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Biomedical subjects

E Vollmer

Publications and source records attributed to E Vollmer.

At least 73 records · Page 4Linked to original sources

The cytogenesis of macrophages and osteoclast-like giant cells in bone tumors with special emphasis on the so-called fibrohistiocytic tumors.

Recent investigations have suggested that osteoclasts and osteoblasts belong to different cell systems: osteoclasts originate from hemopoietic stem cells, most probably via precursors of the mononuclear phagocyte system. Osteoblasts, however, arise from local mesenchyme. The present classification of bone tumors issued by the WHO, however, is still based on the assumption of osteoclasts and osteoblasts being merely different manifestations or differentiations of the same basic cell type. Consequently, histiocytes or macrophages as well as osteoclast-like giant cells are interpreted in most bone tumors as an autochthonous component of the tumor. In the present study, this theory is contradicted by histological immunohistological, electron microscopic, and autoradiographic-electron microscopic results on a larger number of osteosarcomas, chondromas, chondrosarcomas, chondroblastomas, aneurysmal bone cysts, giant cell tumors of bone, malignant fibrous histiocytomas, fibrosarcomas, desmoplastic fibromas, Ewing's sarcomas, fibrous dysplasias, nonossifying fibromas, and malignant hemangioenkdotheliomas of bone. In order to elucidate the role of macrophages and osteoclast-like giant cells, different monoclonal antibodies were applied to bone tumor specimens as markers of mononuclear macrophages and giant cells. The concept of what is called fibrohistiocytic tumors should be reconsidered. Immunohistological studies have shown that in malignant fibrous histiocytoma as well as in giant cell tumors of bone only a certain portion of macrophages will react with the highly specific antibodies, whereas the majority of tumor cells are negative. This finding alone suggests that the infiltration of macrophages is a reactive phenomenon. It is in agreement with earlier autoradiographic and electron microscopic investigations on giant cell tumors of bone, confirming that only the fibroblast-like tumors are actually proliferating. These data were verified in the present study with the aid of double labeling immunohistological techniques, using antibodies against mature tissue macrophages and others against a proliferation-associated nuclear antigen. Only the fibroblast-like cells, which do not react with the macrophage-specific antibody, will express the proliferation-associated nuclear antigen. Analogous results were obtained in malignant fibrous histiocytoma. We may infer from these results that the majority of these tumors must be neoplasms of local mesenchyme, mostly in fibroblastic differentiation, while the considerable number of macrophages is seen as a reactive phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Neoplasms↗

[Immunohistological differentiation of the cells of the arterial wall in transplanted kidneys].

22 nephrectomy specimens of renal allografts in chronic rejection after 3 months to 96 months were studied immunohistologically. The various cell types in the arterial wall were characterised with specific antibodies against different cells of the mononuclear phagocyte system, against smooth muscle cells, and for differentiating lymphatic cells. In addition, the metabolism of lipoproteins was studied using different antibodies against several apolipoproteins. According to our results, subendothelial plaques of foam cells consist of macrophages in foamy transformation. In the stage of intimal fibrosis, smooth muscle cells are more prominent. Lymphatic infiltration consists almost exclusively of T lymphocytes. Apolipoprotein analysis reveals deposits of Apolipoproteins A1 and B, mostly extracellular. On the whole, these results show that not only immunologic factors are involved in the reaction of the arterial wall in chronic transplant arteriopathy, but that like in atherosclerosis, disorders of lipoprotein metabolism, probably due to endothelial dysfunction, play an important role.

Desmin↗

S-100 protein and neuron specific enolase (NSE) expression by chordomas in relation to the composition of their stromal mucosubstances.

The immunoreactivity of S-100 protein and neuron specific enolase (NSE.) was correlated with the composition of stromal glycosaminoglycans in chordomas and human notochords, in a combined histochemical and immunohistochemical study. We found that S-100 protein is negative in notochordal and chordoma cells in the absence of stromal mucosubstances or in the presence of small quantities of hyaluronic acid. The positivity of S-100 immunoreaction was found to be related to the presence of stromal glycosaminoglycans of the chondroitine sulfate A and C type. NSE. was found positive in cells presenting features of high metabolic activity. Consequently S-100 protein and NSE. immunoreactivity cannot have any cytogenetic implications, but they could be considered as markers indicating specific cell-stromal functional interactions.

