PubMed Health⌕ Search

Biomedical subjects

K M Müller

Publications and source records attributed to K M Müller.

At least 235 records · Page 13Linked to original sources
PubMed1992

Cellular autofluorescent pigment and interstitial fibrosis in smoker's lung.

The mechanisms by which cigarette smoking lead to bronchopulmonary diseases are incompletely understood. The most characteristic lesion is a chronic macrophage-alveolitis accompanied by slight fibrosis and emphysema. The macrophages contain a ceroid-like granular autofluorescent pigment in their lysosomes. Using immunohistochemical methods, open lung-, transbronchial biopsies and cells obtained by broncho-alveolar lavage from cigarette smokers were studied: anti-human macrophage serum and anti-human elastase, immune sera against type I, type III collagens and fibronectin were used in the demonstration of the cellular components of alveolitis and the connective tissue constituents of fibrosis. The characteristic red-brown autofluorescent pigment of the macrophages was also found in an extra-alveolar location mainly in peribronchial, septal and pleural scars. Similar emission colour occurred focally in the elastic laminae of fibrotic alveoli and sclerotic arteries. Granular fluorescent pigment was found in many bronchial epithelial cells. The epithelial pigmentation was associated with increased transcription of nucleic acid proteins, revealed by colloid silver (AgNOR) reaction. The results suggest that the autofluorescent pigment substances in macrophages may indicate or also play a role in the development of pathological connective tissue and epithelial changes of smoker's lung, in addition to the known mediators and enzymes.

Adult↗
PubMed1992

[Mesothelioma of the pleura--pathological anatomy].

The examination of the pathology of diffuse malignant mesotheliomas (DMM) is based upon the analysis of 600 pleural tumours of the German Mesothelioma Panel in Bochum. Macroscopically there is a characteristic feature of the tumour growth, often restricted to the pleura, with preference of the basal pleural parts even in advanced stages. The highly variable growth pattern of the tumour phenotype contains parts of epithelial cells (42%), sarcoma-like cells (18%), and biphasic patterns (27%) as revealed by microscopy. Secondary pleural carcinosis are much more frequent (10 x) as diffuse malignant mesotheliomas but may mimic the DMM. Since there is no specific tumour marker for DMM available, additional immunohistochemical staining using different monoclonal antibodies directed against cytokeratins and epithelial antigens are recommended especially for examinations of small biopsies. The morphological security cheque follows the criteria of the European Mesothelioma Panel and is subdivided into 5 groups: A, assured mesothelioma; B, possible mesothelioma; C, probable mesothelioma; D, possibly no mesothelioma; E, certainly no mesothelioma. In the Bochum panel the incidence of A and B is 66%, of C, 6% and of D and E, 28%. In addition to the histomorphological examinations, in dust analysis of nontumourous lung tissue an augmented asbestos charge has been found in approximately 90% of all cases. The significance of asbestos fibers as an essential cause of the pleural mesothelioma could be underlined by our own animal experiments. After instillation of asbestos fibers into the right lung, a transpleural transport of fibers was observed with preneoplastic lesions and transformation of multipotent subserosal cells.

Asbestosis↗
PubMed1991

Sequence analysis of the cystic fibrosis gene in patients with disseminated bronchiectatic lung disease. Application in the identification of a cystic fibrosis patient with atypical clinical course.

The diagnosis of classical cystic fibrosis (CF) is easily made by clinical assessment alone, but may be missed or delayed in cases with an atypical clinical course. In a recent major study the age at diagnosis varied between 2 months and 47 years. For diagnostic purposes we have investigated the cystic fibrosis transmembrane regulator (CFTR) gene in 10 adult patients (age 18 to 45 years) with chronic obstructive pulmonary disease since childhood or adolescence and bronchiectases disseminated through both lungs. Only one subject (a 29-year-old male) had exocrine pancreatic insufficiency (PI); all others were pancreatic-sufficient (PS). The first nucleotide (ATP)-binding fold of the CFTR was analyzed by direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA in these cases. Two patients with different phenotypes (one PI, one PS) were found to be homozygous for the common delta F508 mutation of the CFTR gene, which proved the diagnosis of cystic fibrosis in their cases and allowed genetic counselling. The PS patient had normal sweat tests and had not previously been recognized as having CF. Four other patients were heterozygous for delta F508, with no other mutation in exons 10 or 11 of the gene, and four patients had normal sequences of these exons. Because only about 70% of all CF chromosomes carry delta F508, the unexpectedly high frequency (4/8 = 50%) of heterozygosity for delta F508 among the non-delta F508/delta F508 patients with bronchiectases suggests that some of these might also have unrecognized CF with rare genotypes and mutations in any of the 22 exons not sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Lectin-mediated induction of IL-4-producing CD4+ T cells.

