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Biomedical subjects

X M Zhao

Publications and source records attributed to X M Zhao.

At least 19 recordsLinked to original sources
PubMed2001

Association of thrombospondin-1 and cardiac allograft vasculopathy in human cardiac allografts.

BACKGROUND: Despite the expression of angiogenic growth factors in transplanted hearts, neovessel formation appears scant. We therefore hypothesized that cardiac allografts contain endogenous inhibitors of angiogenesis. In particular, we tested the involvement in cardiac allografts of thrombospondin-1 (TSP-1), a matrix glycoprotein that inhibits angiogenesis and facilitates smooth muscle cell (SMC) proliferation. METHODS AND RESULTS: Levels of TSP-1 mRNA in endomyocardial biopsy samples of human cardiac allografts substantially exceeded those in normal hearts. The ratio of TSP to GAPDH mRNA determined with quantitative RT-PCR was 6.54+/-1.6 in cardiac allografts versus 0.26+/-0.02 (P:=0.001) in normal hearts. Analysis in sequential biopsies revealed a strong association between persistent elevation of TSP-1 in allografts and the development of cardiac allograft vasculopathy (CAV). The CAV score was 2.4+/-0.8 in patients with persistent TSP-1 elevation compared with 0.2+/-0.2 in patients without elevation (P:=0.001). Immunohistochemistry demonstrated intense expression of TSP-1 in cardiac allografts, predominantly in cardiac myocytes and neointimal SMCs. In vitro experiments demonstrated that T cells expressed TSP-1, acidic fibroblast growth factor, and vascular endothelial cell growth factor on allogeneic stimulation. Cytokines known to be elevated in cardiac allografts (interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha) induced TSP-1 in SMCs but inhibited TSP-1 in endothelial cells. CONCLUSIONS: Persistent elevation of TSP-1 in cardiac allografts correlates with the development of CAV. Allogeneic stimulation induces angiogenic growth factors and TSP-1 in T cells. Cytokines differentially regulate TSP-1 expression in SMCs versus endothelial cells. Increased levels of TSP-1 in human cardiac allografts may alter vascular responses to angiogenic growth factors by inhibiting angiogenesis and promoting SMC proliferation characteristic of CAV.

Blotting, Northern↗
PubMed2001

[Determination of enantiomeric purity for lactic acid in fermentation broth by Rhizopus oryzae with high performance liquid chromatography].

A procedure for the resolution of DL-lactic acid and the determination of D-isomer ratio in L-lactic acid fermentation broth by Rhizopus oryzae is described. The effects of pH of mobile phase and concentration of chiral mobile phase additives on resolution of DL-lactic acid were investigated. The optical isomers of lactic acid were resolved by RP-HPLC with 2,3,6-tri-O-beta-cyclodextrin(TM-beta-CD) as a chiral mobile phase additive, and C18 column as stationary phase, and detected at wavelength 210 nm. The results showed that a correction factor should be introduced into the equation for calculation of the percentage of D-lactic acid, because the UV absorption of D-lactic acid and L-lactic acid might not be the same when TM-beta-CD was present. Quantitation was achieved with external standard method, the average recovery was 100.4%, and the relative standard deviation was 0.82%. This method can be used for the determination of the percentage of D-isomer in L-lactic acid fermentation broth by Rhizopus oryzae, and it is simple, rapid and accurate. The results showed that the mass fraction of D-isomer in the fermented broth increased during the period of storage.

Chromatography, High Pressure Liquid↗
PubMed2001

[Clinical value of induced sputum test in monitoring airway inflammation in asthma].

OBJECTIVE: To explore the clinical value of induced sputum test in monitoring airway inflammation in asthmatic patients. METHODS: The induced sputum test was done in 12 normal subjects and 21 asthmatic subjects; The levels of interleukin-8 (IL-8), eosinophil cation protein (ECP), malondialdehyde (MDA) in plasma and induced sputum in all subjects were measured. RESULTS: The levels of IL-8, ECP, MDA in plasma and induced sputum in unstable asthmatic patients were significantly higher than those in stable asthmatic (P < 0.01), in which the levels of IL-8, ECP, MDA in both plasma and induced sputum were significantly higher than those in normal subjects(P < 0.05); In all asthmatic patients, the levels of IL-8, ECP, MDA in induced sputum were significantly higher than those in plasma. CONCLUSION: The levels of IL-8, ECP, MDA in induced sputum could be used for monitoring airway inflammation in asthmatic patients.

Adult↗
PubMed2000

[Determination of lactic acid in fermentation broth of Rhizopus oryzae by reversed-phase high performance liquid chromatography (RP-HPLC)].

