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Biomedical subjects

X Cao

Publications and source records attributed to X Cao.

At least 181 records · Page 10Linked to original sources
PubMed1999

Partial left ventriculectomy for the treatment of end-stage dilated cardiomyopathy.

OBJECTIVE: To report our initial experience of the first 5 cases of partial left ventriculectomy (PLV or Batista operation), a new surgical therapy for treatment of end-stage dilated cardiomyopathy in China. METHODS: From April to August 1998, 5 patients with idiopathic dilated cardiomyopathy received PLV at Anzhen Hospital. The mean age of the patients was 48.4 years (range: 42 to 53 years). Three patients were in New York Heart Association (NYHA) class III and 2 in class IV. All patients had mitral valve insufficiency (3 moderate and 2 severe) and 1 had severe tricuspid valve insufficiency in addition preoperatively. Cardiopulmonary bypass and cardiac arrest with cold blood cardioplegia were used in all patients. The average weight of the resected left ventricle muscle was 46.3 g. All patients underwent mitral annuloplasty and 1 plus tricuspid annuloplasty (De Vega). RESULTS: Echocardiography demonstrated a significant decrease in left ventricular diastolic diameter (8.4 +/- 1.1 cm to 5.4 +/- 0.4 cm, P < 0.01) and an increase in ejection fraction (17.78% +/- 6.26% to 34.82% +/- 3.18%, P < 0.025). One patient died of heart failure on the 6th postoperative day. The mean follow-up period of the 4 discharged patients were 4 months (from 3 to 6 months). One were in NYHA class I and 3 in class II; all had a normal life. CONCLUSION: Batista operation is a new and valuable alternative of the surgical treatment for end-stage dilated cardiomyopathy and the long-term results need further studies.

Adult↗
PubMed1999

[Expression of CDK4 protein in oral carcinogenesis].

OBJECTIVE: To study the expression of cyclin dependent kinase 4(CDK4) protein in oral carcinogenesis. METHODS: An LSAB immunohistochemistry method was applied to 80 cases of paraffine-fixed tissues to study the expression and distribution of CDK4 in normal oral mucosa, oral premalignant lesion (OPL) and oral squamous cell carcinoma. RESULTS: The overexpression of CDK4 protein was observed in the progression of OPL. Meanwhile, a correlation analysis was applied to investigate the relationship between P16 and CDK4 expression, and the result showed that the coefficient of correlation was 0.813, which was statistically significant. CONCLUSION: The overexpression of CDK4 is involved in the progression of OPL, and there is a positive feedback loop between CDK4 and P16.

Cyclin-Dependent Kinase 4↗
PubMed1999

[Rat submandibular gland tumor induced by 3-methylcholanthrene].

OBJECTIVE: To study the genesis and the development of salivary gland tumor (SGT). METHODS: SGT animal models were established by injection of 3-methylcholanthrene (3-MCA) oil solution into 40 submandibular glands of Sprague-Dawley (SD) rats, then histopathology and ultrastructure of induced tumors were observed under microscope, and immunohistochemical detection of keratin and actin was carried out. RESULTS: 32 models of submandibular gland tumors were induced successfully, with 4 rats of squamous cell carcinoma and 28 leiomyosarcoma, and the carcinogenesis of 3-MCA and tissue genesis of induced tumors were discussed. CONCLUSION: Submandibular gland tumor can be induced by 3-MCA, and sarcoma was of high incidence.

Animals↗
PubMed1999

[Effects of IFN-gamma gene-modified hepatocytes on TGF-beta 1 and its receptor in mice infected with Schistosoma japonicum].

AIM: To explore the anti-schistosomal hepatic fibrosis effect and the changes in transforming growth factor-beta 1 (TGF-beta 1) and its receptors (TGF-beta RII) in S. japonicum infected mice after intrasplenic transplantation of gamma-interferon (IFN-gamma) gene-modified hepatocytes. METHODS: At 16 wk after infection with cercariae of Schistosoma japonicum, the mice were intrasplenically transplantated with murine hepatocytes which had been transfected with IFN-gamma gene-combinant adenovirus vector. ELISA, immunohistochemical and dot blot techniques were used to observe the dynamic changes in IFN-gamma, TGF-beta 1, TGF-beta RII and type I, III collagen. RESULTS: The intrasplenic transplantation of IFN-gamma gene modified hepatocytes effectively expressed IFN-gamma and obviously reduced the production and deposition of type I, III collagen as well as TGF-beta 1 and TGF-beta RII. CONCLUSION: IFN-gamma gene transplantation has anti-hepatic fibrosis efficacy in Schistosoma japonicum-infected mice, being related to its role of decreasing the expression of TGF-beta 1 and TGF-beta RII.