Cultured murine CD4+ T cells have been shown to differentiate into IL-2 or IL-4-producing subsets. The factors responsible for the development of CD4+ T cells which produce IL-2 but not IL-4 and cells capable of producing IL-4 but not IL-2 are unknown. Here we describe a system that allows the controlled induction of IL-2- or IL-4-producing T cells after one single round of activation. Freshly isolated CD8-depleted T cells were activated with various polyclonal T cell activators for 48 h, washed, and then expanded under different conditions. IL-2 and IL-4 production were induced by restimulation of T cells and were measured with CTLL cells that respond to both cytokines and mAb to IL-2 and IL-4. T cells produced mainly IL-2 and small amounts of IL-4 when restimulated after expansion culture for 12 days with rIL-2 alone. However, after expansion for 12 days in the presence of rIL-2 plus Con A, we observed a 30- to 100-fold up-regulation of IL-4 activity and a 100-fold down-regulation of IL-2 when assessed by responses of CTLL cells incubated with the supernatant of restimulated T cells and by responses of CTLL cells cocultured with restimulated cells. An increase of IL-4 and decrease of IL-2 was also observed when the results were based on the cell numbers at the beginning of the expansion culture. The induction of IL-4 and the down-regulation of IL-2 1) were not reproduced with alpha-methyl-mannoside-treated supernatant of Con A-stimulated spleen cells, 2) were not dependent on the presence of large numbers of APC, 3) did not result from differential consumption of lymphokines after restimulation, 4) were not due to a difference in the time course of IL-2 or IL-4 release in either T cell population, and 5) were obtained regardless of the agents used to activate or to restimulate the T cells. Because Con A remained detectable on the T cell surface and because expansion of activated T cells with IL-2 plus Con A for several days was necessary, our results indicate that mainly IL-4-producing CD4+ T cells can be induced by prolonged engagement of T cell surface molecules.

Animals↗
PubMed1991

Mononuclear cell-bound CD23 is elevated in both atopic dermatitis and psoriasis.

As patients with atopic dermatitis (AD) frequently have elevated serum IgE levels, the relation of this disease to CD23/Fc epsilon RII, a low affinity Fc receptor for IgE, and its soluble forms, sCD23, was studied. We examined the expression of CD23 on peripheral blood mononuclear cells (PBMC) as well as the serum IgE and sCD23 levels in 33 patients with AD and in 9 patients with psoriasis in comparison with 10 healthy donors. In AD patients, the numbers of CD23+ unfractionated PBMC and CD23+ small adherent cells were significantly elevated (P less than 0.05, resp. P less than 0.005). In psoriatic patients however, CD23 was also significantly elevated on PBMC (P less than 0.05) and on small adherent cells (P less than 0.05). There was no significant difference in the frequencies of CD23+ cells between AD and psoriasis patients. In all donors, CD23 could be detected only on B cells, but not on monocytes/macrophages. In AD patients who were examined twice, an increase or decrease of the clinical AD score was always accompanied by an increase or decrease, resp., of cell-bound CD23. The serum sCD23 level was not significantly increased in either group of patients. Our results suggest that CD23 should be considered as a nonspecific marker for B cell activation in the context of inflammation and not as a specific marker for AD.

Adolescent↗
PubMed1991

Localization of elastase and tumor necrosis factor alpha mRNA by non-radioactive in situ hybridization in cultures of alveolar macrophages.

Digoxigenin is a new tool for labeling probes which can be detected with the help of specific antibodies in the cell by indirect or direct immunostaining. In contrast to the biotin-reaction, the advantage of digoxigenin is that it does not appear in animal or human cells in nature. In comparison to radioactive labeling methods it is favorable in terms of short exposure time and precise localization of signals in the cell. In this paper we describe the localization of elastase and tumor necrosis factor alpha (TNF alpha) mRNA by non-radioactive in situ hybridization of rat alveolar macrophages in cell culture after stimulation with welder steam dusts. Using digoxigenin labeled probes the determination of specific mRNA's expression and their precise localization in the cytoplasm of the cell could be achieved within one day.

Animals↗
PubMed1991

Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum.

In order to describe the ultrastructural features of the early phases of regenerating mesothelium in rat peritoneum, 69 cases were examined after intraperitoneal injection of 0.05-15 mg crocidolite, chrysotile B and other mineral and synthetic fibers. The findings show the presence of intermediate or transition cells between proliferating submesothelial connective tissue cells bearing the ultrastructural phenotype of myofibroblasts and mature fully regenerated mesothelium. Our results and data accumulated in the literature provide strong support for the hypothesis of submesothelial cells origin for regenerating mesothelium.

Animals↗
PubMed1991

Effect of thymectomy and immunosuppressive therapy on anti-neuroblastoma antibody levels in patients with myasthenia gravis.

Antibodies reacting with human neuroblastoma cells (NBL) are distinct from the "classical" anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG). The influence of therapeutic interventions on serum anti-NBL antibody levels was followed in 42 MG patients. Thymectomy alone was performed in 28 patients while immunosuppressive medication was given to 14 patients out of whom 10 also had a thymectomy. In most patients serum anti-NBL antibody titers declined after thymectomy and/or during immunosuppressive treatment, though individual variations in the antibody response could be observed. Sequential examinations of individual patients revealed an association between the clinical severity of MG and anti-NBL antibody levels. No correlation between the treatment-induced changes of anti-NBL and anti-acetylcholine receptor (AChR) antibody titers could be observed during the follow-up period in MG patients positive for both types of antibodies. These findings further emphasize the immunological complexity of MG. Anti-NBL antibodies represent a pathogenic marker of the disease and display a regulation different from that of the anti-AChR antibodies.

