Search Results - (Author, Cooperation:R. Moll)

2012-03-31

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Apoptosis ; Carcinoma, Hepatocellular/drug therapy/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Respiration ; Cell Survival ; Cell Transformation, Neoplastic/genetics ; Disease Models, Animal ; Doxycycline/pharmacology ; Electron Transport ; *Gene Expression Regulation, Neoplastic ; Genes, myc/*genetics ; Glutamine/metabolism ; Homeostasis ; Humans ; Liver Neoplasms/drug therapy/genetics/metabolism/pathology ; Mice ; Mitochondria/metabolism ; Multiprotein Complexes ; Oncogene Protein p55(v-myc)/genetics/metabolism ; Protein Biosynthesis ; Protein Kinases/deficiency/genetics/*metabolism ; Proteins/antagonists & inhibitors/metabolism ; RNA Interference ; Repressor Proteins/antagonists & inhibitors/deficiency/genetics/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism

1365-2559

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

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.

Electronic Resource

1600-0625

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract Human fetal Merkel cells are now generally considered to be epidermal derivatives. Previous studies using antibodies against the simple epithelial cytokeratins (CKs), 8 and 18, have demonstrated the presence of these cells in the epidermis at as early as fetal week 10 to 12. Using antibodies against CK 20 whose expression within the skin is restricted to Merkel cells, we applied immunofluorescence and immunoperoxidase microscopy to analyze earlier embryonic and fetal human skin (wk 7 to 9). We were able to demonstrate the first Merkel cells at as early as fetal wk 8, i.e., at the same time as the epidermis starts to develop an intermediate, third layer, characterized by the expression of CKs 1,10, and 11. Most of these early Merkel cells were localized above the basal layer. Their shape was round to oval, dendrites being infrequent and short. At fetal wk 9, Merkel cells were considerably more numerous. These results persuasively argue for a much earlier fetal development of Merkel cells within the epidermis than previously thought. A hypothesis concerning the differentiation of Merkel cells from embryonic basal keratinocytes is discussed.

Electronic Resource

1600-0625

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. However, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a rare malignant tumor of the skin, have been reported. Hence, lectin- and proteoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilament immunohistochemistry. The lectin binding pattern of tumor cells varied between lectins with different sugar binding specificities, while within a given nominal sugar specificity intensities were remarkably similar between tumors from different patients. The most intensive reaction was observed using Con A (mannose/glucose-specific) followed by LCA with the same specificity and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while no fucose binding sites were detected (UEA-I). In addition, N-Acetyl galactosamine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glycans and not O-linked glycans, typical for mucins of most epithelia, were present. Hence these tumor cells were relatively undifferentiated and resembled stem cells more closely than differentiated epithelia. The tumor stroma was especially evaluated in this study and showed a lectin reaction, which was intermediate between the tumor cells and extra-tumoral stroma. For example, the reactions of N-Acetyl galactosamine-specific lectins were intensive in the extra-tumoral stroma but nearly negative in tumor cells, while the lectin reaction of the intra-tumoral stroma was similar to the cellular reaction. These results indicated an influence of tumor cells on the stromal constituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cells most intensely in – and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected using the chondroitin-6-sulfate antibody. The cellular and membrane-associated reaction for heparan sulfate was less intensive in comparison to epidermal cells. In conclusion the pattern of lectin-binding sites, the high chondroitin(sulfate) specific reactivity and the relatively low intensity of heparan sulfate immunohistochemistry indicate a low degree of differentiation and high malignity of the tumors, which is consistent with the clinical behavior of Merkel cell carcinomas.

