[Measuring cesium 137 concentrations in surgical specimen of gynecologic tumors and breast milk, amniotic fluid and in umbilical cords, 6 years after Chernobyl]. / Messungen der Caesium 137-Konzentrationen in Operationspräparaten gynäkologischer Tumoren sowie in Muttermilch, Fruchtwasser und in Nabelschnüren, 6 Jahre nach Tschernobyl.

In the present study, the cesium 137 content in various human tissues was examined 6 years after the Chernobyl reactor catastrophe. The measurements were performed with a gamma-ray spectrometer by means of a germanium/lithium detector. The median of cesium 137 was 20 mBq/ml in mother's milk, 60 mBq/ml in amniotic fluid, 105 mBq/g in umbilical cords, 51 mBq/g in ovarian tumours, and 140 mBq/g in mammary carcinomas. These values lay far below the permissible limit values of 528 mBq/ml or 528 mBq/g for persons not exposed to radiation. The problems of determining the upper limit were also discussed, and it was ascertained that despite the favorably low values recorded in this study a residual risk to health cannot be absolutely precluded in the light of present-day knowledge.

Immunochemical and ultrastructural studies of an ovarian strumal carcinoid.

An ovarian strumal carcinoid which synthesized peptide hormones, but did not induce the carcinoid syndrome, was analysed histochemically, immunohistochemically and ultrastructurally. Dot-immunobinding assays were performed in order to determine the endocrine gene expression. The amylase resistant colloid was found to be PAS-positive in the follicular portions of the tumour. Carcinoid cells showed Grimelius positive argyophilic granules in the subnuclear position. The Fontana-Masson argentaffin reaction was negative. Immunohistochemistry for adrenocorticotropic hormone (ACTH) revealed strong reactivity in the follicular areas of the carcinoid. The immunoreactivity for somatotropic release inhibiting factor (SRIF) was found positive in the trabecular portion of the carcinoid tumour, thyroglobulin in the follicles. Neuron-specific enolase, protein S-100 A/B, synaptophysin and chromogranin A evoked weak cytoplasmic immunostaining of the tumor cells. Dot-immunobinding assays substantiated these immunohistochemical results, except for the thermolabile protein S-100 A/B. Electron microscopy of tumor cells showed numerous electron-dense cytoplasmic granules, 250 to 350 nm in diameter, both in follicular and trabecular areas of the tumor. Plasma levels of tumor-associated ACTH, SRIF and thyroglobulin were measured by radioimmunoassay and were found to be within the normal range.

Biotin and phosphorus-isotopic labelled DNA/RNA probes for the detection of human papilloma virus sequences.

In this study, the diagnostic accuracy and practicability of different hybridization techniques for the detection of human papilloma virus (HPV) DNA were tested. Cervical cell scrapes (n = 67) were analysed for HPV-DNAs 6/11 and 16, in order to compare a commercially available in situ DNA hybridization-assay with the conventional Southern-blot analysis. The in situ DNA hybridization-assay gave a sensitivity of 81.5%, a specificity of 97.5% and a diagnostic efficiency of 91.0% for HPV-DNAs 6/11. Using the same assay, we observed a sensitivity of 100%, a specificity of 96.3% and a diagnostic efficiency of 97.0% for HPV-DNA 16. The practicability of dot-blot DNA hybridization technique was tested on 176 cervical cell scrapes, in order to determine the prevalence rate of HPV-genotypes 6/11, 16/18 and 31/33/35. In the random control group (n = 106), 1.9% of the cases were HPV-DNA positive. In the cancer prevention group (n = 70), patients with reactive and reparative cell changes showed a HPV-DNA positivity of 55.0%, with mild (slight) dysplasia/CIN 1 of 73.7%, and with moderate to severe dysplasia/CIN 2 to CIN 3, including the carcinoma in situ/CIN 3 of 80.0%. Patients with squamous cell carcinoma of the cervix uteri gave HPV-DNA positive results in 96.2% of the cases. The suitability of in situ DNA hybridization for morphological studies was tested on tissue biopsies (n = 68). The HPV-DNAs 6/11 were found predominantly to 72.7% of the examined condylomas. The HPV-DNA positive cervices increased with the severity of the cytological dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Latent cervical virus infection as a possible cause of early abortion]. / Latente zervikale Virusinfektion als mögliche Ursache des Frühaborts.

