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R Moll

Publications and source records attributed to R Moll.

At least 145 records · Page 8Linked to original sources
PubMed1991

Bellini duct carcinoma: further evidence for this rare variant of renal cell carcinoma.

Bellini duct carcinomas have recently been identified as a new entity in the spectrum of renal cell carcinomas and 10 cases have now been reported. The present paper adds detailed clinical and morphological data on six new cases. In addition, immunohistological and electronmicroscopical results support the origin of these tumours from the renal collecting ducts, especially the papillary ducts (Bellini ducts). A set of immunohistological reactions, including reactions to cytokeratins 13 and 19, vimentin and UEA-1 was found to facilitate the differential diagnosis of Bellini duct carcinomas from other renal cell carcinomas and infiltrating urothelial carcinomas of renal pelvis.

Adult↗
PubMed1991

Intermediate filament protein profiles of human testicular non-seminomatous germ cell tumors: correlation of cytokeratin synthesis to cell differentiation.

The patterns of cytoskeletal differentiation were studied in 20 testicular non-seminomatous germ cell tumors by immunohistochemistry, using diverse monoclonal antibodies specific for different intermediate filament (IF) proteins and for desmoplakin. Immunofluorescence and immunoperoxidase methods on both formalin-fixed and frozen tissues were applied, in some cases together with a gel electrophoretic analysis of IF proteins. The tumors examined included embryonal carcinoma (EC), endodermal sinus tumor (EST), choriocarcinoma and teratoma. Nine of the tumors were composed of only one histological type, the others showed mixed components. Cytokeratins 8 and 18 were identified in all these neoplasms, but their immunostaining was weak in ECs. Cytokeratin 19 was absent or very scarce in ECs, but strongly expressed in ESTs, choriocarcinomas and teratomas, thus allowing the identification of small EST and choriocarcinoma elements in ECs even when they were morphologically not obvious. Occasionally, some cells in ECs and ESTs also stained for cytokeratins 4 and/or 17, indicating potential for epithelial stratification. The majority of the germ cell tumors showed varied amounts of vimentin, often in co-existence with cytokeratins. Neurofilaments were demonstrated in scattered tumor cells in a single case of EST. In the teratomas studied, each type of tissue component present showed the expected IF protein. However, in many germ cell tumors some stromal cells and blood vessels contained, in addition to vimentin and desmin, also cytokeratins 8 and 18. This heterogeneity of the cytoskeletal profile of germ cell tumors is indicative of the varied differentiation potential inherent in these neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1991

Spheroid-cytoplasmic complexes in a congenital myopathy.

The most striking pathological finding in the deltoid muscle biopsy specimens of 2 unrelated adult male patients consisted of large spheroid-cytoplasmic complexes of intricate structure, as previously described only under experimental conditions (Chou and Mizuno, 1986). These large cytoplasmic masses were characterized by a granular centre and a filamentous halo. Immunohistology revealed the presence of intermediate filaments of the desmin and vimentin types. Clinically, both patients showed mild and slowly progressive proximal myopathy of adult onset. In one patient, the myopathy was strongly suspected to be inherited. In concordance with previous reports on cytoplasmic and spheroid body congenital myopathies, these spheroid-cytoplasmic bodies further enlarge the spectrum of late onset congenital myopathies.

Adult↗
PubMed1991

Expression of intermediate filament proteins in fetal and adult human kidney: modulations of intermediate filament patterns during development and in damaged tissue.

The expression of intermediate filament proteins, particularly individual cytokeratins (CKs), vimentin, and glial filament protein, was immunohistochemically investigated using frozen sections and Carnoy-fixed, paraffin-embedded tissue from normal fetal and adult human kidneys as well as from pathologically altered kidneys. In fetal kidneys, the co-expression of CKs and vimentin was detected in the visceral and parietal epithelium of the glomerulus, the proximal tubules, the thin loops of Henle, and the collecting ducts. In contrast, in the tubules of normal adult kidneys, the presence of vimentin and CKs was nearly always mutually exclusive. While CKs 8 and 18 were present in all tubular epithelia, CKs 19 and 7 each exhibited a distinctive distribution pattern, there being a striking alteration between positive and negative segments and, not infrequently, intratubular heterogeneities. In certain segments, particular cell types (e.g., "plica cells," intercalated cells) could thus be recognized. In tubular epithelia altered by various injurious conditions, novel or enhanced expression of vimentin, CK 19 and CK 7, and, less frequently, CK 17 and glial filament protein was noted in certain segments. The increase in intermediate filament protein expression in altered (particularly proximal) tubules appeared to parallel the reduction in the degree of differentiation. Vimentin was never detected in distal tubules. The present results reveal a considerable similarity between the intermediate filament patterns in non-neoplastic proximal tubules of fetal and damaged kidney tissue and those in clear-cell and chromophilic renal cell carcinomas. They also serve to illustrate that the analysis of both fetal development and reactive cell changes may significantly contribute to our understanding of differentiation phenomena in malignant tumors.

