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  • 1
    Electronic Resource
    Electronic Resource
    Distribution pattern of matrix metalloproteinases 1, 2, 3, and 9, tissue inhibitors of matrix metalloproteinases 1 and 2, and α2-macroglobulin in cases of generalized AA- and AL amyloidosis (2000)
    Springer
    Virchows Archiv 437 (2000), S. 521-527 
    Details
    ISSN: 1432-2307
    Keywords: Amyloid Protease Protease inhibitors Matrix metalloproteinases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Matrix metalloproteinases (MMPs) degrade basement membranes and connective tissue and play an essential role in the homeostasis of the extracellular matrix which is disrupted by the deposition of amyloid. This immunohistochemical study investigated the distribution pattern of matrix metalloproteinases (MMP-1, -2, -3, and -9) and their inhibitors [α2-macroglobulin (α2-M), tissue inhibitors of MMPs (TIMP)-1, and TIMP-2] in human AA- and AL amyloid deposits. Specimens of liver, kidney, and spleen from 22 autopsy cases were investigated. Nine patients had suffered from generalized AA amyloidosis, eight from generalized AL amyloidosis, and five from rheumatoid arthritis or tuberculosis with no histological evidence of amyloid. In all amyloidotic and non-amyloidotic patients, each protease and protease inhibitor was detected in almost every organ investigated. In the amyloidotic cases, there was no indication that a specific protease or protease inhibitor was absent or expressed, but a difference was observed in their spatial distribution patterns. The most noticeable difference was found in immunostaining of amyloid. Only MMP-1, -2, and -3, and α2-M were present in AA amyloid deposits, and only TIMP-1 and TIMP-2 were found in deposits of AL amyloid. This is the first study to show that MMP-1, -2, and -3 are present in AA amyloid deposits. They may be involved in tissue remodeling or in proteolysis of the precursor and fibril proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280000271
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  • 2
    Electronic Resource
    Electronic Resource
    Inducible nitric oxide synthase expression in human urinary bladder cancer (2000)
    Springer
    Virchows Archiv 437 (2000), S. 662-666 
    Details
    ISSN: 1432-2307
    Keywords: Nitric oxide synthase Immunohistochemistry Transitional cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Nitric oxide (NO) is generated by a family of enzymes, nitric oxide synthases (NOS), in a wide range of mammalian cells. NO produced by the inducible NOS isoform (iNOS) has been suggested to play an important role in tumor biology with both tumor promoter and antitumor activity. Here, the cellular localization of iNOS in tissue of 100 cases of urinary bladder cancer was assessed immunohistologically using a commercially available antiserum. Positive iNOS immunostaining was detected in all samples of tumor tissue, whereas nonmalignant tissue adjacent to malignant areas did not show any iNOS positivity. The tumor tissue revealed a highly inhomogeneous staining pattern. In addition to uniformly stained tumor specimens, we also found markedly iNOS-positive tumor islets in the midst of unstained tumor tissue and scattered individual tumor cells expressing marked staining. In some cases, the tumor tissue showed no or only weak staining intensity. In some instances, the superficial epithelial layer of papillary carcinomas was extremely immunoreactive, in other cases it was not. Thus we were unable to show a clear correlation to tumor grade or stage. Further studies with a diversity of tumor markers including molecular genetics techniques will be necessary to elucidate how and to what extent NO and bladder cancer of different grades and stages are functionally interrelated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280000296
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  • 3
    Electronic Resource
    Electronic Resource
    p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 388-394 
    Details
    ISSN: 1432-1335
