PubMed Health⌕ Search

Biomedical subjects

R Moll

Publications and source records attributed to R Moll.

At least 199 records · Page 11Linked to original sources
PubMed1987

Desmosomal plaque-associated vimentin filaments in human ovarian granulosa cell tumors of various histologic patterns.

Proteins of intermediate-sized filaments and desmosomal plaques (desmoplakins) of four human ovarian granulosa cell tumors were studied by immunofluorescence and immunoelectron microscopy and by two-dimensional gel electrophoresis of microdissected tissue samples. All tumor cells, irrespective of their specific histologic patterns, contained both vimentin and desmoplakins. Cytokeratin-positive structures were absent or very scant in most tumor regions, but more common in trabecular, insular, macro- and microfollicular structures. Biochemical analysis revealed the presence of Cytokeratin Polypeptides 8 and 18. Desmin filaments, neurofilaments, and glial filaments were not detected. Immunoelectron microscopy showed vimentin filaments attached to desmoplakin-positive plaques of desmosomes. These results indicate that granulosa cell tumors contain true desmosomes, which are associated primarily with vimentin filaments. This phenomenon has so far only been described in meningiomas and in blastema cells of nephroblastomas. Our observations suggest that in most neoplastic granulosa cells one epithelial feature, ie, cytokeratin expression, is greatly reduced, whereas desmosomes are still formed in appreciable frequencies. This unusual constellation of cytoskeletal elements in granulosa cell tumors may be useful in the differential diagnosis from other ovarian neoplasms, especially undifferentiated carcinomas. The importance of the use of antibodies specific for exclusively desmosomal proteins in classifying morphologically ill-defined junctional structures (eg, "rudimentary junctions," "primitive junctions," "desmosome-like junctions") is emphasized.

Aged↗
PubMed1986

Synaptophysin: a marker protein for neuroendocrine cells and neoplasms.

Synaptophysin is an integral membrane glycoprotein (Mr 38,000) that occurs in presynaptic vesicles of neurons and in similar vesicles of the adrenal medulla. By using a monoclonal antibody to this protein (SY38), we have found, by immunohistochemistry and immunoblotting, that an identical or similar protein is also expressed in neuroendocrine tumors of neural type, such as pheochromocytomas and paragangliomas. In addition, this protein occurs in certain neuroendocrine epithelial cells, such as pancreatic islet cells; in a variety of neuroendocrine epithelial tumors, including isletcell adenomas and carcinomas and several carcinoids and neuroendocrine carcinomas of the gastrointestinal and the bronchial tracts; and in medullary carcinomas of the thyroid. Our results show that synaptophysin, and the vesicles that contain it, can occur in normal and neoplastic neuroendocrine cells of neural type, as demonstrated by colocalization with neurofilaments, as well as in those of epithelial type, as shown by colocalization with cytokeratin filaments and desmoplakins. We conclude that synaptophysin is expressed independently of other neuronal differentiation markers and propose that it be used as a differentiation marker in tumor diagnosis.

Adrenal Medulla↗
PubMed1986

Cytokeratin No. 9, an epidermal type I keratin characteristic of a special program of keratinocyte differentiation displaying body site specificity.

Plantar epidermis of the bovine heel pad as well as human plantar and palmar epidermis contain large amounts of an acidic (type I) keratin polypeptide (No. 9) of Mr 64,000 which so far has not been found in epidermis of other sites of the body. We present evidence for the keratinous nature of this protein, including its ability to form cytokeratin complexes and intermediate-sized filaments in vitro. We have isolated RNA from plantar epidermis of both species and show, using translation in vitro, that these polypeptides are genuine products of distinct mRNAs. Using immunofluorescence microscopy with specific antibodies against this protein, we demonstrate its location in most cells of suprabasal layers of plantar epidermis as well as in sparse keratinocytes which occur, individually or in small clusters, in upper layers of epidermis of other body locations. We conclude that cytokeratin No. 9 is characteristic of a special program of keratinocyte differentiation which during morphogenesis is expressed in most epidermal keratinocytes of soles and palms but only in a few keratinocytes at other body sites. This example of cell type-specific expression of a member of a multigene family in relation to a body site-related program of tissue differentiation raises important biological questions concerning the regulation of keratinocyte differentiation and morphogenesis as well as the function of such topological heterogeneity within a given type of tissue.

Animals↗
PubMed1986

Formation of epidermal and dermal Merkel cells during human fetal skin development.

