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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 413 (1988), S. 491-498 
    ISSN: 1432-2307
    Keywords: HPV DNA ; In situ hybridization ; Condylomas ; Carcinomas ; Anus ; Penis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acuminate condylomas from the penis (n=17) and anus (six cases), three anal/penile giant condylomas, anal Bowen's disease (four cases), and intraanal squamous cell carcinomas with associated condylomatous changes (10 cases) including two verrucous carcinoma were studied for human papillomavirus (HPV) infections with nick translated, biotinylated cDNA probes for HPV 6, 11, 16 and 18. In addition, six cases of flat white penile lesions designated as lichen sclerosus et atrophicus were examined. Reannealed complementary DNA strands were detected in situ with either immunoenzyme or immunogold protocols. The in situ hybridizations resulted in 1/6 positive penile lichenoid lesions, 12/17 positive penile acuminate condylomas, 6/6 positive anal acuminate condylomas (including two condylomas with cellular atypias), 2/3 positive giant condylomas, 1/4 positive anal bowenoid lesions, and 4/10 positive keratinized squamous cell carcinomas, two of them being verrucous carcinomas. All penile/anal condylomas and two giant condylomas harboured HPV 6 and/or 11 DNA. The five positive carcinomas (carcinoma in situ/invasive cancer) contained HPV 6 and/or 11 in two cases (including the verrucous carcinomas), and HPV 16 and/or 18 in three cases (one carcinoma in situ, two invasive carcinomas). Recurrent malignancies were seen in one case to harbour the same HPV type as the primary lesions (HPV 16). In one particular patient, a double infection with HPV 16 and HPV 18 was demonstrated in distantly located malignant tumours. Our study confirms the restrictions and the value of non-isotopic hybridization methods applied to archival tissues, and extends the knowledge on the presence and distribution of HPV infections at anogenital sites.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 419 (1991), S. 479-485 
    ISSN: 1432-2307
    Keywords: Papillomaviruses ; Oncogenes ; Uterus ; Vulva ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to investigate papillomavirus (HPV)-DNA in precancer and cancer of the cervix, vulva, and endometrium by in situ/dot blot/ Southern blot hybridization and polymerase chain reaction (PCR).Myc/erbB-2 expression was examined by Northern blot analysis. PCR was the most sensitive HPV detection method, demonstrating HPV-DNA in all preinvasive and invasive cervical lesions (n=21) and most (3 of 4) vulvar carcinomas in contrast to an overall rate of 60% with other techniques. Particular phenotypes (adenoid cystic/basal cell carcinoma of the vulva, cervical adenocarcinoma) were found to contain HPV. Endometrium harboured HPV not only in two cases of cervical cancer, but also in 3 of 8 primary endometrial carcinomas and 3 of 8 non-malignant conditions. activation was confined to three squamous cell carcinomas, most markedly in one HPV-6-positive verrucous variant.ErbB-2 over-expression was only seen in one HPV-18 infected advanced endometrial tumour. Our findings point to a range of HPV-infected lesions broader than previously supposed and possible contributions of HPV-independent molecular events to carcinogenesis in this field.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-2307
    Keywords: Epidermal repair ; Migration ; Fine and intermediate filaments ; Keratinocyte differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidermal repair was studied after the induction of a suction blister on human abdominal skin. The investigation was concerned with keratinocyte migration from the epidermal wound margins and changes at the dermo-epidermal junction. Specific antisera against actin and keratin proteins showed the distribution of fine and intermediate filaments within marginal epithelial cells. Pemphigus- and pemphigoid-autoantibodies allowed the evaluation of the decomposition of extracellular substances. Transmission and scanning electron microscopy were used to analyze the submicroscopical changes in intra- and extraepithelial structures. It was found that suprabasal cells, defined by the presence of keratin polypeptides of 67000 daltons, moved out of the epidermis, thus covering the wound. These cells were strongly labelled by actin-antibodies at the wound margins. The expression of pemphigus antigen was not changed at the wound margins. Components of the basal membrane zone (bullous pemphigoid antigen) were not detected immunohistologically before keratinocytes were present at the surface of the wound. This finding supports the hypothesis that the substances at the junctional zone are partly of epithelial origin. Transmission electron microscopy showed that the lamina densa was present across the wound hiatus. In addition, the development of desmosomes and hemidesmosomes during wound healing was demonstrated. Scanning electron microscopy did not support the concept of cell movement as a coherent sheet, but rather that of an “ameboid” type of cell movement.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-2307
    Keywords: Human papillomavirus-Heck's disease ; In situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 16 cases of focal epithelial hyperplasia (Heck's disease) were studied for the presence of human papillomavirus DNA by means of nucleic acid hybridization. Hybridization was carried out in situ with biotin-labelled probes of HPV 1, 6, 11, 13, 16, and 18 DNA under stringent and non-stringent conditions. Under non-stringent conditions, 6 of 16 cases (38%) hybridized to a mixture of HPV 1, 6, 11, 16, and 18 DNA. When these probes were applied under stringent conditions, only one case could be shown to be weakly positive for HPV 6/11 DNA. Further stringent hybridizations, which were conducted with a HPV 13 probe on 12 of our 16 cases, revealed a positive result in 9 of 12 cases (75%). The results of our study strongly substantiate the concept that HPV 13 or a closely related HPV type is associated with lesions morphologically presenting as focal epithelial hyperplasia.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 434 (1999), S. 23-28 
