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Biomedical subjects

E Grundmann

Publications and source records attributed to E Grundmann.

At least 91 records · Page 5Linked to original sources

New cytomorphologic methods in the diagnosis of bone tumors: possibilities and limitations.

The value of new morphologic methods in the diagnosis of bone tumors is demonstrated in a number of cases. In round cell malignancies (Ewing's sarcoma, malignant lymphoma, neuroblastoma, and anaplastic plasmacytoma) diagnostic accuracy can be improved by electron microscopic and immunohistochemical techniques. New methods are also of value in differentiating the metastatic carcinoma from malignant bone primaries. Electron microscopy may show epithelial cell features (ie, gland structures, desmosomes, and tonofilaments), while immunohistologic investigation of the cytoskeleton may facilitate differentiation of epithelial cells (positive for prekeratin) from mesenchymal cells (positive for vimentin). In the differential diagnosis of typical bone tumors, however, such as osteosarcoma, chondrosarcoma, and malignant fibrous histiocytoma, the value of enzyme histochemical, electron microscopic, and immunohistochemical methods appears somewhat restricted: alkaline phosphatase activity may be increased in both chondrosarcoma and osteosarcoma; collagen type II, the cartilage-specific collagen, is found not only in chondrosarcoma but in osteosarcoma as well. Moreover, osteosarcomas may contain a considerable number of macrophages and histiocytes, and so this feature is worthless in distinguishing osteosarcoma from malignant fibrous histiocytoma. A new approach for appraising the malignancy of bone tumors may be through flow cytometric investigation of nuclear DNA content. Osteosarcomas reveal DNA aneuploidies in more than 80% of cases, with a large proportion of cells in the S phase. These features may prove valuable for discerning osteosarcoma from myositis ossificans. In contrast to typical giant cell tumor of bone, a rare case of malignant giant cell tumor showed aneuploid cell lines indicating the malignant nature of the tumor.

Bone Neoplasms↗

Histological grading and clinical staging of plasmacytoma.

One hundred and forty cases of myeloma were reexamined histologically and classified in three histocytological grades. Close correlations were established between the clinical stages as defined by Durie and Salmon (1975) and the grades of histocytological differentiation. The number of osteolytic lesions correlates with dedifferentiation of malignant plasma cells. Dedifferentiation and high plasma cell counts in the bone marrow are associated with rarefication of hemopoiectic cells and often with an increase of reticular fiber network.

Bone Marrow↗

Combined ultrastructural, histochemical, and autoradiographic study of osteosarcoma after preoperative chemotherapy according to the COSS 80 protocol.

Twelve osteosarcomas treated according to the COSS 80 protocol (preoperative chemotherapy, resection) were studied by light and electron microscopic, histochemical, and autoradiographic methods. Evidence of regressive and necrotic changes was found in many tumor cells, but the alterations were unspecific. Viable tumor cells of high malignancy were also observed regularly, often at the S phase. As the tumor regression continued, a strong reaction of the mononuclear phagocyte system was manifested by the presence of macrophages and giant cells.

Acid Phosphatase↗

Classification and clinical consequences of precancerous lesions in the digestive and respiratory tracts.

The adequate appraisal of precancerous changes is of the utmost importance in our everlasting fight against cancer, and its socio-medical relevance is acknowledged world-wide. In every country where epidemiologists register a rising incidence of malignant neoplasms, endeavours must focus not only on the early diagnosis of existing cancer, but even more on detecting the signs of coming tumors. That is why today the precancerous lesions are a main point of interest in cancer research all over the world for pathologists, radiologists, surgeons, obstetricians, etc.

Adolescent↗

Lymph node reactions to cancer.

Histological, histomorphometrical and histochemical data on the response of regional lymph nodes to tumor development, as recorded in experimental and clinical studies, were coordinated and supplemented by recent findings in experimentally induced autochthonous carcinomas in the rat gastrointestinal tract. The attempted correlation led to the definition of several prognostic parameters: 1) The development of germinal centers and the plasmocytic reaction in tumor draining nodes are morphological expressions of active humoral immune responses that may be specifically directed against the tumor. These reactions attain their maximum usually during late stages of tumor development. Their incidence and prognostic significance may vary depending upon the stage and the type of tumor. 2) Sinus histiocytosis is an immunologically nonspecific lymph node response with debatable prognostic significance. 3) Granulomatous sarcoid-like lesions may be understood as signs of an immunologically mediated antitumor response of macrophages activated by T lymphocytes. They are indicative of a favorable prognosis. 4) Paracortical hyperplasia, characterized by an increased population of lymphocytes and eventually immunoblasts, is an expression of an active T-cell reaction. This reaction occurs typically during early stages of experimental tumors. Correspondingly, it is of favorable prognostic significance in human tumors. 5) Lymphocytic depletion and nodular alteration of T-cell areas, with increased histiocytic infiltration, are reactions most often seen in the draining nodes of an advanced tumor. Both seem to coincide with depression of the cell-mediated immune reactivity. The present assessment of the reactive behavior of diverse lymph node compartments may serve as a first pointer to the proposed histologic immunostaging of malignant tumors.

