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Biomedical subjects

K M Müller

Publications and source records attributed to K M Müller.

At least 145 records · Page 8Linked to original sources
PubMed1997

[Structural analysis of 16 different coronary stent systems].

Parallel with the increasing number of coronary stent implantation procedures, new or more elaborate coronary stents were introduced into clinical use almost every month in 1996. We have studied the architecture, surface-morphology, and shape-conversion of 16 different coronary stent systems. The objective of our study was to detect possible specific design and surface features which might influence the healing process in stent restenosis and stent thrombosis. Using electron microscopy we found ultrasmooth surfaces on 5 stents. All other coronary stents revealed individually varying and partly sharp-edged surface irregularities. Video-based morphometry showed covering between 8.3% and 26.4%. Stent shortening after in-vitro expansion ranged from 0% up to 10.5% of the initial stent length. In some stent systems balloon dilation lead to over-expansion of the stent margin. This over-expansion amounted up to 20% of the balloon diameter and the stents revealed a rather biconcave than homogeneous expansion pattern. This phenomenon was also found after postmortal stent implantation in 20 autopsied hearts.

Angioplasty, Balloon, Coronary↗
PubMed1997

Expression of type IV collagenase correlates with the expression of vascular endothelial growth factor in primary non-small cell lung cancer.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells, known to be involved in physiological (embryogenesis) and pathophysiological (rheumatoid arthritis, tumor) angiogenesis. An increased expression of matrix metalloproteinase type IV collagenase has been reported in invading endothelial cells in vitro and in malignant cells, degrading structures of the basement membranes in various human malignancies. In the present study we investigated the expression of the genes for type IV collagenase and vascular endothelial growth factor (VEGF) in 40 cases of primary non-small-cell lung cancer (NSCLC). Specimens were immunostained by an antibody directed against VEGF and mRNA transcripts of VEGF and type IV collagenase were localized by non-radioactive in situ hybridization. VEGF mRNA was detected in 33 neoplasms, while in 23 cases transcripts of the type IV collagenase gene were visualized by digoxigenin-labeled cDNA probes. Transcripts of both mRNAs were detected in malignant cells. Furthermore, anti-VEGF immunostaining was present in newly formed microvessels close to the atypical cells, and mRNA of type IV collagenase was present in stromal cells adjacent to the tumor. A statistically significant correlation was found between the expression of type IV collagenase and VEGF (P = 0.0061). These data suggest a double role for type IV collagenase in the metastatic process of NSCLC: (1) facilitating the invasion of tumor cells by the proteolytic cleavage of the basement membrane and (2) similarly supporting the endothelial cell invasion essential for tumor angiogenesis. Furthermore, our findings sustain the hypothesis that metastatic spread and angiogenesis are associated with a clonal expansion of highly angiogenic and invasive tumor cell clones.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

The relation between various histological types of lung cancer and the number of years since cessation of smoking.

We studied the relation between various histological types of lung cancer and the number of years of cessation from smoking using data from a recently completed case-control study in Northern Germany. In this context we wanted to answer the question whether smoking cessation is a specific symptom of small cell lung cancer. Defining current smokers as the reference group the odds ratios decreased with years of cessation. Based on the analysis of all male cases and controls in our study, former smokers who stopped smoking 6-10 years ago had an odds ratio of 0.97 (95% confidence interval (C.I.) = 0.65-1.45), ex-smokers with 11-20 years of smoking cessation had a reduced risk of 0.55 (95% C.I. = 0.38-0.79), and for more than 20 years of cessation we found an odds ratio of 0.25 (95% C.I. = 0.16-0.40). Moreover, these calculations are also presented for the major groups of histological types of lung cancer. Our data show that there is no evidence for the presumption that cases with small cell lung cancer stop smoking earlier than cases with other histological types: in no other histological category we found such a big part of current smokers.

Adenocarcinoma↗
PubMed1997

Involvement of E-cadherin in thymus organogenesis and thymocyte maturation.

We examined the role of E-cadherin expressed by thymic epithelial cells and immature thymocytes in thymus organogenesis and thymocyte development. ECCD-1 MAb, which blocks homotypic E-cadherin interactions, inhibited epithelial organization and thymocyte development in reaggregate fetal thymic organ cultures. It also interfered with the differentiation of fetal liver cells or fetal thymocytes within deoxyguanosine-treated thymic lobes, but did not affect thymocyte development in intact cultured fetal thymic lobes. In contrast, antibodies that selectively inhibit interactions between E-cadherin and alpha(E)beta7 integrins did not perturb thymic epithelial organization or thymocyte development, suggesting that homotypic E-cadherin interactions play an important role in thymus development and function.

Animals↗
PubMed1997

p53 gene mutation analysis in tumors of patients exposed to alpha-particles.

