Surface immunoglobulins in human chronic leukemia cells

By means of the cytotoxic and immunofluorescence tests, frequency of various classes of immunoglobulins (IgG, IgA, IgM, IgD, IgE) and light chains was examined in peripheral pathologic blood cells of patients with chronic granulocytic and lymphatic leukemia. The dominant immunoglobulins were of the IgD and IgE classes. Light chains of both types were present in cells of chronic granulocytic leukemia, and kappa type in chronic lymphatic leukemia. Use of the method of resynthesis of digested immunoglobulins in vitro confirmed the monoclonal origin of chronic lymphatic leukemia in humans.     

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.     

Primitive neuroectodermal tumors of the central nervous system

Primitive neuroectodermal tumors are morphologically similar malignant tumors arising in intracranial and peripheral sites of the nervous system, showing varying degrees of cellular differentiation with a tendency to disseminate along cerebrospinal fluid pathways. They occur primarily in children and young adults. Under the designation primitive neuroectodermal tumors are included medulloblastomas and tumors that may differentiate in other directions, such as medulloepithelioma, neuroblastoma, polar spongioblastoma, pineoblastoma, ependymoblastoma, retinoblastoma, and olfactory neuroblastoma. From a practical, histologic point of view, these tumors are often indistinguishable from one another and are best thought of as primitive neuroectodermal tumors with or without differentiating features.     

Increased multiclonal antibody-forming cell activity in the peripheral blood of patients with SLE

21 patients with criteria for systemic lupus erythematosus (SLE) and 12 normal controls were studied for their spontaneous circulating IgM and IgG plaque-forming cells (PFCs) reactive against sheep erythrocytes (SRBC) and against a panel of five haptens. Quantitatively defined active and mildly active SLE patients had significantly elevated IgM- and IgG-producing PFCs in their peripheral blood reactive with the panel of five chemically defined haptens. Those patients having inactive SLE also showed increased circulating IgM PFCs. Significant elevations in circulating hapten-reactive PFCs were found to correlate progressively with disease activity in the inactive, mildly active, and active SLE patient groups. Circulating IgM- and IgG-secreting PFC reactive against SRBC were both significantly elevated only in those patients with active SLE. The data support the concept that SLE patients have a generalized increase in B cell activity against a broad repertoire of determinants, even those ostensibly unrelated to natural tissue antigens.     

A possible role of arachidonic acid in human neutrophil aggregation and degranulation.

Chemotactic factors stimulate neutrophils to aggregate and, in the presence of cytochalasin B, to degranulate. Recently, the authors found that arachidonic acid also stimulates human neutrophils to aggregate but does not stimulate cytochalasin-B-treated or untreated cells to degranulate. In this report the authors examined the effect of three blockers of arachidonic acid metabolism on these cellular responses. It was found that the arachidonic acid analog 5,8,11,14-eicosatetraynoic acid and indomethacin, but not aspirin, inhibited no only the arachidonic-acid-induced aggregation response but also the degranulation responses evoked by C5a or a synthetic oligopeptide chemotactic factor. These results suggest that arachidonic acid may be a precursor of bioactive metabolites that stimulate the aggregation and foster the degranulation responses of neutrophils. Thus, these metabolites may be mediators of neutrophil function. Agents that block their formation may thereby inhibit aggregation and degranulation.