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Biomedical subjects

M Dietel

Publications and source records attributed to M Dietel.

At least 217 records · Page 12Linked to original sources

Paget's disease of the vulva with underlying apocrine adenocarcinoma and local lymph node invasion.

A case of Paget's disease of the vulva with an underlying apocrine adenocarcinoma and local lymph node invasion is reported in a female aged 70. Subjective symptoms of pruritus, burning and pain were associated with typical, but unspecific clinical findings of an erythematous, indistinctly limited, weeping lesion of palm-size with small superficial erosions. Near the right labium majus a solid measuring 2.5 X 1.5 cm in diameter was palpable. The diagnosis was established by microscopic examination of biopsy material, showing intraepidermally the typical Paget's disease with a subjacent, highly differentiated apocrine adenocarcinoma of the sweat glands combined with inguinal lymph node invasion. Other epidermal malignancies were excluded by histochemical reactions. For therapy, telecobalt irradiation combined with high energy electron was applied.

Adenocarcinoma↗

Correlation of electron microscopic and secretory response of human parathyroid adenomas with different calcium concentrations in organ culture.

Twelve parathyroid chief cell adenomas from patients with primary hyperparathyroidism were incubated in a tissue culture system in the presence of different calcium concentrations and for various time periods. The endocrine response of the tissue was examined electron microscopically and radioimmunologically. After incubation in a medium of low calcium concentration the parathyroid adenomas showed ultrastructural signs of stimulation with proliferation of the hormone-synthesizing organelles. The development of the ultrastructural response could first be observed after four hours and increased up to several days. Radioimmunologically, an increase of the hormone secretion could be demonstrated. Converse results were obtained after incubation of the tumor tissue under suppressive culture conditions. To check for de-novo synthesis of the hormone released the tissue was incubated in a 75Se-methionine-containing medium. This resulted in radioactivity of the secreted parathyroid hormone, indicating de novo synthesis in our culture system. The biological potency of the released hormone was demonstrated by comparison of the PTH out of the medium with the international human MRC standard using two different radioassays.

Adenoma↗

The effect of calcium and dibutryl-cAMP on the secretion of parathyroid hormone by human parathyroid adenomas in organ culture.

The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3',5'-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.

Adenoma↗

The effect of 1,25-dihydroxycholecalciferol on the parathyroid hormone secretion of porcine parathyroid glands and human parathyroid adenomas in vitro.

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) on parathyroid hormone secretion by porcine parathyroid glands and human parathyroid adenoma tissue was investigated by in vitro incubation. The addition of 100 nmoles 1,25-(OH)2-D3 to the medium inhibited significantly the release of immunoreactive parathyroid hormone by 63--65%. This suppression was reversible when 1,25-(OH)2-D3 was removed again. The inhibition of parathyroid hormone release observed in human parathyroid adenoma tissue was similar to that in normal porcine parathyroid glands. This indicates that adenoma tissue is sensitive to regulatory influences. As well as calcium, 1,25-(OH)2-D3 may act as another feedback inhibitor of parathyroid hormone secretion.

Adenoma↗

Selection of a high activity ribozyme against cytostatic drug resistance-associated glypican-3 using an in vitro assay containing total tumor RNA.

We tested 11 hammerhead ribozymes for their ability to bind and cleave RNA transcripts of the cytostatic drug resistance-associated glypican-3-encoding gene (GPC3, MXR7, OCI-5). To select the optimum target sequence, the activity of each hammerhead ribozyme was tested in a short in vitro assay using truncated RNA substrates without time-consuming cloning procedures. Glypican-3-derived RNA was cleaved effectively by 3 of 11 hammerhead ribozymes. One of these, the hammerhead ribozyme Rz967, recognized the GUC sequence at nucleotides +965 to +967 of the open reading frame of the glypican-3-encoding mRNA. Rz967 cleaved in vitro-transcribed fragments derived from glypican-3 mRNA (nucleotides +803 to +1036) most efficiently. Cleavage efficiency was confirmed by a rapid in vitro assay using full-length total tumor cell RNA. We were able to demonstrate that this new in vitro assay is suitable for the selection of hammerhead ribozymes that have the capability to cleave glypican-3-encoding mRNA in human tumors.

Base Sequence↗

[Organization of the Pediatric Tumor Cell Bank of the Society of Pediatric Oncology and Hematology (GPOH)].