Animals↗

Biologic characterization of human bone tumors. I. Ewing's sarcoma. A comparative electron and immunofluorescence microscopic study.

Six cases of Ewing's sarcoma were investigated by electron and immunofluorescence microscopy. A layer of basement membrane-like deposits was found between typical principal and secondary tumor cells. To clarify the nature of these ultrastructural deposits, antibodies against collagen type IV were applied to frozen sections of corresponding tumor tissue. This reaction revealed type IV collagen as a regular component of basement membranes in nonneoplastic tumor capillaries, but it was equally able to localize collagen type IV between single tumor cells in capillary-free areas. With the same method, factor-VIII-associated protein, predominantly found in endothelial cells, could be demonstrated in some tumor cells. These results demonstrate that, in addition to anaplastic cells, some tumor cells are found in Ewing's sarcoma that share certain differentiating features with the endothelial cell.

Adolescent↗

Histological classification of gastric cancer from initial to advanced stages.

An ideal classification of malignant tumors should imply not only the histogenesis of the tumor and adequate reproducibility of its specific characteristics by other investigators, but also an exact definition of the stages of tumor development to facilitate prognostic prediction. The present paper proposes a classification of gastric carcinoma with emphasis on the initial stages of malignant transformation. The classification is based on the analysis of early invasive gastric cancer observed in biopsy material from the Institute of Pathology of Münster University. Since 1974, all cases of severe dysplasia or early gastric cancer were selected from a total of 200,000 gastric biopsies and more than 1500 gastric resections, and subjected to special work-up. In analogy to Clark's classification of malignant melanoma (Clark et al., 1969) the proposed classification defines consecutive stages of development in gastric carcinoma with special regard on the maximum depth of invasion and vertical thickness of the tumor, together with its histologic type and the predominant direction of tumor spread.

Adenocarcinoma↗

Intermediate-sized filaments in cells of normal human colon mucosa, adenomas and carcinomas.

The distribution of intermediate - sized filaments in human colon mucosa as well as in adenomas and carcinomas of the colon was studied by means of both immunohistology and electron microscopy. The epithelial cells of the colonic mucosa are definitely labelled with antibodies against prekeratin (cytokeratin). Interwoven filaments of the prekeratin type are present in the basal compartments of the epithelial cells; they surround the nuclei and mucus droplets and form an apical skeletal disc. Pericryptal connective tissue is prekeratin negative and vimentin positive. Benign hyperplastic polyps have a high content of prekeratin. The potential precursors of colonic carcinoma, i.e., the tubular and villous adenomas, also show an increase in intermediate-sized filaments of the prekeratin type. Correspondingly, electron microscopy reveals elongated bundles of intermediate-sized filaments arising from the desmosomes of the lateral and basal cell membranes. The prekeratin content is particularly high in adenocarcinomas and highest in mucinous carcinomas. As expected, the stroma of all neoplasms studied is prekeratin-negative, but distinctly vimentin-positive. In one moderately differentiated adenocarcinoma there was evidence of "vimentin-positive" tumor cells. These changes may be caused by binding of cytokeratins with an unknown substance in vimentin antisera, as observed similarly by Moll et al. (1982) in a transitional cloacogenic carcinoma.

Adenocarcinoma↗

[Mechanisms of malignant growth (author's transl)].

Analysis of invasive malignancy focuses on the particularly high growth rate of tumor cells, and on the aggressive mechanisms of histolysis favoring the infiltration of the malignant cells into the surrounding tissue. Specific significance is attributed to a certain enzyme directed against type IV collagen, and to the auto-locomotion of tumor cells, properties that may also explain the highly selective process of metastazation in at least three consecutive steps: Tumor cells invade a blood or lymph vessel, they are transported along blood or lymphatic pathways, and they eventually infiltrate foreign tissue after penetration and destruction of blood of lymph vessel walls. Among the factors involved in the process of metastazation, special interest is due to blood coagulation and to the coexistence of different tumor cell subpopulations within a primary. These features of malignant growth are based on the loss of functional differentiation as manifested e.g. in the loss of tissue-specific nuclear chromatin structures. Tumor development is triggered by the so-called primary factors which always affect the DNA, i.e. the cell genome. Chemical carcinogens, viruses, and shortwave or ionizing irradiation induce DNA defects which, however, will be reversed and mended by special repair mechanisms in most cases. Thus, the actual development and spread of malignancy is ultimately due to deficient reparation. Co-factors favorizing and promoting carcinogenesis may shorten the latency period, among other several specific chemicals and hormones. Based on current knowledge of tumor dormancy a new concept is proposed for the chronological and morphological sequence of carcinogenesis: Following the development of a primary tumor certain as yet undefined growth factors and especially immunological factors may be responsible for the development of a progressive tumor disease.