A method for determining lactic acid in fermentation broth of Rhizopus oryzae by RP-HPLC is described. The operating conditions were Wakosil-II 5 C18 RS column(4.6 mm i.d. x 150 mm, 5 microns) at room temperature, 0.01 mol/L phosphoric acid solution (pH 2.5) as mobile phase with a flow rate of 1.0 mL/min and UV detection at 210 nm. The retention time of lactic acid was 3.820 min. This method is simple, rapid and accurate. The results will not be affected by other components in the broth. The relative standard deviation was 0.22% (n = 5), and the recovery was over 99%.

Chromatography, High Pressure Liquid↗
PubMed1999

Longitudinal analysis of fibroblast growth factor expression after transplantation and association with severity of cardiac allograft vasculopathy.

BACKGROUND: Vascular smooth muscle cell growth factors are postulated to contribute to cardiac allograft vasculopathy (CAV). Few data quantitatively address the timing, location, or stimuli for growth factor expression and relationship to CAV. METHODS AND RESULTS: Acidic fibroblast growth factor (aFGF) mRNA expression was determined in serial endomyocardial biopsies during the first year after transplantation. Patients with high levels of aFGF mRNA and elevations after the early posttransplant period had significantly more severe CAV than patients with low aFGF and no late elevations. CONCLUSIONS: Parenchymal aFGF expression varies between patients and in the same patient over time and correlates with development of CAV.

Biopsy↗
PubMed1999

A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor.

A missense mutation, A843E, in the seventh transmembrane domain of the human Ca2+ receptor, identified in a subject with autosomal dominant hypocalcemia, was found to cause a constitutive activation while at the same time lowering the maximal response of the receptor to Ca2+. A truncated human Ca2+ receptor lacking the majority of the N-terminal extracellular domain failed to respond to Ca2+ despite an excellent cell surface expression. The A843E mutant version of this truncated receptor showed constitutive activation. These results identify A843 as a critical residue for maintaining the inactive conformation of the human Ca2+ receptor. Substitution of glutamate, but not lysine or valine, for alanine 843 leads to activation of the human Ca2+ receptor in a manner that no longer depends upon Ca2+ binding to the extracellular domain.

Binding Sites↗
PubMed1998

Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor: effects on cell surface expression, dimerization and signal transduction.

Mammalian calcium receptors (CaRs) share with the metabotropic glutamate receptors (mGluRs) the relative positions of 16 cysteine residues in the amino-terminal extracellular domain. To investigate the role of these cysteines, a series of mutants in the extracellular domain of the human CaR was prepared in which each of these 16 cysteine residues and three others not conserved in the mGluRs were replaced by serines. Wild-type and mutant CaR cDNAs were expressed in HEK-293 cells, and evaluated for expression and response to extracellular calcium. Mutation of three non-conserved cysteines and of two conserved cysteines produced proteins with near wild-type phenotype. In contrast, mutation of the other conserved cysteines gave proteins that showed drastic reduction in cell surface expression and/or failed to respond to calcium. We identified 14 cysteines essential for proper trafficking and function of the receptor, two of which may be involved in formation of a disulfide-linked dimer.

Amino Acid Substitution↗
PubMed1998

Histologic and immunohistochemical responses after aortic valve allografts in the rat.

BACKGROUND: Human aortic valve allografts elicit a cellular and humoral immune response. It is not clear whether this is important in promoting valve damage. We investigated the changes in morphology, cell populations, and major histocompatibility complex antigen distribution in the rat aortic valve allograft. METHODS: Fresh heart valves from Lewis rats were transplanted into the abdominal aorta of DA rats. Valves from allografted, isografted, and presensitized recipient rats were examined serially with standard morphologic and immunohistochemical techniques. RESULTS: In comparison with isografts, the allografts were infiltrated and thickened by increased numbers of CD4+ and CD8+ lymphocytes, macrophages, and fibroblasts. Thickening of the valve wall and leaflet and the density of the cellular infiltrate was particularly evident after presensitization. Endothelial cells were frequently absent in presensitized allografts whereas isografts had intact endothelium. Cellular major histocompatibility complex class I and II antigens in the allograft were substantially increased. A long-term allograft showed dense fibrosis and disruption of the media with scattered persisting donor cells. CONCLUSIONS: The changes in these aortic valve allograft experiments are consistent with an allograft immune response and confirm that the response can damage aortic valve allograft tissue.

Animals↗
PubMed1998

Evidence that surface proteins Sn14 and Sn16 of Sarcocystis neurona merozoites are involved in infection and immunity.

