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Biomedical subjects

M Dietel

Publications and source records attributed to M Dietel.

At least 199 records · Page 11Linked to original sources

Blood group substance, CEA, and lectins in ovarian tumors.

The presence of the blood group substances A, B, AB, Lea, and Leb and of CEA was demonstrated by peroxidase-antiperoxidase or fluorescein immunohistochemistry in histological sections of normal ovarian tissue and ovarian tumors of varying differentiation. In surface cells of normal ovaries and of benign tumors, blood group substances (BGS) were found in patterns corresponding to the serum blood group type of the patients. BGS were localized exclusively at the apical border of normal cells. CEA was almost always absent. In borderline lesions the presence of BGS was reduced by approximately 13%. The polar differentiation was often lost, and the BGS were unevenly distributed in the cytoplasm. The percentage of CEA-specific staining increased from less than 5% in normal tissue and benign tumors to 15% in mucinous and 10% in serous borderline tumors. Malignant tumors contained altered distribution patterns of BGS and CEA. In contrast to normal ovarian epithelia, BGS positivity was diminished distinctly; the decrease was particularly evident for Leb presence by reduction from 75 to 10%. CEA was observed in nearly 50% of the carcinomas (more often in mucinous than in serous carcinomas). Our study revealed that expression of blood group antigens was related to benign lesions, whereas its loss was associated with a greater malignant potential. Inverse correlations were found for CEA. Thus, immunohistological determination of these marker substances may be applied to tumor prognosis.

Blood Group Antigens↗

[Changes in the metabolic parameters in patients with acute myocardial infarct in the course of the rehabilitation phase II].

In a prospective study 32 patients with condition after acute myocardial infarction in the rehabilitation phase II were observed concerning the metabolic parameters, beta-lipoproteins, cholesterol, triglycerides, glucose, uric acid and lactate. At the beginning and at the end of the sports therapy the metabolic parameters were tested in rest as well as after exertion. The investigation led to the following results: 1. Increase of the physical efficiency from 134.0 to 142.0 Watt (non-significant); 2. the size of the biochemical parameters (beta-lipoproteins, cholesterol, uric acid, glucose) remained unchanged in the process of rehabilitation. 3. During the exertions themselves (hour of sports therapy, bicycle ergometer) in each case a non-significant increase of the beta-lipoproteins, the cholesterol and the values of uric acid appeared.

Adult↗

Effectiveness of antineoplastic drugs on the proliferation of human mammary and ovarian carcinoma cells in monolayer culture.

Procedures for the in vitro determination of the drug-induced inhibition of mammary and ovarian carcinoma cell growth were established. In monolayer cultures derived from advanced tumors, separation of epithelial carcinoma cells from concomitant cells of fibroblast-like or mesothelial appearance was achieved by differential trypsinization. The carcinoma cell character of the stock cultures was verified by chromosome analyses showing a high degree of aneuploidy for the epitheloid cell lines and euploidy for cells of apparently mesenchymal origin. When cultured carcinoma cells were injected in nu/nu mice, the tissue and cell cultures obtained from the heterotransplantation tumors closely resembled the original tumors and cell cultures in morphology, karyotype, and expression of tumor markers. The action of carcinostatic drugs in the logarithmic phase of the carcinoma cell proliferation was tested by kinetics experiments in multiple experimental cultures. In cell proliferation assays based on cell counts the 50% inhibition dose (ID50) of the drug effects was determined from the dose-response curves. Comparison of the ID50s revealed highly differential effectiveness of the drugs examined. The inhibitory effects were reproducible, rendering the procedures used suitable for testing the chemosensitivity of newly explanted gynecological carcinoma cells by proliferation assays.

Adenocarcinoma↗

[Borderline tumors of the ovary. New aspects on morphologic prognosis determination].

Epithelial tumours of the ovary with a tumour status between benign and malignant are classified as borderline tumours (BOT). They are particularly frequent in women between 30 and 40 years of age, emphasising the need for effecting a therapy directed at preserving fertility. To keep the risk of this therapy at a minimum it is imperative to effect accurate determination of the prognosis on the basis of an examination of the histological preparation. Conventional histology is insufficient for this purpose, thus requiring the use of additional morphological methods. In the present study the DNA of the cell nucleus was determined via quantitative cytophotometry and also via several tumour or differentiating markers by immunohistology, in healthy ovaries, 10 benign and 20 malignant ovarian tumours and in 20 borderline tumours (BOT). The DNA histograms of the tumours classified histologically as BOT, yielded distribution patterns pointing towards a benign, proliferative or malignant potency of the tumours without a correlation to conventional histology being present in each case. Immunohistological identification of the carcinoembryonal antigen (CEA) and of the blood group substances (A, B, Lewis, Lewis) produced characteristic distribution patterns which correlated with the tendency to proliferation in DNA cytophotometry. To achieve relevant determination of prognosis of BOT in individual cases, conventional histology should be complemented by additional examinations using DNA cytophotometry and immunhistology as diagnostic tools.

