The random association of Epstein-Barr virus DNA with host cell metaphase chromosomes of all sizes in Burkitt's lymphoma-derived cell lines was demonstrated by two substantially different techniques, namely fluorescence-activated chromosome sorting and in situ hybridization. The nature and potential importance of this association are discussed.
This study investigated the clonal nature of cold agglutinin disease in a series of nine patients, which included the benign or idiopathic form as well as cases with an underlying lymphoma. Surface marker phenotyping and karyotypic analysis were performed on peripheral blood lymphocytes. An increased proportion of B cells was found in four cases and in three of these patients a monoclonal B cell population was identified with a mu, kappa phenotype. In the same three cases, as well as an additional patient, an aberrant karyotype was demonstrated. The cytogenetic abnormality present in all four cases included trisomy 3; two patients also had a trisomy 12. One of these four patients had a well-differentiated lymphoma and underwent a splenectomy. Splenic lymphocytes were transformed with Epstein-Barr virus and cultured en masse. Eight clones were established producing the same cold agglutinin with identical specificity as that present in the patient's plasma. Five of these clones were studied cytogenetically, and all had the same abnormal karyotype (51,XX,+3,+9,+12,+13,+18) found in peripheral blood and splenic lymphocytes. Thus, in this case, the cold reactive autoantibody was produced by the chromosomally abnormal, neoplastic clone of lymphocytes. Our findings support the view that cold agglutinin disease represents a spectrum of clonal disorders.
X-linked lymphoproliferative disease (XLP) is triggered by Epstein-Barr virus. This virus is also associated with Burkitt lymphoma, a tumor that carries specific chromosome translocations. No such chromosome translocations have been observed in an analysis of XLP-derived cell lines. One XLP patient was found also to have Klinefelter syndrome, having inherited two copies of his maternal XLP-carrying X chromosome.
SummaryA high-capacity, 96-well plate assay in COS-1 cells was developed to screen for inhibitors of the essential HIV-1 Rev response. The assay used Rev-induced expression and cell excretion of the p24 protein from the HIV-1 gagpol gene as a readout. Co-expression of f3-galactosidase was used as a specificity control. Using this assay as a drug discovery screen, the authors discovered a series of 8-alkyl-2-(4-pyridyl)pyrido[2,a-djpyrimidin-5(8H)-ones that inhibited the primary Rev response in COS-1 cells with ICsos in the range 2-20f-LM. These compounds also inhibited HIV-1 strain IIIB replication in human H9 cells (T-cell lymphoma) with ICsos in the same concentration range. Limited structural information suggests that alkyl substituent on N(8) influences potency of this series. These compounds might be the first reported smallmolecule inhibitors of HIV-1 replication which act by inhibiting the essential Rev response; further studies in T-cells are in progress to confirm this hypothesis.
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