Electronic Resource

0014-4827

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Medicine

Electronic Resource

0040-4020

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Electronic Resource

0014-5793

(Archaebacteria) ; Acidophile ; H^+/O ratio ; Proton-motive force

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Physics

Electronic Resource

0003-2670

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Electronic Resource

0309-1651

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Electronic Resource

1434-3940

Schlüsselwörter Speicheldrüsen ; Strahlenschaden ; Kollagen ; Key words Salivary glands ; Irradiation damage ; Collagen IV

Springer Online Journal Archives 1860-2000

Medicine

Summary The extent of radiogenic salivary gland damage depends on the radiation dose, the fractionation, and the localization of the gland in the radiation field. Because extracellular matrix proteins, for example collagen IV, belong to the main components of basement membranes (BM), which are considered to posses cell- and structure-regulating functions, this study set out to describe radiogenic BM changes. The staining profile of collagen IV was studied in 110 female rat mandibular glands depending on age (1 year vs. 1 1/2 years), dosage (2 Gy/d; total dosages 20, 40, or 60 Gy), the radiation field (inside vs. outside), and on the latency period (1/2 year vs. 1 year), using immunohistochemical methods. The stainings were assessed semiquantitatively and differences were evaluated using multivariate analysis. The staining pattern of the polyclonal antibody in rat tissues did not differ from the pattern found in human salivary glands. Collagen IV was detected at variable levels in the glandular and nerve tissue and in vascular walls (negative: adventitia). Irradiated tissues were stained more strongly than non-irradiated, and differences were significant in salivary glands exposed to more than 20 Gy. Age and the latency period had no significant effect on staining. The BM constituent collagen IV showed dose-dependent increasing expression analogous to the salivary gland damage, which could contribute to disturbed cell-matrix interactions following salivary gland radiation exposure. Several tissue structures may be more sensitive to possible scattered radiation. Information on the pretreatment status is mandatory in histopathological studies on the BM of salivary glands.

Zusammenfassung Das Ausmaß der radiogenen Speicheldrüsenschäden ist abhängig von Strahlendosis, Fraktionierung und der Lage der Drüse im Strahlenfeld. Da die Bestrahlung zu Veränderungen der Basalemembran (BM) führt, die mit der Fibrose des Organs einhergehen können, und Kollagen IV ein wesentlicher Bestandteil der BM ist, wurden experimentell radiogene BM-Veränderungen der Speicheldrüsen untersucht. Die Abhängigkeit des Verteilungsmusters des Kollagens IV von Alter, Gesamtdosis, Lage zum Strahlenfeld und Latenzperiode wurde an 110 Mandibulardrüsen weiblicher Wistar-Ratten immunhistochemisch untersucht. Die Ergebnisse wurden mittels Multivarianzanalyse auf signifikante Unterschiede hin geprüft. Bestrahlte Drüsen zeigten ein stärkeres Expressionsprofil als unbestrahlte. Die Unterschiede waren bei einer Gesamtdosis 〉 20 Gy statistisch signifikant. Das Alter und die Latenzperiode hatten keinen signifikanten Einfluss auf das Expressionsmuster. Die dosisabhängige Zunahme der Kollagen-IV-Expression kann zur gestörten Zell-Matrix-Interaktion beitragen und dergestalt die radiogene Fibrose fördern. Einzelne Strukturen zeigten unterschiedlich starke Kollagenanhäufungen. Detaillierte Informationen zur Vorbehandlung sind für die Beurteilung von Speicheldrüsenschädigungen unerlässlich.

Electronic Resource

1432-2307

Respiratory epithelium ; Nasal mucosa ; Metaplasia ; Stem cell ; Cytokeratin

Springer Online Journal Archives 1860-2000

Medicine

Summary To determine the characteristics of metaplastic changes of the nasal respiratory epithelium, the distribution of individual cytokeratins (CKs) was studied immunohistochemically and by two-dimensional gel electrophoresis. The authors define four types of changes of the normal pseudostratified columnar epithelium: (1) transitional pseudostratified epithelium (first unusual CK.: no. 13); (2) stratified columnar epithelium (increased expression of CKs 4 and 13; CKs 7, 8, 18 and 19 reduced); (3) stratified squamous epithelium, non-keratinized (appearance of CK 16); and (4) stratified squamous epithelium, keratinized (expression of CKs 1 and 10, variable CK5 and 14 patterns in basal cells). These phenotypes were found simultaneously within single specimens, resulting in apparent overall variability in the immunohistochemical staining patterns. Spatially, changes in CK expression towards “normal” parts were not abrupt but rather gradual. Biochemical data confirmed the immunohistochemical findings and added CK 6 to the pattern of altered nasal mucosa. The findings of this study suggest a stem cell metaplasia in the nasal epithelium which is based on its inherent bimodal developmental programme. A gradual loss of normal respiratory epithelial differentiation, as seen by the loss of CKs 7, 8, and 18, was paralleled by the appearance of squamous epithelial type CKs, e.g. the expression of CKs 1, 10 and 13. Basal cell types CKs 5, 14, 17 and 19 were maintained during this process. Implications of these results for general concepts of CK expression in the metaplastic process are discussed.

