Increased mucosal inflammatory cytokines in children with Helicobacter pylori-associated gastritis

The concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1-β in tissue homogenates of gastric mucosal biopsy specimens, and in gastric juice samples from Helicobacter pylori-positive and -negative children, were determined. The study population comprised 30 children with recurrent abdominal pain attending upper gastrointestinal endoscopy. Of these patients 18 were infected with H. pylori. Cytokine concentrations in gastric biopsy homogenate supernatants and in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). TNF-α levels in gastric juice and in gastric biopsy homogenate supernatants in patients with H. pylori-positive gastritis were found to be significantly higher than those in children without H. pylori infection. IL-6 levels were also higher in H. pylori -infected subjects, but the difference in IL-6 concentrations measured in gastric juice and biopsy homogenate supernatants did not reach statistical significance. IL-1-β concentrations in both specimens showed no significant difference between the two groups of children. It was suggested that increased levels of inflammatory cytokines, especially TNF-α and IL-6 generated locally within the gastric mucosa might be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.     

人ERRα基因小分子干扰RNA慢病毒载体构建及鉴定

目的构建并鉴定靶向人ERRα基因的小分子干扰RNA的慢病毒载体。方法针对ERRαmRNA设计了4条si RNA,并构建pGCSIL-GFP-siERRα慢病毒质粒,PCR扩增阳性克隆并测序鉴定。用pGCSIL-GFP-siERRα、pHelp-er1.0和pHelper2.0质粒共转染293T细胞包装产生慢病毒,测定病毒滴度。将慢病毒干扰RNA及含有ERRα过表达载体共转染293T细胞,Western-blot检测ERRα表达,观察蛋白表达抑制效果。结果 PCR和测序结果与设计的干扰序列一致,病毒滴度达2×109TU/ml。转染细胞中ERRα蛋白表达显著降低。结论成功构建高表达、高效率的人ERRα基因小分子干扰RNA慢病毒载体,为进一步研究ERRα在细胞核内转导中的作用机制和靶向ERRα治疗奠定基础。     

Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D’) bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets. These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D’) was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.     

Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia

Structural abnormalities of the X chromosome are rarely found in neoplastic disorders. We describe three patients with a history of idiopathic acquired sideroblastic anemia (IASA); each one had an abnormal clone of cells in the bone marrow, characterized by a structurally abnormal X chromosome. In two of these patients, the predominant karyotype was 47,X,2idic(X)(q13); in the other patient, it was 46,X,t(X;11)(q13;p15). Inasmuch as all three of these cases involved chromosome band Xq13, as did two previously published cases, we suggest that band Xq13 may be more prone to structural rearrangement than other X chromosome bands in hematologic disorders. The common Xq13 chromosome breakpoint and clinical presentation (IASA) among these three patients and the occurrence of an X-linked type of sideroblastic anemia may suggest that an association exists between X chromosome abnormalities and IASA. Perhaps alteration of a gene or chromosome structure in or near band Xq13 predisposes to development of IASA. The fact that two of these patients had preleukemia and the third had overt acute leukemia may imply that patients with IASA and X chromosome abnormalities have a poor prognosis. Cases of IASA without associated X chromosome abnormalities are known; thus, if an association between IASA and an abnormal X chromosome does exist, most likely it involves only some patients with IASA.