    Keywords: Key words p53 ; mdm2 ; p53 gene mutation ; Breast carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to analyze p53 gene mutations and the expression of p53 and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results were then correlated with tumor grade, stage, estrogen receptor status, nodal status, and DNA ploidy. The expression of the proteins p53 and mdm2 was determined immunohistochemically using formalin-fixed, paraffin-embedded material. Screening for p53 mutation involved analysis of the highly conserved regions of the p53 gene (exons 5–9) by the polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) technique. PCR products with band shifts were directly sequenced. Immunohistochemical staining of p53 was positive in 9 cases (29.0 %), only 2 of which showed a p53 gene mutation. These were identified as a C→G transversion at the second position of codon 278 in exon 8 and an A→G transition at the second position of codon 205 in exon 6. A third case with a mutation was observed (C→T transition, position 1 of codon 250 in exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive tumors, 2 were moderately differentiated (grade II). The remaining tumors were poorly differentiated (7/9). By contrast, p53-negative carcinomas were well differentiated (grade I) in most cases (P = 0.02). DNA cytometry in 8 of the 9 p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53-negative tumors were diploid (P = 0.01). Mdm2 oncoprotein was detected in 10 tumors (32.2 %), 4 of which were p53-positive, including the 3 with mutations. The grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were always noted to be mdm2-negative (P = 0.04). Overexpression of p53 protein is a complex mechanism and does not merely indicate the detection of mutations in the p53 gene. This study has shown that p53 expression correlates with tumor grade and DNA ploidy. Mdm2 expression was also associated with the tumor grade. Immunohistological demonstration of the p53 protein alone is insufficient as a basis for comment on the functional state of the p53 gene and gene product. The interrelation between recognition of the p53 protein and gene mutation needs more careful assessment to define their roles in the control of neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240122
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  • 4
    Electronic Resource
    Electronic Resource
    Gastrointestinale Stromatumoren (GIST) – Probleme in Diagnostik und Therapie (1999)
    Springer
    Der Chirurg 70 (1999), S. 807-812 
    Details
    ISSN: 1433-0385
    Keywords: Key words: Stromal tumors ; GIST ; Surgical therapy ; Gastrointestinal tract. ; Schlüsselwörter: Stromatumoren ; GIST ; chirurgische Therapie ; Gastrointestinaltrakt.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die gastrointestinalen Stromatumoren (GIST) sind eine seltene, auch heute noch nicht vollständig aufgeklärte Gruppe von Neoplasien des Magen-Darm-Trakts. Trotz vieler Fortschritte der diagnostischen Möglichkeiten ist eine Zuordnung der GIST hinsichtlich ihrer Histogenese und Dignität nicht eindeutig. Im Zeitraum von 1994 bis 1998 wurden in der Klinik für Chirurgie 18 Patienten mit einem GIST operiert. Dabei handelte es sich um 12 (67 %) gastrale und 6 (33 %) intestinale Stromatumoren. Der Primärtumor konnte bei allen Patienten durch eine R0-Resektion entfernt werden. Bei 6 Patienten kam es zu einer hämatogenen Lebermetastasierung, die Größe des Primärtumors betrug bei diesen Patienten mehr als 10 cm. Eine extrahepatische Fernmetastasierung ließ sich in allen untersuchten Fällen nicht nachweisen. Eine Lymphknotenmetastasierung konnte in den regionären Lymphknoten nicht festgestellt werden. Eine systematische Lymphadenektomie ist nicht indiziert. Die histologische Beurteilung der Dignität erfolgte auf der Grundlage der von Lewin, Weinstein und Riddell vorgeschlagenen Richtlinien. Das derzeit gesicherte therapeutische Vorgehen besteht in der kurativen Resektion des Primärtumors sowie der Metastasen mit histologisch tumorfreien Resektionsrändern. Das Tumorrezidiv ist ebenso zu behandeln. Adjuvante oder neoadjuvante chemotherapeutische Ansätze zeigen bisher keine Erfolge.
