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  • 1
    Electronic Resource
    Electronic Resource
    Störung sensibler Gelenkinnervation als begünstigender Faktor für die Arthroseentstehung Eine tierexperimentelle Untersuchung am Rattenmodell (1999)
    Springer
    Zeitschrift für Rheumatologie 58 (1999), S. 148-154 
    Details
    ISSN: 0340-1855
    Keywords: Schlüsselwörter Tiermodell ; Osteoarthrose ; sensible Denervierung ; Capsaicin ; Laufbelastung ; Key words Animal model ; osteoarthritis ; sensible denervation ; capsaicin ; running load
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In the present study we investigated the influence of an altered sensible joint innervation on the development of knee osteoarthritis in a wistar rat model of osteoarthritis. Capsaicin (8-methyl-N-vanillyl-6-noneamide) mediated partial sensible knee joint denervation was performed in a group of 16 male wistar rats. Twelve rats without alterations of the sensible knee joint innervation served as controls. In both groups, halft of the rats underwent strenuous running exercises (total running load of 20km) in a running wheel by intracranial self-stimulation, while the other half did not have any running load. In rats without running, there were no histological sings of knee osteoarthritis according to the Mankin score. In contrast, in rats running a total of 20km significant osteoarthritis changes were observed. Hereby, in rats without altered sensible knee joint innervation, osteoarthritis was mostly classified as mild or moderate, while severe osteoarthritis was the predominant finding in the knee joints of the rats with partial sensible knee joint denervation. In conclusion, our study gives strong evidence for the hypothesis that an altered sensible joint innervation works as a contributing factor in the development of osteoarthritis.
    Notes: Zusammenfassung In der vorliegenden Studie untersuchten wir den Einfluß gestörter peripherer sensorischer Afferenzen auf die Ausbildung arthrotischer Kniegelenksveränderungen in einem Rattenmodell. Dazu führten wir bei insgesamt 16 männlichen Wistarratten eine sensible Teildenervierung der linken Kniegelenke mittels Capsaicin (8-Methyl-N-vanillyl-6-noneamide) durch, während 12 Ratten ohne gestörte sensible Gelenkinnervation als Kontrollgruppe dienten. Anschließend erfolgte bei jeweils der Hälfte der denervierten und der nichtdenervierten Tiere eine exzessive Laufbelastung (Gesamtlaufleistung 20km) im Laufrad mittels intrakranialer Selbstimmulation. Die verbleibenden Tiere beider Gruppen wurden keiner Laufbelastung unterzogen. Die histologische Beurteilung der Kniegelenke mit Hilfe des Mankin-Scores erbrachte bei den Versuchstieren ohne Laufbelastung, unabhängig davon, ob eine sensible Teildenervierung erfolgt war oder nicht, keinerlei arthrotische Veränderungen. Im Gegensatz dazu zeigten alle Tiere mit 20km Laufbelastung deutliche Gonarthrosezeichen. Während es sich bei den Tieren ohne sensible Teildenervierung fast ausschließlich um leichte bis mäßiggradige Veränderungen handelte, zeigte sich in den Kniegelenken der Tiere mit sensibler Teildenervierung vorzugsweise schwere arthrotische Veränderungen. Insgesamt gibt diese Arbeit deutliche Hinweise auf eine potenzierende Wirkung sensorischer artikulärer Defizite auf die Entwicklung osteoarthrotischer Gelenkveränderungen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003930050165
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  • 2
    Electronic Resource
    Electronic Resource
    Performance of a Rapid Whole Blood Test for Helicobacter pylori in Primary Care: A German Multicenter Study (1998)
    Cambridge, MA, USA : Blackwell Science Inc, Boston, USA
    Helicobacter 3 (1998), S. 0 
    Details
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Serological rapid whole-blood tests for the detection of H. pylori are presently being promoted for use in primary care. We conducted a multi-center study to investigate the diagnostic accuracy of the Boehringer Mannheim Helicobacter pylori® test (BM test), which is identical with the Cortecs Helisal® test.〈section xml:id="abs1-2"〉〈title type="main"〉Patients and Methods.A previous diagnosis of H. pylori, a history of peptic ulcer diseases, or proton-pump inhibitor, bismuth or antibiotic use during the preceding month were exclusion criteria. The BM test was performed prior to endoscopy by 7 primary care physicians, 5 practicing gastroenterologists, or a single physician in the university hospital outpatient service. During endoscopy, antral and corpus biopsies were obtained for histology and rapid urease testing (RUT). H. pylori positivity was defined by histology and/or RUT as reference methods. H. pylori IgG-ELISA was performed additionally.