Chordoma↗

Changes in intestinal mucosa above lymph follicles during carcinogenesis in rats. A light and electron microscopic study.

Changes in the intestinal mucosa during carcinogenesis were investigated in 36 rats after weekly s.c. injection of 20 mg dimethylhydrazine/kg bodyweight. More changes were seen in the large than in the small intestine. In the first week, 60% of colonic lymphoid plaques displayed various crypt abscesses and glandular regenerations. These mucosal changes correspond to the glands covering the lymph follicles, in direct contact with lymphoid cells. Beginning in week 8, dysplastic glands developed in these mucosal areas above the lymph follicles. The number of lymphoid plaques with dysplastic glands in the large intestine increased week by week, attaining 75% in week 20. At the end of week 12 the first adenocarcinoma was detected in the cecum by light microscopy, and classified as a poorly differentiated adenocarcinoma with signet ring cells infiltrating the lymph follicles which contained endocrine cells. The majority of adenocarcinomas (10 cases) occurred in week 20. Of these, 7 were localized above the lymphatic plaques in the intestine. Endocrine cells were found in varying numbers in 6 of 10 adenocarcinomas. Three endocrine cell carcinomas, corresponding to human adenocarcinoids or goblet cell carcinoids, developed within the intestinal mucosa; all were identified as poorly differentiated intestinal adenocarcinomas, two of them situated above lymph follicles. These suprafollicular tumors developing from the glandular base, were composed of mucoid cells, endocrine cells, and undifferentiated cells. Microcarcinomas are considered as initial stages of endocrine cell carcinoma.

1,2-Dimethylhydrazine↗

Biological characterization of human bone tumors. X. The proliferation behavior of macrophages as compared to fibroblastic cells in malignant fibrous histiocytoma and giant cell tumor of bone.

Seven giant cell tumors of bone and four malignant fibrous histiocytomas were studied immunohistochemically with different monoclonal antibodies to the mononuclear phagocyte system (MPS), to HLA-DR antigens, and to a proliferation-associated nuclear antigen (KI-67), in order to clarify the role of macrophages in these tumors. A part of the mononuclear cells stained positive with antibodies against the MPS. Antibody 25-F-9 against mature tissue macrophages showed the strongest reaction. The osteoclast-like giant cells also stained positive with this antibody. Fibroblast-like stromal cells, however, showed negative reactions to all antibodies against MPS cells. A double-labeling immunohistological technique was used to detect the proliferating cell population in these tumors. The fibroblast-like cells that were negative for MPS markers, were positively labeled with the monoclonal antibody Ki-67 against a proliferation-associated nuclear antigen, whereas a negative reaction to Ki-67 was seen in cells positive with antibodies to the MPS. These results support the concept that macrophages are a reactive population in these tumors, whereas the fibroblast-like mesenchymal cells are the proliferating tumor cells.

Antibodies, Monoclonal↗

Identification of macrophages and smooth muscle cells with monoclonal antibodies in the human atherosclerotic plaque.

Sections of human atherosclerotic plaques, obtained from 21 autopsy cases with various degrees of atherosclerosis, were stained with the indirect immunoperoxidase technique using specific monoclonal antibodies against macrophages and smooth muscle cells. Distinctive results were found in differing stages: Single blood monocytes were observed in diffuse intimal thickening and the foam cells seen in fatty streaks were mostly identified as mature tissue macrophages, while only very few blood monocytes were present. The spindle cells observed in fibroelastic plaques showed positive reactions to antibodies against desmin, which points to their derivation from smooth muscle cells, whereas only a few macrophage-derived foam cells were seen in these lesions. In the complicated lesions the majority of foam cells were macrophage-derived, but there was also a small number of foam cells positive to antibodies against desmin, suggesting a smooth muscle cell derivation. Our results confirm that in human atherosclerotic plaques the majority of the foam cells are obviously macrophage-derived, which emphasizes the important role of macrophages in the morphogenesis of these lesions.

Adolescent↗

Biologic characterization of human bone tumors IX. Occurrence of macrophages.

