Biomedical subjects

T Zhou

Publications and source records attributed to T Zhou.

At least 163 records · Page 9Linked to original sources

PubMed1995

Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis.

Protein tyrosine dephosphorylation after Fas cross-linking occurred in Fas apoptosis-sensitive CEM-6 cells but not in Fas apoptosis-resistant MOLT-4 cells, and apoptosis in the CEM-6 cells could be inhibited by the protein tyrosine phosphatase inhibitor, pervanadate. The time course and level of dephosphorylation were correlated with increased hematopoietic cell protein tyrosine phosphatase (HCP) activity, but not with the activity of two other tyrosine phosphatases. The level of expression of HCP was correlated with Fas apoptosis function in eleven human and murine Fas-positive lymphoid cell lines. Expression of recombinant HCP in the MOLT-4 cell line converted this Fas apoptosis-resistant cell line to Fas apoptosis sensitive. HCP-mutant mev/mev mice exhibited increased expression of Fas but decreased Fas-mediated apoptosis function in lymphoid organs after anti-mouse Fas antibody treatment in vivo. Thus, HCP-mediated protein dephosphorylation is involved in the delivery of the Fas apoptosis signal in lymphoid cells.

Animals↗

PubMed1995

[Adjuvant chemotherapy in advanced squamous cell carcinoma of the head and neck].

A prospective randomized study in a total of 36 patients with previously untreated advanced squamous cell carcinomas of the head and neck was performed. 20 patients were in group of 120-hour continuous infusion 5-Fu and bolus cisplatin (continuous group). Over-all response rates of continuous group were 90% (complete response 20%, partial response 70%) and of conventional group were 43.8% (6.3%, 37.5%). The differences in the over-all response rates of two groups were statistically significant at P = 0.0039. There was no difference between the two chemotherapy toxicity (P > 0.05), and the toxicity was clinically acceptable. The authors concluded that two or three course of 120-hour 5-Fu continuous infusion and bolus cisplatin is highly effective and safe adjuvant treatment in patients with advanced carcinoma of the head and neck.

Adult↗

PubMed1995

[Expression of adhesion molecules on lymphocyte in patients with systemic lupus erythematosus].

Peripheral blood lymphocyte phenotype (CD3, CD4, CD8, CD20, CD45RA and CD45RO) and adhesion molecule phenotype (CD11a/LFA-1 alpha, CD18/LFA-1 beta and CD54/ICAM-1) were investigated in 35 patients with systemic lupus erythematosus (SLE) by using flow cytometric analysis and dual immunofluorescence staining method. Results demonstrated increase in CD8+ cell and decrease in CD4+ cell, CD4+/CD8+, and CD4+/CD45RA+ cell, as well as decrease in expression of CD11a and CD18 on CD4+ cell surface, Expression of CD11a and CD18 on CD8+ cell, and CD54 on CD20+ cell increased, Moreover, increase in CD18 on CD8+ cell correlated inversely with decrease in CD4+ CD45RA+ cell (P < 0.05) and positively with increase in CD54 on CD20+ cell (P < 0.01). These data suggest that adhesion molecule LFA-1 and ICAM-1 may play an important role in the pathogenesis of SLE.

Adolescent↗

PubMed1995

Molecular and genetic epidemiology of hepatocellular carcinoma: studies in China and Senegal.

To identify environmental, viral, and genetic factors that may influence the risk of developing hepatocellular carcinoma (HCC), large prospective studies are being conducted in Haimen City, China and Senegal, and a case-control study of genetic variation in the detoxification of aflatoxin-B1 was carried out in Shanghai, China. Analysis of 78 HCCs that have occurred among 51,020 men enrolled in a large prospective study in Haimen City, China showed a strong association of HCC with chronic hepatitis B virus (HBV) infection. There were also significant associations of HCC risk with occupation (farming), history of a clinical episode of hepatitis in adulthood, and a family history of HCC. Study of 52 HCC cases and 116 controls for genetic polymorphisms and HCC risk showed a significant association with epoxide hydrolase (EPHX) mutant alleles (1/2, 2/2) and a borderline association with homozygous deletion of the glutathione-S-transferase mu (GSTM1) gene. There was a multiplicative interaction of these polymorphisms with chronic HBV infection such that HBsAg-positive persons who were GSTM1 null and were EPHX 1/2 or 2/2 had 135 times the risk of HCC as HBsAg-negative persons with the wild type genotypes for GSTM1 and EPHX. The risk of HCC is not uniform among persons with chronic HBV or HCV infections. Studies of genetic, viral, and environmental interactions may permit identification of those individuals at highest risk within groups at increased risk of HCC. Prevention strategies could then be targeted at those individuals.