Sarcocystis neurona is the etiologic agent of equine protozoal myeloencephalitis (EPM). Based on an analysis of 25,000 equine serum and cerebrospinal fluid (CSF) samples, including samples from horses with neurologic signs typical of EPM or with histologically or parasitologically confirmed EPM, four major immunoblot band patterns have been identified. Twenty-three serum and CSF samples representing each of the four immunoblot patterns were selected from 220 samples from horses with neurologic signs resembling EPM and examined for inhibitory effects on the infectivity of S. neurona by an in vitro neutralization assay. A high correlation between immunoblot band pattern and neutralizing activity was detected. Two proteins, Sn14 and Sn16 (14 and 16 kDa, respectively), appeared to be important for in vitro infection. A combination of the results of surface protein labeling, immunoprecipitation, Western blotting, and trypsin digestion suggests that these molecules are surface proteins and may be useful components of a vaccine against S. neurona infection. Although S. neurona is an obligate intracellular parasite, it is potentially a target for specific antibodies which may lyse merozoites via complement or inhibit their attachment and penetration to host cells.

Animals↗
PubMed1997

Bioconcentration, elimination and metabolism of 2,4-dinitrotoluene in carps(Cyprinus Carpio L.).

Bioconcentration curves of 2,4-dinitrotoluene(2,4-DNT) in carps (whole fish, liver, intestine and muscle) were investigated using semistatic system. For whole fish, its curve could be described as a gentle peak which began with a rise in concentration to summit or steady state, then declined and reached lower level followed by another steady state. For liver and intestine, their curves both contained two successive peaks, with the second peak followed by slight fluctuation. Bioconcentration factors of 2,4-DNT in whole fish during the first and second steady state were 9.15 and 4.15,(97.86 and 44.39, based on lipid content), respectively. By logarithmic plotting, two straight-lines with different slopes(3.6 and 0.1 d-1) were measured for elimination. According to peaky curves of 2,4-DNT in whole fish, liver and intestine, smaller BCFs than calculated BCFs based on the regression equations for inert chemicals, and large rate constants of elimination, biotransformation was inferred to have happened in tissues such as liver, intestine, and other tissues. Two metabolites were separated from liver and identified as 4-amino-2-nitrotoluene(4A2NT) and 2,4-diamino-toluene(2,4-DAT) on HPLC, their retention times were 23.1 and 8.8 min, respectively. In bioconcentration test of 2,4-DNT in liver, two metabolites and parent were determined at the same time at intervals, higher concentrations of 4A2NT and 2,4-DAT were found when level of 2,4-DNT declined. Such results demonstrated our inference that metabolism caused the declines in bioconcentration curves. A one-compartment model was set up to simulate the bioconcentration, in which biotransformation adhered to Delayed Enzyme-Catalytic Logarithmic Kinetics. Good fit of model curves with measured values could be observed.

Animals↗
PubMed1996

Expression and functional expansion of fibroblast growth factor receptor T cells in rheumatoid synovium and peripheral blood of patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory disorder of the diarthroidial joints, characterized by fibroblast proliferation, angiogenesis, and perivascular CD4+ T cell infiltration. The present study examined the interactions between fibroblast growth factor-1 (FGF-1) and T cells. METHODS: Synovial tissues from patients with RA or noninflammatory arthritis were examined for the expression of FGF-1 and its receptor, FGFR-1, by immunohistology and reverse transcriptase-polymerase chain reaction. Functional assays were used to detect enrichment of FGF-1-responsive peripheral CD4+ T cells in RA. RESULTS: FGF-1 is abundantly expressed by rheumatoid synovium. Enhanced expression of its receptor, FGFR-1, was found in perivascular CD4+ T cells. In addition, T cells that are activated by FGF-1 are increased in the peripheral blood of patients with RA, as compared with other inflammatory conditions. CONCLUSION: The increased frequency of peripheral T cells that respond to FGF-1 in RA is consistent with expansion of FGFR-1-expressing T cells in the rheumatoid synovium.

Arthritis, Rheumatoid↗
PubMed1995

Costimulation of human CD4+ T cells by fibroblast growth factor-1 (acidic fibroblast growth factor).

