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Biomedical subjects

M Kasper

Publications and source records attributed to M Kasper.

At least 127 records · Page 7Linked to original sources

Heterogeneity in the immunolocalization of cytokeratin-specific monoclonal antibodies in the rat lung: evaluation of three different alveolar epithelial cell types.

The distribution of individual cytokeratin polypeptides in the adult rat lung parenchyma was investigated by immunohistochemistry with 44 monoclonal and 2 polyclonal antibodies. Simple epithelial cytokeratins 7, 8, 18 and 19 were found to be expressed differently in alveolar and bronchial epithelial cells. Three distinct types of alveolar cells were detected according to their pattern of immunoreactivity: type II cells strongly expressing cytokeratins 8 and 18 and weakly expressing cytokeratins 7 and 19 in the cell periphery; type I cells predominantly positive for cytokeratins 7 and 19 and weakly for cytokeratin 8; and a newly defined third cell type III (alveolar brush cell) with cytokeratin 18 abundantly expressed but organized in an unusual intracellular ("globular") structure. The latter cell type failed to bind the type II specific Maclura pomifera lectin, and contained no surfactant proteins. Bronchial epithelial cells exhibited a more or less uniform staining pattern for cytokeratins 8, 18 and 19 and focally for cytokeratins 4 and 7.

Animals↗

Immuno- and lectin histochemistry of epithelial subtypes and their changes in a radiation-induced lung fibrosis model of the mini pig.

Cell types of lung epithelia of mini pigs have been studied using a panel of monoclonal and polyclonal antibodies against cytokeratins (CKs) and vimentin and three lectins before and after radiation-induced fibrosis. In normal tissues, CK18 specific antibodies reacted above all with type II alveolar epithelial cells, while CK7 and pan CK-specific antibodies stained the whole alveolar epithelium. In bronchial epithelial cells, CKs 7, 8, 18 and focally CKs 4 and 13 as well as vimentin were found. Cell specificity of the CK pattern was confirmed by double label immunofluorescence using type II cell-specific Maclura pomifera (MPA) lectin, type I cell specific Lycopersicon esculentum (LEA) lectin and capillary endothelium-binding Dolichos biflorus (DBA) lectin. In experimental pulmonary fibrosis, enhanced coexpression of CK and vimentin was observed in bronchial epithelium. Subtypes of alveolar epithelial cells were no longer easily distinguishable. CK18 was found to be expressed in the entire alveolar epithelium. The gradual loss of the normal alveolar epithelial marker, as seen by the binding of MPA to type I-like cells, of LEA to type II-like cells and the partial loss of MPA-binding to type II cells, was paralleled by the appearance of CK4, typical for squamous epithelia, and the occurrence of DBA-binding in epithelial cells. Implications of these results for general concepts of intermediate filament protein expression and lectin binding in the fibrotic process are discussed.

Animals↗

Changes in cytokeratin, vimentin and desmoplakin distribution during the repair of irradiation-induced lung injury in adult rats.

The expression of cytokeratins, desmoplakin and vimentin has been studied immunohistochemically in the rat lung injured by x-irradiation using 14 well characterized monoclonal antibodies. A time-dependent relationship between the cytokeratin expression pattern and the morphological alterations observed was apparent. A cytokeratin 8 and 18 expression in normally cytokeratectable even at 3-6 h after irradiation. Between 14 days and 2 months, a remarkable heterogeneity in the epithelial cell cytokeratin pattern and an increasing immunoreaction for desmoplakin was found. In terminal bronchial epithelial cells, a heterogeneous CK8, 18 and 19 staining and a neoexpression of cytokeratins 4 and 7 was detected. Finally, peribronchiolar and vascular smooth muscle cells were cytokeratin-positive. At 6 months after irradiation, cytokeratin 13 and vimentin were focally present in bronchial epithelial cells and atypical type I and II pneumocytes as well as scattered epithelioid cell complexes were noted. During the course of injury, a loss of type III alveolar epithelial cells was found, which was characterized in the rat by a specific globular cytokeratin pattern and restricted immunoreactivity with cytokeratin-specific antibodies. These results show that the expression pattern of cytokeratins is a sensitive marker in monitoring epithelial alterations during lung injury.

Animals↗

LR Gold and LR White embedding of lung tissue for immunoelectron microscopy.

The immunogold technique in conjunction with LR Gold or LR White embedding was used to localize different antigens in normal rat and mini pig lung tissues. Lycopersicon esculentum and Maclura pomifera lectins and diverse cytoskeletal antigens such as cytokeratins, beta-tubulin, smooth muscle-actin, tropomyosin and villin were labelled well. Factor VIII-related antigen was found in Weibel-Palade bodies of endothelial cells. A 10 kDa Clara cell protein was localized in Clara cells. The morphological preservation of LR Gold-embedded tissue was superior to that of LR White-embedded tissues, but significant differences in antigenicity were not seen.