Cervical smears of 50 women who had an abortion were examined by dot-blot hybridization for human papillomavirus (HPV), herpes simplex virus (HSV) types 1 and 2, and cytomegalovirus (CMV) DNA. HPV DNA type 16 or 18 positivity was shown in 17.6% of the cases; in the aborted material, however, it amounted to 30.8%. IgM-positive titres were present in a few cases. In cervical smears of intact pregnancies, positivity for HPV DNA types 6 and 11 was detected in 9.5% and for the HSV DNA types 1 and 2 and CMV DNA in 48.0% of the cases. In this group of patients mostly positive IgM and IgG titers were present.

[The significance of human papillomavirus infection in cervix cancer and its preliminary stages (including other HPV-induced genital lesions)]. / Die Bedeutung humaner Papillomavirus-Infektionen beim Zervixkarzinom und seiner Vorstufen (einschliesslich anderer HPV-bedingter genitaler Läsionen).

Southern blot analysis, DNA dot blot technique and in situ hybridization were used to examine cells and tissues from lesions of the female genital tracts for infections of human papillomaviruses (HPV) of the types 6/11, 16/18 as well as 31/33 and 35. As the degree of dysplasia increased the proportion of HPV-positive results increased significantly, especially for the HPV types 16/18; there was a decrease in the HPV DNA 6/11-positive cases. In the first follow-up examinations of cervical smears of the Pap. IIID type after 6 months there was a persistence of 84.2%. Of these, 57.8% were HPV 16/18-positive, and 18.2% could be classified as belonging to Pap. group IV. The importance of HPV typing lies in the definitions of the pathogens, risk groups, therapeutic measures and their controls.

Papanicolaou test and enzyme-linked in-situ hybridization. A combined diagnostic system for papilloma virus infections with high prognostic value.

A combined diagnostic system for human papilloma virus (HPV) infections comprising the Papanicolaou test and in-situ hybridization assay was evaluated. Cervical smears from 259 women obtained with a "Cytobrush" were screened. Human papilloma virus genotypes 6/11, 16/18, 31/35/51 were detected by biotin in-situ hybridization in conjunction with a streptavidin-alkaline phosphatase detection complex. The diagnostic sensitivity of this assay was tested by human papilloma virus-DNA-positive human cervical carcinoma cell lines. According to the cytological (Bethesda system) and colposcopical criteria a random control group (n = 80) and prevention (n = 179) were chosen. Compared with Papanicolaou tests the frequency of human papilloma virus-DNA-positive cervices rose with the severity of cell abnormalities. The detection rate of human papilloma viruses-16/18 and human papilloma viruses-31/35/51 and of concomitant infections with human papilloma viruses-6/11 and human papilloma viruses-16/18 and/or human papilloma viruses-31/35/51 increased with the severity of cell dysplasia, whereas the rate of human papilloma virus-6/11 DNAs decreased. The incidence of oncogenic human papilloma virus types 16/18 and 31/35/51 rose with the age of the patients. A follow-up study by Papanicolaou tests of patients with mild (slight) and moderate dysplasias six months after human papilloma virus-DNA-hybridization indicates that human papilloma virus-16/18 DNA-positive lesions are more likely to persist or to progress than human papilloma virus-6/11 DNA-positive cell changes. Human papilloma virus-31/35/51 DNA-positive cell smears exhibited persistent behaviour. Our findings demonstrate that the Papanicolaou test combined with in-situ hybridization is suitable for early diagnosis and prevention of intraepithelial neoplasias and carcinomas of the uterine cervix.

Reliability of in-situ hybridization of smears and biopsies for papilloma virus genotyping of the uterine cervix.

Two sampling methods, biopsy and cell smear, were investigated for their reliability in the biotin in-situ hybridization test for human papilloma virus deoxyribonucleic acid (HPV-DNA)-6/11 and 16/18. Cervical smears and biopsies were obtained simultaneously from 81 women with cervical lesions. The sensitivity of the in-situ hybridization was tested on human cervical carcinoma cell lines. As a reference method, HPV-DNA was probed in biopsies using a Southern blot with 32P-labelled DNA probes. This reference method detected HPV-DNA in 45% of the reactive and reparative cell changes, in 75.9% of intraepithelial neoplasias, and in 83.3% of squamous cell carcinomas of the cervix. Of the examined cervices 61.7% were HPV-DNA-positive. As tested by in-situ hybridization, 56.8% of the biopsies were HPV-DNA-positive. Three biopsies were HPV-DNA-negative by the in-situ hybridization but positive by the Southern blot. One biopsy was HPV-DNA-6/11 positive by the in-situ hybridization but negative in the Southern blot. As tested by in-situ hybridization, 55.6% of the cervical smears were HPV-DNA-positive. Five smears were HPV-DNA-positive by the in-situ hybridization but negative by the reference method, thus demonstrating the dependence of the HPV positive rate on the sampling method. Four cell smears were negative by the in-situ hybridization but positive by the reference method, which shows that the biotin in-situ hybridization is less sensitive. The reference method confirmed the HPV-DNA-positivity of in-situ hybridization for 97.8% of biopsies, and for 91.8% of cell smears.(ABSTRACT TRUNCATED AT 250 WORDS)

