The peptidic antiretroviral enfuvirtide (Fuzeon) is the first clinically approved antiviral fusion inhibitor and the first antiretroviral that must routinely be administered parenterally. Its extracellular activity results both in activity against current drug-resistant strains of HIV-1 and a low potential for systemic toxicities. As a peptide, enfuvirtide also exhibits few interactions with other antiretrovirals and concomitant medications used in HIV disease. Enfuvirtide shows potent antiretroviral activity and significantly improves medical outcomes in highly treatment-experienced patients with HIV-1 infection, but like other antiretrovirals must be given as part of a carefully selected combination regimen to minimise the risk of emergent drug resistance. Despite its subcutaneous route of administration, clinical data indicate that most patients can accept long-term enfuvirtide treatment with little difficulty or impact on daily activities. The only common adverse event associated with enfuvirtide use is injection-site reactions of generally mild-to-moderate severity, which are seldom treatment-limiting.

A conflict in cell cycle progression or DNA damage can lead to mitotic catastrophe when the DNA structure checkpoints are inactivated, for instance when the checkpoint kinase Chk2 is inhibited. Here we show that in such conditions, cells die during the metaphase of the cell cycle, as a result of caspase activation and subsequent mitochondrial damage. Molecular ordering of these phenomena reveals that mitotic catastrophe occurs in a p53-independent manner and involves a primary activation of caspase-2, upstream of cytochrome c release, followed by caspase-3 activation and chromatin condensation. Suppression of caspase-2 by RNA interference or pseudosubstrate inhibitors as well as blockade of the mitochondrial membrane permeabilization prevent the mitotic catastrophe and allow cells to further proceed the cell cycle beyond the metaphase, leading to asymmetric cell division. Heterokarya generated by the fusion of nonsynchronized cells can be driven to divide into three or more daughter cells when Chk2 and caspases are simultaneously inhibited. Such multipolar divisions, resulting from suppressed mitotic catastrophe, lead to the asymmetric distribution of cytoplasm (anisocytosis), DNA (anisokaryosis) and chromosomes (aneuploidy). Similarly, in a model of DNA damage-induced mitotic catastrophe, suppression of apoptosis leads to the generation of aneuploid cells. Our findings delineate a molecular pathway through which DNA damage, failure to arrest the cell cycle and inhibition of apoptosis can favor the occurrence of cytogenetic abnormalities that are likely to participate in oncogenesis.

Evidence indicating cell membrane fusion among cells and their processes where subacute sclerosing panencephalitis (SSPE) virus is present is shown in an ultrastructural study of a brain biopsy. Virus budding from plasma membrane was not seen. These rare findings reinforce the hypothesis of cell-to-cell transmission as the most likely mechanism of SSPE virus infection. The presence of fused membranes between cell processes and cell soma probably explains the rapid spread of this virus throughout the nervous system.

暂无摘要。

A case of acute appendicitis with features of measles inflammatory reaction is studied. Two types of lymphoid polykaryons are seen: Warthin Finkeldey cells inside germinal centres (LN1 ++, LN2 +, L26 +, MB1 +, MB2 +/-) and multinucleate plasma cells in the lamina propria (mu +, alpha ++, kappa +, lambda +). Both types of polykaryon are devoid of inclusions. The search for viral genetic information by in situ hybridization was negative in these cells. A positive signal was observed in interfollicular mononuclear cells and rare enterocytes. A possible mechanism of fusion from without, acting at the beginning of the disease to induce the appearance of polykaryons, is discussed.