Dan-Paul Hartmann

[32] Elimination of macrophages with silica and asbestos

Publisher Summary This chapter discusses the practical use of some of these agents as selective toxins for mononuclear phagocytes. It explores that silica and asbestos are naturally occurring, silicon-containing compounds which are widely distributed within geologic deposits in the earths crust. Asbestos differs from silica in that, unlike silica, asbestos particulates have a fibrous character. The chapter discusses that certain types of asbestos and silica are toxic to macrophages, both in vitro and in vivo . When macrophages are exposed in vitro to these toxic agents, they exhibit extreme cytoplasmic vacuolation, karyopyknosis, disappearance of pseudopodia, and effacement of plasma membranes. Similar morphologic abnormalities have been observed in alveolar macrophages after experimental silica or asbestos inhalation in animals. It reviews that the cytoplasmic enzyme and lactate dehydrogenase have proved to be a useful marker for assessing macrophage cytotoxicity induced by these mineral dusts. Thus, the release of this enzyme into macrophage culture supernatants provides confirmatory evidence of macrophage lysis. The lethal action of silica is believed to result from a hydrogen bonding interaction of silicic acid with membrane protein and phospholipid moieties. Chrysotile asbestos, on the other hand, appears to exert its cytotoxic effect through an electrostatic interaction of its surface magnesium groups with ionized carboxyl groups of membrane glycoprotein sialic acid residues.

The effects of chrysotile and crocidolite asbestos on the lower respiratory tract: analysis of bronchoalveolar lavage constituents

This study was designed to evaluate the effects of amphibole and serpentine asbestos inhalation on the constituents of the lower respiratory tract. Bronchoalveolar lavage (BAL) analyses were performed on three groups of rats: one group was exposed to chrysotile (serpentine) asbestos, another group was exposed to crocidolite amphibole asbestos, while a third group was sham-exposed. Intermittent inhalational exposures lasted three months. The total BAL cell yields and the macrophage content of BAL cells were significantly lower after asbestos exposure, especially in the chrysotile-exposed group. These effects persisted for as long as 1 year after the cessation of exposure. Multinucleated macrophages were seen in BAL cells from both asbestos-exposed groups. Striking ultrastructural alterations of macrophage morphology were noted in BAL cells from both groups of asbestos-exposed rats. Chrysotile fibers were not seen in any BAL cells from chrysotile-exposed animals. However, 15 months after terminating the exposure regimen, a sizeable proportion of BAL macrophages from crocidolite-exposed rats contained phagocytosed asbestos fibers. Significantly higher beta-glucuronidase and lactate dehydrogenase activity was found in BAL fluids from both asbestos-exposed groups and was detected 17-18 months after exposure had ceased. These observations have served as useful correlates of asbestos-mediated injury to the lower respiratory tract. They have also provided evidence of continual pathological sequelae occurring long after withdrawal from asbestos exposure.

Oligodendroglioma with neurocytic differentiation versus atypical extraventricular neurocytoma: a case report of unusual pathologic findings of a spinal cord tumor

Differentiating oligodendroglioma from extraventricular neurocytoma by conventional light microscopy alone can present a diagnostic challenge. We report pathologic findings of an unusual spinal cord tumor from a 33-year-old male patient which showed hybrid features of oligodendroglioma and extraventricular neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary mass in the cervicothoracic region (C7 through T6). Histologic examination revealed a clear cell neoplasm containing ganglion-like cells and calcifications, prompting the differential diagnosis of oligodendroglioma and extraventricular neurocytoma. The immunohistochemical analysis disclosed neural differentiation of the neoplastic cells with strong synaptophysin and neurofilament staining consistent with extraventricular neurocytoma, as well as strong S-100 and glial fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a finding commonly observed in oligodendroglioma. The proliferation index (using antibody MIB1) of the tumor was ∼30%. The morphologic findings and these results strengthen the hypothesis that these tumors may share a common progenitor cell, which has also been observed by others. Because there are differences in patient management and long-term prognosis, it is important to attempt to distinguish between oligodendroglioma and neurocytoma. This unusual case and similar rare reported cases support the need to reclassify tumors showing pathologic features common to both neurocytoma and oligodendroglioma as a unique entity, while the effort continues to identify the cell of origin.

Multimembrane dot-blotting: a cost-effective tool for proteome analysis.

The molecular profiles of protein expression from hundreds of cell lysates can be determined in a high-throughput manner by using fluorescent bead technologies, enzyme-linked immunosorbent assays (ELISAs), and protein microarrays. Although powerful, these tools are costly and technically challenging and thus have limited accessibility for many research groups. We propose a modification of traditional dot blotting that increases throughput of this approach and provides a simple and cost-effective technique for profiling multiple samples. In contrast to traditional blotting that uses a single membrane, we introduce blotting onto a stack of novel, thin, sieve-like membranes. These membranes have a high affinity for binding proteins, but have a lower capacity of protein binding compared to traditional (nitrocellulose) membranes. We compare the linear binding capacity and variability of these novel membranes with nitrocellulose membranes. Also, we describe the use of these membranes in a multilayer dot blot format for profiling mitogen-mediated signal transduction pathways in T cells.

Chronic idiopathic myelofibrosis terminating in extramedullary anaplastic plasmacytoma.

Chronic idiopathic myelofibrosis (CIMF) is a chronic myeloproliferative disorder (CMPD) with progressive fibrosis and extramedullary hematopoiesis. Similar to other CMPDs, the stem cell in CIMF has the potential to differentiate into myeloid or lymphoid lineages, and thus CIMF can culminate in acute leukemia of myeloid or, rarely, lymphoid lineage. We describe an unusual case of CIMF terminating in extramedullary anaplastic plasmacytoma. The patient was a 61-year-old male with an 11-year history of CIMF. His course was complicated by rapidly growing abdominal and inguinal lymphadenopathy. Lymph node biopsy revealed a diffuse undifferentiated infiltrate in the background of extramedullary hematopoiesis. Flow cytometric and immunohistochemical analysis demonstrated plasma cell-related antigens (CD138, CD38, cytoplasmic kappa light chain), epithelial membrane antigen and CD43 in the tumor cells. The myeloid, B-cell or T-cell markers were negative. A clonal immunoglobulin heavy chain gene rearrangement was identified by polymerase chain reaction. The plasma cell origin was further confirmed by electron microscopic examination, which revealed stacks of rough endoplasmic reticulum. Monoclonal gammopathy may occur in CIMF, and rare cases of simultaneous plasma cell myeloma and CIMF have been reported in the literature. However, to the best of our knowledge, this is the first report of CIMF terminating in extramedullary anaplastic plasmacytoma.