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X M Zhao

Publications and source records attributed to X M Zhao.

32 records · Page 2Linked to original sources
PubMed1994

Induction of acidic fibroblast growth factor and full-length platelet-derived growth factor expression in human cardiac allografts. Analysis by PCR, in situ hybridization, and immunohistochemistry.

BACKGROUND: Further understanding of cardiac allograft vasculopathy (CAV) is needed to improve long-term survival after cardiac transplantation. The diffuse hyperplasia of coronary intima characteristic of CAV suggests that growth factors may play a role in the development of CAV. Fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) are potent mitogens for smooth muscle cells (SMCs), and PDGF is an important cofactor in the pathogenesis of native coronary atherosclerosis. METHODS AND RESULTS: Reverse transcriptase/polymerase chain reaction (RT/PCR), in situ hybridization, and immunohistochemistry were used to determine whether transplantation results in increased cardiac expression of acidic (a) FGF, basic (b) FGF, and PDGF-A and -B chains. Sixty-eight myocardial biopsies from 36 heart transplant recipients and 7 normal hearts were analyzed by PCR. aFGF mRNA was present in 54 of 61 allograft biopsies and was not found in any normal heart. In situ hybridization and immunohistochemistry demonstrated diffuse, intense expression of a FGF mRNA and protein in allograft biopsies, predominantly in myocytes and vascular walls. Only scattered aFGF expression was observed in normal hearts. mRNA for the full-length isoform of PDGF-A chain was found in 43 of 61 allograft biopsies and was not detected in any normal heart. In situ hybridization and immunohistochemistry confirmed that full-length PDGF-A chain mRNA and PDGF protein were present in myocytes and vascular walls. CONCLUSIONS: Expression of aFGF and PDGF-A chain is significantly increased in cardiac allografts. Cardiac myocytes and vascular walls are the predominant sources of aFGF and PDGF. Diffuse expression of these growth factors in cardiac allografts may be important in the pathogenesis of CAV.

Adult↗
PubMed1994

Modification of alternative messenger RNA splicing of fibroblast growth factor receptors in human cardiac allografts during rejection.

Accelerated coronary atherosclerosis in cardiac transplants (cardiac allograft vasculopathy, CAV) is characterized by coronary intimal hyperplasia. Acidic fibroblast growth factor (aFGF) is a potent mitogen for vascular smooth muscle cells and endothelial cells, and its expression is increased in cardiac allografts, suggesting it may play a role in the pathogenesis of CAV. The activity of aFGF is dependent on binding to transmembrane receptors. To investigate whether receptors for aFGF are also induced after transplantation, polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to analyze expression of four receptors for aFGF (FGFR1-FGFR4). Expression of mRNA encoding extracellular immunoglobulin-like domains of FGFR1 was increased 35-fold in cardiac allografts compared with normal hearts and was predominantly present in cardiac myocytes and vascular structures. Alternatively spliced mRNA that encodes transmembrane forms of FGFR1, which contain the signal-transducing tyrosine kinase domains, was induced in allografts during rejection, in infiltrating cells, vascular structures, and myocytes. In vitro experiments showed that differential expression of FGF receptor isoforms was induced by aFGF, and also by IL-6 and TGF-beta, which are expressed in cardiac allografts during rejection. The results show that expression of both aFGF and its receptors is altered in cardiac allografts and suggest that these events are important in the pathogenesis of CAV.

Adolescent↗
PubMed1993

The expression of acidic fibroblast growth factor (heparin-binding growth factor-1) and cytokine genes in human cardiac allografts and T cells.