The origin of Merkel cells is still a matter of debate, specifically the question of whether they are derived from epithelial cells of the epidermis or from immigrated neural crest cells. As an argument for the latter hypothesis the occurrence of dermal, nerve-associated Merkel cells in human fetal skin has often been mentioned. Therefore, we analyzed the distribution of Merkel cells in epidermis and dermis of plantar skin of human embryos and fetuses, ranging in gestational age between 7 and 17 weeks. Merkel cells were identified by immunocytochemistry on frozen sections using antibodies against simple epithelium-type cytokeratins and by electron microscopy. In the 17-week-old fetus, 17% of the total cutaneous (epidermal and dermal) Merkel cells were located in the upper dermal compartment, whereas in the 14-week-old fetus only 3.9% of the Merkel cells were dermal, including some cells that seemed to be in the process of traversing the dermal-epidermal junction. Thirteen-week-old fetuses showed even fewer dermal Merkel cells. Twelve-week-old fetuses exhibited 660 epidermal Merkel cells per 100 mm total section length, but none in the upper or deep dermis. In 7- to 9-week embryos, no Merkel cells were recognized. However, at this stage, but not in later stages, the basal cells of the plantar epidermis expressed certain simple epithelium-type cytokeratin polypeptides. These results speak against an invasion of Merkel cells or putative neural crest-derived precursor cells into the epidermis via a dermal passage. They suggest that in plantar skin Merkel cells arise, between weeks 8-12, from precursor stages of epithelial cells of the early fetal epidermis which still express simple epithelium-type cytokeratins. The results further suggest that in subsequent stages of skin development some epidermal Merkel cells detach from the epithelium and migrate into the upper dermis where some of them may associate with small nerves.

Embryonic and Fetal Development↗
PubMed1986

Monoclonal antibodies to various acidic (type I) cytokeratins of stratified epithelia. Selective markers for stratification and squamous cell carcinomas.

We determined the reactivity of two monoclonal antibodies to cytokeratins that are typically expressed in certain stratified epithelia and several human squamous cell carcinomas using immunoblotting techniques and immunofluorescence microscopy. Antibody KS 8.12 reacted specifically with cytokeratin polypeptides nos. 13 and 16, and stained noncornified squamous epithelia in a rather uniform way. The examination of diverse human carcinomas showed all squamous cell carcinomas to be positively stained with this antibody, whereas all adenocarcinomas were negative. Another antibody, KK 8.60, reacted with polypeptides nos. 10 and 11, and uniformly stained the suprabasal layers of the epidermis. In several noncornified squamous epithelia (e.g., tongue, exocervix), in thymus reticulum epithelial cells, and in moderately and well differentiated squamous cell carcinomas this antibody exhibited a nonuniform labeling pattern that allowed the detection of individual cytokeratin-10/11-positive cells scattered throughout the tissue. It is concluded that antibodies KS 8.12 and KK 8.60 represent specific molecular probes for the definition of certain stages of squamous differentiation in normal development as well as in pathological processes such as squamous metaplasia and carcinogenesis. We propose the use of these antibodies in the differential diagnosis of carcinomas and their metastases.

Adenocarcinoma↗
PubMed1986

Expression of glial filament protein (GFP) in nerve sheaths and non-neural cells re-examined using monoclonal antibodies, with special emphasis on the co-expression of GFP and cytokeratins in epithelial cells of human salivary gland and pleomorphic adenomas.

We describe two novel monoclonal antibodies specific for glial filament protein (GFP), i.e., GF12.23 and GF12.24 (both IgG2a]. These cross-react over a broad range of species with epitopes located in the alpha-helical rod domain typical of all intermediate filament (IF) proteins. These monoclonal antibodies were used, in conjunction with other monoclonal GFP antibodies, rabbit antiserum to GFP, and various antibodies to other cytoskeletal proteins, to examine the occurrence of GFP in cells outside of the central nervous system of rodents, cows, and humans. We detected some scattered GFP-containing cells in the neural sheaths in some species but not in others, and we obtained different results when comparing the rabbit antisera with the monoclonal GFP antibodies. In the enteric glia of rats, we observed GFP-positive cells with all of the antibodies used, whereas in human intestine, the various monoclonal antibodies showed no reaction with any intestinal cells. Similarly, no GFP was detected in surface cells of the lens of cows and rats using any of the GFP antibodies, whereas some reaction was seen in murine lens tissue. We were also unable to detect GFP-positive cells in human, bovine, or rat liver with any of the monoclonal antibodies, which is in contrast to the reactivity of the rabbit GFP antisera with some stellate perisinusoidal cells of rat but not bovine or human liver. The possible reasons for the discrepancies between the different species and the different antibody preparations used are discussed. In addition, using double-label immunofluorescence microscopy, we showed that normal human parotid glands contain a certain type of epithelial cell that co-expresses cytokeratins and desmosomal proteins with GFP. The histological distribution of these GFP-positive cells suggests that they represent a subset of the myoepithelial cells present in this tissue. Cells co-expressing cytokeratins and GFP - in some cases, apparently together with vimentin as the third IF protein present - were also identified in tumors derived from this salivary-gland epithelium, i.e., pleomorphic adenomas, in which GFP-positive cells were relatively frequent in the myxoid and chondroid components, thus confirming the work of other investigators. Possible implications for the concept of histogenesis of these tumor cells are discussed, as are possible mechanisms resulting in the co-expression of IF proteins.