Fifty bone tumors were investigated using immunohistological methods for an assessment of the amount and nature of macrophage infiltration. Polyclonal antibodies against lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsin were used as markers, besides certain monoclonal antibodies against blood monocytes and mature tissue macrophages. Particularly high macrophage infiltration was found in malignant fibrous histiocytomas, giant cell-containing osteosarcomas, giant cell tumors of bone, and aneurysmal bone cysts. Moderate infiltrates were seen in some highly malignant osteosarcomas, in fibrosarcoma, and in chondroblastoma. A low macrophage content was observed in some osteosarcomas, in Ewing's sarcomas, chordomas, fibrous dysplasias, aggressive fibromatoses, and cartilage tumors. Osteoclast-like giant cells showed distinctly positive reactions with the monoclonal antibody against mature tissue macrophages. In fibrohistiocytic tumors (MFH, giant cell tumor, non-ossifying fibroma) only macrophages gave positive reactions with those antibodies, whereas the reaction of spindle-shaped tumor cells was always negative. These results strongly indicate that the macrophages found in bone tumors (including those of fibrohistiocytic type) result from reactive infiltration. The autochthonous tumor cells are most probably derived from local mesenchymal cells, and are thus cytogenetically unrelated to the infiltrating macrophages.

Antibodies↗

Malignant lymphomas with primary bone manifestation.

18 malignant lymphomas with initial manifestation in bone were selected from the Bone Tumor Registry of Westfalia at the Münster Institute of Pathology where they had been documented between 1975 and 1985, and evaluated under clinical, radiological and histological aspects. Non-Hodgkin lymphomas were reclassified according to the Kiel nomenclature. Paraffin-embedded material was subjected to immunohistochemical analysis in order to assess the features that could add to the correct characterization of these lymphomas, and to their differentiation from other round cell tumors of bone. Non-Hodgkin lymphomas (NHL) were more common in the collective than Hodgkin's lymphomas (HL). Of 13 NHL, 2 were of low, 11 of high-grade malignancy. The former comprised one centrocytic and one centroblastic/centrocytic, the latter 7 centroblastic, 2 immunoblastic, and 2 lymphoblastic lymphomas. Seven NHL patients with localized tumors survived up to 11 years (mean survival span: 6 yrs) after local therapy (radiation and/or resection). Another NHL patient, however, had multiple bone lesions, and died within a year. Analysis for leukocyte common antigen was positive in 9/12 NHL cases, reaction with Ki-B-3, a marker of B-lymphocytes, was positive in 7/12 cases. No lymphoma cells were found to react positively with lysozyme, alpha 1-antitrypsin, or alpha 1-antichymotrypsin. It is concluded that localized lymphomas of bone respond well to appropriate local therapy; immunohistochemical investigation may be useful to characterize the true cellular origin of these tumors, and may help to differentiate them from other round cell tumors of bone.

Adult↗

Biologic characterization of human bone tumors. VI. The aneurysmal bone cyst: an enzyme histochemical, electron microscopical, and immunohistological study.

The etiology of aneurysmal bone cyst is still unknown. Most theories of the histogenesis of this lesion assume a vascular origin and speculation has focused on the characteristic pseudoendothelial lining of the cyst walls. In the present study, this structure has been subjected to enzyme histochemical, electron microscopical, and immunohistochemical investigation. Of the enzymes tested only alkaline phosphatase was present in the cyst lining. Electron microscopy revealed fibroblast-like cells covering the walls of cystic cavities, but no genuine endothelium, basement membranes or pericytes were identified. For the immunohistochemical studies a panel of poly- and monoclonal antibodies against HLA-DR antigens, mature and immature macrophages/histiocytes, smooth muscle fibers and endothelial cells, as well as the lectin Ulex europaeus I agglutinin were used. None of these markers demonstrated the presupposed vascular characteristics in the cells constituting the pseudoendothelial lining of the cyst walls. Despite current theories to the contrary, it was concluded that aneurysmal bone cyst is unlikely to originate from the vascular system, and that a new concept of its pathogenesis must be sought.

Acid Phosphatase↗

A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non-reactive with normal adult tissues.