    Notes: Summary. Gastrointestinal stromal tumors (GIST), which form a rare group of neoplasias of the gastrointestinal tract, have not yet been fully investigated. Although good progress has been made in their diagnosis, classification of these lesions with regard to their histogenesis and biological behavior remains problematic. Between 1994 and 1998, 18 GIST patients underwere operation in the Department of Surgery. Twelve of these patients (67 %) had stromal tumors in the stomach, and six (33 %) had intestinal stromal tumors. The primary tumor could be removed in all patients with R0 resection. Six patients developed hematogenous liver metastasis, with the size of their primary tumor exceeding 10 cm. Extrahepatic distant metastases were not found in any case. Lymphadenectomy showed that lymph node metastases did not occur. Histological evaluation was made according to the guidelines of Lewin, Weinstein and Riddell. Currently established therapy is limited to complete surgical resection of the primary tumor and its metastases. Adjuvant or neoadjuvant chemotherapy approaches have failed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001040050728
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  • 5
    Electronic Resource
    Electronic Resource
    Is typing of metaplasia at the squamocolumnar junction revealing its aetiology? (2000)
    Springer
    Virchows Archiv 436 (2000), S. 6-11 
    Details
    ISSN: 1432-2307
    Keywords: Key words Intestinal metaplasia ; Squamocolumnar junction ; Gomori’s aldehyde fuchsin ; H. pylori ; Barrett’s mucosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Until recently, intestinal metaplasia (IM) at the squamocolumnar junction (SCJ) was ascribed to Barrett’s mucosa (BM), which arises from gastro-oesophageal reflux. Recent studies, however, have shown that IM at the SCJ can also be induced, for example, by Helicobacter pylori (HP). The aim of this study was to investigate whether the type of IM might be helpful in the differentiation between these two aetiologies. Biopsies from the antrum, corpus and immediately below the Z-line were taken from 443 patients. Eighty-three of them showed IM below the Z-line. In these, the endoscopic aspect of the Z-line was classified as either unremarkable (n=49) or suspected of BM (n=34). Typing of IM was done using Gomori’s aldehyde fuchsin–Alcian blue staining. Overall, age, HP status and erosive oesophagitis had no influence on the IM type. Type-III IM (n=24) was more frequent in men (P=0.0371) and related to endoscopic BM (P〈0.0001). Type-I/II IM (n=59) was associated with an unremarkable Z-line (P〈0.0001) and was linked to multifocal gastric IM (P=0.016) and HP (P=0.0011). In conclusion, it was shown that, in the presence of a normal Z-line, especially in the absence of HP, type-III IM is suggestive of BM. The diagnosis of short or ultra-short segment BM should therefore include endoscopic, histological and histochemical characteristics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008200
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  • 6
    Electronic Resource
    Electronic Resource
    Plasmacytoma of the tonsil with AL amyloidosis: evidence of post-fibrillogenic proteolysis of the fibril protein (2000)
    Springer
    Virchows Archiv 436 (2000), S. 336-344 
    Details
    ISSN: 1432-2307
    Keywords: Key words Amyloid ; λ Light chain ; Osseous metaplasia ; Plasmacytoma ; Protease ; Tonsil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report of a 58-year-old Caucasian man who was referred to the University Hospital with a greatly enlarged left tonsil which showed calcifications on computed-tomography scans. Histopathology revealed a plasmacytoma with secondary AL amyloidosis, ossifications, and multinucleated foreign-body-type giant cells. N-terminal sequencing of amyloid-fibril proteins purified from the formalin-fixed tissue showed the presence of two proteins of different size; these were of λ-light-chain origin (subgroup V), measured approximately 15.2 kDa and 10.5 kDa, and had identical N-terminal ends (YVLTQPP). When the amyloid deposits were immunolabeled with a polyclonal antibody directed against λ light chain, they showed two staining patterns: some deposits showed intense immunolabeling while others were not immunoreactive. Immunostaining of amyloid was completely absent after protease pre-treatment. Immunoelectron microscopy with gold-labeled secondary antibodies showed staining that was spatially related to amyloid fibrils and suggested that the antibody probably detected the fibril protein. Therefore, our hypothesis in this case is that the different immunostaining patterns are due to a post-fibrillogenic proteolysis of the fibril protein at the C-terminal end of the light chain, as indicated by the presence of two differently sized λ-light-chain fragments with identical N-terminal ends.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050456
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  • 7
    Electronic Resource
    Electronic Resource
    Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma (2000)
    Springer
    Virchows Archiv 436 (2000), S. 494-497 
    Details
    ISSN: 1432-2307
    Keywords: Key words Dedifferentiated chondrosarcoma ; p53 mutation ; p53 LOH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman with an osteosarcomatous high-grade component for p53 alteration. The low-grade cartilaginous and the high-grade osteosarcomatous components of the tumor were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4–8 for p53 mutations. The p53 intron 1-polymorphism was investigated for loss of heterozygosity. A functionally relevant p53 missense mutation in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. This evidence of p53 mutation may be regarded as at least a co-factor that ”switched” the preexisting low-grade conventional chondrosarcoma to a highly malignant dedifferentiated tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050478