T cell infiltration is prevalent in wound healing, atherosclerosis, vascular lesions in chronic allograft rejection, and autoimmune diseases. Whether T cells play a role in the migration and proliferation of vascular smooth muscle cells and endothelial cells in these lesions is not known. We previously reported that some human T cells express FGF-1, a potent growth factor for vascular smooth muscle cells and endothelial cells. In this study, we extend this observation and examine the expression and function of FGF receptors on human T cells. Using reverse transcription-PCR, Northern analysis, and immunohistochemistry, we found that some human T cells also express high affinity FGF receptor 1 (FGFR-1) respond to FGF-1. In the presence of anti-CD3, exogenous FGF-1 functions as a costimulator for these T cells, while FGF-1 alone does not induce T cell proliferation. [3H]Thymidine incorporation is sevenfold higher in T cells costimulated with FGF-1 compared with stimulation with anti-CD3 alone. Using limiting dilution, we demonstrate that FGF-responsive T cells are present in normal peripheral blood at a mean frequency of 1:19780 (95% confidence limits, 1:15100-1:23000), and similar T cells are increased in the peripheral blood of heart transplant recipients (mean frequency, 1:4210; 95% confidence limits, 1:3420-1:6781). In addition, a subline of Jurkat, a human T cell tumor, expresses FGFR-1 receptor. The function of FGFR-1 receptor in Jurkat T cells is demonstrated by the production of IL-2 after stimulation with FGF-1 and anti-CD3. IL-2 levels are sevenfold higher in Jurkat T cells costimulated with FGF-1 compared with those stimulated with anti-CD3 alone. FGF-1 alone has no effect on Jurkat T cells. These findings thus provide evidence that a subset of human T cells expresses a receptor for vascular cell growth factors, and this receptor functions to increase IL-2 production consistent with costimulation. The potential role of FGF-responsive T cells in a variety of vascular and inflammatory lesions is discussed.

CD4-Positive T-Lymphocytes↗
PubMed1995

Association of acidic fibroblast growth factor and untreated low grade rejection with cardiac allograft vasculopathy.

Acidic fibroblast growth factor (aFGF) is a potent growth factor for vascular smooth muscle cells and may mediate vasculopathy in cardiac allografts subjected to chronic immunological injury. Therefore, we examined cardiac expression of aFGF, the number of rejection episodes, and other potential risk factors in 32 heart transplant patients who underwent intravascular ultrasound (IVUS) for detection of cardiac allograft vasculopathy (CAV). As defined by IVUS, CAV was present in 21 patients and absent in 11 patients (follow-up time: 52 +/- 21 vs. 51 +/- 12 months, respectively, P = NS). The level of aFGF in myocardial biopsies obtained at the time of IVUS was measured by semiquantitative reverse transcriptase polymerase chain reaction and expressed as the aFGF:GAPDH ratio. Higher level of aFGF were associated with CAV (mean aFGF:GAPDH ratio was 1.45 +/- 0.99 in patients with vs. 0.18 +/- 0.12 in patients without CAV [P < 0.001]). A strong association was found between high levels of cardiac aFGF and CAV, as 18 of 19 patients (95%) with high levels of aFGF (aFGF:GAPDH > 1) but only 3 of 13 patients with low levels of aFGF had CAV (P < 0.001). The relative risk of high level of aFGF for CAV was 4.1. Untreated low grade rejection (ISHLT I), but not treated high grade rejection (ISHLT > 2), was also associated with CAV (average number of untreated low grade rejection episodes was 3.5 +/- 1.8 in patients with vs. 2.1 +/- 1.0 in patients without CAV [P = 0.04]). Among other risk factors examined (age, sex, serum cholesterol, blood pressure, CMV infection, dose of immunosuppressants, and ischemic time), only triglycerides were higher in patients with than those without CAV (P = 0.003). We conclude that increased cardiac production of aFGF is significantly associated with CAV, which suggests that aFGF may serve as an important mediator in CAV. Untreated low grade rejection also poses an increased risk for CAV.

Adult↗
PubMed1995

Confirmation of alternatively spliced platelet-derived growth factor-A chain and correlation with expression of PDGF receptor-alpha in human cardiac allografts.

PDGF is a potent mitogen for vascular smooth muscle cells (SMC) and may play an important role in the pathogenesis of cardiac allograft vasculopathy (CAV). Two isoforms of PDGF-A chain exist as a result of alternative mRNA splicing that either includes (long-form) or excludes (short-form) exon 6. Short-form PDGF-A is expressed in both resting and activated cells, while the long-form is present predominantly in activated cells. Using RT/PCR, we have found previously that long-form PDGF-A chain was expressed in human cardiac allografts but not in normal human hearts. In the experiments reported here, we studied the cellular distribution of PDGF-A chain isoforms and expression of PDGF receptor-alpha in cardiac allografts. In situ hybridization and immunohistochemistry confirmed the PCR data and demonstrated that expression of long-form PDGF-A chain was diffusely increased in cardiac allografts, predominantly in myocytes and vascular structures. Expression of PDGF receptor alpha also was induced in cardiac allografts and was not detected in any of the normal hearts. Induction of PDGF receptor alpha in cardiac allografts was associated with the presence of long-form PDGF-A chain. In vitro experiments with human endothelial cells demonstrated that aFGF, IL-6, and TGF-beta, which are produced in cardiac allografts in vivo, induced expression of long-form PDGF-A chain. Expression of long-form PDGF-A chain and its receptor was markedly increased in cardiac allografts, predominantly in vascular structures and myocytes. Alterative splicing of PDGF-A chain variants may be mediated by growth factors and cytokines produced in vivo.