This report describes a monoclonal antibody (MAb) generated by immunization of mice with cell suspensions of capillary-rich fragments of mammary carcinomas. The antibody (EN 7/44) belongs to the IgM class and detects a 30.5 kDa antigen which is found in the cytoplasm of human placental and umbilical vein-endothelial cells (HUVEC) and on the surface of tumor endothelium. Using indirect immunofluorescence and immunoperoxidase techniques, we did not find the MAb in peripheral blood cells or in any human cell lines tested, nor in endothelial cells from normal, nonproliferating adult tissues. Positively staining endothelium was found in the placenta, the umbilical vein and in proliferating normal tissues (intestine). Positive endothelial cells were found in acute inflammatory reactions and in tumors. In the latter, the strongest reactions were seen in newly formed budding capillaries, which were identified by their reactivity with Ulex europaeus I-lectin and antibodies against F VIII-RAG. In tumor tissues, large vessels could be positively stained with the EN 7/44 antigen, in contrast to inflammatory tissues. It is concluded that endothelial cells at the tip of a budding capillary express distinct phenotypic characteristics.

Adult↗

Improved grading of bone tumors with the monoclonal antibody Ki-67.

A total of 60 bone tumors and tumor-like lesions presenting various grades of malignancy were investigated immunohistologically with the monoclonal antibody Ki-67 directed against a cell proliferation-associated nuclear antigen. The results obtained agree well with those of flow cytometric and autoradiographic studies on similar tumor entities. The monoclonal antibody Ki-67 was found to be a handy and reliable tool for improved grading of bone tumors.

Antibodies, Monoclonal↗

Macrophages and T lymphocytes infiltrating the rat mammary carcinoma HH9-cl 14 in progressive and regressive tumor growth. An immunohistological study.

Ascites tumor cells (2 X 10(6] of a DMBA-induced rat mammary adenocarcinoma (HH9-cl 14) were injected s.c. into tumor-free syngeneic female rats and produced a continuously growing solid tumor in all animals of this group. Inoculation of 2 X 10(7) cells induced a first brief period of tumor growth, followed by complete tumor regression from the 2nd until the 5th week after injection. Both the progressive and the regressive tumors were analyzed immunohistologically at different stages with monoclonal antibodies against different T lymphocytes and macrophages. Obviously these cells appear in different quantity and quality, during the hosts immune response. Possible interactions of T lymphocytes and macrophages with tumor cells are discussed.

Animals↗

Biological characterization of human bone tumors. VIII. Expression of HLA-DR antigens in bone tumors and tumor-like lesions.

A total of 45 cases of bone tumors and tumor-like lesions were studied in order to determine the expression of an HLA-DR antigen by the monoclonal antibody 910-D-7, and its possible correlation with histology, using the indirect immunoperoxidase method on frozen sections. The pattern of antigen expression was nearly constant for the individual cell types, though varying in intensity, and did not depend on the biological behavior of the respective lesions. No clear correlation could be established between antigen expression and cell maturation. Although the biological significance of antigen expression in these tumors is not yet understood, it is clear that here, too, the mere presence of an HLA-DR antigen cannot be interpreted as a sign of malignant transformation.

Bone Cysts↗

Early local reaction and lymph node permeation of rat carcinoma HH9-cl 14 cells. An immunohistological approach.

2 X 10(6) ascites tumor cells of a DMBA-induced rat mammary adenocarcinoma (HH9-cl 14) were injected subcutaneously into tumor-free syngeneic female rats. Investigations were made, in addition to conventional paraffin histology and light microscopy, with immunohistological methods using poly-and monoclonal antisera. From 10 minutes to 2 hrs after inoculation carcinoma cells were seen inert either as single cells or as little clusters between connective and fatty tissue. After 6 hrs the number of tumor cells had decreased, and an increasing quantity of macrophages were found in close contact with them. At this stage some lymphocytes, too, appeared in the inoculation area. 10 minutes after injection, tumor cells were already entering regional lymph nodes and could be observed in the subcapsular sinuses. 2 hours later they had almost traversed the intermediate and medullary sinuses. Up to 6 hours after injection, increasing numbers of macrophages and sinus endothelial cells were seen, and the lymph node's appearance manifested hyperplasia of the paracortical zone. 4 and 6 hrs after injection, the total number of tumor cells in regional nodes decreased again noticeably, and sometimes tumor cells had disappeared. The first lymph node metastases appeared 28 days after inoculation.

9,10-Dimethyl-1,2-benzanthracene↗