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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
    Biologic characterization of human bone tumors (1983)
    Springer
    Journal of cancer research and clinical oncology 106 (1983), S. 234-239 
    Details
    ISSN: 1432-1335
    Keywords: Osteosarcoma ; Collagen types ; Immunofluorescence microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixteen cases of typical highly malignant osteosarcoma were investigated by light, electron, and immunofluorescence microscopy to demonstrate the presence of collagen types I–III. It was shown that, in light-microscopically anaplastic areas of the tumor, collagen type III predominates, while only very few membranes of collagen type I are observed. Ultrastructurally, the cells are characterized by numerous free ribosomes in their cytoplasm and only a few membranes of granular endoplasmic reticulum (ER). In osteoblastic areas, collagen type I is increased, while type-III collagen is decreased. The cytoplasm of cells contains markedly more granular ER. An increasing mineralization of matrix is observed. In fibroblastic areas of the tumors, collagen types I and III are codistributed. Tumor cells have a fibroblast appearance with elongated nuclei and well developed granular ER. The chondroblastic areas, characterized by immature neoplastic cartilage, contain varying amounts of collagen type II. Chondroblast-like tumor cells have typical ring-shaped membranes of granular ER in their cytoplasm. The evidence of different collagen types in osteosarcomas lends additional support to the concept that a pluripotent mesenchymal cell is the stem cell of osteosarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402614
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  • 4
    Electronic Resource
    Electronic Resource
    Combined ultrastructural, histochemical, and autoradiographic study of osteosarcoma after preoperative chemotherapy according to the COSS 80 protocol (1983)
    Springer
    Journal of cancer research and clinical oncology 106 (1983), S. 25-31 
    Details
    ISSN: 1432-1335
    Keywords: Osteosarcoma ; Chemotherapy ; Electronmicroscopy ; Histochemistry ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve osteosarcomas treated according to the COSS 80 protocol (preoperative chemotherapy, resection) were studied by light and electron microscopic, histochemical, and autoradiographic methods. Evidence of regressive and necrotic changes was found in many tumor cells, but the alterations were unspecific. Viable tumor cells of high malignancy were also observed regularly, often at the S phase. As the tumor regression continued, a strong reaction of the mononuclear phagocyte system was manifested by the presence of macrophages and giant cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625048
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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
    Closure of osteochondral lesions using chondral fragments and fibrin adhesive (1983)
    Springer
    Archives of orthopaedic and trauma surgery 101 (1983), S. 213-217 
    Details
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An 75 Kniegelenken von 46 ausgewachsenen Kaninchen wurden Knorpelknochendefekte gesetzt, die einen Durchmesser von 4 mm batten und den subchondralen Spongiosaraum eröffneten. Dreiundzwanzig Defekte wurden offengelassen oder mit Kollagenschaum oder Fibrinkleber oder einer Kombination der beiden letztgenannten Substanzen verschlossen. Zweiundünfzig Defekte wurden mit Pfröpfen aus feinstverteiltem autologem Gelenkknorpel und einem eigens angefertigten Fibrinkleber verschlossen, größtenteil unter Zusatz von Kollagenschaum zur Blutstillung. In den erstgenannten Defekten wurden auch nach 40wöchiger Überlebenszeit nur bindegewebige Regenerate gefunden, nie hyaliner Knorpel. In den mit autologem Knorpel und Fibrinkleber gefüllten Defekten wurde eine lebhafte Chondrozytenvermehrung beobachtet mit Ausbildung eines Hyalinknorpels, der morphologisch und auch in seiner Fähigkeit zur enchondralen Ossifikation dem juvenilen Knorpel entspricht und durch Alcianblau anfärbbare Mucopolysaccharide enthält. Nach Neubildung des subcondralen Knochens wandelt sich das histologische Bild dann zur Erscheinung des adulten Gelenkknorpels. Erklärt wird dieser Vorgang durch eine zweite Adoleszenz des adulten Knorpels, da diesem durch das reiche Substrat- und Sauerstoffangebot aus den Markraumgefäßen ein Milieu geschaffen wird, welches demjenigen vor Ausbildung des subchondralen Knochens bei Wachstumsabschluß gleicht. Es konnten mit diesem Verfahren vollständige hyalinknorpelige Defektverschlüsse erzielt wurden, deren Oberfläche im Niveau der Umgebung liegt.
