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Biomedical subjects

K M Müller

Publications and source records attributed to K M Müller.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Scanning electron microscopic analysis of vessel wall reactions after coronary stenting].

High restenosis rates are still a major factor limiting the use of minimal invasive coronary stenting. Tissue reactions to the implanted alloplastic endoprostheses are still barely understood. 18 coronary artery segments 32 hours up to 340 days after stent implantation of 16 patients were post-mortem investigated. The pathomorphological findings of the vessel wall after stent insertion were studied by scanning electron microscopy (SEM). Stent integration can be divided with intraindividual differences in three phases: In the acute phase (<6 weeks) the border between vascular lumen and arterial wall is constituted by a thin, multi-layered thrombus. During the time course of integration, increasing amounts of Smooth Muscle Cells (SMC) and extracellular matrix can be detected. No endothelial cells can be found in the implantation zone. In the intermediate phase (6 weeks to 12 weeks) the neointima consists of extracellular matrix and increasing numbers of SMC. The borderline between lumen and neointima is generated by SMC and extracellular matrix. Increasing amounts of endothelial cells are found on the luminal surface of the stent neointima. Complete reendothelization is first noted in the chronic phase three months after stenting. Matrix structures are increasing whereas the amount of SMC decreases. In all phases of stent incorporation, the alloplastic stent material is covered by a thin (few nanometer) proteinaceous layer.

Aged↗
PubMed2000

Atherosclerotic carotid arteries--calcification and radio-morphological findings.

OBJECTIVES: Are there any predictable factors influencing the process of calcification in carotid arteries? BACKGROUND: The carotid arteries and especially the carotid bifurcation are one of the predisposed regions of atherosclerotic disease. Whether topography of the carotid sinus, flow patterns or different patient characteristics (e.g., diabetes mellitus, age, sex) are a factor determining calcification of atherosclerotic lesions is still hardly understood. METHODS: Morphological and morphometrical analysis including radiographic classification of different degrees of calcification on postmortal carotid arteries (90 men and 19 women) and 306 surgical samples after intramural desobliterations of carotid arteries (202 patients with diabetes, 104 patients without diabetes). RESULTS: Most common localization of radiographically identified calcified deposits are the carotid bulb (76%) especially on the lateral wall opposite the flow divider and the internal carotid artery (55%) especially the proximal 1 cm section. No difference in degree of calcification was found when comparing patients with and without diabetes (intermediate calcification in 59% of patients with diabetes and 50% without diabetes). More female patients with diabetes show calcification when compared to the group of patients without diabetes. Females produce calcification in atherosclerotic carotid lesions at an older age compared to male patients. CONCLUSIONS: Calcification is a frequent finding in advanced atherosclerotic carotid lesions. There is no difference in regard to degree, pattern of calcification or age distribution when comparing patients with and without diabetes mellitus. Atherosclerotic lesions more frequently found in female patients with diabetes may be due to less vasoprotection by estrogens.

Adult↗
PubMed2000

Benign solitary fibrous tumour of the thigh: morphological, chromosomal and differential diagnostic aspects.

Solitary fibrous tumours (SFTs) are rare and usually benign neoplasms of mesenchymal origin that are often found in the visceral pleura (fibrous pleural tumour, FPT) or other serosal surfaces. They have also been found in soft tissues. We report the case of an SFT localised in the thigh of an 86-year-old woman. The tumour specimen was examined morphologically, immunohistochemically and molecular genetically, using comparative genomic hybridisation (CGH). The latter detects unbalanced chromosomal alterations in human neoplasms by competitive nucleic acid hybridisation and consecutive computer image analysis. The tumour consists of fibroblast-like cells, arranged in a typical "patternless pattern". Immunohistochemically, the tumour stained positively for vimentin, CD34, CD99, and focally for actin and desmin. No reaction occurred with keratin or S100 protein antibodies. CGH detected a single loss on chromosome 13q.

Aged↗
PubMed2000

Patterns of chromosomal imbalances in benign solitary fibrous tumours of the pleura.

Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise 12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible genes involved in early tumorigenesis.

Aged↗
PubMed2000

Patterns of expression and secretion of vascular endothelial growth factor in malignant soft-tissue tumours.