Aflatoxin B1↗

PubMed1994

Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule.

Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. Molecular cloning and nucleotide sequence analysis revealed a human Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the transmembrane domain because of the deletion of an exon encoding this region. The expression of soluble Fas was confirmed by flow cytometry and immunocytochemical analysis. Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas. Levels of soluble Fas were elevated in patients with systemic lupus erythematosus, and mice injected with soluble Fas displayed autoimmune features.

Amino Acid Sequence↗

PubMed1994

Correction of accelerated autoimmune disease by early replacement of the mutated lpr gene with the normal Fas apoptosis gene in the T cells of transgenic MRL-lpr/lpr mice.

MRL-lpr/lpr mice develop a generalized autoimmune disease which includes increased autoantibody production, glomerulonephritis, and development of lymphadenopathy. The lpr genetic defect has been identified as a mutation in the Fas apoptosis gene that results in low expression of Fas mRNA. To determine the significance of the lpr mutation and T cells in the development of the autoimmune disease, we constructed transgenic MRL-lpr/lpr mice using a full-length murine Fas cDNA under the regulation of the T-cell-specific CD2 promoter and enhancer. Here we show that the early correction of the lpr gene defect in T cells eliminates glomerulonephritis and development of lymphadenopathy and decreases the levels of autoantibodies. In this model, early correction of the lpr defect in T cells is sufficient to eliminate the acceleration of autoimmune disease even in the presence of B cells and other cells that express the mutant lpr gene.

Animals↗

PubMed1994

T cell influence on superantigen-induced arthritis in MRL-lpr/lpr mice.

OBJECTIVE: To define the influence of the T cell receptor (TCR) and the lpr autoimmune gene on the induction and progression of superantigen-induced arthritis in V beta 8 transgenic MRL-lpr/lpr mice. METHODS: The time to onset and the extent of synovial hyperplasia after the induction of arthritis by intraarticular injection of staphylococcal enterotoxin B (SEB) were compared in mice having T cells that bear the V beta 8 transgene alone (V beta 8 TCR transgenic MRL-+/+), the lpr gene without the V beta 8 gene (nontransgenic MRL-lpr/lpr), both the V beta 8 gene and the lpr gene (V beta 8 transgenic MRL-lpr/lpr), or neither gene (nontransgenic MRL-+/+). Synovial hyperplasia was compared in SEB-injected V beta 8 transgenic MRL-lpr/lpr mice after treatment with cyclosporin A (CSA), anti-V beta 8 and anti-CD4 monoclonal antibodies, and in V beta 8 transgenic MRL-lpr/lpr mice after injection of a non-V beta 8-reactive superantigen, staphylococcal enterotoxin A (SEA). RESULTS: At day 30, increased synovial cells were observed in all SEB-treated mice, but the increase was greatest in the V beta 8 transgenic MRL-lpr/lpr mice. T cell involvement was indicated by the inability of either heat-denatured SEB or SEA to induce severe arthritis, the reduction in the severity of the arthritis on systemic treatment with CSA or anti-V beta 8, and the correlation of synovial hyperplasia with in vitro SEB reactivity of T cells. CONCLUSION: These observations suggest that superantigens can induce chronic arthritis and that the induction and progression of the arthritis requires an underlying T cell defect in anergy induction in addition to exposure to the superantigen.

Animals↗

PubMed1994

Autoimmune disease. A problem of defective apoptosis.

Human autoimmune diseases share the common feature of an imbalance between the production and destruction of various cell types including lymphocytes (SLE), synovial cells (RA), and fibroblasts (scleroderma). Patients with SLE have increased levels of soluble Fas that inhibit proper apoptosis of lymphocytes. In animal models of autoimmune diseases, mutations of genes involved in apoptosis including Fas, Fas ligand, and the hematopoietic cell phosphatase gene have been identified. Oncogenes, including bcl-2, p53, and myc, that regulate apoptosis are also expressed abnormally. Potent inducers of apoptosis including steroids, azathioprine, cyclophosphamide, and methotrexate are the most efficacious therapies for autoimmune disease currently known. Specific therapies that induce apoptosis without incurring side effects should improve treatment of autoimmune disease.

