PubMed Health⌕ Search

Biomedical subjects

W Böcker

Publications and source records attributed to W Böcker.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Effect of pre-existing lipids on calcinosis of swine heart valve bioprostheses. A study of a dynamic in vitro model].

Calcification is one of the main causes of failure of porcine bioprosthetic heart valves, a problem which has not been satisfactorily solved to date. Previous studies have shown that calcification is decreased in porcine heart valves that have undergone treatment for lipid extraction. The relation between lipid distribution and calcification of seven new commercially available porcine bioprosthetic heart valves (St. Jude Medical, Bioimplant) is assessed by Sudan red III staining to show preexisting lipids. All porcine bioprosthetic valves contained lipids to different degrees. Five valves were subjected to the pulsatile accelerated calcification process for 4 weeks. Distribution and level of calcification were evaluated by radiography and compared to the Sudan red-stained fatty areas. Comparison of the calcifications detected by radiography and the macroscopically detected lipids showed a coincidence of 57-66%. Two porcine bioprosthetic valves were histologically prepared and stained with Hematoxylin and von Kossa's stain, respectively. By light microscopy, the von Kossa staining revealed microcalcifications and polarizing microscopic investigation showed birefractive substances in areas with lipid deposits. These preexisting substances in porcine valve tissue may play a determinative role in the calcification of the tissue. Substantial studies are necessary to further determine the role of preexisting lipids in calcification.

Animals↗
PubMed1998

Metastatic retroperitoneal paraganglioma in a 16-year-old girl. Case report, molecular pathological and cytogenetic findings.

Retroperitoneal paraganglioma is a rare tumor, especially occurring in childhood and adolescence, with a marked tendency to become biologically malignant. It has not been possible to predict the clinical outcome of paraganglioma patients by conventional histology, hence malignancy can only be demonstrated by the occurrence of metastatic lesions. Currently, only limited information on the genetics of this tumor is available. We report on a 16-year-old girl with a large retroperitoneal paraganglioma and an osseous metastasis to the first lumbar vertebra. In addition to morphological and immunohistochemical examinations, a molecular cytogenetic analysis was performed. Comparative genomic hybridization (CGH) revealed imbalanced chromosomal aberrations with a loss of chromosome 1p and a gain of 1q, indicating isochromosome 1q. A loss of chromosome 3 as well as low-level gains of chromosomes 4, 5, 6q, 11q and 13q were detected. A PCR-based microsatellite analysis of 1p confirmed the loss of heterozygosity, including NB1 and NB2 putative tumor-suppressor gene regions. Telomerase activity, which is found in the majority of malignant tumors, could not be detected. The case presented here is the first more comprehensive molecular genetic analysis of a sporadic malignant paraganglioma.

Adolescent↗
PubMed1998

Gains and losses of CD44 expression during breast carcinogenesis and tumour progression.

AIMS: This study was performed to investigate whether the CD44 immunophenotype of breast lesions correlates with the clinical evolution and prognosis of breast cancer. METHODS AND RESULTS: One-hundred and fifty-two routinely processed normal, benign and malignant breast tissue samples were investigated by the following monoclonal antibodies: CD44s (F10-44-2), CD44v3 (3G5), CD44v4 (11.10), CD44v5 (VFF-8), CD44v6 (VFF-18), CD44v7 (VFF-9), CD44v9 (11-24) after wet autoclave pretreatment for antigen retrieval. We found that: (1) in normal breast tissues luminal epithelial cells lacked detectable CD44 in contrast to basal cells, which constitutionally expressed CD44s, v3, v5 v6 and v9 isoforms; (2) in the intraductal compartment of benign hyperplastic lesions, there was scattered or focal staining for CD44s, v5, v6, v7 and v9 isoforms; (3) in neoplastic lesions restricted neo-expression of CD44v3 and v4 was detected; and (4) the CD44 immunophenotype of invasive breast carcinomas was influenced largely by differentiation grade, steroid receptor status of the tumours and significantly correlated with metastatic involvement of the axillary lymph nodes. CONCLUSIONS: Qualitative and quantitative changes of CD44 expression are implicated in early stages of breast carcinogenesis. The restricted neo-expression of certain CD44 isoforms in breast neoplasias suggests that CD44 might be a potential target for future antibody-based tumour therapy.

Breast↗
PubMed1998

Regulation of extracellular matrix proteins in pressure-overload cardiac hypertrophy: effects of angiotensin converting enzyme inhibition.