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  • 8
    Electronic Resource
    Electronic Resource
    Expression of MDR1/p-glycoprotein and multidrug resistance-associated protein in childhood solid tumours (1997)
    Springer
    Virchows Archiv 430 (1997), S. 99-105 
    Details
    ISSN: 1432-2307
    Keywords: Multidrug resistance ; P-glycoprotein Neuroblastoma ; Nephroblastoma ; Reverse transcriptase polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the expression of MDR1/p-glycoprotein in paediatric tumours using reverse transcriptase polymerase chain reaction (RT-PCR), RNA dot blot analysis, and immunohistochemistry on formalin fixed paraffin-embedded material with JSB-1 and C-219 monoclonal antibodies, and compared these three techniques. The expression of multidrug resistance-associated protein (MRP) gene was examined by RT-PCR assay. We studied MDR1/p-glycoprotein and MRP expression in 13 samples from 10 neuroblastoma patients, 11 samples from 10 nephroblastoma patients, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma and 10 benign tumours or tumour-like lesions. Eleven of 13 neuroblastomas, 7 of 11 nephroblastomas, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma, and 7 of 10 benign tumours or tumour-like lesions showed MDR1 PCR products. By RNA dot blot analysis, MDR1 transcripts were detectable in 11 of 34 specimens. Immunohistochemically, we detected positive reaction products for JSB-1 in 26 of 36 samples. There was a significant correlation between the immunoreactivity for JSB-1 and the expression of MDR1 mRNA expression by RTPCR (P=0.0001). However, the presence of p-glycoprotein immunostaining does not correlate with the MDR1 expression shown by RT-PCR in every case. As for MRP mRNA expression, 9 of 13 neuroblastomas and 10 of 11 nephroblastomas revealed PCR products.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01008030
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  • 9
    Electronic Resource
    Electronic Resource
    No correlation of c-myc overexpression and p53 mutations in liposarcomas (1998)
    Springer
    Virchows Archiv 433 (1998), S. 315-321 
    Details
    ISSN: 1432-2307
    Keywords: Key words Liposarcoma ; c-myc gene expression ; p53 gene mutations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although it is well known that oncogenesis is a multistep process involving the activation of normal cellular genes to become oncogenes and/or the inactivation of tumor suppressor genes, this process has seldom been investigated in soft tissue tumours. We screened a group of 36 liposarcomas for genetic abnormalitis in the p53 tumour suppressor gene and c-myc oncogene. Altered c-myc gene expression was examined by differential RT-PCR assay. p53 Gene mutations in exons 4–8 were analysed by using PCR-SSCP analysis and direct sequencing. Elevated c-myc expression was found in 6 of 31 liposarcomas (19.4%). p53 Gene mutations were observed in 5 of 36 liposarcomas (13.9%). Both genetic alterations were associated with the histological subtype of liposarcomas. Whereas c-myc gene expression was a characteristic of myxoid/round cell liposarcomas, p53 gene mutations were found more frequently in pleomorphic variants. Liposarcomas of the well-differentiated subtype showed neither p53 gene mutations nor altered c-myc gene expression. Our results indicate that the c-myc oncogene and the p53 tumor suppressor gene do not seem to cooperate in the oncogenesis of liposarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050255
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  • 10
    Electronic Resource
    Electronic Resource
    The urokinase plasminogen activator (u-PA) and its inhibitor (PAI-1) in embryo-fetal bone formation in the human: an immunohistochemical study (1995)
    Springer
    Anatomy and embryology 192 (1995), S. 363-368 
    Details
    ISSN: 1432-0568
    Keywords: Plasminogen activator ; Plasminogen activator inhibitor ; Bone formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of urokinase plasminogen activator and plasminogen activator inhibitor-1 in human embryofetal bone formation between the 9th and the 20th week of gestation has been studied immunohistochemically. While mature osteocytes of the secondary spongiosa and resting chondrocytes of the bone epiphyses were negative for both antigens in each developmental stage, metabolically active parts of the osseocartilaginous system showed a strong immunoreactivity. Until the end of the 10th week of gestation urokinase plasminogen activator and plasminogen activator inhibitor-1 could not be demonstrated in the shaft of the preexisting cartilaginous models of bones, which correlates with the morphological developmental stage of the embryos. Later, osteoblasts and chondrocytes in the areas of enchondral ossification, and the perivascular chondrocytes of the epiphyseal secondary ossification centres, showed similarly high concentrations of urokinase plasminogen activator and plasminogen activator inhibitor-1. Moreover, the individual ossification stages of the different bones in embryo-fetal development could be demonstrated immunohistochemically. While humeri and femora showed diaphyseal immunoreactivities at an early stage, positive reactions in the phalanges were found only much later. Thus, the enzymes of the fibrinolytic system studied are clearly involved in the desmal and enchondral ossification process in the osseocartilaginous compartment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710105
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