The purpose of this study was to investigate the role of cytokines and growth factors in cardiac allograft rejection and vasculopathy (CAV). The polymerase chain reaction (PCR) was used to detect the expression of IL-1, IL-2, IL-4, IL-5, IL-6, TNF-alpha, IFN-gamma, TGF-beta, TCR-beta chain and aFGF genes in 21 myocardial biopsies obtained from 9 heart transplant patients. There was no statistically significant correlation between cytokine gene expression and rejection, although a trend toward increased IL-6 and TGF-beta expression was noted with rejection (6 of 10 biopsies with vs. 1 of 7 without rejection, and 4 of 9 biopsies with vs. none of 7 without rejection, respectively). IL-2 gene expression was detected in only 2 of 21 biopsies, both positive for rejection. IL-1, IL-4, IL-5, CD8, IFN-gamma, and TNF-alpha were not detected in any of the biopsies. TCR-beta chain mRNA was found in all biopsies, indicating the invariable presence of T cells regardless of histologic diagnosis of rejection. The aFGF gene was expressed in the majority (18 of 21) of biopsies, and its presence was not correlated with rejection. In addition to mRNA for the complete coding sequence of aFGF, two alternatively spliced mRNAs for aFGF were present in myocardial biopsies. Because aFGF and TCR beta genes were expressed in most biopsies, we determined whether aFGF mRNA was expressed in T cells; aFGF transcripts were found in 2 of 5 T-cell clones examined. Thus, aFGF mRNA in cardiac allografts may have been induced within the myocardium or elaborated by infiltrating T cells. The presence of mRNA for aFGF, a potent endothelial and smooth muscle cell mitogen, in allograft myocardium suggests that aFGF may play a role in the pathogenesis of CAV.

Alternative Splicing↗
PubMed1993

Expression of cytokine genes in human cardiac allografts: correlation of IL-6 and transforming growth factor-beta (TGF-beta) with histological rejection.

Cytokines may play critical roles in allograft rejection. Currently, a clear pattern of cytokine production that correlates with rejection has not emerged. Our preliminary studies suggested a trend toward increased IL-6 and TGF-beta gene expression in cardiac allografts during rejection. We have extended these studies using reverse transcriptase/polymerase chain reaction (RT/PCR) to detect the expression of IL-6, TGF-beta, and T cell receptor beta chain constant region (TCR-beta) genes in 21 additional consecutive myocardial biopsies obtained from six heart transplant patients and from five pre-transplant donor hearts. Cytokine gene expression was compared with histological diagnosis of rejection. There was strong correlation between IL-6 as well as TGF-beta gene expression, and histological rejection (6/8 biopsies with versus 0/7 without rejection (P = 0.006) and 7/9 biopsies with versus 0/7 without rejection (P = 0.003) respectively). Neither IL-6 nor TGF-beta transcripts were detected in any pre-transplant donor heart. TCR-beta chain mRNA was found in all allograft biopsies regardless of the presence of rejection, but was absent in pre-transplant donor hearts. Our results indicate that expression of IL-6 and TGF-beta is highly correlated with allograft rejection and thus may play an important role in regulation of cardiac allograft rejection. T cell infiltration of allografted myocardium is invariably detected by PCR regardless of histological rejection. The long-term functional significance of these cells in transplanted hearts needs further investigation.

Base Sequence↗
PubMed1990

Effects of bile salt supplementation on biliary secretion in estrogen-treated rats.

The aim of the present study was to determine whether bile acid feeding to rats can reverse ethinyl estradiol-induced cholestasis. Animals received ethinyl estradiol (2 mg/kg/day) for 6 days or were coinfused with estrogen plus various bile acids (60 mg/kg/day). Cholestasis could be significantly prevented by tauroursodeoxycholic acid, was partly corrected by ursodeoxycholic acid, and was unchanged by chenodeoxycholic acid. Total bile salt secretion was increased in every group. The secretion of the major primary bile acids (cholic acid and beta-muricholic acid) was restored to a large extent in rats supplemented with tauroursodeoxycholate but not in chenodeoxycholate-fed rats. In the former group, the canalicular transport of taurocholate and the bile salt pool size were identical with those of control rats. The hydrophilic-hydrophobic balance of the administered bile salt species appears to be an essential factor in the restoration of bile secretion, the more hydrophilic bile salt having the more hepatoprotective effect.

Journal Article↗
PubMed1989

Dissolution of human brown pigment biliary stones.

The chemical dissolution of human brown pigment stones was studied using various monophasic multicomponent solvents. Among the nine solutions tested for stone powder dissolution capacity, the two most active were retained for further analysis. The solvent containing 26 mM ethylenediaminetetraacetate, 40 mM sodium deoxycholate, 10 mM monoolein and 30% dimethylsulfoxide was efficient for calcium and bilirubin solubilization. The other solvent containing dimethylsulfoxide/methyl tert-butyl ether (70:30) had a high capacity for dissolution of cholesterol and bilirubin. From in vitro stone dissolution experiments, we found that alternating treatment every 2 h with these two mixtures was more effective than using these solvents separately. Within 24 h, 90% of cholesterol, 80% of bilirubin, and 70% of calcium were dissolved. In vivo, we studied the dissolution of human stones surgically implanted in the gallbladder of 6 rabbits. Alternating perfusions with the solvents selected led to complete disappearance of stones within 16 h in 5 out of 6 cases. The residual histological toxicity in the gallbladder wall, 15 days after perfusion, was low and blood parameters did not differ from the normal values.