[Human papillomavirus (HPV) DNA infections of the uterine cervix]. / Humane Papillomavirus(HPV)-DNA-Infektionen an der Cervix uteri.

411 women who had dysplasia, selected from an ambulatory group as well as 240 women from a random control group were examined, by using cervical smears, which were initially diagnosed as human papilloma viruses-DNA (HPV-DNA) of the type 6/11, or 16/18, or 31/33/35. This was achieved by the in-situ nucleic acid hybridisation technique. The results of the HPV-DNA typing were tabulated with the cytological diagnosis (Munich Papanicolaou (Pap.) group-classification). The control group corresponding to Pap.Gr. I, and was HPV-DNA positive in 6 (2.5%) of the 240 cases. The group of 180 patients with a Pap.Gr. II showed a HPV-DNA positive result for 75 cases (41.7%); 57 of 99 cases (57.6%) occurred in Pap.Gr. IIID; 42 of 54 cases 77.8% (L) were found in Pap.Gr. IV (a/b), and 72 of 78 cases (92.3%) appeared in Pap.Gr. V. The HPV-DNA mixed infections became evident as the cellular dysplasia increased. The results of the HPV-DNA positive diagnosis clearly indicate a close correlation with the Pap.Gr.-classification. The HPV-DNA type 16/18 was most frequent in cervical carcinomas (Pap.Gr. V). The cyto-histological control of the 57 HPV-DNA positive cases of the untreated Pap.Gr. IIID showed a regression in 31.6% of the 18 cases after a period of 3 to 6 months (post HPV-DNA typing). These were histologically normal. In 33 cases (57.9%), there was a persisting Pap.Gr. IIID (CIN I/II) and in 6 cases (10.5%) a progredient correlation in Pap.Gr. IV a/b. The Pap. group IV (a/b) was histologically a CIN grade III.

[C-erbB-2 oncogene amplification in breast cancer in correlation to steroid and epidermal growth factor receptor]. / C-erbB-2-Onkogen-Amplifikation bei Mammakarzinom in Korrelation zum Steroid- und epidermalen Wachstumsfaktor-Rezeptor.

The amplification grade of oncogene c-erbB-2 was examined by the polymerase-chain-reaction-method in DNA's of 56 primary mammary carcinomas. 26 (46.4%) of these showed the amplified oncogene c-erbB-2. In the strongly amplified cases, the expression of the c-erbB-2 oncoprotein was verifiable immunohistochemically. Between the progesterone receptor status (PR) and the amplified c-erbB-2 oncogene there was a statistically proven dependency. No correlation was observed between the amplified c-erbB-2 oncogene and the epidermal growth-factor receptor (EGFR).

Comparative analysis of two-dimensional protein patterns in malignant and normal human breast tissue.

Malignant and normal human breast tissue were compared by evaluating two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) maps of frozen tissue samples. Image analyzing software was used to scan and process 34 gels. Eight (8/34) of these gels (4 malignant breast tumor samples, 4 normal tissue samples) were selected on the basis of gel and image quality to build a database to identify and measure the expression of a previously unidentified proteome. Growth factor receptor proteins (GFRs), including ERBB2 (HER2) and ERBB3 (HER3), were expressed in the malignant tissue samples. Growth factor receptor proteins were not expressed in the normal tissue. Also, expression of PS2-protein (pS2) was detected in neither malignant nor normal tissue. In benign breast samples a higher intensity of protein expression could be observed for maspin, desmoglein 3 and keratin 8 than in malignant samples. Other proteins expressed in malignant breast tissue include mitogen-activated protein kinase 3 (MK03), heat shock protein 27 kDa (HS27), growth factor receptor-bound protein (GRB2), cathepsin D, G1/S specific cyclin E1 (CGEI), glucose transporter type 5 (GTR5), and a number of as yet unidentified proteins.