Search PubMed⌕ Search

Biomedical subjects

X Tao

Publications and source records attributed to X Tao.

At least 55 records · Page 3Linked to original sources

Distribution of catechol-O-methyltransferase expression in human central nervous system.

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme crucial to catechol metabolism. Two isoforms exist in the human central nervous system (CNS) and they are encoded by two transcripts (1.3 and 1.5 kb) in most human tissues. Using two alpha-32P-labeled probes, we found only the 1.5 kb transcript in all 16 regions of the human CNS using commercially available Northern blots. Spinal cord had the highest and amygdala had the lowest levels of expression. The other CNS regions shared a similar level of expression. The distributions of COMT gene expression relative to whole brain between both probes were significantly correlated. Our study shows that the expression of the 1.5kb transcript is crucial for COMT activity in all regions of the human CNS.

Blotting, Northern↗

Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production.

OBJECTIVE: Extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, but the mechanism of this therapeutic effect has not been completely delineated. The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E2 (PGE2) and on the expression of the cyclooxygenase isoforms, COX-1 and COX-2, in various human cell types. METHODS: Monocytes from human peripheral blood (HM), fibroblasts from rheumatoid arthritis synovial tissue (RASF), human neonatal foreskin fibroblasts (HFF), and the histiocytic cell line U937 were cultured for designated time periods with or without lipopolysaccharide (LPS), and in the presence or absence of varying concentrations of the following inhibitors: the methanol/chloroform (T2) extract of TWHF, the ethyl acetate (EA) extract of TWHF, a purified diterpenoid component of TWHF (triptolide), dexamethasone, and indomethacin. Culture supernatants were harvested for PGE2 content assays. Total RNA was extracted from the cells and analyzed for COX-1 and COX-2 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction or Northern blotting. RESULTS: Both the T2 and EA extracts inhibited PGE2 synthesis in the LPS-stimulated HM, RASF, and HFF cells, which was reflected by a marked suppression in the levels of mRNA for COX-2. In contrast, neither extract inhibited PGE2 production in U937 cells that did not express COX-2. Triptolide also inhibited LPS-stimulated induction of COX-2 mRNA and synthesis of PGE2, at the same inhibitory concentration as seen with the EA extract. The effects of T2, EA, and triptolide paralleled the inhibitory action of dexamethasone. CONCLUSION: The data indicate that both the T2 and EA extracts of TWHF, as well as the triptolide component, inhibit PGE2 production in a variety of human cells by blocking the up-regulation of COX-2.

Acetates↗

Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism.

CREB is a transcription factor implicated in the control of adaptive neuronal responses. Although one function of CREB in neurons is believed to be the regulation of genes whose products control synaptic function, the targets of CREB that mediate synaptic function have not yet been identified. This report describes experiments demonstrating that CREB or a closely related protein mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel regulatory element as well as a blockade of CREB function resulted in a dramatic loss of BDNF transcription. These findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription. We conclude that the BDNF gene is a CREB family target whose protein product functions at synapses to control adaptive neuronal responses.

Animals↗

Predictors of mammography utilization in Missouri, 1993-1994.

Mammography utilization data were studied for 915 women from a combined sample of 1994 Missouri Behavioral Risk Factor Surveillance System and a Special Breast and Cervical Cancer Control Project Evaluation Survey, as well as similar data from 6,784 new participants in Missouri's Breast and Cervical Cancer Control Project during 1993-1994. Among women aged 40 and over, having some college education and having health insurance coverage were associated with a higher likelihood of ever having a mammogram. Education, age, health care, Pap testing, and smoking were identified as important predictors of compliance with recommended schedule of yearly mammography among women aged 50 and over.

Adult↗

[Will chronic nonproductive cough with bronchial hyperresponsiveness be cough variant asthma?].

OBJECTIVE: The clinical characteristics of the patients suffered from chronic nonproductive cough with bronchial hyperresponsiveness were analyzed, so as to evaluate the value of measurement of bronchial responsiveness in diagnosis of cough variant asthma (CVA). METHOD: 124 patients with chronic nonproductive cough were divided into two groups after the measurement of bronchial responsiveness: cough bronchial hyperresponsiveness positive group (CBH-P, n = 35) and cough bronchial hyperresponsiveness negative group (CBH-N, n = 33). Routine pulmonary function, positive rate of antigen-skin pitting lest, count of blood eosinophil cells, level of blood IgE, positive rate of prednisone test and the number of development of classical asthma in two-year following up were studied. RESULT: The percentage of FEV1.0 in group CBH-P was significantly lower than in group CBH-N, but antigen-skin pitting test, count of blood eosinophil cells, prednisone test and the number of development of classic asthma in two-year following up were all higher than in the latter group. In group CBH-P, there was no significant difference in positive rate of antigen-skin pitting test, routine pulmonary function, reacting threshold(Dmin) and wheezing threshold (DCW/Dmin) between the patients who developed classic asthma and those who did not. CONCLUSION: The measurement of bronchial responsiveness is important for the diagnosis of CVA, but it is not the only diagnostic criteria and should be combined with other clinical data.