〈section xml:id="abs1-3"〉〈title type="main"〉Results.Of the 203 patients included, 151 were H. pylori-positive by reference methods (74.4%). The overall accuracy of the BM test was 77.3%. Eight BM tests were indeterminate, and in the other 195 patients the test performed as follows: sensitivity 80.3%, specificity 81.3%, positive predictive value 92.9%, negative predictive value 57.4%. Using IgG-ELISA as reference, the BM test performance was similar. It also did not differ substantially among the three groups of physicians involved.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions.We found the performance of the BM test to be insufficiently accurate, as both over- and underdiagnosis of H. pylori infection were not infrequent. This test needs to be improved before its use in primary care can be recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1523-5378.1998.08002.x
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  • 3
    Electronic Resource
    Electronic Resource
    The Significance of ras Oncogene Mutation for the Development of Human Breast Cancer (1998)
    Oxford, UK : Blackwell Publishing Ltd
    The @breast journal 4 (1998), S. 0 
    Details
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Activation of ras oncogenes has been described in various human tumors. Additionally there is strong evidence that ras oncogenes are involved in experimental mammary carcinogenesis. The role of these oncogenes in the development of human breast cancer has not yet been fully clarified.We investigated 45 cases of primary human breast cancer for point mutation in the hot spot regions codon 12 and 13 of exon 1 and codon 61 of exon 2 of H-, K-, and N-ras gene, applying polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) technique followed by direct sequencing.One case of an invasive ductal breast cancer showed an activation by point mutation in codon 61, exon 2 of the H-ras gene. We could demonstrate a transversion of adenine to thymine leading to an exchange between glutamine and leucine.Our findings suggest that in spite of experimental carcinogenesis the rate occurrence of ras-oncogene activation by point mutation does not play an important role in human breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-4741.1998.420112.x
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  • 4
    Electronic Resource
    Electronic Resource
    Possible contribution of aminopeptidase N (APN/CD13) to invasive potential enhanced by interleukin-6 and soluble interleukin-6 receptor in human osteosarcoma cell lines (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 857-863 
    Details
    ISSN: 1573-7276
    Keywords: aminopeptidase N ; interleukin-6 ; invasion ; matrigel ; osteosarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed at clarifying the role of Aminopeptidase N (APN), a Zn2+-dependent ectopeptidase localized on the cell surface of human osteosarcoma cell lines treated with proinflammatory cytokines. We investigated the proinflammatory cytokines interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) as well as the anti-inflammatory cytokine transforming growth factor beta (TGF-β) for their influence on APN regulation. Soluble IL-6 receptor (sIL-6R) was always used together with IL-6 to achieve a stable effect. In addition, the invasive potential of the osteosarcoma cell lines MG63 and HOS was examined. Competitive RT-PCR and Ala-pNA activity assays revealed that IL-6 and sIL-6R significantly increased the mRNA expression and activity of APN in both osteosarcoma cell lines. Although IL-1β significantly stimulated APN mRNA expression in both cell lines, it influenced the enzyme activity only in MG63. TNF-α and TGF-β, however, had an effect neither on mRNA expression nor on the enzyme activity of APN in both cell lines. In the Matrigel invasion assay, IL-6 and sIL-6R significantly up-regulated the transmigration of these cell lines, whereas other cytokines did not. The up-regulated invasion was inhibited by bestatin, a specific inhibitor of APN. Cellular migration correlated highly with APN activity (r = 0.79, P 〈 0.002). These findings suggest that APN contributes to the invasive potential of human osteosarcomas enhanced by IL-6 and SIL-6R.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006794617406
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  • 5