Adult↗
PubMed1995

Nitrogen-13-ammonia and PET to detect allograft coronary artery disease after heart transplantation: comparison with coronary angiography.

UNLABELLED: The diffuse nature of allograft coronary artery disease (CAD) suggests that global myocardial blood flow (MBF) may decrease with time after transplantation; therefore the diagnosis of this disease remains problematic. METHODS: To investigate whether PET detects a fall in allograft MBF over time, PET scans (108) were obtained from 43 heart transplant recipients. Thirty-five patients underwent two serial PET scans 1 yr apart. MBF was measured by PET using 13N-ammonia as a tracer. Coronary angiography was performed parallel with PET imaging and compared with perfusion rates measured by PET scans. RESULTS: MBF measured by PET decreased sequentially with time. The mean MBF was 73 +/- 21, 56 +/- 13, 51 +/- 11 and 51 +/- 27 ml/min/100 g of tissue in patients surviving 3 mo, 1, 2 and 3 yr after transplantation, respectively. Significant MBF decrease occurred within 1 yr after transplantation. Sequential PET studies showed a decrease in MBF in 22 of 35 patients (63%). Mean MBF for the first and second scans was 65 +/- 18 and 54 +/- 16, respectively. MBF decrease was more profound in patients (n = 11) angiographic evidence of CAD. There was a trend towards increased rejection and CMV infection rates in patients with decreased MBF. CONCLUSION: With time, PET detects a decrease in MBF in cardiac allografts. The frequency of MBF decrease detected by PET is concordant with the true incidence of allograft CAD, suggesting that sequential PET is a more sensitive modality for monitoring allograft CAD than angiography.

Ammonia↗
PubMed1994

Detection of T cells responsive to a vascular growth factor in rheumatoid arthritis.

The primary lesion in rheumatoid arthritis (RA) is a destructive synovitis characterized by proliferation of endothelial cells, fibroblasts, and vascular smooth muscle cells, and with perivascular lymphocyte aggregates. A nonhematopoietic growth factor, acidic fibroblast growth factor (aFGF), may induce many of the biological features found in rheumatoid synovium, including T cell activation. To determine if aFGF-responsive T cells are increased in RA, we developed an assay to measure the frequency of peripheral blood T cells that are costimulated by aFGF. The data indicate that the frequency of aFGF-responsive T cells is increased in RA and may change with disease activity and treatment.

Arthritis, Rheumatoid↗
PubMed1994

Donor-specific immune response after aortic valve allografting in the rat.

The allospecific immune response in rats to a major histocompatibility complex-disparate aortic valve allograft was investigated using three in vitro assays. In each assay, DA strain (RT-1a) rats served as allograft recipient and syngeneic donor, Lewis strain (RT-1l) rats were allogeneic donors, and Buffalo (RT-1b) rats provided third-party control cells. Mixed lymphocyte cultures using spleen cells demonstrated donor-specific stimulation indices of 3.04 +/- 0.44, 4.14 +/- 0.62, and 6.32 +/- 0.60 at 7, 14, and 28 days, respectively, after aortic valve allografting; 8.19 +/- 2.91, 8.51 +/- 1.25, and 10.80 +/- 0.53 after skin allografting; and 1.84 +/- 0.56, 1.82 +/- 0.38, and 1.82 +/- 0.53 after aortic valve isografting. Limiting dilution analysis of splenocytes showed a donor-specific cytotoxic T lymphocyte precursor frequency at 7, 14, and 28 days of 1:6,853, 1:4,714, and 1:1,964 after aortic valve allografting; 1:4,181, 1:1,611, and 1:1,018 after skin allografting; and 1:14,517, 1:11,882, and 1:10,995 after aortic valve isografting. Flow cytometry detected an increase in the level of donor-specific anti-T cell antibodies in both valve and skin allograft recipients but not in isografted animals. Aortic valve allografting from Lewis into DA rats elicits allospecific cellular and humoral immune responses similar in magnitude to skin allografting but somewhat slower in onset. Investigation of the immune response to aortic allografts in humans is warranted, as donor-specific T cells, antibodies, or both may damage the allograft.

Animals↗