Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.

Objectives-This study was carried out to investigate possible immunological changes in workers with prolonged low exposure to inorganic mercury in a fluorescent light bulb factory. Methods-29 immunological variables were examined in 34 workers with prolonged low level exposure to inorganic mercury (exposed workers) and 35 unexposed workers as the controls. The selected indicator of mercury exposure was concentration of mercury in the urine (U-Hg), which declined progressively from 36.0 pg/l in 1978 to 6.0 igIl in the study year 1994. Results-None ofthe exposed workers had ever shown signs ofeither acute or chronic inorganic mercury toxicity or had shown any form of hypersensitivity. The only changes found in the exposed workers, compared with the controls, were a reduction of the cells that express cluster differentiation (CD25,(T activation antigen (Tac antigen))) and concentrations of tumour necrosis factor-a (TNF-a) in serum. However, the decrease of cells that express CD25 was unrelated to occupational exposure and was, in all likelihood, a chance finding. Conversely, the decline in serum TNF-a was closely associated with occupational exposure. However, no dose-response relation was found between U-Hg and TNF-a concentrations; nor were TNF-a concentrations affected by cumulative occupational exposure to inorganic mercury in over 20 years. Conclusions-Tentatively, we suggest that reduced serum TNF-a concentrations might be indicative ofan in vivo functional defect of the monocyte macrophage system in this particular group of workers even though they were clinically asymptomatic. (Occup Environ Med 1997;54:437-442)

Serum reactivities to a panel of phospholipid antigens, including cardiolipin (CL), phosphatidylserine (PS), sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine, were measured by enzyme-linked immunosorbent assay in 196 human immunodeficiency virus- l+ (HIV-1+) patients with CDC II to IVC clinical disease. Significant levels of IgG to CL, PS, or both were observed in 23 patients lacking evidence of thrombophilic events or any peculiar clinical feature of HIV-1 infection. Fluorescence-activated cell sorting analyses showed that in vitro apoptosis of T cells was increased in patients with high serum anti-PS IgG, whereas the overexpression of Fas/Apo-1 marker was detected in all patients regardless of their antiphospholipid reactivities. Macrophages from patients with significant titers of anti- PS IgG antibodies were not activated by the presence of apoptotic CEM lymphoblasts or by purified anti-PS IgG from the same patients. By contrast, these antibodies greatly improved the effector functions of autologous macrophages in antibody-dependent cellular cytotoxicity (ADCC) assays using 51Cr-labeled CEM cells, whereas polyspecific IgG were unable to induce an equivalent cytotoxicity in all instances. An increasing effect on ADCC was also observed in tests using macrophages from healthy controls to CEM coated with anti-PS IgG. These results support a potential correlation of anti-PS specificity with T-cell apoptosis in HIV-1 infection. Because PS is exteriorized by apoptotic lymphocytes, its persistence may stimulate antibodies which cooperate with macrophages in the clearance of dead cells by an enhanced ADCC mechanism. This interpretation could explain the absence of thrombophilia in HIV-1+ patients with serum elevations of antiphospholipid reactivities.

B‐cell non‐Hodgkin's lymphomas (B‐NHL) and B‐cell areas of reactive lymphadenopathies were investigated immunohistochemically for expression of two distinct ICAM‐1 epitopes, Me14/D12 and P3‐58, and the LFA‐1 α and β chains. Partial or total loss of expression of one or both epitope(s) and/or chain(s) was evident in all B‐NHL in function of increasing Working Formulation (WF) malignancy grade, with most defects in the high‐grade tumors, namely the lowest detectability of the ICAM‐1 Me14/D12 and LFA‐1 α chain, the lowest co‐expression of ICAM‐1 epitopes and LFA‐1 chains, and the most frequent simultaneous loss. The ICAM‐1 and LFA‐1 profiles overlapped within the low‐ and intermediate‐grades, whereas striking differences between the high‐grade subtypes were detected. Specifically, Burkitt's and lymphoblastic tumors always lost both epitopes and both chains. Large cell, immunoblastic tumors occasionally did so, and also showed either uncoordinated expression or co‐expression of these constituents. It is suggested that expression defects of this type may help differentiate malignant from benign lymphoproliferations, and also be involved in the progression of B‐NHL, since most are observed in high‐grade tumors, whose ICAM‐1 and LFA‐1 profiles indicate that their subtypes are the expression of distinct normal B‐cell differentiation stages.

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