Adult↗

Lymphohematopoietic cancers and butadiene and styrene exposure in synthetic rubber manufacture.

The described nested case-control study of lymphohematopoietic cancers occurring in a cohort of synthetic rubber production workers was conducted to determine the associations of these cancers with exposure to butadiene and styrene. Cases have been confirmed through hospital record review of 95 percent of the cancers. Exposures are based on measured values of the two chemicals from personal monitoring data in seven of the eight plants under study. The results indicate that the risk of leukemia increases with exposure to a time-weighted average butadiene measure. The odds ratio at only 1 ppm average butadiene exposure is 1.50 (95% CI 1.07, 2.10). Work in specific areas also contributes to the risk, possibly because these areas have not been completely characterized for differences in butadiene exposure. Hodgkins disease is also associated with butadiene exposure. Multiple myeloma, lymphosarcoma, and all lymphomas are associated with exposure to styrene. Since workers in this industry are apparently exposed to two carcinogenic agents, further effort must be made to distinguish the exposures to each chemical over time and to characterize their interrelationship with the risk of cancers of the lymphohematopoietic system.

Butadienes↗

Distinct biochemical signals characterize agonist- and altered peptide ligand-induced differentiation of naive CD4+ T cells into Th1 and Th2 subsets.

We have recently shown that altered peptide ligands influence differentiation of CD4+ T cells into Th1 and Th2 subsets. In the present study, we have examined the biochemical signals in naive CD4+ T cells after priming with altered peptide ligand (APL) that correlate with differences in cytokine expression. Although we observed zeta-chain phosphorylation in APL-stimulated cells, other signaling events such as ZAP70 and Lnk phosphorylation are not initiated. This altered pattern observed in the early phosphorylation events correlates with a distinct Ca2+ mobilization pattern that characterizes APL-stimulated cells. By changing the calcium signaling environment during T cell priming, we present data indicating that qualitative differences in calcium mobilization are associated with differentiation of naive CD4+ T cells into Th1- and Th2-like effector subsets.

Amino Acid Sequence↗

Strength of TCR signal determines the costimulatory requirements for Th1 and Th2 CD4+ T cell differentiation.

Differentiation of naive CD4 T cells into cytokine-secreting effector Th1 and Th2 cells is influenced by several factors. We have previously reported that the affinity of antigen for TCR and antigen dose can influence the differentiation of Th1 and Th2 cells. Several in vitro and in vivo models have demonstrated a role for the costimulatory molecules, B7-1 (CD80) and B7-2 (CD86), in the generation of distinct effector T cell responses. To determine whether the strength of TCR signaling controls the involvement of CD28 costimulation in selective CD4 T cell differentiation, naive CD4 T cells bearing a transgenic TCR are primed by a weak or strong TCR signal (signal 1) in the presence or absence of B7 costimulatory molecules (signal 2). In this system, IL-4-producing Th2 cells are generated by priming with a weak but not a strong TCR signal. Th2 cell differentiation is dependent on CD28/B7 interactions in that disruption of CD28/B7 interactions inhibits the priming of Th2 cells and cross-linking CD28 with anti-CD28 antibody augments the priming of Th2 cells. In contrast, however, IL-4-producing Th2 cells cannot be generated by priming with a strong TCR signal even in the presence of strong costimulation or high doses of IL-2. Thus, our results suggest that naive CD4 T cells are receptive to CD28-dependent IL-4 production only if they receive a weak TCR signal.

Abatacept↗

Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

3T3 Cells↗

Induction of IL-4-producing CD4+ T cells by antigenic peptides altered for TCR binding.

The adaptive immune responses to foreign Ags are primarily regulated by the cytokines produced by CD4 T cells. The generation of distinct cytokine-producing T cell subsets has been shown to be influenced by a number of factors, including cytokines, different types of APCs, and the amounts of priming Ag. We have previously reported that the affinity of an antigenic peptide for its presenting MHC class II molecules and that different doses of Ag peptide affect the outcome of the functional CD4 T cell response. In the current study, we further examined the impact of the affinity of an antigenic peptide for its TCR on CD4 T cell priming. We generated a panel of Ag peptide variants mutated at positions known to be critical for binding to a well-characterized TCR (known as altered peptide ligands, or APLs). Compared with the WT peptide, these APLs are defective in stimulating the proliferative responses of T cells. However, they can effectively prime in vitro naive CD4 T cells for differentiation into both Th1-like and Th2-like cells. In contrast, the WT peptide primes only for IFN-gamma-producing Th1-like cells. Using highly purified dendritic cells as APCs to present the APL or WT peptide leads to the same pattern of priming as using total splenic APCs. These results indicate that priming by APLs for both IL-4 production and IFN-gamma production does not require two different types of APCs. In summary, our data indicate that APL can directly stimulate naive CD4 T cells to become Th2 effector cells.