Adenoma↗
PubMed1986

Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas (Merkel cell tumors): immunocytochemical and biochemical analysis of twelve cases.

Twelve specimens of cutaneous neuroendocrine carcinomas (Merkel cell tumors) available as fresh tissue were analyzed for intermediate filament (IF) expression by immunocytochemical and biochemical methods. In immunofluorescence microscopy, most cases were positive for both simple-epithelium-type cytokeratins and the neurofilament L- and M-polypeptides. Several different IF staining patterns ranging from presence of plaque-like structures (fibrous bodies) only to nearly exclusive expression of delicate cytokeratin fibrils could be distinguished. In immunoelectron microscopy the labeling for both cytokeratin and neurofilament polypeptides seemed evenly distributed among the IFs of the fibrous bodies. In primary culture, tumor cells maintained the coexpression of both IF types. Desmoplakin-positive true desmosomes were found in 5 specimens. Biochemically, cytokeratins nos. 8, 18 and, variably, 19, as well as IT protein and, in many specimens, the neurofilament L-protein and a putative neurofilament M-protein were detected. Only traces of the neurofilament H-polypeptide were found. Our results show that a coexpression of cytokeratin IFs and neurofilaments in variable patterns is a characteristic feature of cutaneous neoendocrine carcinomas; occasionally, however, neurofilaments may be very scarce. The biological, histogenetic and diagnostic implications are discussed.

Adult↗
PubMed1986

[Cytokeratin expression in normal and malignant tongue epithelium].

Patterns of cytokeratin expression in squamous cell carcinomas of the tongue were examined by two-dimensional gel electrophoresis of cytoskeletal proteins and by immunofluorescence microscopy using antibodies specific for certain cytokeratins. The results were compared with those obtained from normal tongue mucosa. All carcinomas examined synthesized large amounts of cytokeratins as well as of desmosomal proteins such as desmoplakin(s) but differed from the normal tissue by the specific cytokeratin pattern expressed and by their heterogeneity of expression, which in immunofluorescence microscopy resulted in patchy, staining patterns. In general, the carcinomas showed a reduction of the amount of certain cytokeratins such as Nos. 4 and 13 which are abundant in normal epithelium. On the other hand, some other cytokeratins were present in relatively increased proportions, and certain subtypes of lingual carcinomas revealed, in addition, significant levels of cytokeratins 8 and 19 which are commonly considered to be typical of simple epithelial cells and tumours derived therefrom. To explain the differences of cytokeratin patterns between these tumours and normal epithelium as well as between different forms of squamous cell carcinomas two hypotheses are discussed, i.e. clonal selection of certain cells present in the original epithelium, probably in the basal layer(s), and different pathways of differentiation in the cell progeny derived from the transformed cell(s) of origin. The heterogeneity of cytoskeletal protein patterns in different lingual carcinomas, which was also noted for oropharyngeal, hypopharyngeal and laryngeal carcinomas, is discussed in relation to different kinds of response to therapeutical treatment.

Carcinoma, Squamous Cell↗
PubMed1986

The intermediate filament complement of the spectrum of nerve sheath neoplasms.