Acrylic Resins↗

Heterogeneous Dolichos biflorus lectin binding to a subset of rat alveolar macrophages in normal and fibrotic lung tissue.

The distribution of Dolichos biflorus lectin in the rat lung and during fibrosis after irradiation was investigated by lectin histochemical and electron microscopical techniques and double immunofluorescence labelling with the monoclonal antibodies RM-1 and ED-1. The results indicate a selective reaction of Dolichos biflorus lectin with a subpopulation of alveolar macrophages. No binding of the lectin was detectable in ED-1-positive macrophages but strong staining occurred in a part of the RM-1-positive cell population. In fibrotic lung specimens an increased number of Dolichos biflorus lectin-positive macrophages was found in which focally ED-1 reactive and RM-1 negative cells appeared. The finding of changing lectin binding pattern in a radiation-induced lung model emphasizes the suitability of the Dolichos biflorus lectin as a marker of macrophage activation or functional specialization.

Animals↗

Immunohistological detection of lymph node metastases in the testicular center as quick section diagnosis during retroperitoneal lymphadenectomy.

The object of this study was to determine whether the immunohistochemical detection of cytokeratin (CK)-positive cells is useful as quick section diagnosis, and whether the retroperitoneal lymphadenectomy (RLA) can be reduced by this method without any disadvantage for the patient. The RLA represents a combined diagnostic and therapeutic procedure for staging as well as removal of regional lymph node metastases in patients with malignant testis tumors. The disadvantage of the radical RLA is a 40 to 90% loss of potency. The risk of the reduced RLA is the relapse. The metastatic affection of the first retroperitoneal lymph node station, the so-called "sentinale" lymph nodes, allows a judgement for the remaining lymph nodes, and, therefore, for the extent of the necessary operation. The conventional frozen technique has a limited reliability, whereas the paraffin technique needs too much time. We used the immunohistochemistry as alternative method for the rapid as well as reliable evaluation of metastases. A group (7 cases) of 35 patients with non-seminomatous tumors of the testis was only treated by radical RLA after detection of CK-positive cells in the sentinale lymph nodes. The other patients were treated by modified RLA (20 cases) or reduced RLA (6 cases). The results were compared with a control group (48 cases) which was treated by radical RLA only. Using the modified RLA the relapse-free interval was not affected and the loss of ejaculation as a consequence of radical treatment could be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Erectile Dysfunction↗

[The initial results of the implantation of self-expanding nitinol stents into the esophagus in malignant dysphagia].

Nine patients (mean age 64, range 51-83 years), with dysphagia due to incurable malignant obstruction of the esophagus were treated by the introduction of 10 self-expanding metal endoprostheses (Nitinol stents). All cases were technically and functionally successful. In one patient the stent did not expand completely; it had to be removed and a second introduced. There were no other complications from the stent implantation. During the period of observation of 136 +/- 86 days one stent (11%) was reobstructed by tumor growing into the stent. Two patients died after 60 and 119 days, both with open stents. Early experience with the Nitinol stent indicates that good palliation of malignant dysphagia can be achieved with a much lower complication rate than results from tube implantation. The design and application system of the stent is capable of further improvement.

Aged↗

The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas.

The differentiation of the predominant cell types of the mucosal epithelium of the mammalian gastrointestinal tract is characterized by increasing amounts of an intermediate-sized filament (IF) protein designated cytokeratin (CK) 20 which is a major cellular protein of mature enterocytes and goblet cells. Here we report the isolation of the human gene encoding CK 20, its complete nucleotide sequence and the amino acid sequence deduced therefrom that identifies this polypeptide (mol. wt. 48553) as a member of the type I-CK subfamily. Remarkable, however, is the comparably great sequence divergence of CK 20 from all other known type I-CKs, with only 58% identical amino acids in the conserved alpha-helical 'rod' domain of CK 20 and, e.g. CK 14. Using riboprobes corresponding to exon 6 of the gene in Northern blot and ribonuclease protection assays, we show that the approximately 1.75 kb mRNA encoding CK 20 is specifically produced in cells of the intestinal and gastric mucosa, including tumors and cell lines derived therefrom. The appearance of CK 20-positive cells in human embryonic and fetal development and in adult tissues has been studied using immunohistochemistry with CK 20-specific antibodies. CK 20 synthesis has first been recognized at embryonic week 8 in individual 'converted' simple epithelial cells of the developing intestinal mucosa. In later fetal stages, CK 20 synthesis extends over most goblet cells and a variable number of villus enterocytes. The distribution of CK 20-positive cells in the developing gastric and intestinal mucosa is similar to--but not identical with--the pattern in the adult intestine in which all enterocytes and goblet cells as well as certain 'low-differentiated' columnar cells contain CK 20, whereas the neuroendocrine ('enterochromaffin') and Paneth cells are negative. In gastrointestinal carcinomas similarly examined, CK 20 has been detected in almost all cases (50/52) of colorectal adenocarcinomas, including all grades of differentiation and malignancy and also metastatic tumors, whereas CK 20 immunostaining in gastric carcinomas has been found less consistent and more heterogeneous. The possible biological meaning of the specific expression of the CK 20 gene in certain cells of the gastrointestinal tract and carcinomas derived therefrom and the regulatory mechanisms involved in the integration of the protein in the IF cytoskeleton are discussed.