Amino Acid Sequence↗

The Chinese herbal remedy, T2, inhibits mitogen-induced cytokine gene transcription by T cells, but not initial signal transduction.

T2, an extract of Tripterygium wilfordii Hook F, has been reported to be effective in the treatment of a variety of autoimmune diseases, including rheumatoid arthritis. Previous studies have shown that T2 inhibited mitogen- or antigen-induced proliferation of human peripheral blood T cells and B cells, IL-2 production by T cells and Ig production by B cells. In contrast, T2 did not affect monocyte functions, such as IL-1 production and antigen presentation. The current studies sought to localize the immunosuppressive action of T2 more precisely. Results show that T2 prevented [3H]-uridine uptake by mitogen-stimulated T cells and arrested them in the early GI phase of the cell cycle. The inhibitory effects of T2 could be partially overcome by costimulating PHA activated T cells with PMA and completely nullified by costimulation with PMA plus a monoclonal antibody to CD28. Moreover, T2 had no effect on expression of IL-2R or the transferrin receptor (CD71), but inhibited production of a number of cytokines, including IL-2 and IFN-gamma by activated T cells. T2 suppressed IL-2 mRNA levels, but not IL-2R mRNA levels, in activated T cells. T2-mediated inhibition reflected suppression of IL-2 gene transcription as indicated by suppression of the expression of a reporter gene driven by the IL-2 promoter. T2 had little inhibitory effect on either IL-2 gene expression or cell cycle progression when added after initial mitogenic stimulation, indicating that an early step in the cascade of activation events was inhibited. However, initial activation events including protein tyrosine phosphorylation, the generation of diacylglycerol, IP3, and the translocation of protein kinase C were not inhibited by T2. Moreover, T2 did not inhibit the phosphatase activity of calcineurin. These results have localized the effect of T2 to a step in the T cell activation cascade after initial second messenger generation, tyrosine phosphorylation and protein kinase activation, but before IL-2 gene transcription.

Adult↗

[Urinary tract infections in patients with diabetes mellitus and related factors].

We investigated the results of urine culture between the mid-urine and the bladder puncture urine in 30 cases of diabetes millitus. The results showed that female elderly NIDDM and the patients with diabetic retionopathy, nephropathy and neuropathy had higher incidence of urinary infections. When the leukocyte count in routine urine examination was more than 10 increases/HP, the incidence of urinary infection was higher. The urine culture with bladder puncture was more reliable than midurine. In addition, the nuring care for prevention of the urinary infection in diabetes was dicussed.

Aged↗

Changes of plasma endothelin concentrations before and after percutaneous balloon mitral valvuloplasty in patients with mitral stenosis.

Plasma concentrations of endothelin in blood from the femoral vein and the antecubital vein were measured in 35 patients with mitral stenosis and heart failure before and after percutaneous balloon mitral valvuloplasty (PBMV). The basal plasma concentrations of endothelin in blood from the antecubital vein in the patients were significantly higher than those in 32 control subjects (15.40 +/- 3.32 vs. 9.59 +/- 2.66 pg/ml, P < 0.001). Plasma endothelin concentrations in patients in New York Heart Association functional classes II and III were significantly higher than those in control subjects, respectively. The concentrations of endothelin in patients with atrial fibrillation were also significantly higher than those in patients with normal sinus rhythm. Ten to fifteen minutes after PBMV, plasma endothelin concentrations in blood from the femoral vein significantly decreased from 16.14 +/- 3.34 to 13.74 +/- 3.78 pg/ml (P < 0.01). Seventy-two hours after the procedure, the concentrations of endothelin in blood from the antecubital vein had fallen to 12.31 +/- 2.55 pg/ml (P < 0.001 vs. before PBMV and control subjects). Plasma endothelin concentrations still tended to be higher in patients with atrial fibrillation than those in normal sinus rhythm, but the difference did not reach statistical significance. There were weak but significantly correlations of plasma endothelin concentrations with the mean left atrial pressure (r = 0.424, P < 0.001), mean right atrial pressure (r = 0.323, P < 0.01), mean transmitral pressure gradient (r = 0.397, P < 0.001), heart rate (r = 0.350, P < 0.005) and mitral valve area (r = -0.454, P < 0.001) in the patients before and after PBMV.

Adolescent↗

Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae.