Animals↗
PubMed1999

[Operative approach choosing to treat cholesteatoma otitis media (with clinical analysis of 860 cases)].

OBJECTIVE: In order to improve operative effect to cholesteatoma otitis media. METHOD: The clinical data of 860 cases of patients with cholesteatoma otitis media were treated by surgery through three approachs (through epitympanum, cribriform area or combined approach) were analyzed. RESULT: The results showed that the recurrent rates of them were 10%, 11% and 6% respectively; The rates of improvement of hearing were 56%, 40% and 69% five years after operation respectively, and after 5 to 15 years were 45%, 35% and 62%; The rates of different abnormal shapes of tympanic membrane (including retraction, adherence and perforation) were 43%, 47% and 12%. CONCLUSION: According to the location of foci, we regard that various and appropriate operative approach should be selected to treat the cases with cholesteatoma otitis media, and the combined approach tympanoplasty has advantage over the other two.

Adolescent↗
PubMed1998

Repression of Stat3 activity by activation of mitogen-activated protein kinase (MAPK).

STAT proteins are activated by phosphorylation at specific tyrosine residue at the carboxy-terminus which is required for dimer-formation, nuclear translocation, DNA binding and transcriptional activity in cells treated with cytokines and growth factors. Recent studies have indicated that STATs are also phosphorylated by MAPK, or extracellular signal-regulated kinase (ERK) on serine. We investigated the role of ERK on the regulation of STAT activity. Here, we report that ERK2 activated by its upstream kinase, MEK1, represses Stat3 transcriptional activity induced by Src or Jak-2. To unravel the mechanism of repression, we further showed that Stat3 DNA binding activity and its tyrosine phosphorylation are also inhibited under the same conditions. ERK2 phosphorylates Stat3 on three serine-containing peptides and decreases its tyrosine phosphorylation induced by EGF treatment. We also detected an association of ERK2 and Stat3 in vivo which is modulated positively by activation of ERK2, but negatively by Jak2. We propose that MAP kinase cascade may negatively regulate Stat3 activities by decreasing its tyrosine phosphorylation and also possibly by association.

3T3 Cells↗
PubMed1998

Lymphotactin gene-modified bone marrow dendritic cells act as more potent adjuvants for peptide delivery to induce specific antitumor immunity.

Dendritic cells (DC) are regarded as attractive candidates for cancer immunotherapy. Our aim is to improve the therapeutic efficacy of DC-based tumor vaccine by augmenting DC preferential chemotaxis on T cells. Mouse bone marrow-derived DC were transduced with lymphotactin (Lptn) gene by adenovirus vector. The supernatants from Lptn gene-modified DC (Lptn-DC) were capable of attracting CD4+ and CD8+ T cells in a chemotaxis assay, whereas their mock control could not. Lptn expression of Lptn-DC was further confirmed by RT-PCR. Lptn-DC were pulsed with Mut1 peptide and used for vaccination. Immunization with the low dose (1 x 10(4)) of Mut1 peptide-pulsed DC induced weak CTL activity, whereas the same amounts of Mut1 peptide-pulsed Lptn-DC markedly induced specific CTL against 3LL tumor cells. A single immunization with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC could render mice resistant to a 5 x 10(5) 3LL tumor cell challenge completely, but their counterpart could not. The protective immunity induced by Mut1 peptide-pulsed Lptn-DC depends on both CD4+ T cells and CD8+ T cells rather than NK cells in the induction phase and depends on CD8+ T cells rather than CD4+ T cells and NK cells in the effector phase. Moreover, the involvement of CD28/CTLA4 costimulation pathway and IFN-gamma are also necessary. When 3LL tumor-bearing mice were treated with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC, their pulmonary metastases were significantly reduced, whereas the same low dose of Mut1 peptide-pulsed DC had no obvious therapeutic effects. Our data suggest that Lptn-DC are more potent adjuvants for peptide delivery to induce protective and therapeutic antitumor immunity.

Adenoviridae↗
PubMed1998

Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines.

