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Biomedical subjects

A H Graf

Publications and source records attributed to A H Graf.

At least 55 records · Page 3Linked to original sources

Smooth muscle differentiation in human myometrium and uterine leiomyoma.

Smooth muscle differentiation has been analysed in human myometrium and leiomyoma by Western blotting with antibodies to smooth muscle specific proteins. No differences in the expression of h-caldesmon, metavinculin, desmin, alpha-smooth muscle actin and calponin were observed. The technique of two-dimensional gel electrophoresis was used, therefore, to further analyse differences between normal smooth muscle cells and their neoplastic counterparts. By comparing the protein patterns of normal myometrium and leiomyoma, it was possible to identify a protein with a molecular weight of approximately 27 kD that is selectively expressed in normal uterine smooth muscle cells. This protein proved to be a low molecular weight variant of calponin, a smooth muscle specific protein of as yet unknown function. Its immediate downregulation in tissue culture of normal myometrium points to a possible role in the process of dedifferentiation.

Adult↗

Primary carcinoma of the fallopian tube--a retrospective analysis of 115 patients. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

Incidence and prognostic factors of primary carcinoma of the Fallopian tube were studied in a retrospective multi-centre analysis of 115 women during the period 1980 to 1990. Data of 28 departments (university as well as general hospitals) were included in the present study which was designed to evaluate the current diagnosis and treatment of carcinoma of the Fallopian tube in Austria, and to compare the results with those from the literature. Stages were classified according to the modified FIGO-system for ovarian cancer; grading followed the criteria of Hu et al. (1950). The mean age of the patients was 62.5 years. Forty-seven (40.9%) tumours were found to be in stage I, 20 (17.4%) in stage II, 34 (29.6%) in stage III, and 14 (12.1%) in stage IV. In 82 patients, the tumour could be completely removed. The surgical method applied in 95 cases was removal of the uterus, the adnexa, and/or the omentum, or lymph nodes. Postoperatively patients underwent adjuvant therapy which was either irradiation (n = 40; 34.8%), or chemotherapy (n = 49; 42.6%); 26 women (22.6%) had no therapy after operation. The 5-year survival rate for all stages was 36.5%. In stages I and II the 5-year survival was 50.8% compared to 13.6% in stages III and IV. FIGO-stage I and II and a residual tumour less than 2 cm in advanced disease had a prognostically favourable impact, which was proven in univariate as well as multivariate analysis.

Adult↗

[Primary fallopian tube cancer--an Austrian multicenter study].

Incidence and prognostic factors of primary carcinomas of the Fallopian tubes were studied in a retrospective multi-centre analysis of 81 women during the period of 1980 to 1990. Data from 13 departments (university as well as general hospitals) were included in the present study which was designed to evaluate the state-of-the-art of diagnosis and treatment of carcinoma of the Fallopian tubes in Austria, and to compare the results with those from the literature. Stages were classified according to the modified FIGO-system for ovarian cancer; grading followed the criteria of Hu, Taylor and Hertig. The mean age of the patients was 62.1 years. Thirty-seven (45.7%) tumours were found to be in stage I, sixteen (19.8%) in stage II, nineteen (23.4%) in stage III, and nine (11.1%) tumours in stage IV. In 66 Patients, the tumour could be radically removed. The surgical method applied in 68 cases was removal of the uterus, the adnexa, and/or the omentum, or lymph nodes. Post-operatively, patients underwent an adjuvant therapy which was either irradiation (n = 32; 39.5%), or chemotherapy (n = 34; 42.0%). Fifteen patients had no therapy after operation. The five-year survival rate for stages I and II was 75% compared to 17% in stages III and IV.

Adult↗

[Does 3D sonography present new perspectives for gynecology and obstetrics?].

3D-sonography opens a new chapter of ultrasound-imaging. The aim of our study was, to summarise our preliminary experiences in the clinical application of this method. One-hundred and fifty patients were investigated with the use of transabdominal transducers. The scanning is performed after targeting the three-dimensional region by the volume box. The three planes are displayed simultaneously on the screen. Analysis can be performed on any possible plane within the stored volume (tomography). Surface imaging and transparent imaging can be calculated and displayed by a work-station. Three-dimensional ultrasound makes complete imaging and documentation of sonographically investigated structures feasible. The possibility of arbitrarily often repeatable systematic analyses without risk for the patient seems to be the more important advantage than statistical simultaneous imaging. Plastic imaging of structures, especially of foetuses, in the surface and transparent modes has been made possible for the first time. Biometry can also be measured in three dimensions (volumetry). Volume documentation provides the possibility of arbitrarily repeatable "real-time" scanning. By this means, any plane can be reanalyzed, remeasured and reassessed. This kind of documentation provides advantages in clinical, scientific, didactic and legal aspects. The first experiences with this new method seem to be promising. Further studies have to be conducted to evaluate the diagnostic significance of 3D-sonography in our field of specialisation.

