Biomedical subjects
Publications and source records attributed to L Fritsch.
Pneumatosis Intestinalis is a rare benign and often asymptomatic disease; we report the case of a 74 year-old woman with a pneumatosis coli revealed by a pseudo-obstruction; the diagnosis was suspected at radiology. The course under medical treatment was uneventfull.
Terminal differentiation of muscle cells follows a precisely orchestrated program of transcriptional regulatory events at the promoters of both muscle-specific and ubiquitous genes. Two distinct families of transcriptional co-activators, GCN5/PCAF and CREB-binding protein (CBP)/p300, are crucial to this process. While both possess histone acetyl-transferase (HAT) activity, previous studies have failed to identify a requirement for CBP/p300 HAT function in myogenic differentiation. We have addressed this issue directly using a chemical inhibitor of CBP/p300 in addition to a negative transdominant mutant. Our results clearly demonstrate that CBP/p300 HAT activity is critical for myogenic terminal differentiation. Furthermore, this requirement is restricted to a subset of events in the differentiation program: cell fusion and specific gene expression. These data help to define the requirements for enzymatic function of distinct coactivators at different stages of the muscle cell differentiation program.
We report a case of Castleman disease in the mesentery localized to a 58 year-old man. The mass is hypervascular on CT, which can suggest the diagnostic before surgery.
Infections by human and simian immunodeficiency viruses (HIV and SIV) are independent of host cell division since the preintegration complex (PIC), containing the viral DNA, is able to undergo active nuclear import after viral entry. In order to clarify the mechanisms responsible for nuclear import of the PIC, we have analyzed the subcellular distribution and the karyophilic properties of its viral components, matrix protein (MA), integrase (IN), Vpr, and Vpx. Although MA has been reported to contain a nuclear localization signal, the MA/GFP fusions are excluded from the nucleus and associated with cellular membranes. In contrast, both HIV-1 and SIV IN and Vpr localize in the nucleus of transfected cells. Interestingly, only Vpx from SIVsm virus accumulate in the nucleus while SIVsm Vpr is uniformly distributed throughout nucleus and cytoplasm. Coexpression of MA, Vpr, and IN does not induce any change in their respective intracellular localizations. Finally, we confirm the karyophilic properties of HIV-1 IN and Vpr using an in vitro nuclear import assay. These results indicate that the viral proteins IN and Vpr, which are strongly associated with the viral DNA within PIC, may participate in the nuclear import of the HIV PIC.
Human Herpesvirus 8 (HHV-8) has been consistently associated with Primary Effusion Lymphoma (PEL or body-cavity-based lymphoma) but not with other lymphomas. This paper reports on an AIDS patient without obvious malignant effusion in body cavities but with a cutaneous lymphoma where HHV-8 and Epstein-Barr virus (EBV) were detected by PCR and electron microscopy. Both viruses were also detected in all the cells of a malignant cell line (BBG1) established from the patient's peripheral blood mononuclear cells. As in PEL and PEL-derived cell lines, both the tumor and the lines lacked B-antigen expression in immunological studies but were of the same B origin as shown by clonal immunoglobulin gene rearrangements. In contrast to other co-infected cell lines, BBG1 and subclones spontaneously expressed the HHV-8 lytic antigens p40, p27, p60 and the EBV transforming latent antigen EBNA2. These data suggest that the clinical and biological features of HHV-8-and EBV-associated lymphomas could be wider than has been described to date in PEL particularly with the in vivo presence of circulating malignant dually-infected cells engaged in a spontaneous HHV-8 lytic infection.
Human immunodeficiency virus type 1 (HIV-1) has tropism for helper T lymphocytes and cells of the monocyte/ macrophage lineages. HIV-1 can also infect other cell types, including B cells. We show here that 10% of fresh circulating B cells from HIV-1-seronegative donors (i) express the CD4 receptor and CCR5 and CXCR4, two recently described coreceptors for HIV-1 and (ii) are permissive to HIV-1 with de novo proviral DNA integration following ex vivo infection by either SI (syncytium-inducing) or NSI (non-syncytium-inducing) isolates. To get further information on the interaction between HIV and B cells, the susceptibility of several EBV-positive or -negative B cell lines to infection by SI and NSI isolates was checked. Following infection of an EBV- CD4+ CXCR4+ CCR5- B cell line (DG75) by an SI HIV-1 isolate, we obtained a cell line which chronically produced low-level infectious HIV-1 for 2 years (HIV-DG75). Immunocytochemical data, combined with in situ PCR data, established that HIV-DG75 cells consist of at least three populations uninfected cells, infected virus-producing cells, and infected but nonproducing cells. Moreover, HIV-DG75 cells which express p24 antigen do not go into apoptosis, contrary to T lymphocytes. We infer from these results that B cells could constitute a reservoir of infectious virus in infected patients.
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