Dendritic cells (DCs) are the most effective APCs and are being studied as natural adjuvants or Ag delivery vehicles to elicit T cell-mediated antitumor immunity. This study examined whether inoculation of DCs fused with poorly immunogenic tumor cells elicited tumor-reactive T cells for adoptive immunotherapy. DCs derived from bone marrow of C57BL/6 (B6) mice were fused with syngeneic B16 melanoma or RMA-S lymphoma cells by polyethylene glycol. The B16/DC and RMA-S/DC fusion hybrids expressed MHC class I, class II Ags, costimulatory molecules, as well as DC-specific and tumor-derived surface markers. The tumor/DC hybrids were capable of processing and presenting tumor-derived Ags, and immunization of B6 mice with irradiated B16/DC or RMA-S/DC vaccine elicited tumor-specific CTL activities. Vaccination of B6 mice with irradiated B16/DC fusion preparations induced partial host protective immunity against B16 tumor challenge. Reduced tumor incidence and prolonged survival time were observed. Adoptive transfer of T cells derived from B16/DC vaccine-primed lymph nodes into B16 tumor-bearing mice greatly reduced the number of established pulmonary metastases with or without in vivo administration of IL-2. Moreover, adoptive transfer of RMA-S/DC vaccine-primed, cultured lymph node T cells eradicated disseminated FBL-3 tumor. The results demonstrate that tumor/DC fusion products are effective cellular vaccines for eliciting T cell-mediated antitumor immunity.

Adoptive Transfer↗
PubMed1998

Nitric oxide-dependent induction of glutathione synthesis through increased expression of gamma-glutamylcysteine synthetase.

The nitric oxide (NO) donors S-nitrosopenicillamine or DetaNONOate, which release NO at a rate of 0-15 nM sec-1, were exposed to rat aortic vascular smooth muscle cells for a period of 0-24 h. This treatment resulted in an increase in total glutathione levels of two- to threefold under conditions where no cytotoxicity was detected. The signaling pathways do not involve activation of protein kinase G Ialpha nor are they cGMP dependent. Oxidation of reduced glutathione (GSH) was found after exposure to NO for 3-4 h at rates of formation at or above 8 nM sec-1. Increased intracellular GSH was due to enhanced expression of the rate-limiting enzyme for GSH synthesis, gamma-glutamylcysteine synthetase. Since NO has been shown previously to protect cells against oxidative stress, we propose that the increase in GSH by NO is a potential mechanism for enhancing the antioxidant defenses of the cell. This result also has important implications for identifying redox-sensitive cell signaling pathways that can be activated by NO.

Animals↗
PubMed1998

Separation and purification of 10-deacetylbaccatin III by high-speed counter-current chromatography.

High-speed counter-current chromatography (HSCCC) was used for the separation and purification of 10-deacetylbaccatin III from the needle extract of Chinese yew (Taxus chinensis). The crude needle extract (500 mg/5 ml) was first separated with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:5:2:5, v/v) and the partially purified fraction was again purified with a different solvent system composed of n-hexane-chloroform-methanol-water (5:25:34:20, v/v). HPLC analysis of the final fraction showed that the purity of 10-deacetylbaccatin (20 mg) was over 98%. The chemical structure was confirmed by fast atom bombardment MS and 1H NMR.

Chromatography↗
PubMed1998

Stress-induced immediate-early gene, egr-1, involves activation of p38/JNK1.

The Ras/Raf/MAP kinase (ERK) pathway is a major signaling pathway induced by growth factors in mammalian cells. Two other types of mammalian MAP kinases, JNK (SAPK) and p38 (RK, CSBP), are induced by environmental stress. Although the immediate-early gene, egr-1, is induced by growth factors, cytokines, differentiation signals and DNA damaging agents, less is known about its induction by environmental stress and the mechanism involved. Here we report that in NIH3T3 cells, egr-1 is induced by various stress treatments such as heat shock, sodium arsenite, ultraviolet (U.V.) radiation, and anisomycin. p38 and JNK1, but not ERK2, were activated by these stress treatments. Induction of egr-1 by anisomycin is inhibited by a specific inhibitor of p38, SB 203580. We also show that p38 and JNK1 activated by their upstream kinases induce egr-1 promoter activity through activation of the ternary complex factor, Elk-1. The stress treatments also lead to an increase in Egr-1 protein phosphorylation and its DNA binding activity. Together, our data suggest that induction of egr-1 gene by growth factors and stress are mediated through different subgroups of MAP kinases which may also differentially affect egr-1 function on its target genes.

3T3 Cells↗
PubMed1998

Sec35p, a novel peripheral membrane protein, is required for ER to Golgi vesicle docking.

