Ezio Merler

Human and animal solid tumors elaborate a factor which is mitogenic to capillary endothelial cells. This factor has been called tumor-angiogenesis factor. The important components of TAF are RNA and protein. It is suggested that blockade of this factor (inhibition of angiogenesis) might arrest solid tumors at a tiny diameter of a few millimeters.

Human mononuclear leukocytes were fractionated into populations of null, T and B cells by immunoabsorbent column chromatography followed by E-rosette formation and purification of T cells by differential centrifugation and osmotic lysis. The unfractionated and fractionated cell populations were first separately cultured for 14 days in plasma clots in the presence of two international units erythropoietin. Typical erythroid burst-forming unit (BFU-E)-derived colonies grew in the unfractionated cell cultures but not from T- or B-cell cultures. BFU-E colonies grew in null cell cultures but most of the colonies were small and variably hemoglobinized with less than three subcolonies. When intact T cells were added to null cells and cocultured, many typical large BFU-E colonies with more than 10 well homogenized subcolonies appeared. Increasing numbers of large BFU-E colonies in null cell cultures were induced by stepwise addition of T cells but not by the addition of B cells. A conditioned medium in which T cells had been induced to divide by tetanus toxoid substituted for intact T cells in this T-cell-dependent BFU-E colony formation observed in null cells. These findings demonstrate that the BFU-E, a committeded erythroid stem cell, resides in the null cell fraction of peripheral blood, but its proliferative capacity and differentiation in vitro requires a soluble product of T cells. Such experiments now permit a new approach to the assessment of various disorders of erythropoiesis. Erythroid hypoplasia in a particular case may be due to dysfunction of the committed precursor cell or to a failure of a helper effect induced by T cells.

Abstract Circulating T (thymus-derived) and B (bone-marrow-derived) lymphocytes were assessed in 19 patients with common variable or acquired agamma-globulinemia. T-cell number and function were concomitantly depressed in five of these patients who had other debilitating illnesses. B-cell number was normal in 10 patients, increased in five, and markedly reduced in four. Transformation of B cells into immunoglobulin (Ig) secretory cells in the presence of a soluble T-cell-derived lymphocyte mitogenic factor (LMF) was studied in the 15 patients with B cells. B cells from nine of these patients, when stimulated with LMF, failed to synthesize Ig. In five other patients, B cells divided and made Ig, but they failed to secrete it. A single patient had a factor in his serum that inhibited activation of both normal and autologous B cells by LMF. Acquired or common variable agammaglobulinemia is a heterogeneous disease caused by defects occurring at various steps in the maturation pathway of the B cell into an...

Two patients with recurrent bacterial infections associated with dysgammaglobulinemia are reported in whom there was a marked deficiency of 7S gamma-globulins in the presence of elevated concentrations of 19S gamma-globulins. Both patients lacked detectable beta2A-globulins. One of these patients had been known to have congenital agammaglobulinemia and had been followed for a number of years previously. The synthesis of 19S gamma-globulins in this patient was a transient phenomenon associated with renal and hepatic disease, and the ability to synthesize isohemagglutinins, Forssman antibody and anti-typhoid O antibodies. Plasma cells were not seen in the biopsy specimens of liver, spleen and lymph node from one patient, of lymph node from the other, or in bone marrow aspirates from both patients.

Human monocytes in culture release small amounts of prostaglandin E (PGE) into the medium. Addition of Fc fragments of IgG to human monocyte monolayer cultures results in a marked increase in PGE release; Fab fragments, monomeric IgG, and human serum albumin have no effect. An IgG1 myeloma has no effect on PGE levels but addition of the heat aggreagted protein results in a marked increase of PGE secretion. Exposure of the cells to Con A, which binds to a specific monocyte plasma membrane receptor, also results in a large increase in PGE release. The magnitude of the increase in PGE secretion produced by exposure of the monocytes to these ligands greatly exceeds the stimulation observed after the addition of antigen-activated mononuclear cell supernatants, zymosan, Sephadex beads, or endotoxin, to monocyte cultures. Prostaglandin E2 (PGE2) accounts for approximately 70% of the total prostaglandins released by stimulated cells. After addition of Indomethacin to monocyte cultures, the stimulatory effects of the ligands on PGE release are inhibited. Addition of Con A to monocyte cultures results in an increased incorporation of [3H]-arachidonic acid into PGE2. These results suggest that this ligand stimulates synthesis as well as release of this prostaglandin.