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Biomedical subjects

A Fisseler-Eckhoff

Publications and source records attributed to A Fisseler-Eckhoff.

At least 19 recordsLinked to original sources

[Benign fibrous histiocytomas as a differential diagnosis in cavitary lung disease].

Benign fibrous histiocytomas (BFH) are uncommon pulmonary tumours. These lesions usually present as slow-growing, solid masses. We report the rare case of a young man with cavitary BFH. The 20-year-old patient, a non-invasive drug abuser, had suffered from hemoptysis for two months. The chest X-ray showed a solitary pulmonary nodule with a diameter of 2 cm in the left lower lobe with central cavitation. Fiberoptic bronchoscopy showed a normal bronchial system, biopsies were not diagnostic and no acid fast bacilli were found. Considering the patient's history and the cavitary process, a non-specific abscess was suspected and an antimicrobial treatment was started. Since no treatment effect was observed, biopsies from a second bronchoscopy were suspicious of a malignant mesenchymal tumour. Lower lobe resection with lymphadenectomy revealed a benign fibrous histiocytoma. This is--to our knowledge--the first reported case of a BFH presenting with cavitation.

Adult↗

[Malignant lung tumors--histomorphological classification, immunohistological techniques and prognostic factors].

Histological typing of lung tumors is based on the new WHO-IASLC classification of lung and pleural tumors published in 1999. Based on histological growth pattern, the major light microscopic categories of lung carcinomas are squamous cell carcinoma, small cell carcinoma, adenocarcinoma and large cell carcinoma. The further subclassification within the main categories resembles the high degree of lung tumor heterogeneity. Immunohistochemistry may detect differentiation that cannot be seen by routine light microscopy on small bioptically obtained specimens. Evaluation of the proliferation index of tumor cells, hormonal receptors, oncogenes and tumor-suppressor genes is possible. Oncogenes, tumor-suppressor genes, angiogenetical factors as well as single cell dissemination of tumor cells in lymph nodes are discussed as possible prognostic factors.

Carcinoma, Non-Small-Cell Lung↗

[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↗

[Lymphomatoid granulomatosis: differential diagnosis and therapy].

CASE REPORT: In a 59-year-old patient presenting with fever, malaise and pulmonary masses the diagnosis of lymphomatoid granulomatosis was established histologically by open lung biopsy. Despite an immunosuppressive therapy with cyclophosphamide and prednisolone partial remission was achieved for no longer than 8 weeks. Five months later he died in a septic condition. CLINICAL PRESENTATION: In our paper we discuss the present case and give a short review of the literature. Lymphomatoid granulomatosis is a rare angiocentric and angiodestructive condition which shows characteristics of both a lympho-proliferative and a necrotizing aseptic granulomatous process. It involves most frequently lungs, central nervous system and skin. The clinical course is variable, but mortality is high. Malignant lymphoma is a frequent fatal complication. Immunologic dysfunction and EBV-associated B-cell transformation seem to play an important role in the pathogenesis of this disease. TREATMENT: As optimal therapy is unknown, attempts have been made with immunosuppressive therapy according to the Fauci scheme as well as with combined chemotherapy according to the CHOP scheme and radiation. In a recent trial, promising results have been reported for interferon alpha 2b.

Antineoplastic Agents↗

Budesonide for the treatment of collagenous colitis: first results of a pilot trial.

OBJECTIVE: Collagenous colitis is a chronic watery diarrhea disorder characterized by a subepithelial collagen layer and a lymphoplasmacytic infiltration within the lamina propria. However, no standard treatment has been introduced by controlled clinical trials. Aim of the present pilot trial was to investigate the clinical effects of orally administered budesonide (3 mg t.i.d.) in 7 patients with collagenous colitis. In addition, the histomorphological changes after budesonide treatment were described in a group of 3 patients. METHODS: The study was performed as an open label pilot trial. Study end point was the clinical remission of collagenous colitis defined by stool frequency and stool consistency. RESULTS: The results indicate a rapid and sustained clinical response in all patients. Stool frequency significantly decreased (p < 0.001) from 10.43 +/- 5.56 per day (4-20 per day) to 3.3 +/- 1.2 (1-5 per day) after 10 days and to 1.86 +/- 0.69 per day (1-3 per day) after 10 wk. Moreover stool consistency changed from watery (6 patients) or soft (1 patient) to soft (1 patient) or solid (6 patients). Clinical improvement was achieved within the first 10 days in all patients and maintained after dose reduction. In 3 patients no diarrhea recurred within 7, 12, or 15 months after treatment with budesonide was terminated. In these patients control biopsies were taken and showed a marked regression of both characteristics, the collagen band and the lymphoplasmacytic infiltration. CONCLUSIONS: With respect to the preliminary data from this pilot trial, budesonide with its high topical and low systemic effects seems to be of therapeutic clinical benefit in collagenous colitis. A therapeutic effect could be demonstrated for both therapeutic goals, the clinical response and morphological changes. Further studies on the effects of budesonide on mucosal collagen metabolism and long-term follow-up are warranted.

