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Biomedical subjects

D Schuh

Publications and source records attributed to D Schuh.

At least 19 recordsLinked to original sources

Distribution of E-cadherin and Ep-CAM in the human lung during development and after injury.

Paraffin sections were obtained of human fetal, adult, and pathological lung (pulmonary fibrosis after radiotherapy or chemotherapy). The localization of epithelial adhesion molecules E-cadherin and Ep-CAM (former epithelial surface 40 kDa glycoprotein) was investigated by immunoperoxidase and/or immunofluorescence techniques with monoclonal antibodies. During development, the epithelia of the primary pulmonary primordium, the secondary bronchi and the adult bronchial epithelium retained immunoreactivity for E-cadherin and Ep-CAM with lateral immunostaining of cell membranes. In normal adult lungs, Ep-CAM was detected in type I and II alveolar epithelial cells, whereas E-cadherin was confined to the basolateral domain of type II cells. In pulmonary fibrosis, Ep-CAM could be further detected on the cell surface of epithelial remnants. In contrast, E-cadherin expression was characterized by a change of the membrane localization to a spotty, cytoplasmic pattern in the alveolar epithelium, possibly indicating functional inactivation of the protein during fibrogenesis.

Adult

Distinct expression patterns of CD44 isoforms during human lung development and in pulmonary fibrosis.

The transmembrane glycoprotein CD44 represents a family of molecules, all encoded by one gene. The variability of the isoforms is generated by alternative splicing of the nuclear RNA. Apart from the abundant standard form (CD44s), the variant isoforms (CD44v) are mostly restricted to epithelia. The present study demonstrates the expression of CD44s and CD44v isoforms in embryonic and fetal lungs and in normal and pathologically altered (pulmonary fibrosis after radio- or chemotherapy) human adult pulmonary tissues. Using double immunofluorescence and avidin biotin complex (ABC) techniques on paraffin sections, presence of CD44s and CD44v isoforms (CD44v4, CD44v6, CD44v9) has been analyzed. In normal lung tissue, CD44s is present at the cell surface of alveolar macrophages, in some interstitial cells and in epithelial cells. It is also present in epithelial and non-epithelial cells during lung development. CD44v isoforms containing exon v6 and v9 encoded epitopes are selectively detectable in normal epithelial cells with a strong basolateral distribution pattern in the entire population of type II pneumocytes and in basal cells of the bronchial epithelium. During development exon v9 encoded isoforms appear at the pseudoglandular stage, whereas CD44v6 has only been found at the saccular stage. Examination of 12 fibrotic lung samples has revealed major alterations in the CD44 expression in comparison to normal lung tissue. These changes include cytoplasmic deposits of CD44s in alveolar epithelial cells and reduced expression of the CD44v6 and CD44v9 isoforms in alveolar epithelial and bronchial epithelial cells. The results suggest that CD44v isoforms may be utilized by type II pneumocytes in epithelial-mesenchymal interactions and in the maintenance of the pulmonary histoarchitecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Immunohistological detection of the beta subunit of prolyl 4-hydroxylase in rat and mini pig lungs with radiation-induced pulmonary fibrosis.

Polyclonal and monoclonal antibodies to the beta subunit of prolyl 4-hydroxylase, the protein disulphide isomerase, were used to compare the pulmonary cells in 13 normal and in 20 fibrotic rat and mini-pig lungs made fibrotic by X-ray irradiation, using the ABC immunoperoxidase technique. In normal lungs, prominent staining of Clara cells and type II pneumocytes and weaker reactivity with alveolar macrophages, fibroblasts, endothelial and smooth muscle cells were detectable. In pulmonary disease, in which interstitial fibrosis was the characteristic feature, the immunoreactivity was increased in both the epithelial and interstitial cells. Type I pneumocytes remained negative. In the early stages of disease (3 to 4 weeks after irradiation) when little morphological alteration was seen, capillary endothelial cells had already become immunoreactive. These results underline the complex involvement and interaction of different lung cell populations in the process of pulmonary fibrogenesis.

Animals

Localization of surfactant protein A (SP-A) in alveolar macrophage subpopulations of normal and fibrotic rat lung.

The colocalization of surfactant protein A (SP-A) and the alveolar macrophage markers ED1 and RM-1, as well as various lectins of the N-acetyl-galactosamine group [Maclura pomifera lectin (MPA), Dolichos biflorus lectin (DBA), soybean agglutinin (SBA)] and of the mannose group [Canavalia ensiformis lectin (ConA), Galanthus nivalis lectin (GNA)] was studied in normal and fibrotic rat lung tissues. In normal tissue, SP-A was located preferentially in the alveolar macrophage subpopulation lacking specific binding sites for lectins of the N-acetylgalactosamine group (DBA and SBA), although 50% of MPA-binding macrophages contained SP-A. The ED1-positive cells were SP-A-negative, whereas SP-A uptake could be detected among the RM-1 immunoreactive as well as the ConA and GNA binding macrophages. In fibrotic lung tissue, however, a small number of DBA and SBA binding macrophages contained SP-A and the percentage of GNA and ConA binding alveolar macrophages exhibiting SP-A immunoreactivity was reduced. Additionally, the number of ED1+/SP-A+ macrophages was found to be increased. Immunoelectron microscopy revealed accumulation of SP-A in the extracellular space. The differing SP-A content in different alveolar macrophage subpopulations suggests a more complex mechanism of uptake and degradation of surfactant proteins in normal and pathological conditions, which cannot simply be explained by the glycoconjugate pattern on the surface of alveolar macrophages.