Adenocarcinoma↗

Subtypes of non-transformed human mammary epithelial cells cultured in vitro: histo-blood group antigen H type 2 defines basal cell-derived cells.

Normal (non-transformed) human mammary epithelial cell lines derived from reduction mammoplasties were analyzed by immunocytochemistry with more than 80 monoclonal antibodies (mAbs) and other specific reagents to tissue-specific and developmentally regulated antigens at different passage levels. A subpopulation of poorly differentiated, proliferating epithelial cells, corresponding to the 'selected' cell type of late passages, is shown to be characterized by a new marker, the histo-blood group antigen H type 2, probably carried on a membrane-bound glycolipid. These cells also express a number of other onco-developmental carbohydrate antigens [Le(y), Le(x), sialosyl-Le(a), precursor of Thomsen Friedenreich antigen (Tn), but not Thomsen-Friedenreich antigen and sialosyl-Tn]. Their cytokeratin (CK) phenotype, as assessed by reactivity with monospecific mAbs and two-dimensional gel electrophoresis, is CK 5, 6, 14 and 17, with CK 19 being consistently absent, and varying minor amounts of CK 7, 8 and 18, as well as 15 and 16. The reactivity of these cells with a panel of 11 mAbs specific for CK 18 varies considerably even after cloning, indicating heterogeneity of epitope expression or accessibility. Our data strongly suggest that the H type 2+ cells develop from the basal cell layer of the mammary gland.

Adult↗

[Cytokeratins in inverted papillomas of the urinary bladder. (Part 1.)].

Inverted papilloma (transitional cell papilloma, inverted type) is a rare, benign urothelial tumor. The distribution of cytokeratin (CK) expression in 22 cases was investigated and compared with normal urothelium and urothelial carcinomas: CK7/8, basal increased positivity; CK13, diffuse positivity; CK18, loss of intensity and loss of umbrella cell staining; CK19, reduction of positivity; CK20, reduction of umbrella cell staining. The data indicate that the inverted papilloma is a basal cell urothelioma.

Biomarkers, Tumor↗

Cytokeratins in intracranial and intraspinal tissues.

The intermediate filament distribution pattern in cells and tissues of vertebrates reflects their differentiation or functional specialization state, their histogenesis, and their malignant transformation. In the case of cytokeratins, the characteristic epithelial intermediate filaments representing a complex group of about 30 polypeptides, extensive attention has been given to their expression in diverse epithelial and epithelioid cells. However, little is known about their distribution during fetal development and in neuroectodermal cells. This review specifically focuses on the data concerning cytokeratin expression in intracranial and intraspinal tissues, as expressed alone or as coexpressed with other intermediate filament proteins. Furthermore, the expression pattern of individual cytokeratin polypeptides was investigated by immunocytochemistry in diverse human and animal tissues using a broad panel of monoclonal antibodies. Only the cytokeratins typical of simple epithelia with the primary keratin pair 8/18 as a significant component have been detected in neuroectodermal tissues such as the choroid plexus and ciliary body epithelia, the retinal pigment epithelium, the subcommissural organ, and the ependymal cell clusters in fetal pineal gland (only in humans) as well as in various "unspecialized" ependymal cells of brain ventricles and spinal cord ependyma. Focal cytokeratin 19 expression in rat ciliary body and ventricle ependyma represents a rare exception. In addition, a group of intracranial and intraspinal tissues with controversial histogenesis express solely the cytokeratins 8 and 18: endocrine pituitary cells, arachnoid cells, and corneal endothelium. In most cases of tissues with neuroectodermal derivation, coexpression of cytokeratins and vimentin, or triple expression of cytokeratin, vimentin, and GFAP (fetal and neonatal choroid plexus of humans, rat and guinea pig ependymal cells in the neighborhood of the subcomissural, folliculostellate cells of human and guinea pig pituitary) is detectable. The coexpressions are discussed in the light of several hypotheses based on morphological and functional data concerning intermediate filament protein expression. Both the occurrence of more than one intermediate filament protein and the individual cytokeratin composition in the corresponding tumors of neuroectodermal origin reflect, in principle, the patterns found in their normal tissues. In the fetal neuroectodermal tissues studied, the cytokeratin pair 8/18 is the first one to be expressed during embryonic development.(ABSTRACT TRUNCATED AT 400 WORDS)

Central Nervous System↗

Cytokeratin expression and early lens development.