Electronic Resource

1432-0711

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-0711

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-2307

Intermediate filaments ; Desmosomes ; Testicular tumours Germ cell tumours ; Immunohistochemistry

Springer Online Journal Archives 1860-2000

Medicine

Summary Seminomas and non-seminomatous testicular germ cell tumours were studied for the presence of cytokeratin and vimentin filaments and desmosomes using immunohistochemical methods. In the majority of the classical seminomas and in seminomatous areas of mixed tumours most tumour cells appeared to lack cytokeratin filaments. Some seminomas contained a focally variable proportion of cells exhibiting cytokeratin-positive structures while other cases contained only few seminoma cells with a well developed fibrillar cytokeratin network. Gel electrophoresis of cytoskeletal proteins from microdissected regions revealed cytokeratin polypeptides nos. 8 and 18 typical of simple epithelia. In one seminoma, however, all, or almost all, tumour cells contained cytokeratin filaments. This finding is in line with the assumption of transitional forms between seminoma and embryonal carcinoma. Despite the lack - or variable expression - of cytokeratin filaments most seminoma cells contained desmosomes, although often few in number and irregularly distributed at the circumference of the cells. Loosely arranged and often very sparse vimentin fibrils were found in many, but not all seminoma cells. Double label immunofluorescence microscopy suggested that the majority of desmosomes was associated with intermediate filaments of the vimentin type. In contrast, in carcinoma cells of malignant teratomas, in well differentiated epithelial cells of intermediate-type malignant teratomas and in trophoblastic cells present in trophoblastic-type malignant teratomas cytokeratin filament bundles as well as desmosomes were decorated. The arrangement and density of the cytokeratin filament skeleton and of desmosomes varied with degree of maturation of the tissue. The most regular distribution and intensive staining of cytokeratin filaments and desmoplakin was found in “mature” tissues. Vimentin was demonstrated in mesenchymal areas and stroma cells. The results show that seminomas are distinguished from most other germ cell and non-germ cell tumours by the presence of true desmosomes together with scanty vimentin filaments in most tumour cells. In addition, they indicate that seminoma cells can be heterogenous in their cytoskeletal complement and may include cells with cytokeratin expression, indicative of a multi-potential character of the initially transformed cell(s).

Electronic Resource

1432-2307

Mucoepidermoid mammary carcinoma ; Squamous metaplasia ; Cytokeratins ; Histogenesis ; Malignancy status

Springer Online Journal Archives 1860-2000

Medicine

Summary The histological features of mucoepidermoid mammary carcinomas (MMCs) are presented, and criteria for distinguishing these tumours from squamous epithelial metaplasia in other mammary carcinomas are considered. Immunohistochemical and gel-electrophoretic analyses of the intermediate-filament proteins in one MMC case revealed a complex pattern of cytokeratin polypeptide expression. The simple-epitheliumtype cytokeratins 7, 8, 18, and 19 were detected mainly in nonsquamous (including mucinous) cells, while the stratified-epithelium-type cytokeratins 5, 6, 14, 16, and 17 were present in squamous cells. However, in both the nonsquamous and squamous regions of the tumour, cytokeratins of the “reverse” type were detected in individual cells. This pattern of single-cell heterogeneity with respect to cytokeratin polypeptide expression suggests that the mixed phenotype of this tumour is not caused by the clonal divergence of tumour cell types. Rather, histogenetically, a pluripotent stem cell with the ability to differentiate into squamous (epidermoid) or mucinous cells might be the starting-point of such a tumour and such differentiation processes may continue to occur during tumour growth. The present case also revealed that mucoepidermoid tumours are not necessarily of low malignancy; there are highly malignant forms with rapid metastasis.