OBJECTIVE: Left ventricular hypertrophy (LVH) is characterized by remodeling of both myocyte and interstitial compartments of the heart. The aim of this investigation was to study the effects of angiotensin converting enzyme (ACE) inhibition on alterations in the composition of the interstitium in chronic pressure-overload hypertrophy. DESIGN: LVH was induced in weanling rats by banding the ascending aorta. Animals with aortic banding received either vehicle (n = 20), hydralazine (20 mg/kg per day, n = 20), or the ACE inhibitor ramipril (10 mg/kg per day, n = 20) during weeks 6-12 after banding. RESULTS: Compared with sham-operated, untreated rats (n = 20), aortic-banded vehicle and hydralazine-treated rats displayed substantially increased left ventricular weights and myocyte diameters whereas ramipril significantly blunted the hypertrophic response at the myocyte level (each P < 0.001) as well as the increase in left ventricular weight (each P < 0.01). In addition, image analysis revealed a significant induction of perivascular and interstitial tissue accumulation in vehicle- and hydralazine-treated rats (2.5-fold, each P < 0.0001). In contrast, ramipril-treated rats displayed attenuated interstitial and perivascular fibrosis, both being significantly diminished compared with vehicle- and hydralazine-treated rats (each P< 0.001). Further, vehicle- and hydralazine-treated rats were characterized by elevated steady-state messenger (m)RNA levels of fibronectin (2.7- and 2.8-fold, P< 0.005), collagen I (2.0- and 1.8-fold, P < 0.0005), collagen III (both 2.2-fold, P < 0.001) and laminin B (1.6- and 1.6-fold, P < 0.005). In parallel, the corresponding immunohistochemical signals were markedly enhanced in these groups. In comparison, ramipril significantly blunted the induction of collagen I and III, laminin B and fibronectin at both the mRNA and protein levels. These morphological and molecular differences between the hydralazine and ramipril groups could not be attributed to differences in left ventricular-pressures, which were markedly elevated in all aortic stenosis rats (1.9-fold, each P < 0.001 versus sham). In fact, given that ramipril but not hydralazine blunted the hypertrophic response to pressure overload, the echocardiographic measurements revealed that left ventricular systolic wall stress was higher in the ramipril group (70 +/- 1 versus 34 +/- 0.7 kdyn/cm2; P < 0.02). CONCLUSIONS: ACE inhibition may limit both myocyte and interstitial remodeling despite ongoing cardiac pressure overload.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Relationship between AgNOR proteins, Ki-67 antigen, p53 immunophenotype and differentiation markers in archival breast carcinomas.

The present study investigated (i) the relationship between standardised morphometric AgNOR parameters (argyrophilic nucleolar organiser region-associated proteins) and MIB1 growth fraction, and (ii) their correlation with immunohistochemical p53, sex steroid receptor status and histopathological differentiation grade in serial paraffin sections from 39 breast carcinomas. Ten sections were double-stained for AgNOR/MIB1. AgNOR parameters correlated significantly with MIB1 growth fraction and p53 protein expression. Significant inverse correlation was found between proliferation markers and oestrogen/progesterone receptor status and histopathological grade. AgNOR expression was significantly higher in cycling (MIB1 positive) tumour cells, than in resting (MIB1 negative) ones, however with exceptions. We conclude, that standardised AgNOR parameters correlate with markers of increased malignant potential in breast carcinomas. However, AgNORs seem to reflect proliferation independent cellular and nucleolar activity of tumour cells, as well. We recommend the use of standardised AgNOR analysis for obtaining sound results in routine paraffin sections.

Antibodies, Monoclonal↗
PubMed1998

Telomerase activity in human proliferative breast lesions.

Telomerase, a cellular reverse transcriptase, has been detected in the majority of human malignant tumors, where it provides an escape mechanism from proliferative limitations due to progressive telomere erosion with each cell division. In this study, we used a non-radioactive telomeric repeat amplification protocol (TRAP) with an internal telomerase assay standard for the detection and semiquantitative analysis of 98 single frozen sections of normal breast tissue and benign and malignant breast lesions on an automated laser-fluorescence sequencer. Telomerase activity was detected in 36 of 40 (90%) infiltrating breast carcinomas, whereas no activity was found in nonmalignant breast tissues including blunt duct adenosis, papilloma, ductal hyperplasia and atypical ductal hyperplasia. However, telomerase activity was detected in 59% of ductal in situ carcinomas, suggesting that telomerase reactivation is an early event in breast carcinogenesis. We found a positive correlation between telomerase activity levels and cell proliferation determined by MIB1 immunostaining. No correlation, however, could be demonstrated between telomerase activity and other known breast cancer prognostic indicators. Telomerase activity was also detected in 60% of fibroadenomas indicating that careful interpretation of analysis of telomerase activity in fine needle aspirates is required, since low telomerase activity may not necessarily be an indicator of malignancy in breast tissue.