The p53 gene was examined for point mutations in archived, alpha-radiation-associated lung and liver cancers. Lung tumors of 50 uranium miners in Germany were screened by restriction fragment length analysis for the putative hotspot mutation at codon 249 (Arg-->Met) previously detected in a significant fraction of miners from the Colorado Plateau, USA. This mutation has been proposed as a marker of radon exposure. None of the tumors we examined harbored the hotspot mutation. Five of the 50 tumors, however, did indeed harbor exon 7 mutations, as determined by subsequent mutation analysis of exon 7. These mutations were dispersed among various codons and may be attributable to heavy tobacco smoking in this cohort. In support of this interpretation, we found no mutations in exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by injection of Thorotrast, an alpha-emitting radiocontrast agent. We propose that if the p53 tumor suppressor gene is a target for the carcinogenic action of alpha-particle radiation, loss of suppressor function may occur preferentially by mechanisms such as intrachromosomal deletions, rather than by base substitution mutations.

Aged↗
PubMed1997

[Placentoid malformation of the lung as differential diagnosis of localized emphysema].

In a 50-year old patient with a long history of chronic obstructive airway disease and pulmonary emphysema, unusual solid spongious areas adjacent to bullous tissue were detected by bullectomia because of mediastinal displacement and dyspnoea on exertion. Pathological anatomical diagnosis showed villous framework in the marginal regions of bullous transformed parenchyma. According to pathognomonic histological finding the lesion is known as placentoid malformation or placentoid bullous transmogrification, respectively. This disease must be differentiated against rare cystic tumours such as alveolar adenoma or sclerosing haemangioma as well as congenital lesions e.g. adenomatoid cystic malformation. The lesion presented here includes hamartomatous features, such as the presence of leiomyomatoid proliferations of smooth muscle cells and fatty tissue embedded in the villous stroma. The clinically predominant emphysematous transformation of the adjacent lung tissue is pathogenetically the result of a valve formation in combination with unphysiological traction forces. The ectatic lymphatic vessels in peripheral tissue may perhaps be of etiological importance. According to former studies this may be an congenital malformation with progressive development. Resection of affected lung parenchyma seems to be curative: so far, no recurrences have been noticed.

Choristoma↗
PubMed1997

[Correlation of radiologic and pathologic-anatomical findings in dust-induced pneumoconiosis in former coal miners].

The ILO classification of small and large opacities is the basis for the compensation of patients with pneumoconiosis. In order to validate the radiological findings, we compared the ILO classification with the gradings of pneumoconiosis in the post mortem investigation (n = 126). An ILO classification of 1/0 used as the threshold value for accepting the diagnosis of a pneumoconiosis was 100% sensitive with a specificity of 2%. With a value of 2/3 the sensitivity decreased to 60% and specificity increased to 74%. The grading of large opacities in the radiograph correlated well with the post mortem findings (rs = 0.71; p < 0.001). For accepting the diagnosis pneumoconiosis from the radiograph alone a threshold value of 1/0 is not specific. The ROC-plot revealed that specificity reached acceptable levels with an ILO classification of at least 2/3.

Coal↗
PubMed1997

Chronic bronchitis--alterations of the bronchial mucosa.

The mucociliary transport system is usually an important defense system which protects the body against a variety of noxious agents. Reactions of the bronchial mucosa to chronic infections are seen in the ciliated cells, the amount of globlet cells, in modifications of the basement membrane underlying the bronchial epithelium and an altered percentage of inflammatory cells. In ciliated cells the following atypia can be seen: thickening of the ciliar membrane, swollen cilia, formation of compound cilia, disarrangement of microtubules. Common alterations of the basement membrane are: increased diameter of the basement membrane zone, inhomogeneous staining pattern of the basement membrane zone, formation of cytoplasmatic protrusions, formation of double layers of the basement membrane and increased number of cytoplasmatic bound vesicles. Structural abnormalities of the basement membrane will lead to disturbances of the zone of transition and have to be interpreted as a sign of disregulation in the process of diffusion and resorption. The inflammatory response of the epithelium during chronic bronchitis and asthma shows many similarities. The bronchial epithelium has a specific reaction pattern which supports the response against different noxious agents. So all findings have to be interpreted as unspecific pathological changes. All alterations may show different degrees of severity and are dependent on individual pattern and the severity of chronic process. Electronmicroscopical examinations in combination with lightmicroscopical findings and immuno-histochemistry and seen in context with clinical data help to understand the mechanism of the inflammatory process.

Basement Membrane↗
PubMed1996

[Neuropsychiatric symptoms in vitamin B12 deficiency and microcarcinoidosis. The complications of chronic atrophic gastritis].