Electronic Resource

1432-2307

Lymph nodes ; Cytokeratin-positive cells ; Extrafollicular cells ; Reticulum cells

Springer Online Journal Archives 1860-2000

Medicine

Abstract A total of 291 enlarged lymph nodes showing a range of reactive-inflammatory processes, primary and metastatic neoplasms were studied to determine the distribution and immunoprofile of their cytokeratin-positive interstitial reticulum cells (CIRC) in comparison with normal nodes. In 258/291 nodes (89%), CIRC numbers were distinctly increased in the subcapsular, paracortical and, occasionally, in the medullary zones; often, these increased CIRC formed networks around follicles, sinuses and vessels. CIRC had comparatively small, irregularly shaped bodies and dendritic processes; occasionally, giant forms were noted. CIRC contained cytokeratins (CK) 8 and 18 but not 19, as shown by immunohistochemistry, and by gel electrophoresis with subsequent immunoblotting. They co-expressed vimentin consistently, alpha-smooth-muscle actin frequently, and desmin less frequently. They did not contain desmoplakins, Factor VIII, S-100, LCA, B and T lymphocyte- and macrophage-associated antigens, chromogranin A, synaptophysin or the A-80 glycoprotein. We found no clear correlation between the increased CIRC and given nodal disease processes. However, CIRC were most abundant in nodes free of but draining malignant tumours; bizarre CIRC assemblies were noted in HIV lymphadenopathy. CIRC appear to represent a subset of the so-called “fibroblastic reticulum cells” of lymph nodes. Their function remains undetermined; their increase in diverse lymphadenopathies suggests that they partake in nodal reactions to injury. It remains unclear whether the increase in CIRC relative number is due to proliferation or to CK gene induction processes but their presence and potential capability to undergo hyperplasia with dysplastic forms should alert pathologists to possible diagnostic pitfalls. In addition, we discuss that CIRC may undergo transformation and represent the “cell of origin” of certain CK-positive tumours restricted to lymph nodes.

Electronic Resource

1432-2307

Key words Intermediate filaments ; Alcoholic liver disease ; Alcoholic hyalin

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Mallory bodies (MBs) are eosinophilic cytoplasmic inclusions observed predominantly in alcoholic liver disease. Although linked to disease activity, their pathogenesis is still unclear. Since intermediate filaments (cytokeratins) are major components of MBs, their cytokeratin polypeptide composition was analysed with monospecific antibodies for cytokeratins 7, 8, 14, 18, 19, and 20 by immunohistology. MBs were identified by light microscopy and ubiquitin immunostaining. All MBs were positive for cytokeratins 8 and 18. A significant percentage of the MBs was strongly positive for cytokeratins 19 and/or 20, which are not detectable in hepatocytes of normal liver and, in the case of cytokeratin 20, in hepatocytes of diseases devoid of MBs. MBs were essentially negative for cytokeratins 7 and 14. De novo expression of cytokeratins 19 and 20 was independent of the aetiology, occurring in all MB-associated diseases analysed, and seemed to precede MB formation, since in some hepatocytes a cytoskeletal-type staining pattern for these cytokeratins was present. In hepatocellular carcinomas cytokeratins 19 and 20 were frequently detected, but their cellular distribution was less closely associated with MBs. The ectopic expression of cytokeratins 19 and 20 appears to be related to MB formation and may take part in the derangement of the intermediate filaments during MB formation.

Electronic Resource

1432-2307

Stomach neoplasms ; Pancreatic neoplasms ; Cell differentiation ; Histocompatibility antigens ; Interferon gamma