The intermediate filament complement of the spectrum of nerve sheath neoplasms including 12 typical benign schwannomas, 1 ancient schwannoma, 2 cellular schwannomas, 6 neurofibromas and 4 malignant schwannomas was investigated by immunofluorescence microscopy, two dimensional electrophoresis, and immunoblot analysis. Studies were performed on freshly frozen tumor tissue samples; a broad spectrum of antibodies against all classes of intermediate filaments was utilized. Samples were also studied by electron microscopy, and immunohistochemically for S-100 protein and desmoplakins. By immunofluorescence microscopy, all nerve sheath neoplasms revealed intense positivity for vimentin throughout the cytoplasm while 2 benign schwannomas displayed co-expression of vimentin and glial filament proteins. Two-dimensional gel electrophoresis and immunoblot analysis confirmed the presence of vimentin and showed that it was the predominant protein in all tumors. Electrophoretic analysis of the 2 benign schwannomas that immunostained for glial filament proteins confirmed the presence of this protein which was shown to comigrate with a known human control sample. Neither immunofluorescence microscopy nor biochemical analyses revealed cytokeratin polypeptides, neurofilament proteins, desmin, or desmoplakin in any of the tumors. We conclude that while vimentin is the predominant intermediate filament expressed by the entire spectrum of nerve sheath neoplasms, at least occasional benign schwannomas are capable of co-expressing glial filament proteins. It remains to be determined whether the subgroup of nerve sheath neoplasms that co-expresses vimentin and glial filament proteins is otherwise distinguishable from their more frequent counterparts that express vimentin exclusively.

Adolescent↗
PubMed1985

Can villin be used to identify malignant and undifferentiated normal digestive epithelial cells?

We have investigated the presence of villin (a Ca2+-regulated actin binding protein) in various tissues (normal or malignant) and in established cell lines by using sensitive immunochemical techniques on cell extracts and immunofluorescence analysis on frozen sections. Our results show that villin is a marker that can be used to distinguish normal differentiated epithelial cells from the simple epithelia lining the gastrointestinal tract and renal tubules. Villin is found in the absorptive cells of the small and large intestines, in the duct cells of pancreas and biliary system, and in the cells of kidney proximal tubules. Furthermore, undifferentiated normal and tumoral cells of intestinal origin in vivo and in cell culture express villin. Therefore, expression of villin is seen in cells that do not necessarily display the morphological features characteristic of their terminally differentiated state, such as the microvilli-lined brush border. We suggest the possible clinical implications of using villin as a marker in the diagnosis of metastatic adenocarcinomas.

Animals↗
PubMed1985

Cells of extramammary Paget's disease express cytokeratins different from those of epidermal cells.

The patterns of expression of cytokeratin polypeptides which are closely correlated to routes of differentiation of epithelial cells were studied in extramammary Paget's disease. Cytokeratins of uninvolved and involved epidermis were analyzed by two-dimensional gel electrophoresis of microdissected tissue preparations as well as by immunofluorescence microscopy using cytokeratin antibodies with different specificities. In uninvolved epidermis, cytokeratins Nos. 1, 5, 6, 10, 11, 14, and 16, characteristic of keratinocytes, were found. Epidermis infiltrated by Paget's cells contained the same components and, in addition, cytokeratins Nos. 7, 8, 18, and 19, the latter being characteristic of simple and glandular epithelia, including apocrine and eccrine skin glands. By immunohistochemistry, broad-spectrum antibodies to cytokeratins decorated both keratinocytes and Paget's cells. Antibodies selective for cytokeratins Nos. 1, 10, and 11 stained suprabasal keratinocytes but not Paget's cells. In contrast, antibodies to cytokeratin No. 18 were negative on keratinocytes but the Paget's cells were selectively stained, as were the secretory cells but not the ductal cells in apocrine and eccrine glands. The results show that the cytoskeleton of Paget's cells is different from that of keratinocytes and ductal cells of skin glands and suggest that these tumor cells express the glandular type cytokeratins Nos. 7, 8, 18, and 19. This provides cell biologic support for a relationship of cells of Paget's disease to secretory cells of apocrine and eccrine glands. The histogenesis of extramammary Paget's cells is discussed in relation to these findings.

Aged↗
PubMed1985

Different patterns of cytokeratin expression in the normal epithelia of the upper respiratory tract.