HISTORY AND FINDINGS: A 69-year-old woman reported marked restriction of voluntary movements of the hands in the preceding 6 months. She had also experienced loss of motivation, memory and concentration. Her skin was pale yellow, and scratches on her skin indicated marked pruritus. INVESTIGATIONS: Neurological examination revealed decreased vibratory sense in both legs. Haemoglobin concentration was 8.3 g/dl, mean corpuscular volume 114 fl, vitamin B12 level < 100 ng/l, folic acid level normal. Antibody titre against parietal cells was increased, vitamin B12 resorption diminished. Gastroscopy revealed small raised lesions, made up of hyperplastic cells which stained with chromogranin, indicating a diagnosis of microcarcinoid of the gastric mucosa. TREATMENT AND COURSE: On administration of cobalamine (1,000 micrograms i.m. daily for 2 weeks, twice weekly for 6 weeks, then once per week for the last 7 months) the blood picture returned to normal, but the microcarcinoids, the psychological symptoms and the apraxia of the hands were unchanged.

Aged↗
PubMed1996

Neovascularization in hyperplastic, metaplastic and potentially preneoplastic lesions of the bronchial mucosa.

Angiogenesis is important in a large number of normal and pathological processes including tumour growth and development, inflammation and in wound healing. We investigated whether neovascularization exists in hyperplastic, metaplastic and potentially preneoplastic lesions of the bronchial mucosa as prestages for lung cancer. Biopsy specimens from 86 patients were investigated light microscopically. Formalin-fixed and paraffin-embedded specimens of regular bronchial mucosa including epithelium, basement membrane zone and tunica propria (n = 12) without inflammation were compared with specimens with inflammatory reaction (n = 9), basal cell- and goblet cell hyperplasia (n = 24), squamous cell metaplasia (n = 9), squamous cell metaplasia with different degrees of dysplasia (n = 11), specimens of micropapillomatosis (n = 9) and 13 cases with carcinoma in situ. The grade of neovascularization was assessed by the microvessel density, which was obtained by an immunohistochemical staining of endothelial cells using factor VIII-related antigen and determined by an automatic image-analysing-system. Microvessels were counted in selected areas of highest neovascularization on a x 100 field 0.4 mm underneath the basement membrane zone in the tunica propria. Microvessel count, minimal and maximal diameter of the vessels were chosen as morphological variables. A significantly increased microvessel count with 33 vessels/0.6 mm2 was found in specimens with inflammation of the tunica mucosa (regular bronchial mucosa: 20 vessels/0.6 mm2). Microvessel diameter (surface of cut section) increased in specimens of bronchial mucosa with inflammation to 11.3 x 10(-4) mm2 (regular bronchial mucosa: 9.04 x 10(-4) mm2). Microvessel count increased in cases of squamous cell metaplasia (33 vessels/0.6 mm2) squamous cell metaplasia with different degrees of dysplasia (50 vessels/0.6 mm2) and carcinoma in situ with 61 vessels/0.6 mm2. With increasing dysplasia, increasing neo-vascularization was found in close vicinity to the basement membrane zone. Simultaneously, interepithelial sprouts of endothelial cells were seen. Qualitative and quantitative differences were thus found in potentially preneoplastic lesions.

Bronchi↗
PubMed1996

Studies on tumor-cell-induced platelet aggregation in human lung cancer cell lines.

We investigated the ability of human lung cancer cells of different histological subtypes to cause platelet aggregation. Tumor-cell-induced platelet aggregation (TCIPA) was studied in vitro in 13 human lung cancer cell lines [small-cell lung cancer (SCLC), squamous-cell lung cancer, large-cell lung cancer, adenocarcinoma and alveolar-cell lung cancer]. Three tumor cell lines failed to aggregate platelets in platelet-rich plasma, whereas platelet aggregation was induced by 12 cell lines when added to washed platelets and minimal amounts of platelet-poor plasma (0.5% v/v). The thrombin antagonist hirudin inhibited TCIPA in non-small-cell lung cancer cell lines (NSCLC). In SCLC, TCIPA was fully abolished only when the ADP scavenger apyrase was added to hirudin. Thus ADP and thrombin generation by these tumor cell lines are responsible for platelet aggregation. The ability to activate platelets independently of coagulation factors VII and X was demonstrated for 8 cell lines. Electron-microscopically, direct tumor-cell/platelet contact was found to be the initiating mechanism of TCIPA in SCLC, whereas tumor-cell/platelet contacts in NSCLC could only be observed at the peak of the aggregation curve. Lung cancer cells activate platelets in vitro by generation of thrombin and/or ADP.

Blood Platelets↗
PubMed1996

[Proliferation kinetics of bronchioloalveolar tumorlets].