Breast↗
PubMed1998

[Comparative genomic hybridization (CGH) for detecting a heretofore undescribed amplified chromosomal segment in high-grade medullary osteosarcoma].

Osteosarcoma is one of the most commonly biopsied primary tumor of bone. High-grade osteosarcomas in particular exhibit a wide spectrum of cytogenetic changes. Molecular cytogenetic studies on osteosarcomas have shown that genomic amplification, especially of both the TP53-binding MDM2 gene and the flanking SAS gene, plays an important role in the biology of these tumors. We applied CGH in order to obtain a global view of DNA-sequence losses and gains in osteosarcoma. CGH was performed on 20 high-grade medullary osteosarcomas (13 primary tumors prior to chemotherapy, 5 tumors after chemotherapy, 2 established cell lines [MB63, HOS58]) using genomic DNA of snap-frozen tumor specimens. CGH revealed DNA copy number aberrations, mostly gains, in all the tumors studied with an average of 18.5 aberrations/tumor (range 8-32). High-level amplifications were observed in all cases (average 4.1 amplifications/tumor [range 1-10]). Amplicons affecting at least five tumors were mapped to 1p21-31 (9/20 cases), 3q25-qter (6/20), 6p12-21 (6/20), 8q12-qter (10/20), 12p11-12 (9/20), 12q12-15 (enclosing MDM2 and SAS loci, 7/20). Losses were most frequently seen at 3p, 10q, 11p and 13 (all 10/20). In conclusion, our CGH data indicated that genomic amplification plays an important role in the biology of osteosarcoma. CGH demonstrated the complexity of genetic aberrations in osteosarcomas. The detection of novel non-random DNA amplifications in our study has defined regions for further targeted molecular genetic research aimed at identifying those oncogenes that are characteristic of osteosarcoma development.

Bone Neoplasms↗
PubMed1998

[Evidence of genetic alterations in chromosome 11 in embryonal and alveolar rhabdomyosarcoma].

Various chromosome 11 alterations have been described in rhabdomyosarcoma (RMS). Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS), whereas an increase in the expression of the Igf2 gene located on 11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS). The aim of our study was to analyse chromosome 11 alterations of RMS by combining different molecular-genetic and cytogenetic methods. 16 RMSs (7 aRMS with proven 2;13 or 1;13 translocations, 9 eRMS) were studied by a PCR-based microsatellite analysis of loci 11p15.5 and 11q23. Comparative genomic hybridization (CGH) was performed in 8/16 cases. The ploidy status of chromosome 11 was evaluated using the FISH technique. A RT-PCR analysis of Igf2 gene region was performed to evaluate the imprinting status. Allelic losses (LOH) of 11p15.5 were observed in 4/7 aRMS and 8/9 eRMS. These losses were accompanied by LOH of 11q23 in 2/7 aRMS and 5/9 eRMS, respectively. CGH of all the eRMSs and one aRMS studied revealed gains of genetic material mostly involving the entire length of chromosome 11. One aRMS showed a loss of chromosome 11 material, both in CGH and LOH analysis. In 2/9 aRMS, which neither in CGH nor in LOH analysis had exhibited chromosome 11 alterations, biallelic IGF-II expression was revealed. Our results show that chromosome 11 alterations play a major role in the biology of both alveolar and eRMS. Combining the data of our study, we demonstrated that three different chromosome 11 alterations are involved in the tumorigenesis of RMS: 1) LOH resulting in hemizygosity of chromosome 11. 2) LOH with simultaneous gains of chromosome 11 material due to uniparental polysomy. 3) loss of imprinting for the Igf2 gene in the absence of gross chromosome 11 alterations.

Chromosome Aberrations↗
PubMed1997

Inducible heat shock protein 70 in rat cardiac allograft and its immunohistochemical localization in cardiac myocytes.