Congenital Abnormalities↗

Application of silver acetate autometallography and gold-silver staining methods for in situ DNA hybridization.

In situ hybridization using biotinylated DNA probes has become an important tool in histopathology. It is well known that the sensitivity of the methods used to demonstrate viral DNA in formalin-fixed and paraffin-embedded specimen depends strongly on the detection system used. In the present study, an optimized in situ DNA hybridization protocol was combined with four different approaches of gold-silver staining methods. For silver enhancement, the recently described method of silver acetate autometallography, a technique allowing highly efficient development without the necessity of dark room illumination has been used. The most efficient detection method found in our experiments was the use of gold-adsorbed anti-biotin antibodies with subsequent silver enhancement. This staining procedure can be completed in 5 hours including hybridization and is a highly sensitive alternative to peroxidase and alkaline phosphatase detection systems.

Cytomegalovirus↗

Growth-stimulating effect of adrenal androgens on the R3327 Dunning prostatic carcinoma.

Adrenal androgens are discussed as a reason for tumor progression after androgen ablation therapy. Because of the difference in the secretion of androgens by the adrenals of humans and rats, there is no reliable tumor model to study the role of adrenal androgens in tumor progression. Therefore, the main adrenal androgens were administered to rats in order to mimic human endocrine conditions. Application of dehydroepiandrosteron-sulfate (DHEA-S) alone or a mixture of androstendione (A), 11 beta-hydroxyandrostendione (OHA), dehydroepiandrosterone (DHEA), and its sulfate (DHEA-S) to castrated rats caused only a slight increase of prostate and seminal vesicle weight. Contrary to these findings, growth of the R3327 prostatic carcinoma in castrated rats was greatly stimulated by these adrenal androgens up to the level of the intact control. Thus, in spite of androgen ablation, tumor progression could be induced by exogenous adrenal androgens.

Adenocarcinoma↗

Paragangliomas: neuroendocrine features and cytometric DNA distribution patterns. A clinico-pathological study of 22 cases.

Paragangliomas from 22 patients with extraadrenal tumours of this type were studied. Neuroendocrine features were examined using immunohistochemical techniques. Twenty-two antisera raised against neuroendocrine "markers", regulatory peptides, serotonin and intermediate filament proteins were studied in this group and cytometric DNA assessments were made by means of image cytometry. One normal and 5 hyperplastic carotid bodies were used as controls in the DNA cytometric investigations. Clinical and/or histopathological evidence of "malignancy" was present in 5 cases. The tumour cells showed heterogeneity with regard to their expression of different peptides, and the immunohistochemical analyses did not permit differentiation between benign and malignant paragangliomas. An euploid nuclear DNA distribution pattern was found in all controls and in 17 of the tumours; all except 1 were clinico-pathologically benign. An aneuploid DNA pattern was observed in 5 of the cases and some malignant features were present in 4 of these cases. DNA data may give further information apart from that obtained from the histopathological findings which may be of value in predicting the biological behaviour of this tumour type.

Adult↗

Regulatory peptides and general neuroendocrine markers in human nasal mucosa, soft palate and larynx.

Various peptide immunoreactivities in the respiratory system have been reported, indicating complex physiological mechanisms. There is only little information on the upper respiratory system of man. The present study was carried out to demonstrate regulatory peptides in the nasal mucosa, larynx (vocal cords and ventricular folds) and soft palate of man using highly efficient immunocytochemical methods. In addition, some peptide immunoreactivities were measured by use of radioimmunoassay (RIA). Using indirect immunofluorescence and immunogold-silver staining (IGSS) with silver acetate autometallography, a series of peptides could be detected, including vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), galanin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide tyrosine (NPY), C-flanking peptide of NPY (CPON) and somatostatin. In addition, antibodies to protein gene-product (PGP) 9.5, neuron-specific enolase (NSE), S-100, PHE-5 and neurofilament proteins gave positive reactions in tissue sections. Using RIA, CGRP, substance P, and neurokinin A were measured. Our results demonstrate a complex network of regulatory peptide-containing nerve fibers and the possible existence of endocrine cells regulating various functions of the upper respiratory system, which need to be further investigated.

Biomarkers↗

The tumor-inhibiting effect of diethylstilbestrol and its diphosphate on the Nb-H and Nb-R prostatic carcinomas of the rat.