Antigens, Surface↗

PubMed1994

T cells of staphylococcal enterotoxin B-tolerized autoimmune MRL-lpr/lpr mice require co-stimulation through the B7-CD28/CTLA-4 pathway for activation and can be reanergized in vivo by stimulation of the T cell receptor in the absence of this co-stimulatory signal.

The CD28/CTLA-4 receptors on T cells interact with the B7 molecule on antigen-presenting cells (APC) to produce a co-stimulatory signal that determines the outcome of activation. The role of this co-stimulatory signal in T cell activation and loss of tolerance in autoimmune MRL-lpr/lpr mice has not been investigated previously. The present study examines the contribution of the CD28/CTLA-4 co-stimulatory pathway to the loss of T cell tolerance in V beta 8 transgenic MRL-lpr/lpr and (-)+/+ mice in which neonatal tolerance has been induced by the superantigen staphylococcal enterotoxin B (SEB). An artificial APC transfected with the murine B7 gene, and a CTLA-4-Ig fusion protein were used to analyze the significance of the CD28/CTLA-4 pathway in vitro. The CTLA-4-Ig fusion protein was also used to inhibit the pathway in vivo. Our results demonstrate that CD28 and CTLA-4 mRNA was overexpressed in the lymph nodes of lpr/lpr mice (MRL, C57BL/6, C3H and AKR), but not in +/+ mice of the same background strain. Lymph node T cells and thymocytes from SEB neonatally tolerized MRL-lpr/lpr mice that had undergone tolerance loss, proliferated when cultured with SEB and B7+ fibroblasts in vitro, but did not proliferate when the SEB was presented in the context of B7- fibroblasts. This in vitro tolerance loss could be prevented by blocking of B7 signaling by CTLA-4-Ig. This loss of tolerance did not occur in lymph node T cells from thymectomized MRL-lpr/lpr mice. SEB challenge of tolerized MRL-lpr/lpr mice in vivo led to weight loss, increased serum cytokine levels and depletion of V beta 8+ T cells. These effects were blocked by blocking of the co-stimulatory pathway by treatment with the CTLA-4-Ig fusion protein prior to and during challenge with SEB. T cells from thymus and lymph nodes of these mice did not proliferate later in response to stimulation in vitro with SEB even in the presence of B7+ APC. Nonresponsiveness was not due to deletion of V beta 8+ CD28+ T cells, as the number of these cells was increased after treatment with SEB and the CTLA-4-Ig fusion protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Abatacept↗

PubMed1994

Defective clonal deletion and anergy induction in TCR transgenic lpr/lpr mice.

Although autoreactive T cells are thought to play a prominent role in autoimmune disease in MRL-lpr/lpr mice, it has been difficult to directly determine if autoreactive T cells escape from the thymus and react with self-antigens in the periphery. To identify a possible defect in clonal deletion or clonal anergy induction of auto-specific T cells, we have studied C57BL/6-lpr/lpr transgenic mouse expressing TCR genes that recognize a known self-antigen, the male H-Y antigen and analyzed clonal deletion and tolerance induction after neonatal tolerance induction with the class II MHC reactive superantigen staphylococcal enterotoxin B (SEB) in V beta 8 TCR transgenic and non-transgenic MRL-lpr/lpr mice. In lpr/lpr mice, the main defect was a thymic-dependent loss of self-tolerance by auto-specific T cells and also a small defect of clonal deletion of autoreactive thymocytes. Defective expression of the Fas apoptosis antigen results from the insertion of the ETn retrotransposon. The fas defect can be partially corrected in TCR-beta TCR transgenic mice in which accelerated T cell development prevents the lymphoproliferative disease and in CD2-fas transgenic mice in which fas expression is corrected in T cells. These results suggest that expression of the TCR-beta, fas and retrovirus genes are co-regulated during early thymocyte development, most likely by common enhancer transcription factors.

Animals↗

PubMed1994

Heparin potentiation of the effect of acidic fibroblast growth factor on astrocytes and neurons.

Acidic fibroblast growth factor (aFGF) could stimulate the proliferation of astrocytes and promote the survival of neurons from newborn rat brain in vitro. The effects of aFGF on both astrocytes and neurons were significantly potentiated by heparin. The effect of aFGF (2 ng/ml) with heparin (10 mu g/ml) on the survival of neurons was a hundredfold more potent than that of aFGF (200 ng/ml) without heparin.

Animals↗

PubMed1994

Apoptosis defects analyzed in TcR transgenic and fas transgenic lpr mice.