Antibodies, Monoclonal↗
PubMed1991

Molecular diversity of cytokeratins: significance for cell and tumor differentiation.

Normal and transformed epithelial cells are characterized by the expression of a distinct class of intermediate filaments (IFs), the cytokeratin (CK) filaments. Their constituents, the CKs, comprise a complex multigene family of related proteins which can be subdivided into two sequence types (I and II). In the various epithelial cell types (excluding trichocytes), 19 different CK polypeptides (CKs 1-19) have been distinguished until recently. An additional cytoskeletal polypeptide of Mr 46,000 has been detected, by gel electrophoresis and by immunocytochemistry, in certain types of epithelia including gastric foveolar epithelium, small and large intestinal epithelium, urothelium, and epidermal Merkel cells. On the basis of its biochemical properties and considerable sequence homologies with several type I CKs, this new cytoskeletal protein is suggested to be included in the catalogue of human CKs as CK 20. The various CK polypeptides, as detected by gel electrophoretic and/or immunocytochemical analysis, are expressed in different epithelia and carcinomas in various combinations in a differentiation-dependent manner. Moreover, co-expressions of CKs with other IF classes (vimentin, neurofilaments, glial filaments) are also characteristic of certain epithelial differentiation lineages. Both non-neoplastic epithelial alterations as well as malignant transformation may result in similar modifications of the IF expression profiles although there is a considerable tendency of conservativity. In several instances, a reduced degree of differentiation is paralleled by an increased complexity of the IF protein pattern. CK (and IF) typing can be successfully used in the tracing of developmental lineages as well as in the histological differential diagnosis of primary and metastatic carcinomas. Certain CK polypeptides (CKs 5, 6, 14, 16, 17) identify squamous cell carcinomas including poorly differentiated ones, while other CKs, including CK 20, are typical of primary and metastatic urothelium-derived carcinomas. Among simple-epithelial tumors, CK analysis is of potential diagnostic value in the distinction of mesotheliomas from adenocarcinomas, the discrimination of different carcinomas within the gastrointestinal tract, and the distinction of certain gastrointestinal carcinomas from other adenocarcinoma types including breast and lung carcinomas. Among the individual CKs, CKs 5, 7, 13, 14, 19, and 20 appear to be particularly useful for diagnostic purposes. An important task in the future will be the development of additional monospecific CK-antibodies, particularly such which work on routine paraffin sections.

Cell Differentiation↗
PubMed1990

Expression of epithelial antigens Exo-1 and EPM-1 in human epidermal keratinocyte maturation and benign and malignant neoplasia.

Exo-1, a polar neutral glycolipid, and EPM-1, a high molecular weight glycoprotein, are developmental antigens of human epithelial cells, initially described as components both on the cell surface and in secretions of gastrointestinal epithelial and respective tumors. In order to assess the biological significance of both antigens for epithelial cell differentiation and neoplastic transformation, their expression during human skin development and benign and malignant neoplasia was analyzed in fresh frozen tissue specimens of skin biopsies and of human epidermal keratinocytes growing in experimental model systems. Antigen expression was assessed immunohistochemically with specific monoclonal antibodies. During fetal development Exo-1 was temporarily expressed in intermediate cells but was absent in normal adult human skin. Exo-1 expression reemerged in neoplasias, both benign and malignant, but was restricted to spinous-like differentiated cells. Similarly, Exo-1 was not expressed in transplants of normal keratinocytes mimicking the normal epidermis but was clearly visible in differentiated areas of transplants of malignantly transformed keratinocytes. EPM-1 appeared first in basal epidermal cells in the second half of gestation and remained detectable in the stratum basale of adult skin. While squamous cell carcinomas continued to express EPM-1, it was not detectable in basal cell epitheliomas and in normal epidermis after invasion by neuroectodermal tumor cells. In experimental models, EPM-1 was present in the basal layers of normal human keratinocytes and of transformed keratinocytes with benign growth characteristics whenever a well stratified and keratinized epidermis-like epithelium had formed in transplants. In transformed keratinocytes with malignant growth behavior, EPM-1 was expressed irregularly, as in squamous cell carcinomas in situ. Thus, expression of Exo-1 is a marker for an early embryonic differentiation pathway of human keratinocytes and in adult tissue reveals abnormal differentiation associated with certain stages of hyperproliferation. EPM-1 expression is part of developmental programs and is influenced by microenvironmental interactions and alterations of tissue homeostasis.