ABO Blood-Group System↗

[Localization diagnosis of enlarged parathyroid glands: 201Tl-99mTc-subtraction scintigraphy compared with 5-MHz-sonography].

Fifty patients clinically suspected of having primary hyperparathyroidism were examined by scintigraphy (201Tl-99mTc subtraction) and sonography (5 MHz). In 28 cases, the results of subtraction scintigraphy, and in 26 cases, the results of sonography were checked by operation. In 25 patients there was a solitary parathyroid adenoma and in two, primary hyperplasia. In one patient all four parathyroid glands were normal. Subtraction scintigraphy had a sensitivity of 90% and a specificity of 98%, while sonography had a sensitivity of 82% and a specificity of 95%. The combination of 201Tl-99mTc subtraction scintigraphy as a functional investigation and sonography as a structural imaging method produced a sensitivity of 96% and is therefore superior to all other methods of localisation for normally situated glands. Diagnostic certainty is reduced by the presence of a nodular thyroid.

Humans↗

[Morphology and growth behavior of ovarian tumors. Studies using DNA cytophotometry, immunohistology and tissue culture].

Antigens A, B, Lea, Leb, CA 12-5, CA 19-9 and CEA were prepared immunohistologically, a DNA-cytophotometry was carried out and the value of a new in vitro proliferation assay to test cytostatic drugs investigated. Material was as follows: 20 normal ovaries and 105 ovarian tumors. Blood group antigens were expressed at a high percentage from well-differentiated epithelial cells, CEA in 50% and CA 12-5 in 70% of the ovarian carcinoma. Predictions about the dignity of borderline tumors can be made with DNA-cytophotometry. The efficacy of 6 different cytostatic agents was investigated in a new in vitro proliferation assay.

Antigens, Neoplasm↗

[Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma. Experimental animal studies with 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125].

The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. The transplanted tumors corresponded to the human cancers concerning histology, grading, immunohistochemistry and secretion of tumor-associated antigens. 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. These antigens are found in the serum of more than 90% of patients with pancreatic carcinoma at the time of first diagnosis. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden, as shown by experiments in 8 mice bearing 4 different human pancreatic carcinomas, 3 with positive and 1 with negative affinity to CA 19-9: the tumor retentions and the effective half-lives of 131I-anti-CA 19-9 were measured after intratumoral (100 microCi/mg tumor) or intravenous (30 and 190 microCi/g body weight) application.

Animals↗

Alteration of steroid hormone sensitivity during the cultivation of human mammary carcinoma cells.

During early cultivation steps of the newly derived and karyotyped human mammary carcinoma line EFM-19, the cells developed faster growth rates and became increasingly less responsive to the presence of serum in the culture medium. No drastic alterations of the morphology and of the karyotype were observed, and carcinoembryogenic antigen remained expressed during the course of the cultivation. In experimental incubations at various time intervals after the explantation, the cell proliferation was analyzed for dose-dependent effects of estradiol, cortisol, progesterone, and testosterone. After 16 wk of cultivation of the stock culture in the presence of estradiol, the cells had acquired a distinct sensitivity to estradiol resulting in permanent growth enhancement. The withdrawal of cortisol from the medium of the stock culture subsequently provoked the loss of the initially noted stimulation of the proliferation by cortisol. The stimulatory effect of progesterone on the proliferation was reversed to inhibition when the stock culture was deprived of cortisol in the growth medium. The results indicate that the choice of steroid hormones in the stock culture medium was determining the quality of the cellular growth responses.

Blood↗

In vitro growth promotion of human mammary carcinoma cells by steroid hormones, tamoxifen, and prolactin.

Individually different growth responses of 10 cell lines newly derived from metastasizing mammary carcinomas were determined by cell counts in experimental incubations with the steroid hormones 17 beta-estradiol, progesterone, testosterone, hydrocortisone (cortisol), the antiestrogenic compound tamoxifen, or prolactin. Of 7 cell lines derived from ductal carcinomas, 5 were stimulated by prolactin. The growth of 4 of 7 cell lines established from the tumors of postmenopausal or ovariectomized patients was enhanced by doses of testosterone, which are in the range of the physiologic serum level. The proliferation of 5 cell lines was promoted by hydrocortisone in the physiologic concentration of 100 nM, supporting the notion that concentrations of testosterone or hydrocortisone normally present in body fluids may facilitate the in vivo growth of breast cancer. The in vitro growth of cells derived from tumors after relapse under treatment with medroxyprogesterone acetate or tamoxifen was markedly enhanced by progesterone or tamoxifen (CAS: 10540-29-1) in concentrations corresponding to therapeutical serum levels and in accordance with in vivo resistance to the endocrine therapy applied before cell sampling. The results of this suggest the occurrence of positive endocrine selection mechanisms operating in vivo on human mammary tumor cell populations.

Adult↗

Differential calcium response of normal and adenomatous parathyroid glands.

