α-促黑素细胞激素和白细胞介素8在病理性瘢痕组织中的表达及意义

目的:检测α-促黑素细胞激素、白细胞介素8在增生性瘢痕、瘢痕疙瘩、正常瘢痕和正常皮肤组织中的表达,探讨其在病理性瘢痕中的作用及意义。方法:①对象:收集2005-08/10中南大学湘雅医院烧伤整形科手术切下的瘢痕标本46例(其中增生性瘢痕18例、瘢痕疙瘩12例、正常瘢痕16例)和正常皮肤标本12例(患者和供皮者均知情同意)。②实验过程:标本用40g/L甲醛固定,行连续切片,厚4μm,应用链菌素生物素-过氧化物酶标记物免疫组织染色法染色。③实验评估:观察α-促黑素细胞激素和白细胞介素8在上述标本组织中的表达及相关性,采用着色强度和阳性细胞率二者评分相结合的方法判断结果。结果:①增生性瘢痕、瘢痕疙瘩中α-促黑素细胞激素的表达评分值和强阳性率高于正常瘢痕、正常皮肤(P<0.05);增生性瘢痕与瘢痕疙瘩比较、正常瘢痕与正常皮肤比较差异无显著性意义(P>0.05)。②增生性瘢痕、瘢痕疙瘩中白细胞介素8的表达评分值和强阳性率高于正常瘢痕、正常皮肤(P<0.05);增生性瘢痕与瘢痕疙瘩比较、正常瘢痕与正常皮肤比较差异无显著性意义(P>0.05)。③α-促黑素细胞激素、白细胞介素8在增生性瘢痕、瘢痕疙瘩和正常瘢痕中表达呈正相关(P<0.05),在正常皮肤中无相关性。结论:α-促黑素细胞激素、白细胞介素8在增生性瘢痕、瘢痕疙瘩中的表达显著高于正常瘢痕和正常皮肤,且二者在病理性瘢痕和正常瘢痕组织中表达呈正相关,提示α-促黑素细胞激素、白细胞介素8对促进病理性瘢痕的发生、发展可能起一定作用。     

Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus

Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.     

Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia

The relationship between the level of retinoblastoma protein (RB) expression and the survival of 113 newly diagnosed acute myelogenous leukemia (AML) patients was studied. Western blotting was used to determine the level of RB protein present in peripheral blood leukemia cells and results were confirmed in 26 patients by immunohistochemistry. The leukemic cells from 22/113 AML patients (19%) contained RB protein at levels that were equal to or less than the level of RB observed in the mononuclear cell fraction of peripheral blood from normal individuals (Low RB). Levels of RB greater than that of normal blood (Elevated RB) were seen in 91 patients (81%). The median survival of patients with low RB was significantly shorter than that seen in patients with elevated RB, 12 weeks versus 40 weeks (P = .02). Remission induction frequency was 36% in low RB patients compared with 68% in AML patients with elevated RB (P = .01). Multivariate analysis showed that low RB protein level was an independent prognostic factor predictive or poor survival after allowing for other known prognostic factors. These data suggest that a low level of the RB protein at the time of diagnosis is associated with shortened survival in AML patients because of inferior response to conventional therapy. Monitoring of the RB level could identify a subgroup of AML patients with an extremely poor prognosis when treated with chemotherapy alone, who would be eligible for alternative therapeutic strategies.     

