Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95)

Morphological studies have shown that macrophages and microglia undergo apoptosis in the central nervous system (CNS) in acute experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative levels of macrophage and microglial apoptosis, and the molecular mechanisms involved in this process, we used three-colour flow cytometry to identify CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the inflammatory cells isolated from the spinal cords of Lewis rats 13 days after immunization with myelin basic protein (MBP) and complete Freund's adjuvant. Simultaneously, we analyzed the DNA content of these cell populations to assess the proportions of cells undergoing apoptosis and in different stages of the cell cycle or examined their expression of three apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and Bcl-2. Microglia were highly vulnerable to apoptosis and were over-represented in the apoptotic population. Macrophages were less susceptible to apoptosis than microglia and underwent mitosis more frequently than microglia. The different susceptibilities of microglia and macrophages to apoptosis did not appear to be due to variations in Fas, FasL or Bcl- 2 expression, as the proportions of microglia and macrophages expressing these proteins were similar, and were relatively high. Furthermore, in contrast to T cell apoptosis, apoptosis of microglia/macrophages did not occur more frequently in cells expressing Fas or FasL, or less frequently in cells expressing Bcl-2. These results indicate that the apoptosis of microglia and CNS macrophages in EAE is not mediated through the Fas pathway, and that Bcl-2 expression does not protect them from apoptosis. Expression of FasL by macrophages and microglia may contribute to the pathogenesis and immunoregulation of EAE through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high level of microglial apoptosis in EAE indicates that microglial apoptosis may be an important homeostatic mechanism for controlling the number of microglia in the CNS following microglial activation and proliferation.      

用点突变的方法组建巨细胞病毒抗原决定簇基因的表达克隆

研究资料表明，人巨细胞病毒（ＨＣＭｖ）单一蛋白的单一抗原决定簇只能被部分患者阳性血清识别。组建在血清学诊断中能够替代全病毒抗原的基因工程抗原，需要含有病毒多种主要抗原蛋白的抗原决定簇。为搞清在表达载体中重复插入某一抗原决定簇基因是否能表达出更高抗原效价的融会蛋白，我们用点突变的方法，在表达载体中分别插入了人ＨＣＭｖ的ｐｐＵＬ３２蛋白羧基端一个抗原决定簇基因的１个、２个和３个拷贝。在免疫转印检测中，这些克隆表达的融合蛋白与特异性阳性血清的反应性差别不明显。这表明，插入表达载体中目的基因的多寡对表达蛋白的抗原效价没有显著影响。     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.     

Embryonic implantation in carcinoma of the endometrium

We recently encountered a patient in whom placental implantation occurred directly in carcinoma of the endometrium. At the time of surgery for a presumed tubal pregnancy, the 33-year-old patient was discovered to have bilateral ovarian tumors that were histologically identical to the endometrial neoplasm.     

Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. The Retrovirus Epidemiology Donor Study

BACKGROUND: Since the mid-1980s, blood banks in the United States have screened donors for elevated alanine aminotransferase (ALT) in an effort to prevent posttransfusion hepatitis. The present study was designed to quantitate the residual value of ALT screening following the implementation of hepatitis C virus (HCV) assays. STUDY DESIGN AND METHODS: Two approaches were used. First, a database of 2.3 million donations made by 586,507 volunteer blood donors between 1991 and 1993 was used to compare the incidence of seroconversion to hepatitis B virus (HBV) and HCV marker positivity in donors with elevated ALT values and with normal ALT values. Second, the duration of ALT elevation prior to HBV and HCV seroconversion was determined from 34 well-documented cases of posttransfusion HBV and HCV; elevated-ALT window periods were multiplied by rates of HBV and HCV incidence in donors to project the yield of ALT screening. Predictive value and cost- effectiveness analyses were also performed to compare the value of ALT screening before and after HCV screening was implemented. RESULTS: Both approaches indicate that ALT testing does not detect HBV in the window phase but does currently identify approximately 3 HCV window-phase donations per 1 million donations; this contrasts with ALT detection of approximately 1800 HCV-infectious units per 1 million donations prior to anti-HCV screening. Currently, only 8 in 10,000 donated units with elevated ALT (negative anti-HCV) are infected with HCV. The cost of continued ALT screening was estimated at $7,931,000 per quality- adjusted year of life saved. CONCLUSION: The yield, predictive value, and cost-effectiveness of ALT screening of blood donors have declined dramatically with the implementation of progressively improved anti-HCV assays. ALT screening of volunteer blood donors should be discontinued.