Springer Online Journal Archives 1860-2000

Medicine

Abstract Two new cell lines from stomach cancers and one from a pancreatic carcinoma are presented. MZ-GC-1 was established from a hepatic metastasis of a well differentiated gastric adenocarcinoma. MZ-GC-2 was derived from ascites induced by a poorly differentiated gastric adenocarcinoma. MZ-PC-1 originated from the pleural effusion of a moderately well differentiated pancreatic ductal adenocarcinoma. MZ-GC-1 cells were adherent and partially polarized, connected tightly via desmosomes. In contrast MZ-GC-2 cells consisted of slightly adherent or floating subpopulations and displayed no desmosomes. MZ-PC-1 cells were adherent and showed polarized growth, connected by apical junctional complexes. Cell doubling times were 7 days for MZ-GC-1 and 45 h for MZ-GC-2 and MZ-PC-1 cells. MZ-GC-2 and MZ-PC-1 gave rise to nude mouse tumours, resembling the original lesions. Chromosome analysis of the cell lines revealed a high range of numerical abnormalities. Each cell line had cytokeratin patterns fitting well to typical in vivo patterns. Furthermore the cell lines expressed a panel of antigens typical for gastrointestinal epithelia. Unique for MZ-PC-1 were high amounts of secreted Ca19-9. γ-Interferon enhanced HLA-class I antigens up to twofold and induced ICAM-1 expression on each cell line. HLA-class II antigens were differentially enhanced by γ-interferon. Due to their distinct characteristics the three tumour cell lines may be useful models in the investigation of the cell biology and immunogenicity of gastrointestinal tumours.

Electronic Resource

1432-2307

Key words Desmosomal cadherins ; Pemphigus ; Hemidesmosomes ; Basement membrane ; Bullous skin diseases

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Intraepidermal and dermal-epidermal cohesion are of paramount importance for the integrity of the skin. Some constituent molecules of keratinocyte adhesion complexes and basement membrane-associated structures are the targets of antibody-mediated autoimmune reactions that give rise to various (muco-)cutaneous blistering diseases. The current state of our knowledge about these molecules – along with the main clinical, histological, and immunohistochemical features of the corresponding autoimmune diseases and their pathogenetic mechanisms – comprise the subjects surveyed in this review. Among the desmosomal cadherins (desmogleins and desmocollins) that mediate epidermal cell–cell adhesion, it has been demonstrated that desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, both diseases that result in intraepidermal blistering. Further, desmocollin autoantibodies may be involved in IgA pemphigus. Paraneoplastic pemphigus is associated with autoantibodies directed against the desmosomal plaque protein, desmoplakin. Of the constituents of hemidesmosomes, the plaque protein, BP230 (BPAG1), and the collagen-like transmembrane protein, BP180 (BPAG2), are the autoantigens of bullous pemphigoid and pemphigoid gestationis, the manifestations of both of which include subepidermal blistering. Several diseases arise from autoimmune reactions against certain proteins associated with the basement membrane located beneath hemidesmosomes, for example laminin 5 (cicatricial pemphigoid), ladinin (LAD-1; linear IgA disease), uncein, and collagen VII (epidermolysis bullosa acquisita), the last of which is the constituent protein of the anchoring fibrils. Such recent advances in the elucidation of the molecular nature of autoantigens may serve as the basis for the development of novel molecule-based therapeutic strategies.

Electronic Resource

1432-2307

Human renal cell carcinoma ; Cell line ; Proto-oncogene ; Tumour suppressor gene ; p53

Springer Online Journal Archives 1860-2000

Medicine

Abstract Four new permanent cell lines (RCC-A, -B,-C, and -D) derived from different human renal cell carcinomas of the clear cell type were established in tissue culture. The cell lines displayed characteristic differences in cell size and shape, which allowed individual identification by phase contrast microscopy. Ultrastructurally, the cell lines exhibited varying amounts of cytoplasmatic glycogen and lipid. Immunohistochemistry revealed co-expression of vimentin and cytokeratin in all cell lines. The mean population doubling time ranged from 27 h (RCC-A) to 104 h (RCC-D). RCC-B and -C cells produced slowly growing tumours after heterotransplantation into nude mice, whereas RCC-A and RCC-D cells were non-tumorigenic. The modal chromosome number was either near-diploid (RCC-A, -B, and -C) or near triploid (RCC-D). Clonal abnormalities affecting the short arm of chromosome 3 were seen in all cell lines. Northern blot analysis revealed no expression of the proto-on-cogenes c-fos, c-ros, and c-mos, whereas c-Ki-ras expression was observed in all cell lines. Expression of c-myc was observed in RCC-A, RCC-B, and RCC-D cells, whereas c-raf expression could be detected in RCC-B and RCC-D. Tumour suppressor gene p53 mRNA was observed in the cell line RCC-D.

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