The diphtheria tox repressor (DtxR) of Corynebacterium diphtheriae plays a critical role in the regulation of diphtheria toxin expression and the control of other iron-sensitive genes. The crystal structures of apo-DtxR and of the metal ion-activated form of the repressor have been solved and used to identify motifs involved in DNA and metal ion binding. Residues involved in binding of the activated repressor to the diphtheria tox operator, glutamine 43, arginine 47, and arginine 50, were located and confirmed by site-directed mutagenesis. Previous biochemical and genetic data can be explained in terms of these structures. Conformational differences between apo- and Ni-DtxR are discussed with regard to the mechanism of action of this repressor.

Amino Acid Sequence↗

Transition metal ion activation of DNA binding by the diphtheria tox repressor requires the formation of stable homodimers.

The diphtheria tox repressor (DtxR) is a transition metal ion-dependent regulatory element that controls the expression of diphtheria toxin and several genes involved in the synthesis of siderophores in Corynebacterium diphtheriae. In the presence of transition metal ions apo-DtxR becomes activated and specifically binds to its target DNA sequences. We demonstrate by glutaraldehyde cross-linking that monomeric apo-DtxR is in weak equilibrium with a dimeric form and that upon addition of activating metal ions to the reaction mixture a dimeric complex is stabilized. Addition of the DNA-binding-defective mutant apo-DtxR(delta 1-47) to apo-DtxR in the absence of transition metal ions inhibits conversion of the apo-repressor to its activated DNA-binding form. We also show that the binding of Ni2+ to both apo-DtxR and apo-DtxR(delta 1-47) is cooperative and that upon ion binding there is a conformational change in the environment of the indole ring moiety of Trp-104. For the wild-type repressor the consequences of this conformational change include a shift in equilibrium toward dimer formation and activation of target DNA binding by the repressor. We conclude that the formation of DtxR homodimers is mediated through a protein-protein interaction domain that is also activated on metal ion binding.

Apoproteins↗

Molecular cloning, DNA sequence analysis, and characterization of the Corynebacterium diphtheriae dtxR homolog from Brevibacterium lactofermentum.

A homolog of the Corynebacterium diphtheriae dtxR gene was isolated from Brevibacterium lactofermentum. The product of the B. lactofermentum dtxR gene was immunoreactive with polyclonal anti-DtxR antibodies and functioned as an iron-activated repressor capable of regulating the expression of beta-galactosidase from a diphtheria tox promoter/operator transcriptional fusion in recombinant Escherichia coli. The extents of induction by increasing concentrations of the chelator 2,2'-dipyridyl were identical in cells expressing DtxR from either C. diphtheriae or B. lactofermentum.

Amino Acid Sequence↗

[In vitro effect of metronidazole ester on Trichomonas vaginalis and Entamoeba histolytica].

Metronidazole ester, a new nitroimidazole drug, was synthesized by the Department of Physical Chemistry, School of Pharmacy, Shanghai Medical University. The trichomonadicidal and amoebicidal activity of metronidazole ester was evaluated in vitro by the cultivation of Trichomonas vaginalis and Entamoeba histolytica at different drug concentrations. The results indicated that the 100% lethal concentration for T. vaginalis and E. histolytica was 2.6 micrograms/ml and 40 micrograms/ml, respectively after incubation with metronidazole ester for 48 h. In comparison with metronidazole, the effect of metronidazole ester for both protozoa was similar.

Animals↗

The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract (T2) of Tripterygium wilfordii Hook. F.

A variety of preparations of Tripterygium wilfordii Hook.F (TWHF) have been reported to be effective in the treatment of autoimmune diseases, including a chloroform methanol extract termed T2 and an ethyl acetate (EA) extract. The immunosuppressive activity of the EA extract was analyzed and the components accounting for this effect determined and compared to those of T2. More than 0.25 microgram/ml of the EA extract inhibited antigen- and mitogen-stimulated human T cell proliferation. The inhibitory effect of the EA extract on T cell proliferation resulted largely from suppression of interleukin-2 production. At concentrations that inhibited T cell function, the EA extract also profoundly suppressed [3H]-thymidine incorporation by mitogen-stimulated B cells, but it did not inhibit antigen presentation by monocytes and only modestly affected interleukin-6 production by lipopolysaccharide-stimulated monocytes. The profile of inhibition was comparable to that previously reported for the chloroform-methanol extract of Tripterygium wilfordii Hook.F, T2. To delineate the components of these extracts that might account for their immunosuppressive effect, we analyzed the composition of diterpenoid compounds. Both extracts contained triptolide and tripdiolide as the major immunosuppressive diterpenoids, but at different concentrations. Comparison of the composition of these extracts and the inhibitory capacity of the purified components indicated that the triptolide concentration of the EA extract can account for its immunosuppressive activity, although the combination of both triptolide and tripdiolide or other unknown components may be necessary to explain the inhibitory effects of T2.

Acetates↗