In vitro parathyroid hormone secretion of normal (n = 10) and adenomatous (n = 20) human parathyroid glands was compared in response to different calcium (Ca++) concentrations. The glands, prepared for tissue culture immediately after surgical removal, were incubated under identical conditions for 6 h. The medium was changed hourly and analyzed for PTH and cAMP using radioimmunoassay. During the first 2 h of the experiment, the Ca++ concentrations of all preparations was kept constant at 1.2 mM equivalent to the normal Ca++ level of the intercellular space. The PTH level of the 2nd h was defined as reference value corresponding to 100%. After the 2nd h of incubation the Ca++ concentration in the medium was shifted either to low (0.9 or 0.6 mM) or to high (1.9 or 2.6 mM) values. In low Ca++ concentrations (0.6 mM) the normal parathyroid glands responded by stimulation of the PTH release up to 310% in relation to the reference value, whereas the adenomas enhanced the PTH release to 160% only. The incubations in 0.9 mM Ca++ resulted in a slightly lower degree of stimulation. During the incubation in high Ca++ the PTH secretion was reduced to 28% by normal glands and to 52% by adenomatous parathyroid glands. Movements of cAMP measurements paralleled PTH values. The study provides evidence for an abnormally low responsiveness of parathyroid adenomas to Ca++ when compared with normal glands. The reduction in Ca++ responsiveness of adenomatous cells appears to have a fundamental role in primary hyperparathyroidism since the tumour cells may obviously recognize normal Ca++ levels as 'hypocalcaemic' and react by a stimulated PTH secretion.

Adenoma↗

Immunohistochemistry in detection of paraneoplastic secretion of calcium regulating hormones.

29 non-endocrine tumors with clinical suspicion of paraneoplastic hypercalcemia were examined using immunohistochemistry specific for PTH and CT. In 19 of these cases intracellular immunoprecipitates have been demonstrable thus showing the paraneoplastic production of peptide hormones (18 PTH, 1 CT). Four of these tumors have been tested in tissue culture for in vitro production of endocrine active substances. In all cases the incubation medium yielded a positive reaction for PTH. The use of immunocytochemistry in the differential diagnosis of hypercalcemia in tumor patients is discussed.

Calcitonin↗

Cell lines derived from human ovarian carcinomas: growth stimulation by gonadotropic and steroid hormones.

Carcinoma cell lines established from 5 patients with advanced tumors of ovarian location were characterized by karyotypes and growth properties in serum-free medium. In early passages of the cultivation, the growth of cell lines derived from tumors of fairly differentiated histology was stimulated by human follicle-stimulating hormone or human chorionic gonadotropin-human luteinizing hormone. Cells obtained from poorly differentiated carcinomas were unresponsive to gonadotropins. The proliferation of cell lines derived from a malignant clear cell carcinoma and from the ovarian metastasis of an advanced mammary carcinoma was enhanced by cortisol. The results imply that hormonal factors in concentrations physiologically occurring in human serum may support the in vivo growth of ovarian tumors.

Carcinoma↗

[Functional morphology and pathology of the parathyroid glands. Secretion study using tissue culture, electron microscopy, ultrahistochemistry, immunohistochemistry, morphometry and radioimmunoassay].

The subject of this volume provides an overview on current investigational trends in parathyroid research comprising morphology, function, and regulation of function. After describing calcium homoeostasis and disorders induced by parathyroid hypo- or hyperfunction, problems associated with surgical pathology and morphological diagnostics of parathyroid tissue from hyperparathyroid patients and of tumors with paraneoplastic PTH secretion are discussed. Experimental investigations by the author using tissue culture techniques have revealed details of structure, regulation, and secretion of PTH in human and porcine parathyroid glands drawing special attention to the secretory and morphological differences between normal and adenomatous parathyroid tissues. The combined application of methods available in morphology (electron microscopy, immunohistochemistry, ultrahistochemistry, morphometry) and biochemistry (radioimmunoassay, gel-filtration) allows the direct correlation of structure and function in the organ culture system, resulting in a functional morphology and pathology of parathyroid glands. Clinical pathology of primary hyperparathyroidism. The quantitative distribution of 220 operatively obtained parathyroid tumors consisting of 90% adenomas, 8.6% hyperplasias, and 1.4% carcinomas is in agreement with published data of the literature. The intraoperative discrimination between parathyroid and non-parathyroid tissue, necessary for successful search, is a prerequisite for the adequate therapy. A summary of macroscopical criteria will be helpful in improving the intraoparative first-look diagnostics. Problems arising with rapid intraoperative frozen section diagnostics and histological discrimination between adenoma, hyperplasia, and carcinoma are described. Functional morphology and pathomorphology of the parathyroid glands Cellular distribution of PTH and calcium. The chief cells of normal parathyroid glands often cannot be distinguished from those of adenomas if only conventional light- or electron microscopy are applied. However, by using immuno- and ultrahistochemistry evidence was established that adenomatous chief cells contain less PTH than normal chief cells, and that tumor cells are in an activated state. The intracellular calcium content of tumor cells was distinctly lower than in normal parathyroid chief cells, although in primary hyperparathyroidism the extracellular calcium concentration is elevated. The increased amounts of extracellular calcium finds a correlation in the accumulation of calcium deposits in the intercellular space and at the plasmalemma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