Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.     

Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.     

癌症患者同伴支持量表的汉化及信效度检验

目的 汉化癌症患者同伴支持量表,并检验其信效度。方法 通过正译、回译、文化调试和预调查对原量表进行汉化,形成中文版癌症患者同伴支持量表。于2021年3月—6月选取长沙市2所三级甲等医院的128例青年癌症患者进行问卷调查,分析量表的信效度;2021年7月—2022年3月选取该2所医院招募的241例患者进行问卷调查,用于验证性因子分析。结果 中文版癌症患者同伴支持量表包括3个维度、11个条目。量表水平的内容效度指数为0.948,条目水平的内容效度指数为0.714～1.000。探索性因子分析提取出3个公因子,各条目因子载荷为0.535～0.872,累计方差贡献率为69.64%,方程拟合良好。量表总的Cronbach’s α系数为0.923,折半信度为0.860。验证性因子分析结果 显示,模型拟合度良好。结论 中文版癌症患者同伴支持量表的信效度良好,适用于青年癌症患者同伴支持感的评估。     

Lyme disease—another transfusion risk?

Lyme disease (or Lyme borreliosis) is caused by a spirochetal bacteria, Borrelia burgdorferi. Increased recognition of the disease and increased exposure to the vector (ticks) capable of spreading B. burgdorferi from animal hosts have resulted in a rise in the number of cases of Lyme borreliosis reported in the United States. There are three stages of the clinical course of Lyme borreliosis; however, not all those infected will have typical manifestations of each stage, such as the arthritis of the third stage. Routine blood cultures will rarely document bacteremia and serologic testing is not yet reliable. Early treatment can prevent later stages of Lyme borreliosis. There is evidence that transmission of B. burgdorferi by blood transfusion is possible, but, to date, there has been no documentation of transfusion- associated Lyme borreliosis. Thus, no new recommendations for screening donors to identify possible carriers of B. burgdorferi are suggested at this time.     

三维重建射频损伤区域观察猪舌根射频损伤体积与射频能量及时间的关系

目的：目前临床进行隧道法舌根射频治疗时,其作用参数的设置仍缺乏统一的标准,故通过计算机三维重建射频损伤区域,分析猪舌根射频损伤体积与射频能量、时间的关系,从中得出应用舌根隧道法射频治疗的最佳作用能级和作用时间。 方法：实验于2006-06/2007-05在上海交通大学耳鼻喉科研究所完成。将36只实验用猪以射频作用能级1,2,3,4,5,6随机分成6组,每组6头猪,各个猪舌的作用时间分别设置为2,5,10,15,20,25s。用Coblation射频发生仪及Reflex55刀头进行猪舌根射频操作。射频作用后的舌根组织行连续冰冻切片,苏木精-伊红染色后,进行序列组织切片的全貌二维图像采集,对拟重建的结构进行边界提取和图像分割。将提取分割图像导入Image-Pro Solution图像处理软件,利用3D Constructor插件进行三维重建,并根据设定参数进行体积计算。用SPSS10.0统计学软件对所测数据进行统计学分析。 结果：①作用能级固定时,舌根组织射频损伤体积随时间延长而增大,符合Logarithmic回归曲线。②作用时间固定时,舌根组织射频损伤体积随能级增大而增大,符合直线回归。③射频损伤体积随能量增大而增加亦符合Logarithmic回归曲线。④Coblation射频治疗系统在能级6时,在作用10s之前,损伤体积随作用时间增加而迅速增加,其后变化趋势平缓,超过20s后损伤体积无显著增加。 结论：①舌根区域射频治疗时,舌根组织射频损伤体积与时间或能量呈Logarithmic曲线相关,与能级呈直线相关。②Coblation射频治疗系统在能级6时,最佳作用时间范围为10-20s。     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.