    ISSN: 1432-2307
    Keywords: Key words p16 ; Rb ; Uterus ; Endometrium ; MTS1 ; Carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  P16MTS1/CDKN1 and the retinoblastoma protein Rb are both involved in negative regulation of G1/S progression in the mammalian cell cycle. Inactivation of one of these tumour suppressor genes is involved in many malignant tumours, and in some studies a negative correlation of p16 and Rb expression has been found. In order to study this interaction in endometrial carcinogenesis, we investigated 36 endometrial carcinomas, 11 cases of hyperplasia, 23 normal endometrial samples, and two uterine carcinoma cell lines by immunohistochemistry or RT-PCR. Rb was expressed in normal endometrial epithelium, hyperplasia, cell lines, and most carcinomas; negative immunostaining was only detected in 1 of 36 tumours. In contrast, p16 expression was weak in normal endometrium and increased in most cases of hyperplasia, but negative or minimally positive in 74% of the carcinomas and the Hec1B adenocarcinoma cell line, and there was no significant association with Rb immunostaining. Strikingly high p16 expression was found in foci of squamous metaplasia within hyperplastic or carcinomatous tissue. Deletion and mutation analysis of the p16 gene was performed in DNA from microdissected tumour samples and cell lines. No p16 deletion was found, and mutations were detected in only one tumour sample and Skut1B uterine mixed mesodermal tumour cells. Our data indicate that in spite of low or absent p16 expression, genetic alterations of the p16 and Rb tumour suppressor genes are rare in endometrial carcinogenesis.
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  • 16
    ISSN: 1432-2307
    Keywords: Key words: Protein p53 ; Breast cancer ; Immunohistochemistry ; p53 mutation ; Temperature-gradient gel electrophoresis (TGGE)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mutations of the p53 gene appear to be one of the most common abnormalities in human cancer. Although many studies have been published about p53 alterations in breast cancer, data on molecular biological detection of p53 mutations in in situ lesions are still rare, and the implications for breast cancerogenesis are unclear. Tissue samples from 83 patients with different stages of breast cancer and from 13 patients with benign breast lesions were screened for p53 gene mutations by polymerase chain reaction (PCR) followed by temperature-gradient gel electrophoresis (TGGE). p53 protein accumulation was analysed by immunohistochemistry (IHC). Samples were gained from fresh-frozen tissue, scrapings, or paraffin embedded tissue. Additionally, 23 pairs of primary tumours and corresponding lymph nodes were examined. p53 gene aberrations were found in 55.7% of the infiltrating carcinomas, in 31.5% of the ductal carcinomas in situ (DCIS) and in one atypical ductal hyperplasia. A positive correlation was seen with high-grade tumours and with comedo. There was no statistically significant relationship with respect to age, menopausal status, tumour size, hormone receptor status or lymphatic invasion. Concordance between TGGE and IHC was seen in only 63% of the cases analysed. However, with regard to p53 mutation screening by TGGE, a high significance (P = 0.0008) was seen between standard tissue extraction and our scrape preparation technique. Among 8 pairs of primary tumours and their corresponding lymph node metastases, only 3 harbored identical p53 mutations in the same exon, while in 5 cases with mutant p53 in the primaries, no mutation was seen in the lymph node. Our data indicate that p53 mutations are frequent in breast tumours associated with unfavorable prognosis, including high-grade or the comedo histotype. There is evidence that p53 gene alterations occur early in breast cancerogenesis, as mutations were detected not only in in situ carcinomas but also in atypical ductal hyperplasia.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1432-2307
    Keywords: Bowen's disease ; Bowenoid papulosis ; S 100 Protein ; KL 1 Keratin ; HPV-DNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study 55 paraffin embedded samples defined as Bowen's disease or bowenoid papulosis were investigated with antibodies against S 100 protein and keratins (KL 1). S 100-positive cells were quantified and related to defined section area of the epidermal compartment by computer-assisted image analysis. The density of S 100-positive cells was compared with normal skin and was particularly related to growth patterns and keratinization of the different lesions under study. S 100-positive dendritic cells were found to be reduced overall in bowenoid lesions when compared with normal skin. Lesions with high counts of S 100-positive dendritic cells most frequentty showed a solitary growth pattern with highly conserved architecture and differentiation and no tendency to stromal invasion. In contrast, cases with low counts of S 100-positive cells very often showed multifocal development, a high degree of architectural disturbance and dedifferentiation. In this group, stromal invasion (cases of invasive carcinoma associated with Bowen's disease) was seen more often. Interestingly, this latter group of cases also revealed a peculiar keratin pattern. Frequently, the basal cell layer was decorated with KL 1 antibody, which usually recognizes only suprabasaly located keratinocytes. No differences between Bowen's disease and bowenoid papulosis were found in terms of densities of S 100-positive dendritic cells and keratin pattern. In our experience, extragenital Bowen's disease and genital Bowen's disease can not be distinguished on purely morphological grounds or with the immunocytochemical approach presented here. Interestingly, when employing in situ hybridization with HPV 16 probes three of seven samples of genital Bowen's disease harboured HPV 16 DNA, whereas six cases of extragenital disease were negative.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1432-2307