SEC35 was identified in a novel screen for temperature-sensitive mutants in the secretory pathway of the yeast Saccharomyces cerevisiae (. Genetics. 142:393-406). At the restrictive temperature, the sec35-1 strain exhibits a transport block between the ER and the Golgi apparatus and accumulates numerous vesicles. SEC35 encodes a novel cytosolic protein of 32 kD, peripherally associated with membranes. The temperature-sensitive phenotype of sec35-1 is efficiently suppressed by YPT1, which encodes the rab-like GTPase required early in the secretory pathway, or by SLY1-20, which encodes a dominant form of the ER to Golgi target -SNARE-associated protein Sly1p. Weaker suppression is evident upon overexpression of genes encoding the vesicle-SNAREs SEC22, BET1, or YKT6. The cold-sensitive lethality that results from deleting SEC35 is suppressed by YPT1 or SLY1-20. These genetic relationships suggest that Sec35p acts upstream of, or in conjunction with, Ypt1p and Sly1p as was previously found for Uso1p. Using a cell-free assay that measures distinct steps in vesicle transport from the ER to the Golgi, we find Sec35p is required for a vesicle docking stage catalyzed by Uso1p. These genetic and biochemical results suggest Sec35p acts with Uso1p to dock ER-derived vesicles to the Golgi complex.

Amino Acid Sequence↗
PubMed1998

Initial docking of ER-derived vesicles requires Uso1p and Ypt1p but is independent of SNARE proteins.

ER-to-Golgi transport in yeast may be reproduced in vitro with washed membranes, purified proteins (COPII, Uso1p and LMA1) and energy. COPII coated vesicles that have budded from the ER are freely diffusible but then dock to Golgi membranes upon the addition of Uso1p. LMA1 and Sec18p are required for vesicle fusion after Uso1p function. Here, we report that the docking reaction is sensitive to excess levels of Sec19p (GDI), a treatment that removes the GTPase, Ypt1p. Once docked, however, vesicle fusion is no longer sensitive to GDI. In vitro binding experiments demonstrate that the amount of Uso1p associated with membranes is reduced when incubated with GDI and correlates with the level of membrane-bound Ypt1p, suggesting that this GTPase regulates Uso1p binding to membranes. To determine the influence of SNARE proteins on the vesicle docking step, thermosensitive mutations in Sed5p, Bet1p, Bos1p and Sly1p that prevent ER-to-Golgi transport in vitro at restrictive temperatures were employed. These mutations do not interfere with Uso1p-mediated docking, but block membrane fusion. We propose that an initial vesicle docking event of ER-derived vesicles, termed tethering, depends on Uso1p and Ypt1p but is independent of SNARE proteins.

Animals↗
PubMed1998

Accelerated recovery of irradiation-induced bone marrow depression by fibroblast-mediated interleukin 6 gene therapy in combination with bone marrow transplantation in mice.

BACKGROUND: Both fibroblast-mediated cytokine gene therapy and bone marrow transplantation (BMT) have proven to be efficient protocols for the recovery of bone marrow depression. In this report, the effects of fibroblast-mediated interleukin (IL)-6 gene therapy, in combination with BMT, on the recovery of irradiation-induced bone marrow depression were investigated. METHODS: NIH3T3 fibroblast cells engineered to secrete IL-6 (NIH3T3-IL-6) or NIH3T3 cells transduced with the neomycin gene (NIH3T3-Neo), in combination with 10(7), 10(6), or 10(5) syngeneic bone marrow cells, were implanted into irradiated mice. RESULTS: The platelets and white blood cells in the peripheral blood of the irradiated mice increased greatly 12 days after implantation of NIH3T3-IL-6 cells and BMT, the white blood cell counts were restored to a normal level 32 days after the combined therapy, and the platelet number was obviously higher than that in mice implanted with NIH3T3-Neo and BMT. Twenty and 25 days after the combined therapy, the mice showed accelerated recovery of colony-forming unit (CFU)-granulocyte/macrophages and CFU-megakaryocytes when compared with the mice implanted with NIH3T3-Neo cells and BMT. Ten days after lethal irradiation with gamma rays, the spleens formed more CFU-spleen in mice implanted with NIH3T3-IL-6 cells and BMT than in mice injected with phosphate-buffered saline or NIH3T3-Neo cells. Combined therapy with NIH3T3-IL-6 cell implantation and BMT delayed the survival period of the hematopoietic-depressed mice significantly when compared with therapy with NIH3T3-Neo cell implantation and BMT. CONCLUSIONS: These data demonstrated that the combined therapy of fibroblast-mediated IL-6 gene therapy and BMT could significantly promote the recovery of irradiation-induced hematopoietic depression.

3T3 Cells↗
PubMed1998

Effects of fibroblast-mediated interleukin 3 and interleukin 6 gene therapy on hematopoiesis in mice treated with 5-fluorouracil.