Animals

Immunohistochemical localization of the beta subunit of prolyl 4-hydroxylase in human alveolar epithelial cells.

The beta subunit of prolyl 4-hydroxylase, the protein-disulfide isomerase (PDJ), catalyzes the hydroxylation of proline residues of collagens and proteins with collagen-like structure, a step essential for the folding of the procollagen chains to form triple-helices. In the present study, we report the selective immunohistological localization of PDI in type II alveolar and bronchial epithelial cells. The detection of the hidden antigen with the monoclonal antibody 5B5 is usually not successful in paraffin sections but was possible after microwave pretreatment of tissue sections. In cases of severe lung injury (fibrosing alveolitis) enhanced immunoreactivity was found for this enzyme in epithelial, endothelial as well as interstitial cells and in alveolar macrophages. The results indicate a possible involvement of the pulmonary epithelial cells in the upregulation of collagen production during the process of fibrosis.

Antibodies, Monoclonal

Bauhinia purpurea lectin (BPA) binding of rat type I pneumocytes: alveolar epithelial alterations after radiation-induced lung injury.

In the rat lung, we found that the Bauhinia purpurea lectin (BPA) specifically binds to the type I alveolar epithelial cells and to the alveolar macrophages. Double label fluorescence employing FITC-coupled Maclura pomifera lectin (MPA) and bBPA-avidin-Texas Red showed that BPA binding was confined to type I cells. In addition, a minor staining of the luminal border of the terminal bronchiolar epithelium was found. The sequence of tissue injury following X-radiation was examined in rats. BPA is a suitable marker which indicates epithelial changes during the early stage of pneumonitis and the subsequent development of fibrosis.

Animals

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

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

[Granular cell tumor of the vermiform appendix. Case presentation with discussion of histogenesis].

Granular cell tumor is a rare lesion to the appendix. A case of that kind was recorded by the authors from a man, 32 years of age, who underwent surgery for appendicitis. Presence of a granular cell tumor was histologically, histochemically, and immunohistologically verified. Histogenesis of granular cell tumors is not well known, which prompted the authors to summarise some of their recent findings for discussion.

Adult

[Radiogenic pneumopathy--synopsis of roentgen image and electron microscopy findings].

Radiation-induced pneumapathia is one of the most frequent complications after radiotherapy to the chest and occurs especially after radiation of bronchial carcinoma (frequency 40-70%, using 50 Gy). The broad ranges of reported frequency indicate differences in defining the degree of radiation-induced damage (clinical picture, plain film, and lung function parameters). This study is to compare plain film findings with electromicroscopy in order to correlate radiological signs with the underlying histo-morphological process.

Animals

[Epidemiology of cancer of the exocrine pancreas 1979-88 in the area of Dresden].

In the catchment area of two Pathological Institutes in Saxony with a population of approximately 1.3 million people all autopsies with the diagnosis of exocrine pancreatic cancer were evaluated with respect to age and the number of autopsies carried out in the period of the past ten years (1979-1988). The trend of this type of cancer within this group of all dissected cancer patients was followed. Absolute increase rates of 48% for males and 32% females could be calculated. An increasing incidence of pancreatic cancer was observed not only in the 7th and 8th decade of live--as was typical so far--but also from the age of 50 years onwards. Rates of increase were also found with regard to all cancer autopsies: 6% for males and 34% for females. The data agree with other observations of an increased pancreatic cancer incidence in all industrialized countries.

Adult

[Radiogenic effects on liver tissue].

In a review of literature the presented studies on radiogenic liver injuries are summarized. Whereas in the past the liver tissue was supposed to be radioresistant nearly completely, to newer knowledge this organ has to be classed with most radiosensitive tissues at all. The early picture of a liver injury in man is characterized by the veno-occlusive syndrome. Like in Budd-Chiari-Syndrome a congestion begins in the central veins and the centrolobular sinusoids, that has severest threatening consequences for the patients with extensive liver irradiation. The clinic picture is demonstrated. At present no suitable animal model exists for this disease yet. The presented pathological and electron microscopical findings do not allow any final estimation of the pathogenesis in this disease. The radiogenic late-effects are manifested in the liver in a centrolobular fibrosis, also starting from the Glisson's triangles, with cirrhotic reconstruction of liver architecture. The great compensatory power of the organ does not cause clinical pictures to be effected in radiotherapeutic practice with only partial liver irradiation in most cases. The dose-time-relation of the radiogenic hepatitis shows a very little alpha-/beta-value. With this the liver renders as typical late-effect tissue and should be spared effectively by choice of small single doses.