Animals↗
PubMed1989

Haemorheological study during the process of tumor development after subcutaneous transplantation of mouse forestomach carcinoma (FC) cells.

A metastatic tumor model of mouse forestomach carcinoma (FC) was used in this study. Tumor cells were subcutaneously transplanted into right costal region of inbred 615-strain mice. Animals were killed on the 3rd, 6th, 9th, 12th and 15th day. Histological and haemorheological examinations were performed. Based on the histological findings the development of the tumor was divided into 5 stages; i.e. latent stage, invasive stage, early stage of metastasis, middle stage of metastasis and late stage of metastasis, corresponding with 3rd, 6th, 9th, 12th and 15th day after transplantation of mouse forestomach carcinoma. Results of haemorheological studies indicated that plasma and blood viscosity elevated in the invasion and early metastatic stages and the increased viscosity of blood was able to promote metastasis during the early stage of tumor development, while the tumor developed in the middle and late metastatic stages when the values of plasma viscosity, blood viscosity, aggregation of red blood cells and haematocrit decreased but the rigidity of red blood cells increased in these periods.

Animals↗
PubMed1988

Dissolving agents of human mixed cholesterol stones.

Methyl tert-butyl ether which is a powerful cholesterol monohydrate solvent does not completely dissolve mixed cholesterol gallstones when directly infused into the biliary tree. In this work, we compared the effect of various solvents containing different proportions of methyl tert-butyl ether and dimethylsulfoxide in anhydrous and aqueous systems on the in vitro solubilization of human cholesterol stones. The dissolution rates of cholesterol obtained in the presence of methyl tert-butyl ether was markedly decreased when 10 p. 100 water was added. In contrast, the addition of dimethylsulfoxide (30 p. 100) to methyl tert-butyl ether-water system enhanced the stone-solvent contact, improved the cholesterol dissolution rates and left less stone debris. A subsequent dissolution with an alkaline, pH = 8.8, aqueous dimethylsulfoxide-ethylenediaminetetraacetic acid solution strongly reduced the non cholesterol residues. In vivo, nearly complete dissolution of human cholesterol stones implanted in the gallbladder of rabbits was obtained within 8 hours when methyl tert-butyl ether/dimethylsulfoxide (70/30) solvent was infused at a rate of 0.6 ml/h/kg. With methyl tert-butyl ether, only 84 p. 100 of the original stone weight was dissolved. The infusion of these solvents leads to morphological changes in the gallbladder wall with some focal ulcerations. These alterations can be almost completely recovered after two weeks. No histologic evidence of hepatic, duodenal or renal damage was found. We conclude that the mixture methyl tert-butyl ether/dimethylsulfoxide (70/30) constitutes a good solvent for mixed cholesterol stones. Compared with pure methyl tert-butyl ether, the mixed system allows for a more rapid and a more complete dissolution of gallstones.

Animals↗
PubMed1984

[Use of acyclovir in the prevention of herpes infections after allogenic bone marrow grafts].

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.

Acyclovir↗
PubMed1983

Prophylaxis of herpes infections after bone-marrow transplantation by oral acyclovir.

In a double-blind controlled study, oral acyclovir was compared with placebo in 39 consecutive patients undergoing bone-marrow transplantation. Acyclovir was given at a dose of 200 mg every 6 h from 8 days before to 35 days after bone-marrow transplantation. Pharmacokinetic studies showed good absorption of the drug, despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease. There was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group compared with the placebo group even in patients with high anti-HSV antibody titres before transplantation. The same protection was observed against cytomegalovirus (CMV) infection. The frequencies of HSV and CMV infections were the same in both groups after the cessation of treatment.

Acyclovir↗
PubMed1983

Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation.

In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.

Acyclovir↗