depletion of pools of dCTP. 5FU/IFN treatment had no effect on these pools. When pools of dCTP and dTTP were repleted by treatment with cytidine or thymidine, 20 microM, however, there was only partial reversal of cytotoxicity induced by 5FU/IFN + PALA, suggesting that the synergy observed did not result solely from a sequential anti-pyrimidine effect. The incorporation of 5FU into RNA was also studied; PALA enhanced the incorporation of [6-3H]5FU into RNA by 83-150%, but not into DNA, suggesting an alternative mechanism of drug interaction.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Regulation of translation initiation factor gene expression during human T cell activation.

Activation of quiescent T cells leads to a dramatic increase in the rate of protein synthesis. It is believed that this pronounced increase of protein synthesis is regulated primarily at the level of translational initiation. Although considerable evidence demonstrates that translational initiation can be regulated at the post-translational level by the phosphorylation/dephosphorylation of translation initiation factors (eIFs) such as eIF-4E and eIF-2 alpha, additional mechanisms of eIF gene expression may also play a role in the regulation of translation in quiescent cells and/or during their subsequent induction to enter the cell cycle. To address this issue, gene expression of eIF-2 alpha, -4E, and -4A was studied in quiescent human peripheral blood T cells following stimulation through the T cell receptor-CD3 complex. Quiescent T cells expressed low levels of eIF-2 alpha, -4E, and -4A mRNAs and proteins as compared to proliferating T cells. Activation of resting T cells resulted in a rapid increase (20-50-fold) in the levels of these three mRNAs. This increase did not require new protein synthesis. Furthermore, transcription rates of these three eIF genes showed only minor increase over the induction period as measured by nuclear run-on assays. Despite the rapid increase in initiation factor mRNA levels, increases in eIF protein levels lagged significantly behind. Western blot analysis also showed that the protein levels of the three eIFs were differentially increased. eIF-4A protein levels increased in proportion to the observed increase in cellular protein synthetic activity while the increases in eIF-4E and eIF-2 alpha proteins were proportionately less. The low levels of eIF proteins in quiescent T cells appear to correlate with low protein synthesis rate in such cells. The induction of eIF proteins by post-transcriptional/translational mechanisms appears to contribute to the pronounced stimulation of protein synthesis that occurs during T cell activation.

Animals↗
PubMed1992

Effect of vitamin C supplementations on iron deficiency anemia in Chinese children.

A total of 65 children with mild iron deficiency anemia (IDA) were divided into 5 groups, and received 0, 25, 50, 100 and 150 mg/day of vitamin C (VC) respectively every day for 8 weeks. Hemoglobin, serum ferritin, free erythrocyte and hematocrit were determined every week. At a daily average intake of about 30 mg of VC and 7.5 mg of Fe, the results of the study indicate that: (1) VC supplement alone could effectively control children's IDA, and a dose-dependent relationship was observed. (2) 50 mg/day of VC is the most efficient dosage and 6 weeks is the shortest time for an effective therapy. (3) With a diet predominantly comprised of plant foods, it is suggested that appropriate dose of VC should be supplemented for the children during winter and spring in northeastern areas of China.

Anemia, Hypochromic↗
PubMed1991

[Study on relationship between human ABO blood groups and type A behavior pattern].

Investigation of the relationship between ABO blood groups (ABO BG) and Type A behavior pattern (TABP) was performed. No significant correlation was found between human ABO BG and TABP (P less than 0.05). However, CH and TH + CH scores in individuals with blood type A and type A personality were significantly lower (P less than 0.05). The values of TH-CH scores among tested people were of no statistical significance (P greater than 0.05). Moreover, nearly half of the examinees (41.32%) had higher CH score and the distribution of the individuals was obviously different in statistics (P less than 0.005). In addition, L score of examinees with blood type A and type B personality was relatively lower.

ABO Blood-Group System↗
PubMedDate not supplied

Molecular cloning and sequence analysis of cDNAs encoding a beta-toxin-like peptide and two MkTx I homologues from scorpion Buthus martensii Karsch.

Three full-length cDNAs, one encoding the precursor of a beta-toxin-like peptide (named BmKBT) and the other two encoding those of (MkTx I) homologues (named MkTx II and MkTx III, respectively), were isolated from a venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch, by screening with a cDNA fragment generated by PCR. The encoded precursor of BmKBT contained 83 amino acid residues including a signal peptide of 19 residues, a mature peptide of 63 residues and an extra basic residue (Lys) which have to be removed in the processing step. The deduced amino acid sequence of BmKBT showed 52% homology to that of beta-neurotoxin TsVII isolated from scorpion Tityus serrulatus. However, the positions of disulfide bridges have a little variation between the two peptides. The precursors of MkTx II and MkTx III both contained 85 amino acid residues including a signal peptide of 19 residues, a mature peptide of 64 residues and two extra residues (Gly-Arg) which have to be removed in the processing step, too. There was high sequence similarity (90%) between the two peptides. The sequences of mature MkTx II and MkTx III were highly homologous with MkTx I isolated from scorpion Buthus martensii Karsch, both showing 90% identities.

Amino Acid Sequence↗
PubMedDate not supplied

Molecular cloning and genomic organization of a K(+) channel toxin from the Chinese scorpion Buthus martensii Karsch.

A full-length cDNA encoding the precursor of a K(+) channel toxin (BmTX2) was first isolated from a venom-gland cDNA library of the Chinese scorpion Buthus martensii Karsch. The precursor is composed of a signal peptide of 21 residues and a mature toxin of 37 residues with three disulfide bridges. The genomic gene of BmTX2 was also cloned and sequenced. It consisted of two exons, disrupted by an intron of 81 bp inserted in the region encoding signal peptide.

Amino Acid Sequence↗
PubMedDate not supplied

Characterization of Bangor virus proteins by using monoclonal antibodies.

A new virus was isolated from a finch in quarantine in Northern Ireland in 1973. The virus had the morphological characteristics of a paramyxovirus, and was named Bangor virus (BaV). In order to identify the structural proteins of BaV and to investigate the biological characterization of the virus, 28 monoclonal antibodies (mAbs) directed against BaV were prepared. Eight of these mAbs reacted with the nucleocapsid protein (NP), 10 with hemagglutinin-neuraminidase (HN) protein, and 10 with fusion (F) protein. With the aid of these mAbs, the structural proteins of BaV were determined, namely, p52, gp74, gp63, and gp51 were identified as the NP, HN, F0, and F1 proteins, respectively. The biological activities of the mAbs directed against the envelope glycoproteins of BaV were examined. Intriguingly, it was found in the neutralization assay that four mAbs directed against the HN protein of BaV can enhance the fusion of HeLa cells infected with BaV, showing the presence of a potential third function of the HN protein that affects the fusion activity of the F protein. Furthermore, all of the anti-F protein mAbs showed neutralizing activity.

Animals↗