BACKGROUND: Heat shock proteins (HSP) are induced by a variety of stress and are presumed to play an important role in protecting cells from the effects of stress. Some evidence exists that HSP is involved in allograft rejection. Recently, an increase of inducible HSP 70 in heterotopic rat heart allografts was shown by quantitative Western blotting. To determine a possible mRNA induction and the localization of inducible HSP 70, we examined 19 heart transplants in rats. METHODS: Fisher F344 rat hearts were heterotopically transplanted into Lewis recipients (n=10), and nine cardiac isografts (Fisher to Fisher) were performed. The 19 native hearts of the recipients served as controls. Animals were killed on posttransplantation days 1, 3, and 5. The hearts were examined immunohistologically for inducible HSP and analyzed by a semiquantitative polymerase chain reaction for inducible mRNA. RESULTS: The level of HSP 70 mRNA in the allograft increased from day 1 to 3 and day 3 to 5 after transplantation and was significantly higher than that of time-matched isografts (0.92+/-0.49 vs. 0.49+/-0.05 and 1.14+/-0.53 vs. 0.53+/-0.15; P<0.05). The native hearts showed no elevated HSP 70 expression compared with isografts. Immunohistochemically, the majority of inducible HSP was located in cardiomyocytes adjacent to infiltrating lymphocytes, which where consistently negative. CONCLUSIONS: These results demonstrate that HSP mRNA expression in cardiac allografts is time-dependent, and its protein is expressed in cardiomyocytes.

Analysis of Variance↗
PubMed1997

Expression of neural BC200 RNA in human tumours.

BC200 RNA is a 200-nucleotide-long non-messenger RNA that is selectively expressed in the primate nervous system, where it has been identified in somatodendritic domains of a subset of neurons. BC200 RNA is not normally expressed in non-neuronal somatic cells; it has been shown, however, to be expressed in germ cells and in cultured immortal cell lines of various non-neural origins. In order to investigate whether the neuron-specific expression of BC200 RNA is also deregulated during tumourigenesis in non-neural human tissues, 80 different tumour specimens, representing 19 different tumour types, were screened for the presence of the RNA. BC200 RNA was expressed in carcinomas of the breast, cervix, oesophagus, lung, ovary, parotid, and tongue, but not in corresponding normal tissues. BC200 RNA was not detectable in bladder, colon, kidney, or liver carcinoma tissues examined in this study. These results demonstrate that BC200 expression is deregulated under certain neoplastic conditions. The expression of BC200 RNA in non-neural tumours may indicate a functional interrelationship with induction and/or progression of such tumours.

Blotting, Northern↗
PubMed1997

[Acute thoracic aortic dissection with occlusion of the left coronary artery].

Aortic dissection is the most common fatal condition that involves the aorta. Occasionally, symptoms mimic acute myocardial infarction leading to thrombolytic treatment. Accurate diagnosis in patients with chest pain is therefore essential. We describe a case of acute aortic dissection which resulted in myocardial infarction due to obstruction of the left coronary ostium. A 65-year-old female patient with no previous cardiac history was admitted to a local hospital because of severe chest pain of acute onset. Physical examination was normal except for a low blood pressure (90/50 mm Hg), heart rate 45 beats/min and parasthesia in both hands. The ECG showed sinus bradycardia with negative T-wave in VI and with 1 mm ST-segment elevation in V3. A chest X-ray was normal. Five hours later, the patient experienced once more severe chest pain followed by non-sustained polymorphic ventricular tachycardia (Figure 1). Another ECG showed bifascicular bundle branch block (right bundle branch block and left anterior fascicular block). The ECG was interpreted as showing acute myocardial infarction and treatment with intravenous streptokinase started. Since the patient remained severely hypotensive despite infusion of dobutamine, she was intubated, ventilated and transferred to our hospital. Cardiac catheterization showed acute dissection of the ascending aorta with an aortic intimal flap and an occlusion of the left coronary artery (Figures 2a and b). During catheterization, she suffered a cardiac arrest from which she could not be resuscitated. A postmortem examination confirmed the acute aortic dissection which reached to the ostium of the left coronary artery (Figures 3a and b, 4a and b) and an anterior myocardial infarction probably due to intermitted diastolic obstruction of the ostium of the left coronary artery by an aortic intimal flap.

Aged↗
PubMed1997

[Ductal hyperplasia and ductal carcinoma in situ. Definition--classification--differential diagnosis].