Vascular endothelial growth factor (VEGF) is an important cytokine especially in the process of tumour angiogenesis. A total of 46 soft-tissue sarcomas were analysed for the expression and possible secretion of VEGF by immunohistochemistry, in-situ hybridisation, and enzyme-linked immunosorbent assays (ELISA). VEGF was demonstrated immunohistochemically in tumour tissue in 45 of 46 cases. The detection of mRNA transcripts yielded evidence of synthesis of VEGF in these sarcomas. ELISA could be performed in 21 cases. Higher concentrations of VEGF were found in tumour-related intraoperatively sampled venous blood in 16 out of 21 patients (76%) than in systemic concentrations taken preoperatively. The results indicated the secretion of VEGF by tumour cells although these raised concentrations were not statistically significant. In 12 out of these 16 patients (75%) a concurrent moderate to strong immunoexpression of VEGF was detected. The relevance of VEGF blood concentrations as a potential "progress parameter" for the course of disease remains questionable. This is mainly due to the lack of statistical significance in the difference between systemic VEGF concentrations in patients and those of a control group. Further long-term follow-up studies are needed, which should include patients with tumour recurrences.

Adolescent↗
PubMed2000

p53 tumour-suppressor gene in non-small-cell lung cancer with neoadjuvant therapy.

In a phase II study for optimizing therapeutic management of locally advanced non-small-cell lung cancer the prognostic and therapeutic relevance of the p53 status was investigated. Biopsy or mediastinoscopy samples, collected prior to neoadjuvant chemoradiotherapy and corresponding resection specimens, were analysed immunohistochemically (CM1 antiserum) for p53 accumulation and molecular biologically (polymerase chain reaction/single-strand conformation polymorphism) for p53 mutations. The results were correlated to the response to therapy (regression grade) and to the survival times. p53 accumulation was found in 41.7% (prior to neoadjuvant therapy) and in 40.0% (after surgery) of the tumours. p53 mutation was demonstrated in 45.4% (prior to neoadjuvant therapy) and in 46.4% (after surgery) of the investigated tumours. Neither before nor after therapy was any correlation to the survival times or to the response to therapy seen in the collective analysed. Thus, such investigations are not suitable for identifying patients with locally advanced non-small-cell lung cancer who might benefit, to different extents, from neoadjuvant therapy.

Adult↗
PubMed2000

APC and beta-catenin in alveolar soft part sarcoma (ASPS)--immunohistochemical and molecular genetic analysis.

Apart from its role in cell-adhesion, beta-catenin is regarded as an oncoprotein, the cytoplasmic level of which is regulated by APC as a tumor suppressor protein. Changes of chromosome 5q, the region that includes the APC-gene, are known to be important in the pathogenesis of fibromatosis; however, little is known about the significance of APC and beta-catenin in other mesenchymal tumors. Therefore, we used immunohistochemistry and DNA-analysis to investigate four cases of alveolar soft-part sarcoma (ASPS) as a mesenchymal tumor with a distinct histologic appearance. In three cases of ASPS the APC-gene product was found to have strong nuclear expression and only faint cytoplasmic staining. Beta-catenin showed a partly membranous, partly strong intracytoplasmic expression. No gene mutations for APC and beta-catenin were detected in any of the four cases. These investigations suggest that, apart from their function in carcinogenesis and fibromatoses, APC and beta-catenin play a role in the pathogenesis of soft tissue tumors such as ASPS. The significance of a striking nuclear accumulation of non-mutated, virtually functionally active APC-tumor suppressor protein has not yet been investigated. A nuclear function of APC in ASPS in down-regulating nuclear transcription processes linked to overexpression of beta-catenin, as is known in colorectal carcinogenesis, may be hypothesized.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen.