For many years, diethylstilbestrol (DES) and its diphosphate (DESPP; Honvan) have been standard therapies for prostatic carcinoma. The effects of DES, its monophosphate (DESP) and of DESPP on the weights of accessory sex organs of mice and rats, and on the experimental Noble Nb-H and Nb-R prostatic carcinomas of the rat were, therefore, compared. In intact mature mice, all three compounds led to a strong and dose-dependent inhibition of seminal vesicle weights and testosterone levels, whereas only a slight antiandrogenic activity in castrated mice was found. In intact rats, DES, DESP and DESPP strongly inhibited accessory sex organ weights and testosterone levels. In castrated rats, however, no antiandrogenic activity was determinable. The prostate carcinoma-inhibiting effects of DES and DESPP were tested in comparison with castration in the transplantable hormone-sensitive Nb-H and Nb-R prostatic carcinoma in rats. Whereas castration caused only a retardation of tumor growth, DES and DESPP (3 x 0.1 mg/kg and 1.0 mg/kg weekly s.c.) led to an almost complete inhibition, which was significantly (P less than 0.01) better than the effect of castration. As the weights of accessory sex organs were identically reduced by either castration or the estrogens, a direct tumor-inhibiting effect of DES and DESPP in addition to their testosterone-lowering activity is obvious. This was proved in an experiment with castrated rats. The only slightly inhibitory activity of castration was strongly potentiated by concomitant administration of DES. Moreover, histological examinations revealed that Nb-H and Nb-R tumors were much more damaged by treatment with DES or DESPP than after castration. Morphometry of the tumors showed that tumor reduction is associated with a decrease in the ratio of the epithelial to the stromal density, i.e. there was an even more pronounced decrease in epithelial cells than that found by merely measuring tumor area. These studies show that the prostate carcinoma-inhibiting effect of DES and DESPP in the Nb model is superior to the effect of castration and that they act directly on the tumor cells used, even in castrated rats.

Androgen Antagonists↗

Gastrin- and somatostatin-immunoreactive cells of the antral mucosa in patients with duodenal or gastric ulcers. An immunocytochemical study.

Gastrin- and somatostatin-immunoreactive cells in biopsies taken from the prepyloric portion of the antrum from 15 patients with duodenal ulcer, 16 patients with gastric ulcer, and a control group of 19 patients without histopathological alterations of the antral mucosa were studied using peroxidase anti-peroxidase and immunogold-silver staining methods in combination with morphometry. Numerical densities and sizes (immunoreactive areas) of the cells demonstrated were measured and compared between all three groups. Gastrin- and somatostatin-immunoreactive cells were located most frequently in the lower midzone of the gastric crypts. None of the parameters measured showed a correlation with age or sex. The group with duodenal ulcer tended to exhibit gastrin- and somatostatin-cell-hyperplasia whereas the size of both cell types remained unchanged. In comparison with the control group, the numerical density of gastrin-immunoreactive cells was significantly increased in gastric ulcer patients, whereas the numerical density of somatostatin-immunoreactive cells was decreased in this group. Immunoreactive areas of both cell types were significantly increased in patients with gastric ulcer.

Adult↗

[Application of silver acetate autometallography in histopathology: a new detection method for use in immunogold silver staining, lectin histochemistry and in situ hybridization].

Modern histochemical techniques allow the specific detection of tissue constituents in situ. Routinely formalin fixed, paraffin embedded tissues may present problems to the pathologist since destruction of substances can lead to false negative results. Immunogold-silver staining (IGSS) can be a way to overcome some of these problems. A highly efficient method allows silver enhancement to be carried out without the necessity of a dark box (silver acetate autometallography). To test the new modification, antisera to a variety of antigens were used on paraffin and semithin resin sections. The system was also tested for its applicability in multiple immunostaining techniques and for the in situ hybridisation of viral DNA and for demonstration of carbohydrates by lectin histochemistry. It showed a very high detection efficiency with low background staining.

Acetates↗

Site preference of metastatic tumours of the brain.

Amongst 15,000 autopsies performed between 1969 and 1984 in the Department of Pathology of the University Hospital of Innsbruck (Austria) 237 cases (1.6%) with brain metastases were found. The mean age of patients was 61.2 years and 148 patients out of 230 cases with satisfactory records were male (64.3%). Multiple lesions were found in 58%. In absolute figures carcinoma of the lung, followed by malignant melanoma and breast carcinoma were, as in other series, the most frequent primary site for brain metastases. The relative frequency of brain metastases in various anatomical regions of the brain showed that malignant melanoma tends to metastasize to the frontal and temporal lobes, breast carcinoma to the cerebellum and the basal ganglia, large cell carcinoma of the lung to the occipital lobe and squamous cell carcinoma of the lung to the cerebellum. Metastases of small cell carcinoma of the lung were found equally distributed in all regions of the brain. Our study supports the results of several experimental investigations, suggesting the possibility that specific cell surface properties of metastasizing tumour cells and particular properties of the vascular endothelium of the target organs of metastasis are responsible for the location of metastases. The results of this study suggest that there are substantial differences in regard to these properties even within one target organ.

Adult↗