    Keywords: Polymerase chain reaction ; Human papillomavirus ; Cytomegalovirus ; Epstein-Barr virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The use of chelating resin in a simple, rapid and efficient pre-treatment protocol to process formalin-fixed, paraffin-embedded specimens for the polymerase chain reaction (PCR) is described and compared to other pre-treatment techniques. With this modified PCR protocol, a variety of human autopsy and biopsy specimens were investigated for presence of DNA of human papil-lomaviruses, cytomegalovirus or Epstein-Barr virus. These viruses were detected in a productive or non-/low-productive state. Amplimers generated ranged from 88 to 450 base pairs length. Under the specified technical conditions, a considerable range of DNA molecules can be amplified from paraffin-embedded material, some older than 10 years.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 20 (1999), S. 6-8 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Medizingeschichte ; Gynäkopathologie ; Biopsiepathologie ; Key words Medical history ; Gynecopathology ; Biopsy pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Empirical knowledge, daily diagnostic efforts and scientific spirits are the prerequisites of theoretical and practical progress in gynecopathology. The current standards in this field have their root in the continuous interests of gynecologists educated and skilled in pathology. In Germany, however, there is no more the gynecologist, who is in charge for both the clinical and pathological diagnostic business. Also, it is no more a rule for gynecologists to pass through a fellowship in pathology during their specialization. This development leads to more distance between gynecology and pathology, which per se is a potential source of misunderstandings. One of the tasks of this introduction and subsequent articles is to describe controversial areas and to offer ways out of the conflicts. Yet, the master key for avoiding misunderstandings is the close interdisciplinary cooperation in the perioperative management of the patient.
    Notes: Zusammenfassung Erfahrungswissen, Alltagsdisziplin und Forschergeist sind wesentliche Vorausetzungen für erkenntnistheoretische und praktische Fortschritte in der Gynäkopathologie. Das gegenwärtige Niveau in diesem Spezialgebiet wurzelt ganz wesentlich in dem wissenschaftlichen Engagement morphologisch geschulter Frauenärzte. Anstelle der früher häufigen Personalunion morphologischer und klinischer Tätigkeit ist aber heute die interdisziplinäre Zusammenarbeit getreten. Diese kann gar nicht eng genug angelegt sein, wie diese Einleitung und nachfolgende Artikel belegen sollen.
    Type of Medium: Electronic Resource
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 114 (1988), S. 565-574 
    ISSN: 1432-1335
    Keywords: Monoclonal antibodies ; Immunohistochemistry ; Macrophage/monocyte antigen ; Fibrohistiocytic bone tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study fresh frozen tissue samples of benign osseous tumors (five non-osteogenic fibromas, one fibrous dysplasia, one chondromyxoidfibroma), tumors of uncertain biological behaviour (eight cases of histiocytosis X, two giant-cell tumors), and of malignant intraosseous tumors (two malignant fibrous histiocytomas, two malignant histiocytosis, four osteosarcomas, one chondrosarcoma and two Ewing sarcomas) were studied with a panel of monoclonal antibodies reactive with monocyte/macrophages and various types of dendritic cells. In addition, tumors were further defined with a broad spectrum of antibodies against filamentous proteins and lymphocyte differentiation antigens. The specimens were stained with a triple-layer immunoalkaline phosphatase protocol. Tumors stained with these antibodies could be roughly divided into two groups. The first group comprised tumors with one predominant cell population reactive with one particular monoclonal antibody. In this group, cases of histiocytosis X were found to be consistently labelled with CD-1 antibodies. The giantcell tumors showed a very homogeneous staining with certain monocyte/macrophage antibodies (Ki-M8). Nevertheless, even in these tumors, heterogeneity was demonstrated by the occurrence of cells with monocytic differentiation in histiocytosis X and conversely by the occurrence of cells with differentiation antigens of the dendritic cell system in giant-cell tumors. An exception has to be made for the two cases of malignant histocytosis examined. These tumors were selectively labelled with antibodies against monocyte/macrophages (Ki-M8, IOM-1). The second group comprised tumors showing a high degree of heterogeneity demonstrated by the varying amounts of tumor cells reacting with the applied markers of the monocyte/macrophage and dendritic cell systems. In most cases it was difficult to ascribe labelled cells to the tumor cell population as opposed to an “innocent bystander” inflammatory cell population. This distinction was especially difficult in malignant fibrous histiocytomas underlining the current concept that these tumors are of primitive mesenchymal rather than true histiocytic origin.
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