Showing papers by "Erwin W. Gelfand published in 1987"

Reversal of chronic polymyositis following intravenous immune serum globulin therapy.

Abstract: POLYMYOSITIS is an inflammatory disease of striated muscle, which has been attributed to a vasculopathy. Although the pathogenesis is unknown, studies suggest that an immune mechanism may contribute to this disorder. The evidence consists of the presence of tissue-bound immunoglobulins and complement within blood vessels of involved muscle1and the in vitro cytotoxic effect of patients' lymphocytes on muscle cells grown in culture.2,3 The mainstay of therapy in polymyositis is corticosteroids. This treatment results in improvement of prognosis and life-style in most patients with this disorder.4-10However, some individuals are refractory to steroid therapy or demonstrate only a partial response.11,12In other patients, short- or long-term toxic reactions to corticosteroids force discontinuation of the drug. Such patients who are resistant to or intolerant of corticosteroids have been treated with immunosuppressive agents, including methotrexate sodium,13-17azathioprine sodium,18-20cyclophosphamide,17,21,22and cyclosporine.23 Although patients may

T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.

Abstract: We have analyzed T cell receptor alpha-chain gene configuration using three genomic joining (J) region probes in 64 children with acute lymphoblastic leukemia (ALL). 11 out of 18 T-ALLs were T3 positive; alpha-chain gene rearrangements were demonstrated in only two of 18, indicating that the majority of T-ALLs would have rearrangements involving J alpha segments located upstream of these probes. In contrast, 15 out of 46 B-precursor ALLs showed rearrangements of the alpha-chain gene and J alpha segments located approximately 20-30 kb upstream of the constant region were involved in 13 of these patients. Nine of 15 B-precursor ALLs with rearranged alpha-chain genes had rearrangements of both gamma- and beta-chain genes, whereas the remaining six had no rearrangements of gamma- and beta-chain genes. These findings indicated that alpha-chain gene rearrangement is not specific for T lineage cells and gamma- and/or beta-chain gene rearrangement does not appear essential for alpha-chain gene rearrangement, at least in B-precursor leukemic cells.

Induction of human B cell proliferation and differentiation by the combination of phorbol ester and ionomycin.

Abstract: Phorbol esters and Ca2+ ionophores are known to mimic intracellular messengers involved in cell activation. We studied the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) and ionomycin on tonsil and peripheral blood-derived B lymphocytes. We show that TPA and ionomycin are co-mitogenic and induce B lymphocyte differentiation. Although TPA in high concentrations is mitogenic to B lymphocytes by itself, submitogenic concentrations of TPA in combination with ionomycin trigger 50% of B lymphocytes to synthesize DNA. Stimulation of B lymphocytes with TPA plus ionomycin resulted in increased magnitude and a shift in the kinetics of c-fos and c-myc expression compared with either agent used alone. Activation markers such as the transferrin and interleukin 2 (IL 2) receptors were markedly increased after 24 h incubation with TPA and ionomycin. In parallel to the rapid proliferative burst, we observed evidence for B lymphocyte differentiation with an increase in the number of cells expressing cytoplasmic immunoglobulin (Ig) and the disappearance of the B1 surface marker. Since the cells remained surface Ig+ and secreted only small quantities of Ig, our results suggest that the combination of TPA and ionomycin is a potent inducer of B cell proliferation and early differentiation; terminal differentiation to an Ig-secreting state, however, is not achieved.

Poly(L-lysine) plaque assay for the measurement of antigen-activated human B lymphocytes.

Abstract: Publisher Summary This chapter provides a overview of the poly(L-lysine) plaque assay procedure, which was instrumental in many studies of antigen-specific human B cell function. Culture procedures may only be considered where they directly impact on plaque-forming cell (PFC) assay results and their evaluation. It focuses on the assay technique itself, discusses its pitfalls, and the cellular and biochemical parameters of direct concern to plaque assay results. Although PFC and enzyme-linked immunosorbent assay (ELISA)/RIA techniques are both able to measure antibody responses, the two experimental approaches are by no means equivalent. PFC assay procedures are among the most sensitive techniques developed for the measurement of biological function in single cells. In any application of hemolytic plaque assays, the most obvious pitfall is pseudoplaque formation by extraneous antibody introduced during the culture period. In assays detecting Igs other than IgM, these pseudo plaques can be of other isotypes as well. Inclusion of appropriate controls, in particular cycloheximide or similar agents, is important in all such experiments. More importantly, these studies provided unique insights into a growing number of the human immunodeficiency disorders.