This review emphasizes the pathology of premalignant ductal breast diseases and its practical relevance to the patients management. The histological criteria for recognizing Ductal Hyperplasia (DH) are now well established. These include an intraluminal heterogeneous proliferation of glandular cells positive for keratins 8/18/19 and epithelial cells with expression of keratins 5/6/14. As a hyperplastic process the epithelial cells disclose an haphazard irregular growth with slit like irregular lumina (fenestrated growth pattern). The florid DH indicates a slight subsequent increased risk for cancer development. Our knowledge of the nature of noninvasive ductal neoplasia continues to evolve. Recent molecular genetic and immunohistochemical efforts have disclosed that atypical ductal hyperplasia (ADH) constituted a clonal neoplastic proliferation of an epithelial cell. Histological hallmarks of ADH are their cytologic features of uniformity and monotony of proliferation of cells and its micropapillary, cibriform or solid growth pattern. So from histology ADH simulates the highly differentiated DCIS, but can be distinguished from the latter quantitatively by the aggregate cross sectional diameter or the number of ducts that are completely involved by the atypical proliferation. ADH indicates a few fold subsequent increased risk for developing carcinoma. So this lesion requires a close follow up with 3 to 4 examinations per year and annual mammograms. Ductal carcinoma in situ (DCIS) consists of cytologically malignant cells in the parenchyma that have not invaded into the stroma. Recent studies have shown that DCIS is a heterogeneous group of tumors. Attempts have been made to classify it into histologic patterns, nuclear grades, tumors with or without comedo-necroses etc. We can draw the conclusion from several studies that the most important histologic feature is the nuclear grade. Holland et al. have suggested a very useful classification scheme that includes nuclear grade and histological features. The modifiers of treatment are as follows: 1. nuclear grade or differentiation of the DCIS 2. extension of the lesion 3. excision with clear margins So efforts to classify DCIS underscore the central role of pathology in determining the grade of the DCIS, its size and the adequacy of the surgical excision in terms of free margins. All three parameters are included in a score system of the Van Nuys Prognostic Index.

Breast↗
PubMed1997

[Significance of adhesion molecules in oncology].

Cell-Cell-and cell-extracellular matrix interactions are important in the process of tumor cell invasion and metastasis. These interactions are mediated by adhesion molecules e.g. CD44, integrins, E-cadherin and N-CAM. The role of adhesion molecules along metastatic cascade as well as their importance in tumor differentiation and progression are discussed herein.

Animals↗
PubMed1997

Ultrastructural localization of IgG and TPO in autoimmune thyrocytes referring to the transcytosis of IgG and the antigen presentation of TPO.

While autoantibodies against thyroid peroxidase (TPO) are known to produce cytotoxicity in vitro, their in vivo effects are still obscure. In addition, the mechanism of TPO autoantibody creation needs to be disclosed because the localization of TPO on thyrocytes is considered to be restricted to the apical membrane, which is not in contact with immunocompetent cells. In order to study these crucial processes in the pathogenesis of thyroid autoimmunity, the ultrastructural localization of TPO and IgG was determined and quantified in thyrocytes of normal thyroid gland and thyroid tissue of patients suffering from Graves' disease. This was done by using ultrathin frozen sections and the immunogold method. IgGs were detected in the follicular lumen, close to the apical membrane, in transport vesicles, the endoplasmic reticulum, and the Golgi apparatus of thyrocytes from patients with Graves' disease. The labeling of TPO in the basolateral membrane was distinctly lower than that of the apical membrane, but was significant in comparison to the plasma membrane labeling of fibroblasts present in the same sections. These data indicate that thyroid autoantibodies may perform their cytotoxic function in intracellular compartments besides the plasma membrane. TPO molecules on the basolateral membrane of HLA class II antigen-positive thyrocytes may initiate antigen presentation of TPO as well as the formation and uptake of TPO autoantibodies.

Autoantigens↗
PubMed1997

Factor XIIIa expression in granulomatous lesions due to sarcoidosis or mycobacterial infection.

The a-subunit of the clotting factor XIII (FXIIIa) has previously been shown to be synthesized by cells of monocyte lineage such as macrophages and histiocytes. Thus, besides clot retraction, a possible role of FXIIIa has also been postulated in inflammation. In order to test this hypothesis, FXIIIa-expression in granulomatous lesions due to sarcoidosis and mycobacterial infection was investigated. In the 12 cases (six cases each) examined, FXIIIa-positive macrophages were consistently detected by immunohistochemistry. They were predominantly observed in the periphery of granulomas, whereas the centers were generally devoid of these cells. We did not find any difference in the distribution of FXIIIa-positive cells in both conditions; thus FXIIIa did not improve the differential diagnosis between sarcoidosis and tuberculosis. However, FXIIIa-producing macrophages seemed to contribute to the centripetal fibrosis in granuloma. These results further suggest that the basic pathogenetic mechanisms in granuloma formation are very similar, regardless of their origin from sarcoidosis or tuberculosis.

Adolescent↗
PubMed1997

Prognostic value of histobiological factors (malignancy grading and AgNOR content) assessed at the invasive tumour front of oral squamous cell carcinomas.

Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front.

Analysis of Variance↗