Immunohistochemical analysis of cytokeratins and vimentin in human, rabbit and rat lens epithelium during development revealed transient coexpression of both types of intermediate filaments. Cytokeratins were still detectable after the closure of the lens vesicle (rat and rabbit embryos 13 days post conception) and in the epithelial cells located at the anterior side of the lens in 7-week-old human embryos. Different monoclonal antibodies against cytokeratin 8 reacted differently in lens cells but not in other embryonic tissues. In addition, early human and rabbit specimens exhibited cytokeratin immunostaining in the neuroectodermal cells of the eye cup as well as in the surrounding mesenchyme, and in the hyaloid artery. Possible explanations for the loss of cytokeratins during the differentiation of ectodermal and neuroectodermal cells are discussed.

Animals↗

Changes in cytokeratin expression accompany squamous metaplasia of the human respiratory epithelium.

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, nonkeratinized (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.

Adolescent↗

Localization of thromboxane synthase in human tissues by monoclonal antibody Tü 300.

Using the monoclonal antibody Tü 300 we localized thromboxane synthase, a secondary enzyme of the arachidonic acid cascade, employing the alkaline phosphatase anti-alkaline phosphatase method and indirect double labelling immunofluorescence in frozen sections of human tissues. Aside from platelets, the source of the antigen, all cells of the mononuclear phagocytic system were positive, including epithelioid cells and associated giant cells, starry sky macrophages, dendritic cells of T-cell areas, Langerhans cells and Kupffer cells. In addition, some epithelial cells such as epithelia of tonsillar crypts, reticular epithelia of the thymic cortex and ductular epithelia in liver, pancreas, female breast and salivary glands showed occasional focal reactivity for thromboxane synthase. We suggest that the mAb Tü 300 is a key marker for the macrophage system and the thromboxane generating system in normal and pathological conditions. It may detect functional activities of as yet unknown significance in some specialized epithelial cells.

Blood Platelets↗

A screening and counseling program for prevention of osteoporosis.

Prevention of osteoporosis is an increasingly salient public health concern as our society ages. This report describes the procedures used at an osteoporosis center to which people come for screening and counseling. The patients on whom this report is based were 53 non-smoking women, 1-10 years postmenopausal at the time of their first visit to the center, who chose not to undertake estrogen therapy, and who returned for a second visit in 12-18 months. They were classified as to adequacy of calcium intake (at least 750 mg/day) and exercise (at least 3 h/week of weight-bearing exercise) at both visits; complete data on calcium intake and exercise were available on 46 of the women. Bone densities were measured at the femoral neck and lumbar spine with dual energy X-ray absorptiometry, and at the distal radius with single photon absorptiometry. At the first visit, 67% of the women reported adequate exercise and 43% reported adequate calcium intake. At the second visit, the percentages in the adequate categories had increased to 74% for exercise (p = 0.06) and 70% for calcium intake (p = 0.02). Age at the first visit was inversely correlated with femoral (r = -0.40, p = 0.003) and spinal (r = -0.36, p = 0.009) bone densities; the correlation with radial bone density did not achieve significance (r = -0.27, p = 0.55). Rather than declining, as would be expected in early postmenopausal women, bone density rose slightly, but not significantly, between visits for all three sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Cytokeratin and vimentin heterogeneity in human cornea.

The body of information on cytokeratin expression in non-epithelial and epithelioid cells is steadily increasing. In this immunocytochemical study using a panel of monoclonal cytokeratin antibodies, we regularly observed cytokeratins no. 8 and 18 together with vimentin in the corneal endothelium of the human eye, but the antibodies exhibited a heterogeneous reactivity pattern. In fetal eye specimens, cytokeratins were already present at the 10th week of gestation, and disappeared at about the 22th week of fetal development. Corneal and conjunctival epithelial cells in the same specimens usually showed uniform cytokeratin 8 and 18 expression, beside the well documented presence of corneal and squamous epithelium type cytokeratins. In 2 of our 7 cases of adults, cells coexpressing cytokeratin and vimentin were observed in the corneal epithelium. The data provide another example of modulation of cytokeratin and vimentin expression, in which simplistic rules cannot be applied.

Adult↗