Although autoreactive T cells are thought to play a prominent role in autoimmune disease in MRL-lpr/lpr mice, it has been difficult to directly determine if autoreactive T cells escape from the thymus and react with self-antigens in the periphery. Defective expression of the Fas apoptosis antigen in MRL-lpr/lpr mice results from the insertion of the ETn retrotransposon. The fas defect can be partially corrected in CD2-fas transgenic mice in which the expression of fas is corrected in T cells. To identify a possible defect in clonal deletion or clonal anergy induction of auto-specific T cells, we have studied C57BL/6-lpr/lpr transgenic mice that express TcR genes that recognize a known self-antigen, the male H-Y antigen. In addition, we have analyzed clonal deletion and tolerance induction after neonatal tolerance induction and superantigen-induced arthritis with the class II MHC reactive superantigen staphylococcal enterotoxin B (SEB) in V beta 8 TcR transgenic and non-transgenic MRL-lpr/lpr mice. Neonatal tolerance induction to SEB was normal in lpr/lpr mice. However, over time a loss of tolerance (thymic or peripheral) was observed in lpr/lpr mice but not in +/+ TcR transgenic mice. This defect in lpr/lpr mice was thymic-dependent and was due to increased CD28/CTLA4 signaling. These results suggest that an apoptosis defect involving both thymocytes and peripheral lymphoid cells leads to autoimmune disease in lpr/lpr mice. The challenge in the future will be to determine the role of defective apoptosis in other autoimmune diseases.

Animals↗

PubMed1994

Studies on the condition of fermentation of pullulan by Aureobasidium pullulans.

Studies on optimal conditions for pullulan fermentation based on the results obtained from a shaking flask were carried out in a 16-L auto-controlling fermentor. It found that the optimal DE value of starch hydrolyzate was 40-50 when 10% starch hydrolysate was used as carbon source. The optimal concentration of ammonium sulfate in the medium for fermentation was different from that of the shaking flask. The fermentation kinetics and effects of seed age, seed volume, airflow rate, pressure of tank, agitation speed and number of vane group on the production of pullulan were investigated.

Biomass↗

PubMed1993

Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene.

The MRL-lpr/lpr mouse strain is a model of systemic autoimmune disease. In this model, intrinsic defects of intrathymic T cell development include defective deletion of self-reactive T cells and expression of endogenous retroviruses. Defective deletion of self-reactive T cells in the thymus has been proposed to be due to germline mutation in the Fas apoptosis gene. Using different fragments of a Fas cDNA probe, we determined that the lpr/lpr mutation is a 5.3-kb insertion of DNA within the second intron of the Fas gene. cDNA corresponding to this region was then derived from thymic RNA from MRL-lpr/lpr and MRL- +/+ mice using the polymerase chain reaction. All thymic RNA samples from MRL-lpr/lpr mice yielded a unique product that was 168 bp larger than that of MRL- +/+ mice. Complete sequence analysis indicated that this inserted sequence had 98% homology with a sequence from the 3' long terminal repeat of the early transposon (ETn). RNA analysis indicated higher expression of ETn RNA in the thymus of MRL-lpr/lpr than MRL- +/+ mice. The interdependence of ETn expression and abnormal Fas expression was then analyzed in a CD2-Fas transgenic mouse model in which a full-length murine Fas cDNA under the regulation of the CD2 promoter and enhancer was used to correct defective Fas expression in T cells of MRL-lpr/lpr mice. In these mice, reduced thymic ETn expression was observed, confirming that high ETn expression is related to abnormal Fas expression. These results establish a link between endogenous retrovirus expression, abnormal Fas expression, and autoimmune disease.

Amino Acid Sequence↗

PubMed1993

7S nerve growth factor has different biological activity from 2.5S nerve growth factor in vitro.

It is considered that two molecular forms of nerve growth factor (NGF), that is 7S NGF and 2.5S NGF have the identical neurotrophic effect on neurons. We now report that 7S NGF has different biological activities from 2.5S NGF in vitro. 7S NGF could promote the survival and neurite outgrowth of neurons from newborn rat hippocampus, cortex and cerebellum and stimulate the proliferation of astrocytes in vitro, but 2.5S NGF had no such effect.

Animals↗

PubMed1993

Origin of CD4-CD8-B220+ T cells in MRL-lpr/lpr mice. Clues from a T cell receptor beta transgenic mouse.