    Electronic Resource
    Electronic Resource
    p53 gene mutations in soft-tissue sarcomas-correlations with p53 immunohistochemistry and DNA ploidy (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 211-218 
    Details
    ISSN: 1432-1335
    Keywords: Soft-tissue tumors ; p53 gene mutation ; p53 immunohistochemistry ; PCR SSCP analysis ; DNA ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The significance ofp53 mutations in a group of 67 soft-tissue tumors was examined using single-strand conformation polymorphism and direct sequencing analysis. Molecular findings were correlated with immunohistochemical detection of thep53 protein and DNA ploidy status. Mutations of thep53 gene were detected in 13 (19.5%) out of 67 cases of soft-tissue tumors. Only there were localized outside the conservative regions of thep53 gene. Six mutations were described for the first time in these tumors. Most of the mutations were point mutations in exons 5–8 and, in one case, a deletion at the 3′-splice site of exon 5 could be demonstrated. There was no significant correlation between the occurrence ofp53 mutations and the histological grade, although a high number of mutations were defined in poorly differentiated tumors (grade 3). Molecular finding of ap53 gene mutation and immunohistochemical detection ofp53 expression did not correlate, which may be due to the high percentage of nonsense mutations in our study (50%). We confirm that only DNA sequencing allows a unique identification and differentiation of mutations in thep53 gene. Other factors may be responsible for the detection ofp53 protein in many cases. Histological grade correlated with aneuploidy. The frequency of mutations observed was in accordance with values quoted in the literature. Generally,p53 mutations andp53 overexpression are more likely to represent a late event in the oncogenesis of soft-tissue tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240317
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  • 6
    Electronic Resource
    Electronic Resource
    Expression of multidrug resistance-associated protein gene in Ewing's sarcoma and malignant peripheral neuroectodermal tumor of bone (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 237-239 
    Details
    ISSN: 1432-1335
    Keywords: Ewing's sarcoma ; Multidrug resistance gene ; Anti-cancer-drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of multidrug resistance-associated protein (MRP) mRNA was examined in ten samples of Ewing's sarcoma of bone (ES) and in one nude mice transplantable ES and two malignant peripheral neuroectodermal tumor (MPNT) cell lines using an RT-PCR assay. MRP mRNA expression was recognized in eight of the ten clinical specimen and in all three cell lines. On the other hand, the expression of multidrug resistance gene (MDR1) was demonstrated in three of the ten clinical samples and all three cell lines. Our results may contribute to elucidation of the mechanism of anti-cancer-drug resistance in this tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240323
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  • 7
    Electronic Resource
    Electronic Resource
    Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas (1996)
    Springer
    Journal of cancer research and clinical oncology 122 (1996), S. 161-165 
    Details
    ISSN: 1432-1335
    Keywords: Soft-tissue sarcoma ; MRP mRNA ; Multidrug resistance ; MDR1 ; RT-PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the mRNA expression of the multidrug-resistance-associated protein gene (MRP) in soft-tissue sarcomas and compared it with the expression of the multidrug resistance gene (MDR1), using the reverse transcriptase/polymerase chain reaction. We investigated 39 samples from 33 cases of soft-tissue sarcomas (11 liposarcomas, 9 malignant fibrous histiocytomas, 6 leiomyosarcomas, 4 malignant schwannomas, 3 fibrosarcomas, 3 synovial sarcomas, and 3 epithelioid sarcomas) and 7 benign softtissue tumors. All samples were obtained prior to chemotherapy. An expression ofMRP mRNA was noted in 56% of soft-tissue sarcoma specimens. The co-expression ofMRP andMDR1 was recognized in 15 samples (38%) (5/11 liposarcomas, 5/9 malignant fibrous histiocytomas, 3/6 leiomyosarcomas, 2/3 fibrosarcomas) and significantly correlated with histological grade (P=0.0165). A positive and significant correlation was found betweenMRP andMDR1 expression in soft-tissue sarcomas (P=0.0013). In benign soft-tissue tumors, 1 chemodectoma and 1 neurothekeoma showed lowMRP expression; however, no case showed co-expression ofMRP andMDR1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01366956