Antigens↗
PubMed1990

Multidirectional differentiation in a newly established human epithelioid sarcoma cell line (GRU-1) with co-expression of vimentin, cytokeratins and neurofilament proteins.

A new permanent cell line (GRU-1) derived from the lymph-node metastasis of a human epithelioid sarcoma was established in tissue culture. Immunohistochemically, the original tumor had exhibited an intriguing potential for multidirectional differentiation with features of mesenchymal, epithelial and neural differentiation, evidenced by the co-expression of vimentin, cytokeratins and neurofilament proteins, respectively. This capability for multidirectional differentiation was fully preserved in the cultured cells. GRU-1 tumor cells proved to be uniformly positive for vimentin and a considerable proportion of the tumor cells exhibited a positive reaction for cytokeratins and neurofilament proteins. The neural markers neuron-specific enolase (NSE) and synaptophysin were observed in a small proportion of GRU-1 cells. Ultrastructurally, GRU-1 cells showed desmoplastic activity in vitro, being enmeshed by collagen fibrils. DNA distribution, as studied by flow cytophotometry, revealed DNA-diploidy (DNA index = 1) and a G0/G1-proportion of 70.5%. After heterotransplantation in nude mice, GRU-1 tumor cells expressed vimentin and cytokeratin only, whereas the neural markers could not be further demonstrated.

Adult↗
PubMed1990

Collateral pathways in portal hypertension.

In a retrospective study angiographic image material of percutaneous direct portographies carried out in 43 patients was evaluated according to anatomic and radiologic criteria. These examinations were performed for therapeutic purposes (embolisation of vessels supplying varices). All the hepatofugally perfused veins were analyzed according to their localisation and course. Apart from the known portocaval collateral pathways a number of other collaterals not yet described could be documented by means of angiography.

Aged↗
PubMed1990

Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns.

A major cytoskeletal polypeptide (Mr approximately 46,000; protein IT) of human intestinal epithelium was characterized by biochemical and immunological methods. The polypeptide, which was identified as a specific and genuine mRNA product by translation in vitro, reacted, in immunoblotting after SDS-PAGE, only with one of numerous cytokeratin (CK) antisera tested but with none of many monoclonal CK antibodies. In vitro, it formed heterotypic complexes with the type II CK 8, as shown by blot binding assays and gel electrophoresis in 4 M urea, and these complexes assembled into intermediate filaments (IFs) under appropriate conditions. A chymotrypsin-resistant Mr approximately 38,000 core fragment of protein IT could be obtained from cytoskeletal IFs, indicating its inclusion in a coiled coil. Antibodies raised against protein IT decorated typical CK fibril arrays in normal and transformed intestinal cells. Four proteolytic peptide fragments obtained from purified polypeptide IT exhibited significant amino acid sequence homology with corresponding regions of coils I and II of the rod domain of several other type I CKs. Immunocytochemically, the protein was specifically detected as a prominent component of intestinal and gastric foveolar epithelium, urothelial umbrella cells, and Merkel cells of epidermis. Sparse positive epithelial cells were noted in the thymus, bronchus, gall bladder, and prostate gland. The expression of protein IT was generally maintained in primary and metastatic colorectal carcinomas as well as in cell cultures derived therefrom. A corresponding protein was also found in several other mammalian species. We conclude that polypeptide IT is an integral IF component which is related, though somewhat distantly, to type I CKs, and, therefore, we propose to add it to the human CK catalogue as CK 20.

Amino Acid Sequence↗
PubMed1990

Cytoskeletal heterogeneity of an epithelioid sarcoma with expression of vimentin, cytokeratins, and neurofilaments.

We studied an unusual sarcoma with morphologic features diagnostic of epithelioid sarcoma by conventional light microscopy, transmission electron microscopy, and immunohistochemistry. The primary tumor, which was located in the deep soft tissues of the buttock of a 32-year-old woman, and its metastases to lymph nodes, liver, and lung were available for investigation. The histomorphological and ultrastructural appearance of the primary tumor and its metastatic deposits were typical of epithelioid sarcoma. Immunohistochemistry revealed a strong and uniform reactivity for vimentin in both the primary tumor and its metastases. In contrast, a marked cytoskeletal heterogeneity became evident for cytokeratins and neurofilaments, which were observed exclusively in lymph node metastasis. To our knowledge, the observation of neurofilaments in epithelioid sarcoma has not previously been reported.