Adolescent↗
PubMed1991

Pulmonary alveolar lipoproteinosis in a seven-year-old girl. A follow-up over six years.

Alveolar lipoproteinosis is a rare disease in childhood, and its outcome is considered unfavourable compared to adults. We report on the spontaneous improvement of the disease over a six-year period in a child now 13 years of age. At the time of diagnosis the vital capacity was reduced to 65% of the mean predicted for her height, but deteriorated to 40% during the following year. A bronchoalveolar lavage was performed with small amounts of fluid but it did not immediately reverse the pulmonary alterations. Contrary to expectation, in the following years there was a continuous and gradual increase of the vital capacity to 70% of the mean predicted without specific therapy. This observation underlines the importance of an individual approach to prognosis in this disease and contributes to discussion of therapeutic procedures in the paediatric age group.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Capillary hemangioma of the right main bronchus treated by sleeve resection in infancy.

Respiratory distress developed in a 5-month-old female infant with roentgenographic evidence of hyperinflation of the right lung. Bronchoscopy revealed a vascular tumor extending from the medial wall of the right main bronchus leading to a check-valve mechanism. Radionuclide lung scans showed ventilation and perfusion of the right side reduced to 36 and 11% of the total lung ventilation and perfusion, respectively. At the age of 7 months a sleeve of the right main bronchus was resected and a reanastomosis performed. The operation specimen contained a capillary hemangioma measuring 1.2 X 0.6 cm. The postoperative course was uneventful. Perfusion of the right lung had markedly improved 6 months after the operation, and at the age of 2 yr and 9 months it was completely normal. Capillary hemangiomas must be considered a cause of bronchial obstruction in infancy, and surgery can be performed successfully.

Bronchi↗
PubMed1991

[Small cell bronchial cancer--pathologic anatomy].

Examinations of 635 biopsies and 163 surgical specimens resulted in a morphological description of characteristics of small cell cancer of the lung (cell diameter 9 microns, medial diameter of nuclei 7 microns). Histological diagnosis reflects only a rough phenotypic parameter of this tumor entity. At thorough examination of small cell cancer squamous, adenoid and/or giant cell differentiation can be found within the same tumor tissue in about 20% of specimens. Histological examination of spontaneous and therapeutical induced tumor regression in resected specimens yielded findings such as necrosis, scar development and endangitic blood vessel transformations. Results of electron microscopy, immunohistochemistry and in situ hybridisation also underline a wide range of heterogeneity in the special group of small cell cancer of the lung. The documentation of a broad spectrum of morphological findings in specimens from resected tumors demonstrates that a 2-mm biopsy represents only a rough parameter of a biologically complex tumor.

Biomarkers, Tumor↗
PubMed1991

[Cytokeratin expression in fetal lung--immunohistochemical studies].

This paper is to give information about the pattern of expression of cytokeratin in bronchial mucosa, alveolar epithelium, lung stroma and pleura during the prenatal development of the lung. Our immunohistochemical investigations occurred in the lung of a 6 week old embryo and in 21 lungs of intrauterine died fetuses from the 12th to the 36th week of gestation according to the modified avidin-biotin-method. Findings of investigations will be compared with expression patterns in tumors and normal lungs of adults. In summary the investigations showed the following results: 1. Immunohistochemically in fetal lungs proteins are demonstrable that are used in the pathology of adults as markers for the histogenetic differentiation of various cell forms. 2. An expression of cytokeratins we could constantly prove in epithelial cells of fetal lungs after the 6th week of gestation. 3. Cytokeratins are mostly found at the cell membranes. 4. With increasing differentiation in direction to alveolar epithelium changes the composition of cytokeratin in the cells. 5. Cells of the pleura mesothelium are expressing cytokeratins in a pattern similar to that of bronchiolar epithelium. All in all the pattern of antigenic expression in fetal lungs considerably assimilates to that in adult lungs during the fetal lung development.

Bronchi↗
PubMed1991

[Immunohistochemical markers in lung tumors--a status evaluation].

Immunohistochemical investigations on tumours of the lung and pleura led to an enlarged knowledge about the characterization of the tumours biology and the typical morphological feature of lung tumours. A helpful tool was the elaboration of monoclonal antibodies against different cellular proteins and proliferation markers which revealed a detailed information on proliferation tendency and immunological reaction of the tumour. The most informative parameter in adenocarcinomas was the distinguished expression of the carcino embryonic antigen (CEA). The immunohistochemical investigations are helpful for the differentiation of primary and secondary lung- and pleural tumours, but also pointed out a high heterogeneity of malignant lung tumours. Nevertheless the present tumour markers--be considered to give an indication for diagnosis, therapy and prognosis of the development of the disease--have to be correlated with clinical and biochemical data for further estimation of their value.

Adenocarcinoma↗