[HMGB1/SREBP-1 mediated IFN-gamma-induced lipid deposition in mouse mesangial cells].

OBJECTIVE: To explore the possible mechanism of lipid deposition induced by interferon-gamma (IFN-gamma). METHODS: The mouse mesangial cells (MMC) were randomly divided into control group, stimulation group, stimulation + control vector group (sh-HMGB1) and stimulation+ specific sh-vector group (sh-SREBP-1). RT-PCR was used to detect the expression of HMGB1, SREBP-1 and fatty acid synthetase (FAS) mRNA; the protein expression was determined by Western blot. RESULTS: The Oil Red O staining revealed that the mouse mesangial cells showed significant lipid droplet in IFN-gamma group. IFN-gamma up-regulated the expression of HMGB1, SREBP-1, FAS mRNA and protein time-dependently; Transfection of MMC with HMGB1 siRNA resulted in the suppression of SREBP-1, FAS protein levels induced by IFN-gamma, following with decrease of lipid deposition. Stimulation with HMGB1 markedly induced expression of SREBP-1, FAS expression and peaked at 8 h, decreased at 12 h compared with that at 8 h. Sh-SREBP-1 decreased the lipid deposition induced by HMGB1 in MMC. CONCLUSION: IFN-gamma might induce lipid deposition in mouse mesangial cells partly by up-regulating the expression of HMGB1/SREBP-1/FAS.

[Prevention of central pontine myelinolysis in rats by early treatment with dexamethasone].

OBJECTIVE: To explore the effect and mechanism of dexamethasone (DEX) in the prevention of central pontine myelinolysis (CPM) in rats. METHODS: Hyponatremia was induced in rat by subcutaneous injection of Vasopressin Tannate and intraperitoneal injection of 2.5% dextrose in water for 3 d, the rats of Group A received a bolus of 1 mol/L NaCl (2 ml/kg) and DEX (5 mg/kg) simultaneously at the 4th day; the rats of Group B were treated with DEX after 24 h of the injection of 1 mol/L NaCl; the rats in Group C received a bolus of 1 mol/L NaCl and saline simultaneously; Group D was the control group. The demyelinative lesions were evaluated by myelin staining. The Evans blue (EB) contents of brain were detected to evaluate the blood-brain-barrier permeability after rapid correction of hyponatremia. The expression of inducible nitric oxide synthase (iNOS) in brains was evaluated by Western blotting. RESULT: CPM was induced successfully in rats. The EB contents of Group A, B and C had no significant difference at 0 h after injection of hypertonic saline compared with Group D. The EB contents of Group C began to increase significantly at 6 h after injection of hypertonic saline, peaked at 24 h; the expression of iNOS in brains began to increase after 3 h after the rapid correction of hyponatremia. The rate of morbidity in Group C was 66.7%. The demyelinative lesions were rarely seen in Group A, the EB contents of brain decreased significantly compared with Group C at the same time point (P<0.05), the iNOS expression was also inhibited. DEX could not prevent the attack of CPM at Group B, the rate of morbidity (75%) had no significant difference compared with Group C (P>0.05). CONCLUSION: Early treatment with DEX can protect blood-brain-barrier and inhibit the expression of iNOS to prevent the attack of CPM.

[Antitumor effect of immunizations with fusions of dendritic and hepatocellular carcinoma cells in mice].

OBJECTIVE: To investigate the effects of immunization with fusions of dendritic cells and H22 cells on tumor-bearing mice and their possible mechanisms. METHODS: Fusion cells of DC and H22 cells were prepared with polyethylene glycol (PEG). Expression of MHC and costimulatory molecules by dendritomas were determined by FACs. To study the antitumor immune preventative and therapeutic effects, fusions were subcutaneously injected into tumor-bearing mice. The cytotoxic T lymphocyte (CTL) activity was determined by LDH method, the expression of TNF-a and IFN-g in tumors were assayed by RT-PCR. RESULTS: The data showed that the hybridomas of DC and H22 cells acquired both DC and H22 cell phenotypes. Immunization of BALB/C mice with DC/H22 fusions induced potent CTL activity (mean CTL activity=0.624+/-0.024, compared with DC + H22, DC, H22 groups, F = 65.46) and a protective immunity against a high dose of H22 tumor challenge. After treatment with hybridomas, the survival time of tumor-bearing mice was greatly extended (x2=18.45). The expression levels of TNF-a and IFN-g mRNA were remarkably increased (TNF-a, F = 47.84; IFN-g, F = 37.23). CONCLUSIONS: The hybridomas of DC and H22 cells could induce effective antitumor immune responses and may have a useful potential in prevention and management of the recurrences and metastases of HCC.

Orthotopic liver transplantation in treatment of 77 patients with end-stage hepatic disease.

OBJECTIVE: To summarize the experience of human orthotopic liver transplantation (OLTx) in treatment of patients with end-stage hepatic disease and their perioperative management. METHODS: A retrospective analysis was made on OLTx performed in 77 patients from April 1993 to September 2001 in our department included combined liver-kidney transplantation (6 patients) and living related liver transplantation (2). Among them, 76 were adults and 1 was infant (67 males and 10 females). The donors included 75 non-heart beating donors and 2 living related donors. Veno-venous bypass was used only in 45 cases during the operation. immunosuppressive agents consisted of cyclosporine, cellcept, ALG corticosteroids and FK506. RESULTS: The one-year survival rates of grafts and recipients with benign hepatic disease were 75%. The recipients this year are surviving with good function of grafts. CONCLUSION: Liver transplantation is the best therapeutic method for a large number of patients with end-stage hepatic disease in China.