OBJECTIVES: The aim of our study was to analyze the cellular components of neointimal tissue regeneration after coronary stenting. BACKGROUND: High restenosis rates are a major limiting factor of coronary stenting. To reduce the occurrence of restenoses, more insights into the mechanisms leading to proliferation and expression of extracellular matrix are necessary. METHODS: Twenty-one autopsy cases with coronary stents implanted 25 h to 340 days before death were studied. The stented vessel segments were analyzed postmortem by light microscopy and immunohistochemical staining. RESULTS: In the initial phase stents are covered by a thin multilayered thrombus. Alpha-actin-positive smooth muscle cells (SMCs) are found as the main cellular component of the neointimal tissue. Later (>6 weeks) extracellular matrix increases and fewer SMCs can be found. In every phase the SMC layers are loosely infiltrated by inflammatory cells (T lymphocytes). In the early postinterventional phase all endothelial cells are destroyed. The borderline between the vessel lumen and the vascular wall is constituted by a thin, membranous thrombus. Six weeks after stenting, SMCs form the vessel surface. Complete reendothelialization is first found 12 weeks after stenting. CONCLUSIONS: Stent integration is a multifactorally triggered process with proliferating SMCs generating regenerative tissue. In the early phase predominantly thrombotic material can be observed at the site of stenting, followed by the invasion of SMCs, T lymphocytes and macrophages. The incidence of delayed reendothelializations and the occurrence of deep dissections may be associated with excessive SMC hyperplasia.

Actins↗
PubMed2000

Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal features. Comparative genomic hybridization evidence for a mesothelioma subgroup.

Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart from the three classical patterns, predominantly epithelioid, sarcomatoid, and biphasic, some rare variants do exist. In some cases, one can find uncommon additional mesodermal tumor components. These tumors have previously been called "mesodermomas" and, like regular mesotheliomas, are usually associated with a previous asbestos exposure. We examined eight cases of mesodermomas by light microscopy, immunohistochemistry and comparative genomic hybridization (CGH). Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous, or even angioblastic elements may be found to varying degrees. Immunohistochemical analysis shows similar staining results as with regular mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per case; range, 11-27). In 10 classical biphasic mesotheliomas that served as a control, defects of comparable number and severity could not be detected (8 per case; range, 2-16). The most frequent defects of mesodermomas (losses on 1p, 4pq, 9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in mesotheliomas of the classical type. Thus, our results support the classification of the so-called mesodermomas as a separate tumor subgroup while maintaining the relationship to the classical mesotheliomas. Therefore, we propose to use the term mesodermoma for this subgroup.

Aged↗
PubMed2000

Healing characteristics of small-calibre vascular prostheses coated with plasmin-treated fibrin--an experimental study.

BACKGROUND: The autogenous vein represents the graft material of choice in crural and pedal bypass surgery. Because of the numerous problems concerning the graft harvesting and the quality of autogenous vein material an equally good allogenous graft is urgently needed. Up to the present times no such graft material has been able to achieve the success of vein grafts. METHODS: We investigated the knitted polyester prosthesis Terumo PF-V (Terumo Comp., Japan), diameter 5 mm with outer reinforce, which is characterized by a new coating of plasmin-treated fibrin. Grafts were implanted as bypass into the ligated carotid (n = 10) and femoral arteries (n = 10) of 10 dogs (beagles). As a control 5 mm-ePTFE-prostheses (Impra Carboflo) were implanted simultaneously on the contralateral side. RESULTS: After 6 months, seven of 20 PF-V-grafts and 8 of 20 PTFE-grafts were patent. All prostheses presented with good macroscopic healing characteristics. In the patent grafts, angiography showed no substantial stenoses. The histological examination of the material was performed using light microscopy, transmission polarising microscopy, scanning electron microscopy, and transmission electron microscopy. Both types of prostheses showed the typical pattern of graft healing by migration of mesenchymal cells through the prosthesis, formation of capillaries, and growing of a neointima with endothelium-like cells. All failed bypass grafts presented with an occluding proliferation from the arterial wall into the anastomotic region. CONCLUSIONS: Using clinically or histologically evaluation, neither graft demonstrated superiority over the other. The results indicate that the coating plays only a minor role for graft healing if any. For proper graft function, the arterial wall proliferation at the anastomotic region, which is not dependent on the type of prosthesis, appears to be most important. The overall results concerning both types of prostheses were disappointing.

Animals↗
PubMed2000

Beta-catenin in soft tissue sarcomas: expression is related to proliferative activity in high-grade sarcomas.

