Acute myelomonocytic leukemia with histologic features resembling sarcomatoid carcinoma in bone marrow.

We report a case of primary acute myelomonocytic leukemia involving the bone marrow that resembled sarcomatoid carcinoma. The neoplastic cells in bone marrow biopsy specimens formed cohesive-appearing clusters and cords separated by an immature fibroblastic proliferation and myxoid stroma. Blasts in the bone marrow aspirate smears formed clusters and sheets, and a subset of blasts exhibited erythrophagocytosis. Dysgranulopoiesis was also present. Lineage was confirmed by immunohistochemical analysis of formalin-fixed, paraffin-embedded tissue. The tumor cells showed strong reactivity for lysozyme, myeloperoxidase, CD45, and CD68 and were negative for keratin, S100, CD20, and CD3. The serum lysozyme concentration (110 microgram/mL) was 13 times greater than the normal value (8 microgram/mL). Cytogenetic studies performed on bone marrow aspirate material revealed a complex karyotype, including trisomy 8 and abnormalities of chromosome 11q. We report this case of acute myelomonocytic leukemia because the neoplastic cells appeared cohesive and spindled, resembling sarcomatoid carcinoma, and therefore caused diagnostic difficulty. Other monocytic neoplasms with similar resemblance to carcinoma or sarcoma have been reported in the literature, suggesting that the tendency to appear cohesive may be an inherent characteristic of neoplastic cells with monocytic differentiation.

Acute and chronic actions of ethanol on endogenous calmodulin content in synaptic plasma membranes from rat brain.

The present study was designed to demonstrate that endogenous calmodulin (CaM) content in synaptic plasma membranes (SPM) is altered by acute and chronic administration of ethanol and is a sequel to the kinetic characterization of ethanol inhibition of [125I]CaM binding to SPM reported in our previous study. In rats, an acute ethanol injection (2 g/kg, i.p.) rapidly reduced CaM content in SPM from cerebral cortex, whereas chronic ethanol treatment [6% (w/v) in a liquid diet for 3 weeks] led to an up-regulation of the CaM content. In both cases, the alteration of CaM content in SPM occurred in the EGTA-dissociable pool of CaM (77% of total membrane CaM); the EGTA-nondissociable pool (23% of total CaM) was not affected. In animals receiving chronic ethanol treatment, CaM content in SPM was not altered significantly by the acute ethanol dose that produced rapid reduction of CaM content in control animals, indicating that resistance to ethanol develops. This resistance to ethanol can be attributed to alterations of membrane properties. In control SPM, ethanol at 50 mM markedly accelerated the temperature-dependent dissociation of endogenous CaM, whereas in SPM from animals chronically treated with ethanol, significant acceleration of CaM dissociation required ethanol concentrations as high as 150-200 mM. These findings on SPM in vitro were consistent with the data on CaM content obtained in vivo. Since CaM mediates a variety of biochemical processes in synaptic membranes, we hypothesize that the effects of ethanol in altering the content of membrane-bound CaM may lead to a cascade of consequences in synaptic membrane function.

Anti-C-reactive protein inhibits the calcium-dependent stage of natural killer cell activation.

The studies described in this publication were designed to determine which stage of the NK lytic mechanism is inhibited by anti-C-reactive protein (CRP). Although anti-CRP prevents target cell lysis, it does not block E:T cell conjugate formation. In parallel experiments, the number of conjugates observed in the presence of anti-CRP was normal, whereas the number of target cells killed by this same group of effector cells was greatly inhibited. Since an early stage of NK-mediated lysis requires calcium, conjugates can be synchronized by incubating effector and target cells in the absence of calcium. When conjugates were formed in the absence of calcium, and anti-CRP and calcium were then added to cultures at the same time, anti-CRP inhibited maximally. Anti-CRP continued to inhibit somewhat throughout the calcium-dependent stage but did not block lysis when added after the completion of calcium requiring events. Events that are blocked by anti-CRP must be required for the generation of NK cytotoxic factor because anti-CRP blocks the production of this factor. Once generated, however, anti-CRP does not block the activity of NK cytotoxic factor. This evidence indicates that anti-CRP blocks NK-mediated lysis at the calcium dependent stage of lysis. Events that follow this stage in the lytic process are also inhibited.

Effect of herpesvirus infections on T-lymphocyte subpopulations and blastogenic responses in renal transplant recipients receiving cyclosporine.

The immunosuppressive effects of three herpesviruses--cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV)--were assessed in 29 renal transplant recipients treated with cyclosporine and prednisone. The ratios of Leu 3-positive ("helper-inducer") to Leu 2-positive ("suppressor-cytotoxic") T lymphocytes in peripheral blood were only moderately and transiently decreased during primary CMV infection, with or without concurrent reactivated EBV and HSV infections. This effect was due to an increase in absolute numbers of Leu 2-phenotypic and decrease in Leu 3-phenotypic T cells and was associated with symptomatic viral illness. Reactivated CMV infection alone or together with reactivated EBV and HSV infections resulted in less significant alterations in T-cell subsets than did primary CMV infection. Lymphocyte blastogenesis was not significantly altered during the herpesvirus infections. The data suggest that cyclosporine treatment inhibits the activation of suppressor cells and depression of cellular immune function that have been associated with herpesvirus infections in renal transplant recipients undergoing conventional immunotherapy.

Lymphocyte subsets and natural killer cell responses during cytomegalovirus mononucleosis.

Cell-mediated immunity in seven patients with cytomegalovirus mononucleosis was assessed by monoclonal antibody to lymphocyte subsets, lymphocyte blastogenesis, and natural killer cell activity. The patients had decreased ratios of helper (Leu 3a) to suppressor-cytotoxic (Leu 2a) T cells as compared with normal donors. Leu 2a+ T cells from the patients were uniquely sensitive to overnight culturing, which resulted in a 2.6-fold increase in the helper/suppressor cell ratio and the appearance of an unusual third Leu 1+ 2a- 3a- T cell subset. This correlated directly with enhanced blastogenesis to concanavalin A after preculture. Base-line and interferon-boosted natural killer cell responses versus K562 cell targets during cytomegalovirus mononucleosis did not differ from those of normal donors. This suggests that certain cellular immune functions are depressed during cytomegalovirus mononucleosis in correlation with the emergence of a culture-sensitive subset of suppressor T cells. In contrast, cytotoxic lymphocytes appear to function normally and may aid in the resolution of the illness.