    Notes: Summary In 75 knee joints of 46 adult rabbits osteochondral defects of 4 mm diameter were placed by a drill reaching the cancellous bone. Twenty-three defects were left untreated, or closed by collagen foam or fibrin adhesive, or a combination of both. Fifty-two defects were closed with very small autologous cartilage fragments and a special fibrin adhesive. The adhesive differed from commercially supplied types by adigested alpha chain of fibrinogen for increase in concentration, and by the addition of alpha-2-macroglobuline as protease-inhibitor. In most cases small pieces of collagen foam were added for hemostasis. In the first group of 23 joints observed over up to 40 weeks, no hyaline cartilage was found histologically in any of the defects. In the second group a rapid proliferation of chondrocytes appeared with development of hyaline cartilage with alcianblue-positive matrix. It resembled juvenile cartilage in its histologic appearance and with regard to the induction of ossification. The phenomenon is interpreted as a “second adolescence” of the adult cartilage induced by the rich nutritional and oxygen supply from the cancellous vessels, which resembles the environmental conditions before the forming of subchondral cortical bone at the end of the growth period. This method enabled us to achieve a complete closure of defects by hyaline cartilage on the very level of the surrounding articular surface.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00436773
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  • 9
    Electronic Resource
    Electronic Resource
    The submicroscopic structure of a chondroblastic osteogenic sarcoma (1984)
    Springer
    Archives of orthopaedic and trauma surgery 103 (1984), S. 100-106 
    Details
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurden zwei Fälle vom typischen chondroiden Osteosarkom, deren Struktur auch submikroskopisch analysiert wurde, beschrieben. Das klinische und radiologische Bild, sowie der schnelle letale Verlauf der Erkrankung unterstützten die Diagnose eines Osteosarkoms. Dagegen zeigten die histologische und elektronenmikroskopische Untersuchung einen überwiegenden Anteil vom malignen Chondroid. Der Fortschritt in den Behandlungsmethoden des Osteosarkoms zeigt aus diagnostischen, therapeutischen und prognostischen Gründen die Wiedereinführung der Subklassifikation der Osteosarkome, sowie die Korrelation ihres morphologischen Bildes mit ihren biologischen Eigenschaften, als unentbehrlich. Nach den derzeitigen Erfahrungen vermindert die chondroblastische Komponente in keinem Fall die schnelle maligne Penetranz eines Osteosarkoms. Es ist grundsätzlich wichtig, diese Tumoren von den meist weniger malignen Chondrosarkomen zu unterscheiden, auch wenn das maligne Chondroid in diesen Osteosarkomen überwiegt. Danach muß auch die Therapie entsprechend radikal und kombiniert durchgeführt werden.
    Notes: Summary Two patients are reported with a chondroid form of osteosarcoma, whose structure was also analyzed submicroscopically. The clinical and radiologic picture and the rapid lethal progress of the disease indicated an osteosarcoma, while both histologic and electron-microscopic investigation suggested the prevalence of malignant chondroid. Progress in the treatment of osteosarcoma makes it essential for diagnostic, therapeutic and prognostic reasons to reintroduce subclassification of these tumors in an attempt to correlate their morphological picture with their biologic properties. According to our experience to date, it seems that the cartilaginous component in no way ameliorates the rapid malignant penetration of the osteosarcoma. It is essential to distinguish these tumors from the usually much less malignant chondrosarcomas and to place the chondroblastic osteogenic sarcoma among in spite of the clear predominance of the malignant chondroid, and thus also introduce highly radical and combined therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00389580
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  • 10
    Electronic Resource
    Electronic Resource
    Biologic characterization of human bone tumors I. Ewing's sarcoma (1982)
    Springer
    Journal of cancer research and clinical oncology 104 (1982), S. 171-180 
    Details
    ISSN: 1432-1335
    Keywords: Ewing's sarcoma ; Type IV collagen ; Factor-VIII-associated protein ; Endothelial differentiation ; Electron microscopy ; Immunofluorescence microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six cases of Ewing's sarcoma were investigated by electron and immunofluorescence microscopy. A layer of basement membrane-like deposits was found between typical principal and secondary tumor cells. To clarify the nature of these ultrastructural deposits, antibodies against collagen type IV were applied to frozen sections of corresponding tumor tissue. This reaction revealed type IV collagen as a regular component of basement membranes in nonneoplastic tumor capillaries, but it was equally able to localize collagen type IV between single tumor cells in capillary-free areas. With the same method, factor-VIII-associated protein, predominantly found in endothelial cells, could be demonstrated in some tumor cells. These results demonstrate that, in addition to anaplastic cells, some tumor cells are found in Ewing's sarcoma that share certain differentiating features with the endothelial cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402065
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