Besides its role in cell adhesion, beta-catenin exerts a function as an oncoprotein. The aim of this study was the characterization of its expression, possible mutation, and the assessment of beta-catenin as a prognostic indicator for soft tissue sarcomas. A total of 115 soft tissue sarcomas were analyzed using immunohistochemistry, immunogold-electron microscopy, and DNA analysis. Information from 56 patients was available for follow-up. A statistically significant correlation was found between intracellular distribution of beta-catenin and the proliferative activity (MIB-1 expression) in high-grade sarcomas (P = .0008). Beta-catenin was identified with intracytoplasmic and nuclear accumulation, showing additional membranous staining in sarcomas with epithelioid pattern. Ultrastructurally, a colocalization between beta-catenin and nuclear heterochromatin was demonstrated. In 22 analyzed tumors, only one (yet undescribed) mutation of the beta-catenin gene (C-A transversion) could be detected. Prognostic validity of the cellular expression of beta-catenin, however, was not proven. Apart from its membranous function as an effective molecule for cell-adhesion in sarcomas with epithelioid pattern, beta-catenin may act as an oncoprotein in sarcomas with intracytoplasmic and nuclear localization with binding to nuclear DNA. A previously discussed stimulation of cell proliferation caused by an increased beta-catenin level can also be postulated for high-grade soft tissue sarcomas in correlation with the rate of proliferation. Mutations of the beta-catenin gene are probably of lesser importance for the accumulation of beta-catenin in soft tissue sarcomas.

Adult↗
PubMed2000

łGradation of sideropneumoconiosis.

Pathological-anatomical analyses of biopsy and autopsy samples of 43 men with anamnestically established occupational exposure to welding fumes showed in 38 specimens (88%) characteristic alterations of varying degrees of sidero pneumokonioses. Based on recurrent histological findings of increase and activation of iron storing macrophages (siderophages) and varying degrees of fibrosis, sidero pneumokonioses are classified into three grades. Intraindividually and also toporegionally different degrees may well be present. Based on morphological criteria of the three grades, seven samples were classified as grade I, 21 specimens as grade II, and 10 samples as grade III. The results show that exposure to welding fumes may well cause pulmonary alterations reaching an impairment level, depending on length, extent and special circumstances of the respective exposure. In cases of so-called welders lungs, an obliging statement in an expert's opinion on the degree of functional impairment, however, can only be given when histological findings, detailed information on the occupational history and clinical functional parameters are combined.

Autopsy↗
PubMed2000

Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation.

The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.

Animals↗
PubMed2000

Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases.

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.

Adult↗
PubMed2000

[Differential diagnosis of primary lung tumors and pulmonary metastases].

The lungs are frequent metastatic targets for metastases of extrapulmonary cancer with or without known primary tumor. Metastases of extrapulmonary tumors are found in 20 to 50%. Metastatic carcinoma of unknown primary localizations contributes to about 4% of all diagnosed carcinomas. Within this group adenocarcinomas can be found in 60%, squamous cell carcinomas in 15%, unspecified tumors including small cell and undifferentiated tumors in 25% histogenetically. Due to overlapping histologic features a histopathological distinction of primary and secondary tumors might be difficult. Topography, size and form of pulmonary growth pattern are important aspects for the differential diagnosis. Primary lung tumors are mainly localized in upper lobes as singular nodules, metastases in lower lobes as multiple lesions. For the distinction of endobronchial primary or secondary squamous cell carcinomas findings of severe dysplasia and CIS of the bronchial epithelium are important. Stroma and vascularisation pattern of primary and secondary lung tumors differ in distribution, arrangement and extracellular matrix components. Pulmonary vascular changes in primary tumors are characterized by vascular infiltration, destruction and occlusion whereas in secondary tumors intravascular embolisation and extravasation predominate. Immunohistochemical techniques using different algorithms of antibodies (cyto-keratins, neuroendocrine markers, TTF-1, vimentin, HMB 45, LCA, oncogenes, tumor suppressor genes etc.) give vital clues as to the origin of the primary tumor. Metastases of thyroid or prostate carcinomas, melanomas, sarcomas, lymphomas etc. can be reliably differentiated. Molecular investigations are up to now only subject in research.

Algorithms↗