Decreased inducible expression of CD80 and CD86 in human monocytes after ultraviolet-B irradiation: its involvement in inactivation of allogenecity

Ultraviolet-B (UV-B) irradiation of antigen presenting cells (APCs) modifies their allogenecity, resulting in inhibition of the proliferative response of T cells in mixed lymphocyte reaction (MLR). Costimulation by the CD28 ligand CD80 (B7/B7-1) and CD86 (B70/B7-2) plays an important role during T-cell proliferation by augmenting synthesis of interleukin-2 (IL-2) and other cytokines. In this study, we demonstrated induced expression of both CD80 and CD86 during allogeneic MLR, though human freshly isolated monocytes express CD86 constitutively with a much lower level of CD80. A monoclonal antibody (MoAb) against CD86, but not CD80, efficiently inhibited allogeneic T- cell proliferative responses stimulated with highly purified monocytes. UV-B exposure (0 to 1,000 J/m2) of monocytes inhibited the proliferation of T lymphocytes in MLR in a dose-dependent manner. Flow cytometric analysis showed that UV-B exposure of monocytes impaired the constitutive expression of CD54 (intercellular adhesion molecule-1) by 24 hours after irradiation, but the effect on CD86 was relatively less. The surface expression of CD80, CD86, CD54, and HLA-DR on monocytes was further augmented by interferon (IFN)-gamma; this cytokine-induced expression was dose-dependently reduced by UV-B irradiation. Similarly, the upregulation of these molecules following allogeneic MLR was downregulated by UV-B irradiation. UV-B irradiation of monocytes inhibited the expression of IL-2 mRNA in monocyte-stimulated allogeneic MLR. In contrast, the addition of anti-CD28 MoAb at the onset of MLR prevented, at least partially, the reduction of IL-2 mRNA. These results strongly suggest that the impairment of inducible expression of CD86 and CD80 may contribute to the reduced MLR response following exposure of monocytes of UV-B.     

Hepatitis G virus infection in patients with hepatitis C virus infection undergoing liver transplantation

BACKGROUND & AIMS: Hepatitis G virus (HGV) is transmissible by blood transfusion, but its role in chronic liver disease is unknown. The aim of this study was to determine the prevalence of HGV infection in patients infected with hepatitis C virus (HCV) undergoing transplantation and evaluate the effects of HGV coinfection on the course of posttransplantation HCV infection. METHODS: One hundred twenty-four patients infected with HCV undergoing liver transplantation were studied. Serum samples were tested for HCV and HGV RNA; HCV RNA was quantitated by branched DNA assay, and HCV genotype was determined. RESULTS: The prevalence of pretransplantation and posttransplantation HGV infection was 24% and 28%, respectively. Pre-transplantation HGV infection was positively correlated with posttransplantation HGV infection (P < 0.001). Pretransplantation clinical features were not different in patients infected with HCV with and without HGV infection. Posttransplantation HCV RNA levels were not significantly different in patients with and without HGV coinfection, but HCV genotype 1b was more frequent in patients with HGV coinfection. There were no differences in the histological severity of posttransplantation liver disease, graft, and patient survival between patients with and without HGV infection. CONCLUSIONS: Although HGV coinfection is frequent in patients with end- stage HCV disease undergoing liver transplantation, there is no association between the presence of HGV coinfection and the severity of liver disease post-transplantation, graft, or patient survival. (Gastroenterology 1996 Dec;111(6):1569-75)     

Adult Primary Intradural Spinal Cord Tumors: A Review

Primary spinal cord tumors constitute 2% to 4% of all central nervous system neoplasms and are characterized based on their location as intramedullary, intradural extramedullary, and extradural. A contemporary literature review of primary intradural spinal cord tumors was performed. Among intramedullary tumors, ependymomas are more common and often can be surgically resected. However, astrocytomas infiltrate the spinal cord and complete resection is rare. Intradural extramedullary tumors include schwannomas, neurofibromas, and meningiomas and are usually amenable to surgical resection. Radiotherapy is reserved for malignant variants and recurrent gliomas, whereas chemotherapy is administered for recurrent primary spinal cord tumors without surgical or radiotherapy options. Early recognition of the signs and symptoms related to primary spinal cord tumors facilitates timely discovery, treatment, potentially minimizes neurologic morbidity, and may improve outcome. Treatment consists of surgical resection, and predictors of outcome include preoperative functional status, histologic grade of tumor, and extent of surgical resection.