Adult↗

Monoclonal gammopathies in Sézary syndrome: a report of four new cases and a review of the literature.

Clinical and laboratory findings of four patients with Sézary syndrome and monoclonal gammopathy are presented. In the literature five cases with the association of these symptoms have been reported. Among the authors' series of 13 patients with Sézary syndrome, monoclonal gammopathy was observed far more often than could be expected from its natural incidence. It appears likely that monoclonal gammopathy is related to Sézary syndrome.

Aged↗

Benign fibrous histiocytoma of bone. Light- and electron-microscopic observations.

Case report of a patient with an unusual, rapidly growing bone tumor in the third and fourth cervical vertebrae. Histological and electron-microscopic investigations reveal a tumor composed of histiocytic cells, xanthomatous cells, giant cells of Touton type, and fibroblastic cells. No cellular features of malignancy are observed. From its cytologic appearance the tumor has to be classified as a benign fibrous histiocytoma. Regarding its ultrastructural features, the tumor may not be distinguished from non-ossifying fibroma of bone, but its clinical pattern shows obvious differences of localization and growth potential. the term "benign fibrous histiocytoma of bone" is proposed for these tumors which must be differentiated from non-ossifying fibroma.

Adult↗

Is ligandin relevant for the uptake and storage of phallotoxins in liver cells?

To exclude an involvement of ligandin in the uptake and storage of phalloidin in hepatocytes equilibrium-dialysis studies were made with phalloidin, cholic acid and bromosulfophthalein (BSP). Binding studies with isolated ligandin indicated that the affinity of ligandin for phalloidin is low (KD = 0.8 X 10-3 M). Phalloidin neither displaced BSP (KD = 1.3 X 10-7 M) or cholic acid (KD = 7.6 X 10-5 M) from ligandin, when preloaded with these substrates. Hepatocytes prepared from rats after daily treatment with phenobarbital during 5 days contained 3-4-fold concentrations of ligandin and bound greater amounts of BSP than controls, Nevertheless the velocity of the uptake both of [3H]-demethylphalloin ([3H]-DMP) and of [35S]-BSP was not augmented. Also the sensitivity of liver cells to phalloidin was not drastically modified after induction with phenobarbital and agrees with earlier findings in vivo. We conclude that ligandin plays a negligible role in the uptake and a minor role in a storage of phallotoxins in liver cells.

Alkaloids↗

Tumor cell types in osteosarcoma as revealed by electron microscopy. Implications for histogenesis and subclassification.

Ultrastructural studies in 26 osteosarcomas of high grade malignancy which were in diverse locations and of varied histological types revealed seven different tumor cell types. They were characterized by their features as follows: 1) anaplastic cells of malignant blast structure: 2) osteoblastic cells -- some of them with dot-like intranuclear bodies; 3) osteocyte-like cells surrounded by mineralized matrix; 4) fibroblast-like cells; 5) cells of myofibroblastic differentiation; 6) chondroblast-like cells in chondroblastic areas, and even 7) angioblastic cells that may be differentiated from the angioblastic and endothelial structures of capillaries. Histogenetically, osteosarcoma may be derived from stromal mesenchymal cells with a potential for differentiation into these seven tumor cell types, any tumor including, however, the osteoblastic and the osteocyte-like cells with tumor osteoid. This matrix serves as the specific criterion for identifying a tumor as "osteosarcoma", but almost every osteosarcoma of high grade malignancy will show these seven tumor cell types. The predominance of one or the other cell in the population may provide the basic information for achieving a cytologic subclassification of osteosarcoma in order to obtain relevant morphologic criteria in terms of prognosis.

Adolescent↗

Early changes in the distribution and organization of microfilament proteins during cell transformation.

During the onset of transformation, Rous sarcoma virus-infected cells undergo characteristic morphological changes that reflect the biochemical events induced by the viral src gene. Temperature downshift experiments using chick embryo cells infected with transformation-defective temperature-sensitive viral mutants have shown two major morphological changes occurring at different times in the transformation process: ruffle-like flowers appear on the dorsal cell surface as early as 15 min after temperature shift, while later, between 6 and 12 hr, cytoskeletal stress fibers disappear and the cells round up. We report that flowers contain large accumulations of the cytoskeletal proteins actin, alpha-actinin, myosin and tropomyosin. Furthermore, since flowers stain very intensely with fluorescein-labeled phalloidin, a cyclopeptide that selectively binds to F-actin and not to G-actin, we suggest that these structures result from an early reorganization of microfilaments.

Animals↗