The distribution and type of cytokeratins present in the normal human epithelia of the nasopharynx, oropharynx, tongue, palatine tonsil, epiglottis, vocal cord, and laryngeal ventricle were studied using immunohistochemical techniques and by gel electrophoresis of cytoskeletal proteins microdissected from frozen tissues. Noncornifying stratified epithelia covering the oropharynx, tongue, surface of the palatine tonsil, pharyngeal surface of the epiglottis, and vocal cord were all found to contain cytokeratins nos. 4, 5, 6, 13, 14, and 15, together with minor amounts of cytokeratin no. 19, i.e., a pattern similar to that previously reported for esophageal epithelium. The immunohistochemical reaction with KA4, an antibody specific for cytokeratins nos. 14, 15, 16, and 19, revealed reactivity confined to the basal epithelial cells of the tongue, oropharynx, pharyngeal epiglottis, and two out of five samples of vocal cords. This same antibody reacted with the entire thickness of three out of the five true vocal cords which were shown by gel electrophoresis to also contain cytokeratins nos. 16 and 17. Gel electrophoresis revealed that the pseudostratified columnar epithelium covering the laryngeal ventricle was more complex, in that it contained cytokeratins nos. 5, 13, 14, 15, and 17, which are typical of stratified epithelia, as well as cytokeratins nos. 7, 8, 18, and 19, which are characteristic of simple epithelia. This pattern is similar to that found in bronchial epithelium. The laryngeal surface of the epiglottis exhibited cytokeratins nos. 4, 5, 7, 8, 13, 14, 15, 17, 18, and 19, i.e., a pattern combining features of both esophageal- and bronchial-type epithelia. The reaction of these epithelia containing columnar cells with antibody RGE-53, which is specific for cytokeratin no. 18, revealed a staining reaction confined to the superficial columnar cells, whereas KA1 stained only the basal cells of these epithelia. The results of our study make it possible to distinguish two types of noncornifying stratified squamous epithelium, namely the 'esophageal type' which covers the tongue, oropharynx, and pharyngeal surface of the epiglottis, and another type which overlies the vocal cords and the transitional zone between the pharyngeal and laryngeal surfaces of the epiglottis. Furthermore, there appear to be variants of pseudostratified columnar epithelium, i.e., the usual bronchial type lining the laryngeal ventricle, and a type with a thicker subcolumnar cell compartment that is found on the laryngeal surface of the epiglottis. The patterns of expression of cytokeratins in the respiratory tract are compared with those of other epithelia.

Antibodies, Monoclonal↗
PubMed1985

Cytoskeletal differences between human neuroendocrine tumors: a cytoskeletal protein of molecular weight 46,000 distinguishes cutaneous from pulmonary neuroendocrine neoplasms.

The cytoskeletons of various human neuroendocrine (NE) tumors were analyzed immunohistochemically using antibodies against intermediate-filament (IF) proteins as well as by two-dimensional gel electrophoresis of proteins from microdissected tissue samples. All of the tumors studied were found to contain cytokeratin filaments and are therefore referred to as 'NE tumors of the epithelial type'. In addition, neurofilaments were found in most cutaneous and some pulmonary NE tumors, as well as in medullary carcinomas of the thyroid and in pancreatic islet cell tumors. The neurofilament staining was frequently concentrated in cytoplasmic IF aggregates. Gel-electrophoretic analyses showed that all NE tumors examined synthesize 'simple epithelium-type' cytokeratin polypeptides, cytokeratins nos. 8 and 18 being the most prominent ones, whereas cytokeratin no. 19 was found in variable and usually minor amounts. A new cytoskeletal protein, designated IT protein, with a relative molecular weight of 46,000 and an isoelectric pH value of approximately 6.1 (in 9.5 M urea) was detected in all 9 cases of cutaneous NE tumors ('Merkel-cell carcinomas'), including 2 lymph-node metastases, but was not found in any of the 17 cases of pulmonary NE tumors. In addition, 2 medullary carcinomas of the thyroid, 2 islet cell tumors of the pancreas, and 1 intestinal carcinoid tumor also seemed to lack this protein. A protein indistinguishable from IT protein by electrophoresis and tryptic peptide mapping was found in cytoskeletal preparations of mucosal cells of human intestine and in cultured human colon carcinoma cells of line HT-29. A possible relationship between IT protein and the type-I subfamily of cytokeratin polypeptides is discussed. Our study shows that the co-expression of cytokeratin filaments and neurofilaments may provide a criterion which is useful for the recognition of some NE tumors but which does not distinguish between NE tumors of different types and origins. In contrast, IT protein seems to be present specifically in cutaneous NE tumors, but absent in pulmonary NE tumors. The implications of these findings for the elucidation of the histogenesis of cutaneous NE tumors and for the histopathological differential diagnosis of NE tumors of cutaneous and pulmonary origin are discussed.

Carcinoid Tumor↗