Anti-Inflammatory Agents↗

Epidermal-growth-factor receptor correlates negatively with cell density in cervical squamous epithelium and is down-regulated in cancers of the human uterus.

The role of the epidermal-growth-factor receptor (EGFR) in cervical cancer is controversial, due to technical difficulties in localizing or in quantifying EGFR by homogenate assays or immunohistochemistry. Our autoradiographic approach, in combination with morphometry, allowed cell-type-specific quantification of EGFR, leading to the following observations: (i) In normal cervical epithelium, EGFR levels per cell were high in non-dividing squamous cells of the upper layers of normal epithelium, where a mitogenic function of these EGFRs can be excluded. (ii) In contrast to earlier findings in tissue homogenates, but consistent with our observation in normal cervical epithelium that cells of the proliferating strata (basal and parabasal cells) express intermediate and comparatively reduced levels of EGFR per cell, cervical cancers displayed a significant reduction both of specific EGF binding and of EGFR levels per cell as compared with normal epithelium. (iii) A significant negative correlation of cell density and EGFR number per cell was obtained. In normal cervical epithelium, cervical intra-epithelial neoplasia and invasive cervical cancer (p = 0.002). This negative correlation was most evident in normal epithelium, where large changes of cell density occur within one slide (p < 0.001). (iv) Specific EGF-binding was also significantly reduced in endometrial cancers when compared with normal endometrium. It is proposed that in uterine tissues low or intermediate levels of EGFR do not exclude their function as mediators of cell proliferation.

Autoradiography↗

Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure.

Superoxide dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2. However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.

Asbestos, Crocidolite↗

[Carcinoid tumors of the lung and asbestos. Clinical aspects for insurance medicine].

Lung dust analyses were performed on tumor-free lung tissue from surgical samples of 28 carcinoid tumors. The measured levels in one surgical sample may easily be correlated with the increased asbestos load of the lung due to the patients' occupation as stone mason. No evidence supporting the correlation of increased chronic asbestos load of the lungs and the development of typical carcinoid tumors of the lung was found.

Adolescent↗

mRNA expression of ligands of the epidermal-growth-factor-receptor in the uterus.

Six different ligands of the epidermal-growth-factor receptor (EGFR) have been identified in the past. In some cervical squamous-cell carcinomas, an increased amount of proteins binding to the EGFR has been reported. In order to identify the mRNA of EGFR ligands (EGFRL), which might be overexpressed in cervical and endometrial cancers, we performed semi-quantitative reverse-transcription/polymerase chain reactions (RT-PCR) for all 6 EGFRL in RNA extracts of normal and malignant tissue samples of the human uterus. PCR products from RNA extracts of 83 patients were quantitated relative to the housekeeping gene and internal standard pyruvate dehydrogenase by analyzing the PCR kinetics of product synthesis. In extracts of normal cervix, the level of mRNA expression of the EGFRL was significantly higher than in endometrium. No significant difference was detected between normal cervix and cervical carcinomas. However, both in cervical and in endometrial cancers, mRNA expression was non-parametrically distributed and in some cervical cancers overexpression of transforming growth factor alpha (TGF-alpha), amphiregulin or EGF was observed. In endometrial cancers, mRNA levels of all EGFRL were higher than in normal endometrium. This increase was significant (p < 0.005) for TGF-alpha and amphiregulin. Thus, TGF-alpha mRNA is overexpressed in approximately 10% of cervical cancers and in the majority of endometrial cancers. Since TGF-alpha anti-sense therapy might represent a future strategy in such cancers, we also determined the absolute level of TGF-alpha mRNA expression by quantitative PCR using a cloned standard.

Cloning, Molecular↗

[Immunohistochemical studies with middle ear mucosal remnants in cholesteatoma].

The development of a middle ear cholesteatoma is usually associated with chronic inflammation and displacement of the mucosa present by the invading squamous epithelium. To analyze the clinically different behaviors of both epithelia, we used immunohistochemical methods to study the distribution and expression of interleukin-1 (Il-1), transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), epidermal growth factor-receptor (EGF-R), the proliferation marker MIB 1, c-myc proto-oncogene product and activation marker 4F2. Results stromal that keratinocytes in a cholesteatoma exhibited a much higher activation and proliferation rate when compared to middle ear mucosa cells. Middle ear epithelial cells showed no immunoreactivity for TGF-alpha, EGF-R, Il-1 and c-myc in contrast to the markedly positive immunoreactivity found in cholesteatoma matrix. The local release of cytokines and growth factors, such as TGF-alpha, EGF and Il-1 by inflammatory cells seems to be an important factor for the hyper-proliferative behavior of cholesteatoma epithelium. Our findings could contribute to the pathogenesis of middle ear cholesteatoma and give a possible explanation for the sustained progression of its growth leading to displacement of the middle ear mucosa.

Biomarkers↗

Argyrophilic nucleolar organizer regions in auditory meatal skin and middle ear cholesteatoma.