Animals

[Endophlebitis hepatica obliterans. Unusual cause of liver insufficiency in early childhood in a dizygotic twin].

Findings recorded from obliterative hepatic endophlebitis are described in this paper and are compared with international literature. They had been obtained from a male twin who had died with clinical symptoms of hepatic failure. Differential diagnosis of liver insufficiency in early childhood is discussed in some detail. Also recorded was obliterative angiitis of intramural blood vessels in the ileum. Systemic vasculitis is postulated, possibly developed on the basis of an immunological reaction. Intra-uterine infection had probably been the most likely cause.

Budd-Chiari Syndrome

Induction of thyroid neoplasms in the rat. A histochemical, immunohistochemical, autoradiographic and ultrastructural study.

Papillary carcinomas of the thyroid gland induced in rats by combined methylthiouracil (MTU)/nitrosomethylurea treatment were studied electron microscopically and histochemically for their acid phosphatase activity, radioactive iodine uptake and for their thyroglobulin synthesis. The papillary carcinomas accumulated radioactive iodine, synthesized thyroglobulin and showed a perinuclear localization of acid phosphatase activity in the cytoplasm. After omitting the reactive thyrotropic effect (cessation of MTU administration) a decrease of both iodine organification and acid phosphatase activity was observed. The synthesis of thyroglobulin was also reduced. The changes in the ultrastructure of tumour cells corresponded to the respective functional activities. The results suggest that the papillary carcinomas may have a functional dependence on thyroid-stimulating hormone.

Acid Phosphatase

[Immunohistochemical detection of thyroglobulin].

An antiserum against human thyroglobulin isolated by gelfiltration from the human thyroid gland was raised in rabbits. The specificity of the antiserum to detect human thyroglobulin was determined by an immunoperoxidase technique on formalin-fixed and paraffin-embedded tissue sections of 17 primary thyroid carcinomas and 80 carcinomas of other origins, such as pancreas, colon, breast, bladder, ovary, testis, and larynx. Positive reactions to immunological staining were recorded only from differentiated thyroid carcinomas, while no reactions were exhibited by the other malignant tumours tested in this study.

Adenocarcinoma

[Radiation pneumonitis. Morphology and pathogenesis].

Radiation-induced pulmonary damage is an inflammatory process which progresses in stages. The quantity rather than quality of pulmonary reactions depends on the given radiation dose. Damage to endothelial cells of capillaries and of respiratory epithelium is the initial event in the development of radiation pneumonitis. Release or activation of cytogenic and serum-derived mediators, increased permeability of the capillary wall, and damage to pneumocytes II are the most important factors in pathogenesis. There is no morphological latent stage. The latency between exposure to irradiation and manifestation of clinical symptoms of pneumonitis may be explained by the morphologic findings. Several non-radiation-induced lung diseases are predisposing factors. There is a tendency to bacterial, viral or mycological superinfections in patients with radiation pneumonitis. Radiotherapy leaves behind a latent pulmonary lesion with continuously changing reactions to most various irritations.

Humans

[Pericardial mesothelioma. Apropos of a case].

A 74 year old woman without previous cardiovascular disease presented with pericardial effusion and tamponade. Two-dimensional echocardiography displayed a pericardial mass, but a diagnosis of tumour was not envisaged. Pericardiocentesis produced an exudative fluid with lymphocytes but no malignant cells. Pericardial biopsies through axillary thoracotomy indicated chronic progressive pericarditis. As the patient's haemodynamics deteriorated, sternotomy was carried out showing diffuse pericardial sclerosis corresponding, at histology, to a mixed, predominantly fibroblastic pericardial mesothelioma. The authors describe the main clinical characteristics of pericardial mesothelioma, always discovered belatedly at surgery or necropsy. They insist on the value of non-invasive methods (two-dimensional echocardiography, computed tomography) to diagnose a pericardial tumour, and on the poor prognosis of mesotheliomas, treatment still being uncertain due to the small number of cases and to the early occurrence of cardiac complications.

Aged

Detection of Dirofilaria immitis microfilariae in peripheral blood. A quantitative comparison of the efficiency and sensitivity of four techniques.

Four techniques for the detection and quantification of Dirofilaria immitis microfilariae in peripheral blood were compared, namely the conventional thick smear, thick films prepared by cytocentrifugation, filtration of blood through polycarbonate membranes, and density gradient centrifugation followed by membrane filtration. The efficiency of the methods and their sensitivity was assessed by determining quantitatively the recovery of known numbers of microfilariae from defined volumes of blood. Polycarbonate membrane filtration either alone or in combination with density gradient centrifugation showed an efficiency of 0.9 and 0.8, respectively, and reached 100% sensitivity with microfilariae densities of greater than or equal to 10 microfilariae per ml of blood. Conventional thick smears and cytocentrifugation were of considerably lower efficiency (0.02 and 0.03, respectively) and reached 100% sensitivity with more than 200 microfilariae per ml.

Animals