Abnormal development of T cells in the thymus is thought to be related to autoimmune disease and the expansion of the unusual CD4-CD8-B220+ peripheral T cel subset that results in lymphadenopathy in MRL-lpr/lpr mice. Although we and others have previously shown that rearranged TCR-transgenes alter T cell development in the thymus and abrogate lymphoproliferative disease in lpr mice, the origin and developmental pathway of the LN CD4-CD8-B220+ T cells has not been fully elucidated. We therefore undertook the systematic analysis of the effect of a TCR-beta transgene on the production and differentiation of (lymph node) LN T cells and the production, differentiation, and release of thymocyte T cell populations. In nontransgenic mice, there was increased proliferation of CD4-CD8-B220+ T cells in the LN of adult MRL-lpr/lpr mice compared to MRL(-)+/+ mice, as measured by in vivo BrdU labeling. These proliferating LN T cells were greatly reduced by thymectomy of adult MRL-lpr/lpr mice 1 wk before bromodeoxyuridine labeling, indicating that recent thymic emigrants or factors were required to sustain proliferation. In the thymus, there was increased production and accumulation of CD4+CD8+TCRdull thymocytes in nontransgenic MRL-lpr/lpr compared to MRL(-)+/+ mice. As the rate of maturation from CD4+CD8+TCRdull to CD4+CD8+TCRbright was the same (6%) in both MRL-lpr/lpr and MRL(-)+/+ mice, the accumulation of the immature population in the MRL-lpr/lpr mice could not be due to a maturation defect. However, there was a decrease in apoptosis and intrathymic death of CD4+CD8+TCRdull thymocytes in MRL-lpr/lpr compared to MRL(-)+/+ mice. Introduction of the TCR-beta transgene into lpr/lpr mice normalized the proliferation of T cells in the LN. In the thymus, the TCR-beta transgene resulted in a dramatic increase in maturation efficiency and a reduction in apoptosis in MRL(-)+/+ mice. These data suggest that the TCR transgene inhibits lymphoproliferation by reducing the production of "neglected" CD4+CD8+TCRdull thymocytes that will undergo Fas Ag-mediated apoptosis. They further suggest that in lpr mice, which express a mutated Fas Ag, the "neglected" thymocytes are able to continually escape to the periphery, where they proliferate.

Animals↗

PubMed1993

A comparison of the inhibitory effects of sodium nitroprusside, pinacidil and nifedipine on pressor response to NG-nitro-L-arginine.

1. The inhibitory effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on mean arterial pressure (MAP) responses to NG-nitro-L-arginine (L-NNA) (NO synthase inhibitor), angiotensin II (AII) and noradrenaline (NA) were compared with those of pinacidil (KATP channel opener) and nifedipine (L-type calcium antagonist) in conscious, unrestrained rats. 2. Intravenous bolus injections of L-NNA (1-64 mg kg-1), AII (0.02-1.28 micrograms kg-1) and NA (0.25-16 micrograms kg-1) dose-dependently increased MAP to similar maxima. Intravenous infusions of SNP (1, 4 and 16 micrograms kg-1 min-1) dose-dependently increased ED20S of L-NNA, AII and NA. However, the maximum response evoked by L-NNA, but not by AII nor NA, was dose-dependently reduced by SNP. Moreover, the inhibitory effect of SNP on the pressor response to L-NNA ceased when the infusion of SNP was terminated. 3. Pinacidil (80 micrograms kg-1 min-1 for 30 min followed by 5 micrograms kg-1 min-1) increased ED50S of L-NNA, AII and NA but did not decrease the maximum responses to any of these agents. 4. Nifedipine (1 mg kg-1 min-1) non-selectively reduced maximum responses to L-NNA, AII and NA to similar levels and increased ED50S of AII and NA but not L-NNA. 5. The results show that SNP causes a selective, non-competitive and reversible inhibition of the pressor response to L-NNA. This inhibition by SNP is unlikely to be related to hypotension, the opening of ATP-sensitive potassium channels or blockade of L-type calcium channels.

Angiotensin II↗

PubMed1993

Characterization of recombinant human acidic fibroblast growth factor: comparative studies with bovine acidic fibroblast growth factor.

Recombinant human acidic fibroblast growth factor (haFGF) was purified from E. coli lysate by heparin-sepharose affinity chromatography. The purified haFGF exhibited potent mitogenic activity in stimulating DNA synthesis in 3T3 cells and this activity could be significantly increased by heparin. By analysis of mitogenic activity and immunological properties, a marked difference was found between haFGF and bovine aFGF (baFGF). The main difference was that the heparin-dependence of haFGF was stronger than that of baFGF.

3T3 Cells↗