Comparative silver-staining of argyrophilic nuclear organizer regions (AgNORs) was performed to study the proliferative activity of auditory meatal skin and middle ear cholesteatoma. AgNOR expression patterns were counted by standardized methods in two centres, Bochum and London, and mean numbers of dots per nucleus were calculated. Specimens of normal auditory meatal skin showed 1.54 dots/nucleus (n = 12) in the Bochum study, whereas cholesteatoma had 3.71 dots/nucleus (n = 21). In the London study normal meatal skin showed two dots/nucleus (n = 4), whereas acquired cholesteatoma (n = 8) gave a mean of 4.90 dots/nucleus and congenital cholesteatoma a mean of 4.70 dots/nucleus (n = 2). Our findings confirm the hyperproliferative state of middle ear cholesteatoma, suggest that the congenital variety of cholesteatoma may have a similar activity and indicate that AgNOR staining is a useful technique for assessing cellular proliferation in cholesteatoma and objectifying and quantifying its aggressive behaviour.

Cell Division↗

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↗

Monoclonal antibodies against human chondrocytes.

Cell-specific antigens are mainly found in cells or membrane surfaces rather than in the surrounding matrix. However, until now it was not possible to produce antibodies specific for cellular structures of chondrocytes. In 1989, Lance (Immunol. Lett. 21:63-73; 1989) first established specific monoclonal antibodies for human articular chondrocytes tested only by immunofluorescence. Studies describing the specificity of these five antibodies (HUMC 1-5) and their relevance for immunohistological analysis of cartilage tissue were not available until now. Therefore, the aim of the following study was to investigate the distribution of HUMC 1, 2, 3, 4, and 5 in mesenchymal cells in vivo and in vitro immunohistochemically. Further investigations concentrate on the localization of chondrocyte specific antigens using immunoelectron microscopy. Immunohistological studies showed positive immunostainings with all five antibodies in human chondrocytes in vivo and in vitro. A cross-reaction with human fibroblasts and osteoblasts for the antibodies HUMC 2 and HUMC 5 was observed. Furthermore, a parallel loss of immunoreactivity for HUMC 1, HUMC 3, and HUMC 4 was observed in cultured chondrocytes indicating that the specific antigens vanish during differentiation observed in vitro. Subsequent immunoblot analysis employing collagens as antigens did not show any reactivity. Using immunoelectron microscopy, gold particle labeling was observed in intracytoplasmatic vesicles of isolated chondrocytes. Our results indicate that HUMC 1, HUMC 3, and HUMC 4 are specific for cartilage cells and might be suitable for immunohistological analysis of different cartilage tissues and pathologically altered chondrocytes.

Antibodies, Monoclonal↗

[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↗

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↗

Basement membrane in middle ear cholesteatoma. Immunohistochemical and ultrastructural observations.

We investigated the distribution of basement membrane zone (BMZ) components collagen type IV, collagen type VII, and fibronectin in human middle ear cholesteatoma, auditory meatal skin, and middle ear mucosa using both immunohistochemical and ultrastructural methods. Collagen type IV immunoreactivity of skin and middle ear mucosa is continuous in the BMZ, whereas cholesteatoma frequently showed absent immunoreactivity or focal discontinuities. Collagen type VII immunoreactivity is detected similarly within the BMZ of cholesteatoma and skin. Fibronectin immunoreactivity is observed within the dermoepithelial junction of skin and middle ear mucosa. In cholesteatoma, however, fibronectin immunoreactivity is markedly increased within the extrinsic BMZ and the subepithelial connective tissue. The ultrastructural arrangement of the BMZ of cholesteatoma is like that of skin; however, it exhibits distinct alterations of the lamina fibroreticularis and lamina densa. Our results outline cholesteatoma as a disease with disturbed cell matrix interactions analogous to those of wound reepithelialization.

Basement Membrane↗

Expression of a cell-cycle-associated nuclear antigen (MIB 1) in cholesteatoma and auditory meatal skin.

Middle ear cholesteatoma is often invasive with consequent bone destruction. Inflammatory stimulation of the underlying connective tissue, as well as an autocrine mechanism, may be responsible for the dysregulation and abnormal proliferative features of the keratinocytes in cholesteatoma. Comparative investigations were performed to assess the epithelial cell kinetics of cholesteatoma and normal auditory meatal skin. Monoclonal antibody MIB 1 immunostaining (which recognizes a nuclear antigen expressed by dividing cells) was applied using the alkaline phosphatase antialkaline phosphatase immunolabeling method. Specimens of normal auditory meatal skin (n = 7) revealed an average MIB 1 score (quotient of the MIB 1-positive cells and the total number of cells) of 7.6 +/- 2.2%. Cholesteatoma samples (n = 13) showed an average MIB 1 score of 17.4 +/- 8.9% and a heterogeneity of proliferating epithelial areas. Epithelial cones growing toward the underlying stroma exhibited high mitotic activity. Statistically, the results of this study confirm a highly significant increase in the proliferation rate of cholesteatoma keratinocytes, which had an MIB 1 score that was 2.3 times higher than the score for keratinocytes of normal external auditory meatal skin.

Antibodies, Monoclonal↗