Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals

JC virus (JCV) infection is regularly asymptomatic in healthy individuals. In contrast, in immunocompromised individuals, highly activated virus replication may lead to PML. Peripheral blood cells (PBCs) are found to habor JCV DNA in healthy and diseased individuals and it is discussed that they might be responsible for dissemination of the virus to the central nervous system (CNS) during persistence. To better understand the role of JCV DNA in PBCs for persistent infection and pathogenesis, the authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs]) of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals. Virus activation in PBMCs from healthy JCV-infected individuals was found at a rate of 0% to 38% at low polymerase chain reaction (PCR) sensitivity. In progressive multifocal leukoencephalopathy (PML) patients, a stronger signal was found, indicating increased virus activation. JCV DNA was regularly detected in T and B lymphocytes and in monocytes at low levels. However, granulocytes were shown to be the predominant reservoir of JCV DNA harboring high copy numbers. Although the overall distribution of viral genomes holds true for the population studied, in the individual, a markedly changed pattern of distribution can be found.     

Role of 4-1BB in Allograft Rejection Mediated by CD8+ T Cells

Blockade of traditional costimulatory molecules fails to inhibit rejection in many models where CD8+ T cells are sufficient to mediate rejection. This observation demonstrates that in many settings CD8+ T cells are not dependent upon CD28 or CD154 signals to mediate rejection. 4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models. Here we show that blocking the 4-1BB pathway significantly inhibited rejection of intestinal allografts by CD8+ but not CD4+ T cells. This effect was associated with significantly decreased expression of the genes encoding TNFalpha and secondary lymphoid chemokine (SLC) within the spleens of recipient mice. Disruption of the 4-1BB pathway also impaired the priming of alloantigen-specific CD8+ T cells and the accumulation of recipient dendritic cells within the spleen. These data directly demonstrate an important role for 4-1BB in allograft rejection; particularly rejection mediated by CD8+ T cells. Our data suggest that in addition to providing a direct costimulatory signal to T cells, the 4-1BB pathway may regulate other important steps in the immune response such as the migration of T cells and dendritic cells.     

Chromosomal imbalances in clear cell ependymomas.

Clear cell ependymoma is a rare and diagnostically challenging subtype of ependymoma, whose genetic features are essentially unknown. We studied 13 clear cell ependymomas (five cases WHO grade II, eight cases WHO grade III) by comparative genomic hybridization (CGH). Chromosomal imbalances were found in 12/13 cases. The most common aberrations overall were +1q (38%), -9 (77%), -3 (31%), and -22q (23%). Clear cell ependymomas of WHO grade II were characterized by -9 (40%), whereas WHO grade III cases mainly showed +1q (63%), and +13q (25%), as well as -9 (100%), -3 (38%), and -22q (25%). In contrast to other ependymal tumors, clear cell ependymomas of WHO grade II showed fewer imbalances than WHO grade III samples (1.4 vs 3.5 per case). Although some of the implicated chromosomes have previously been shown to be involved in other ependymoma variants, the striking frequency of +1q, -9, and -3 suggests that aberrations differ between clear cell and other types of ependymomas, in particular, for loss of chromosome 9 which can be regarded as the molecular hallmark of clear cell ependymomas.     

Liver pathology associated with the use of anabolic-androgenic steroids

Abstract: This review examines the liver-damaging side effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved that AAS can cause development of hepatocellular carcinomas when used in the usual therapeutic doses. Tumours reported as hepatocellular carcinomas caused by AAS seem to be hyperplastic lesions of a benign nature able to regress with withdrawal of the putative agent. The effects of untraditional combinations and high-dose AAS are not yet known, leaving the possibility of a carcinogenic effect in those cases.     

Serial tomographic imaging with technetium-99m-sestamibi for the assessment of infarct-related arterial patency following reperfusion therapy.

The purpose of this study was to determine the relationship of changes in the severity and extent of hypoperfusion on serial tomographic 99mTc-sestamibi images with patency of the infarct related artery during acute myocardial infarction. We studied 109 patients with acute myocardial infarction using tomographic 99mTc-sestamibi imaging acutely and at 18-48 hr later. Perfusion defect extent and defect area, an index of defect severity, were measured on both studies. Both defect extent and defect area were significantly (p = 0.0001) greater for anterior infarctions than for inferior and lateral infarctions. By two factor analysis of variance, the change in defect area varied significantly with both infarct location (p = 0.0001) and patency of the infarct-related artery (p = 0.002). The change in defect extent also varied significantly with both infarct location (p = 0.0001) and with patency of the infarct-related artery (p = 0.004). In patients with inferior myocardial infarction, a change in defect extent or defect area of greater than 4% or 0.017, respectively, had a positive predictive accuracy of 96% and 93%, respectively, for the identification of a patent infarct artery. Therefore, sequential changes on tomographic 99mTc-sestamibi images are of potential value for the noninvasive assessment of patency of the infarct-related artery.