Adult↗
PubMed1990

Intraepidermal formation of Merkel cells in xenografts of human fetal skin.

An experimental transplantation model using human fetal skin was applied to approach the question of the embryologic origin of human Merkel cells. Palmar and plantar skin from five fetuses, between 8 and 11 weeks of estimated gestational age (EGA), was xenografted to subcutaneous beds of nude mice. After 4 or 8 weeks of growth, biopsies were taken from these xenografts and examined for the presence of Merkel cells, using immunocytochemistry with antibodies specific for simple epithelial-type cytokeratins and neuron-specific enolase (NSE) as well as using electron microscopy. Skin from the same fetuses at the time of transplantation was screened in the same way. In all fetuses, no (or very scarce) epidermal Merkel cells were detected at the transplantation time, but in all cases abundant epidermal Merkel cells of apparent human origin were found after 4 or 8 weeks in xenograft culture. Dermal nerve fibers, as recognized by neurofilament antibodies, were scarce or essentially absent in the xenografts. These results indicate that Merkel cells regularly develop in epidermis dissected and xenografted in an early fetal stage, although the dissection implies the interruption of the dermal nerves. The results strongly support the notion of the origin of Merkel cells from epidermal precursor cells. The apparent absence of dermal Merkel cells and dermal nerve fibers in the xenografts suggests that the presence of dermal sensory nerve fibers may be required for the dropping off of epidermal Merkel cells into the upper dermis, which occurs in normal fetal development.

Animals↗
PubMed1990

Antibodies to cytoskeletal proteins in patients with Crohn's disease.

The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy-proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti-nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera were also negative for antibodies to double-stranded DNA, anti-mitochondrial antibodies, and antibodies to gastric parietal cells. Using sensitive enzyme-linke immunosorbent assays with purified antigens and Western blotting with cytoskeletal proteins of human intestinal cells, the following antibodies could be demonstrated: cytokeratin 18 autoantibodies (IgG 20.0%; IgM 6.7%; IgA 13.3%), actin antibodies (IgG 36.7%; IgM 48.3%, IgA 26.7%), desmin antibodies (IgG 6.7%; IgM 15.08%; IgA 5.0%), vimentin antibodies (IgG 3.3%; IgM 16.7%; IgA 10.0%) and tropomyosin antibodies (IgG 3.3%; IgM 3.3%, IgA 5.0%). Statistically significant correlations could be found for levels of cytokeratin 18 antibodies (IgM-type) and the BEST index of activity, and for levels of desmin antibodies (IgM-type) and the van HEES index of activity. Highest levels could be measured for actin antibodies (IgG-type) in patients with isolated disease manifestation in the colon. The mechanism of induction of autoantibodies against cytoskeletal components in Crohn's disease still remains obscure. Unmasking of hidden antigens after cell injury during the inflammatory process of disease might lead to sensitization and antibody production. The pattern of antibodies in patients with Crohn's disease seems to be different compared with that of connective tissue diseases.

Adolescent↗
PubMed1990

Heterogeneity of intermediate filament expression in human testicular seminomas.

Testicular seminoma has in the past been considered to represent a germ cell tumor incapable of further differentiation. In recent years this view has been challenged on the basis of morphologic and chromosomal studies. Moreover, studies of intermediate filaments (IF) of seminoma cells have provided evidence of the capability of seminoma cells to differentiate in different directions. In the present study of the IF protein profile of 26 human testicular seminomas, using frozen as well as formalin-fixed, paraffin-embedded tissues, we report evidence of a heterogeneous differentiation potential inherent in these neoplasms. Thus, in 4 of the seminomas neither cytokeratins nor vimentin were detected; 3 showed vimentin positive cells but no cytokeratins; in 4 seminomas only cytokeratins were detected. In the remaining 15 cases both cytokeratins and vimentin were present, with occasional cells demonstrating coexpression of cytokeratin and vimentin. While the cytokeratins present were mostly of the "simple epithelial type", in 2 instances seminoma cells also contained cytokeratins 4 and 17, normally found in stratified and/or complex glandular epithelia. Furthermore, in 3 cases scattered tumor cells stained for desmin and in 2 other seminomas neurofilaments were identified. All of the cases showed variable positive staining for desmoplakins and desmoglein, indicative of the presence of desmosomes. It can therefore be concluded that, while some seminomas seem to be devoid of IFs, most of them show varied differentiation patterns usually with epithelial features but occasionally also with components commonly regarded as characteristic of myogenic or neurogenic differentiation. These observations may help to elucidate the relationship of seminomas to other germ cell tumors, and also contribute to our understanding of the histogenesis of these neoplasms.

Desmin↗