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  • 8
    Electronic Resource
    Electronic Resource
    Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone (1993)
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 172-178 
    Details
    ISSN: 1432-1335
    Keywords: p53 protein ; Point mutation ; Osteosarcoma ; Bone tumour ; Immunohistochemistry ; Immunoelectron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewing's sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giantcell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01229533
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  • 9
    Electronic Resource
    Electronic Resource
    Immunohistochemical analysis of nm23 protein expression in malignant bone tumors (1995)
    Springer
    Journal of cancer research and clinical oncology 121 (1995), S. 667-673 
    Details
    ISSN: 1432-1335
    Keywords: nm23 protein ; Malignant bone tumors ; Osteosarcoma ; Chondrosarcoma ; Immunohistochemistry ; Metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression levels of nm23 protein in 72 malignant bone tumors comprising 41 osteosarcomas, 22 chondrosarcomas, 6 Ewing's sarcomas, and 2 malignant fibrous histiocytomas were examined immunohistochemically, using anti-nm23 protein polyclonal antibody, and compared with 51 cases of benign bone tumors or tumor-like lesions. Malignant bone tumors showed significantly higher nm23 protein expression than benign bone tumors or tumor-like lesions (P〈0.0001). In chondrosarcoma, nm23 expression increased in high-grade tumors (grade I versus grade II and III:P=0.0229). In the cases of osteosarcoma, however, grade IV osteosarcomas showed decreased expression of nm23 compared with grade III tumors (P=0.0122). There was no significant relationship between nm23 expression and histological type. nm23 expression had no correlation with metastatic potential in osteosarcoma, although the therapy was not uniform in our cases. Furthermore, in 6 cases of osteosarcoma and 1 case of Ewing's sarcoma, there was no clear tendency for a decrease of nm23 in the metastatic sites compared with primary sites, as reported in breast cancer. These results showed that, in contrast to reports on breast cancer and experimental models, nm23 protein expression in human bone tumors may be associated with malignant potentiality, except in cases of osteosarcoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01218525
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  • 10
    Electronic Resource
    Electronic Resource
    On telomere shortening in soft-tissue tumors (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 165-171 
    Details
    ISSN: 1432-1335
    Keywords: Key words Telomeres ; Soft-tissue tumors ; Telomerase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Specific simple DNA repeats occur at the telomeric ends of mammalian chromosomes. Loss of (G+C)-rich repeats can result in genetic instability, associated with tumorigenesis. So far, data on telomere shortening have not been available for different types of soft-tissue tumors. Methods: Using tumor material and the blood of the corresponding patient, high-molecular-mass DNA was prepared by digestion with proteinase K and extraction with phenol/chloroform. A 10-μg sample of DNA was digested with the restriction enzyme HinfI. DNA fragments were separated in a 0.7% agarose gel, and in-gel hybridization was performed with the telomere-specific repeat probe (TTAGGG)3. Results: Shortening of the telomere repeat was observed in 14/30 soft-tissue tumors; 5 tumors showed elongated telomere repeats, whereas the telomeres appeared unchanged in 11 tumors. Decreased telomere repeat length correlated with advanced age, DNA ploidy, and a higher proliferation index. There was no association between telomere repeat length and tumor grade. Interestingly, in contrast to other entities, all malignant schwannomas and leiomyosarcomas showed significantly reduced telomere lengths. An explanation for the telomere heterogeneity in liposarcomas may include differential telomerase reactivation in well and poorly differentiated tumors. Conclusions: Telomere shortening is frequent but not a uniform phenomenon in different types of soft-tissue tumor. Studies on telomerase activity should be performed in the same cohort of sarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050150
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