Bronchiolo-alveolar tumorlets--mostly clinically asymptomatic--generally are noticed as "contingent findings" in the diagnoses of interstitial fibrosing lung diseases. The growth fraction of these epithelial proliferates in the WHO classification summarized in the group of tumor like lesions was explored by immunohistochemical stainings with the PCNA and Ki67 (MIB1) antibodies and correlated with (pre-) neoplastic lesions of the lung. The proliferation indices varied between 0.029 to 0.67 (MIB1) and 0.057 to 0.81 (PCNA). Depending on the main disease the observation of cuboid metaplasias, areas of bronchiolization via tumorlets in inactive interstitial lung fibrosis up to bronchiolo alveolar tumorlets following interstitial lung disease after cytostatic treatment showed increasing proliferation indices. Accordingly to prencoplastic changes of the bronchial epithelium the findings suggest that interpretation of bronchiolo alveolar tumorlets as basic cells of malignant peripheral lung tumors seems to be possible. The value of these findings in relationship to the associated interstitial lung disease is discussed in the context of reflections related to the formal pathogenesis of so called scar cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1996

[Differential diagnosis of multiple pulmonary coin lesions. Lymphomatoid granulomatosis].

In addition to metastasis, the differential diagnosis of multiple pulmonary nodules also includes tuberculosis, sarcoidosis, and silicosis. Rarer diseases such as amyloid tumors, rheumatic nodules and plasma-cell granulomas can be the cause of this finding. This depends on the clinical manifestation. Based on clinical findings of lymphomatoid granulomatosis, the problems in diagnostics using bronchoscopy, mediastinoscopy and thoracoscopy are outlined. Etiology, morphology and differential diagnosis of lymphomatoid granulomatosis versus necrotizing inflammatory or neoplastic lesions are discussed. Treatment and prognosis are described.

Biopsy↗
PubMed1996

Cytokeratin expression in preneoplastic lesions and early squamous cell carcinoma of the bronchi.

Cytokeratins are expressed in varying combination in the course of differentiation of epithelial cells and tumor cells. This is the first report of systematic immunohistochemical (ABC-method) investigations concerning the expression of different cytokeratin types (KL 1, CK 4, 10 and 17) within the transformation of the bronchial mucosal epithelium with epithelial hyperplasia to potential preneoplasia and early squamous cell carcinoma of the lung. In bioptical obtained specimens from 35 patients, 63 areas with diagnosis of regular bronchial mucosa (n = 10), basal cell hyperplasia (n = 9), goblet cell hyperplasia (n = 10), squamous cell metaplasia (n = 11), dysplasia I-III (n = 13), carcinoma in situ in the border zone of squamous cell carcinoma (n = 10) and in 5 surgically obtained specimens with findings of an early squamous cell carcinoma of the bronchus (n = 5), the expression of different cytokeratin types was investigated. The specimens were fixed in formalin and embedded in paraffin for lightmicroscopical and immunohistochemical investigations (ABC-method). KL 1 was detected in all regular and pathological mucosal epithelia, CK 4 in basal cells, squamous cell metaplasia, potentially preneoplastic changes and early squamous cell carcinoma of the bronchus. CK 10 was expressed only in early squamous cell carcinoma of the bronchus, and CK 17 in varying quantity in hyperplastic, preneoplastic and cancerous lesions of the bronchial mucosa. Our results reveal an increasing expression of squamous epithelial type-cytokeratins (CK 4, CK 17) in hyperplastic and metaplastic lesions of the bronchial mucosa. In dysplastic lesions and carcinomata in situ, a quantitative, as well as qualitative decrease of the CK 4- and CK 17-expression with a heterogeneous expression pattern for CK 17 was found. The heterogeneous neo-expression of CK 10 in early squamous cell carcinoma of the bronchus has to be emphasized.

Bronchial Neoplasms↗
PubMed1996

[Evaluating the measuring accuracy of intravascular ultrasound].

AIM: Intravascular ultrasound investigations are new tomographic imaging methods for evaluation of artery dimensions and wall morphology. The present study was performed to test accuracy and observer variability. METHOD: 3 plastic phantoms and 1 iliacan artery were assessed. The quantitative measurements were made by computerised 3D reconstruction. RESULTS: The plastic phantoms showed ultrasonically three layers of echogenic structures. An intimal fibrous thickening was seen in the iliac artery. The cross sectional diameters were ultrasonically overestimated by 12.6 +/- 5.6%. Due to the lower velocity of sound in water than in blood there were no significant differences to the true diameters. The intra- and interobserved variabilities were determined to 1.4 +/- 0.8% and 2.6 +/- 1.2%. CONCLUSIONS: Intravascular ultrasound provides a reproducible method for measuring vessel lumen diameters with excellent intraobserver and interobserver variabilities. For in vitro examinations the different velocities of sound in different media have to be taken into account.

Humans↗