Fibroblast-mediated cytokine gene therapy has proven to be a promising strategy for restoring hematopoiesis following repeated chemotherapy. Interleukin 3 (IL-3) and interleukin 6 (IL-6) can synergistically promote the recovery of hematopoiesis following chemotherapy. In this investigation, combined use of fibroblast-mediated IL-3 and IL-6 gene therapy was tested for hematopoietic effects on mice with or without 5-fluorouracil administration. The results demonstrated that combined therapy with IL-3 gene-modified NIH3T3 cell (NIH3T3-IL-3) and IL-6 gene-modified fibroblast NIH3T3 cell (NIH3T3-IL-6) implantation achieves obvious stimulation of hematopoiesis in normal mice and accelerates recovery of hematopoiesis. In normal mice the quantities of platelets, neutrophils, and total white blood cells in peripheral blood increased significantly after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells. The numbers of colony-forming unit (CFU) granulocyte/macrophage (CFU-GM) and CFU megakaryocyte (CFU-MK) formed by stem cells in bone marrow was significantly higher after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells than after the implantation of NIH3T3-IL-3 alone, NIH3T3-IL-6 alone, or neomycin gene-modified NIH3T3 cells. In hematopoiesis-depressed mice induced by preinjection with 5-fluorouracil at the dose of 150 mg/kg before cell implantation, the platelets, neutrophils, and white blood cells showed accelerated recovery, and the numbers of CFU-GM and CFU-MK formed by bone marrow cells were also markedly higher after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells than in control groups. Our data show that combined use of fibroblast-mediated IL-3 and IL-6 gene therapy may be of clinical relevance for the recovery of hematopoietic depression for patients after chemotherapy.

3T3 Cells↗
PubMed1998

Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DL-alpha-lipoic acid.

The study was aimed at evaluating changes in lens antioxidant status, glucose utilization, redox state of free cytosolic NAD(P)-couples and adenine nucleotides in rats with 6-week streptozotocin-induced diabetes, and to assess a possibility of preventing them by DL-alpha-lipoic acid. Rats were divided into control and diabetic groups treated with and without DL-alpha-lipoic acid (100 mg x kg body weight(-1) x day(-1), i.p.). The concentrations of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione, glycolytic intermediates, malate, alpha-glycerophosphate, and adenine nucleotides were assayed in individual lenses spectrofluorometrically by enzymatic methods, reduced glutathione and ascorbate--colorimetrically, and taurine by HPLC. Free cytosolic NAD+:NADH and NADP+:NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. Sorbitol pathway metabolites were found to increase, and antioxidant concentrations were reduced in diabetic rats compared with controls. The profile of glycolytic intermediates (increase in glucose 6-phosphate and fructose 6-phosphate, decrease in fructosel,6-diphosphate, increase in dihydroxyacetone phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate, and no change in lactate), and 5.9-fold increase in alpha-glycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD+:NADH ratios, ATP levels, ATP/ADP x inorganic phosphate (Pi), and adenylate charge were reduced in diabetic rats while free cytosolic NADP+:NADPH ratios were elevated. Diabetes-induced changes in the concentrations of antioxidants, key glycolytic intermediates, free cytosolic NAD+:NADH ratios, and energy status were partially prevented by DL-alpha-lipoic acid, while sorbitol pathway metabolites and free cytosolic NADP+:NADPH ratios remained unaffected. In conclusion, diabetes-induced impairment of lens antioxidative defense, glucose intermediary metabolism via glycolysis, energy status and redox changes are partially prevented by DL-alpha-lipoic acid. The findings support the important role of oxidative stress in lens metabolic imbalances in diabetes.

Adenine Nucleotides↗
PubMed1998

Chemoattractive effect on the effector cells of the supernatants from melanoma cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene.

By using the Boyden chamber system, the chemoattractive activity of the supernatants from the B16 melanoma cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene was investigated. We found that supernatants from IL-2- or IL-6-gene-transfected B16 melanoma cells showed chemoattractive activity on natural killer (NK) cells, CD4+ T cells and CD8+ T cells, while the supernatants from IL-4-gene-transfected B16 melanoma cells showed chemotactic activity on macrophages but not on NK cells and T cells. Further, the chemoattractive activity of the supernatants from cytokine-gene-transfected B16 cells might be the direct effects of the cytokine that they have been engineered to secrete. These results indicate that reduced tumorigenicity and increased immunogenicity of cytokine-gene-transfected B16 cells may be attributed to the direct recruitment of immune effector cells by the secreted cytokine, which plays an important role in the induction of the local antitumor immunity.

Animals↗