Characterized cell lines are absolutely necessary in applied research of cell biology and medicine. For the completion of diagnosis and therapy especially in pediatric oncology we are establishing a Cell Bank for Pediatric Tumors. The Cell Bank for Pediatric Tumors collects tissue samples of different types of solid malignant tumors from children and young adults. The specimens are transferred to in vitro culture (guidelines of the American Type Culture Collection-ATCC), the resulting cells are characterized to assure accordance with the histogenesis of the original tumor and stored in liquid nitrogen. The cell cultures are characterized morphologically (phase contrast microscopy) and immunocytochemically (ABC-method). To prove the malignancy of cells in primary culture the amount of hypertetraploid cells was determined (DNA-Scanning-Cytophotometry). Cell lines are checked to find out whether they develop tumors in nude mice followed by an analysis of the karyotype. Additional investigations (e.g. in vitro test of cytostatic drug resistance) are carried out on request by the sender. Part of the tumor tissue which is used to start the cell culture is in parallel diagnosed histopathologically at the Children's Tumor Register, Kiel and/or at the Charité. By the end of the year 1995 the Cell Bank for Pediatric Tumors had received 183 different specimens including 123 solid tumors (e.g. 24 neuroblastomas, 18 osteosarcomas, 12 Wilms' tumors, 13 rhabdomyosarcomas), 44 tissue specimens without any malignant cells, 8 probes without vital cells and 8 leukemias and lymphomas. We were able to establish primary cell cultures of 50% of the sterile tumor tissue probes, to cultivate them for a minimum of 5-10 passages, to characterize and freeze them. Six out of these tumor cell lines were already cultivated for one year and are available to the scientific community.

Adolescent↗

Thermosensitivity of multidrug-resistant human gastric and pancreatic carcinoma cells.

Often, tumour cells acquire drug resistance phenotypes, which include the classical multidrug resistance (MDR) phenomenon accompanied by the synthesis of the P-glycoprotein (Pgp) and atypical MDR phenotypes mediated by different, in part unknown, mechanisms. To investigate the susceptibility of tumour cells exhibiting different kinds of MDR to treatment with heat, the hyperthermic survival of established human gastric and pancreatic carcinoma cell lines were studied and sublines exhibiting a classical and an atypical MDR phenotype were derived, respectively. Arrhenius analysis of this panel of gastrointestinal tumour cells revealed that both the classical and the atypical MDR variants exhibited no breaking points (T*) in contrast to the parent tumour cells. The activation enthalpies E(A) were about 40% lower at T > T* in comparison to the E(A) at lower temperatures. Classical MDR variants of both gastrointestinal tumour cell types exhibited a similar E(A) value, whereas the E(A) of atypical MDR gastric carcinoma cells was 1.6-fold higher than the E(A) of corresponding pancreatic carcinoma cells. In comparison to the parent lines, the drug resistant variants exhibited a 2.1-fold (gastric carcinoma, classical MDR), 2.7-fold (gastric carcinoma, atypical MDR) and 1.4-fold (pancreatic carcinoma, classical MDR) increase of activation enthalpies and a nearby unchanged E(A) in pancreatic carcinoma cells exhibiting an atypical MDR.

Antineoplastic Agents↗

Unfavorable prognostic value of CD24 expression in sections from primary and relapsed ovarian cancer tissue.

Expression of CD24 represents a poorly recognized, unfavorable prognostic factor. Expression of the protein is supposed to facilitate extravasation of tumor cells. Our study aimed at examination of prognostic significance of CD24 estimation in samples obtained from primary surgeries (PS) and secondary cytoreductions (SCR) (after chemotherapy) in ovarian cancer patients. The analyses were performed on sections originating from 73 tumor samples. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies against CD24. Kaplan-Meier's analysis showed that a significantly shorter overall survival time and progression-free time was demonstrated to characterize cases with cytoplasmic membranous expression of CD24 (CD24c-m) (P < 0.001). The calculations performed demonstrated also a significantly higher proportion of CD24c-m positive cases in sections from SCR as compared to that from PS (P= 0.04) and in cases of progressive disease as compared to complete response at PS and SCR (P= 0.002 and P= 0.05, respectively). Summing up, in this study, we have demonstrated a negative prognostic significance of a cytoplasmic membranous expression of CD24 in cases of ovarian cancer.

Antibodies, Monoclonal↗

Expression of aminopeptidase N/CD13 in human ovarian cancers.

Aminopeptidase N/CD13 (EC 3.4.11.2) is suggested to play a role in cancer cells invasion, and its activity can be inhibited using specific inhibitors. CD13 inhibitors evoke apoptosis of CD13-positive cancer cells. However, expression of CD13 has not been described in specimens obtained from ovarian carcinomas. Thus, in the present study, the expression of CD13 and its significance was examined in samples of ovarian cancers. The analyses were performed on sections originating from 73 tumor samples (43 from primary laparotomies [PL] and 30 from secondary cytoreductions [SCRs]). Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies against CD13. The analysis demonstrated no relationships between the expression of CD13 on one hand and clinical variables and pathologic variables of the patients on the other hand. Expression of CD13 was demonstrated to be significantly more pronounced in samples obtained in PLs as compared to samples from SCRs (P < 0.001). Thus, the data indicate that a potential treatment of ovarian carcinoma with CD13 inhibitors should be performed before chemotherapy or in parallel to first-lapse chemotherapy.

Aged↗

Fetal autopsy: the most important contribution of pathology in a center for perinatal medicine.

OBJECTIVE: The aim of the current paper is to analyze the significant changes in fetal autopsy made by pathologists in a center for perinatal medicine in response to the recent rapid developments in prenatal medicine. METHODS: We use our technical equipment (interdisciplinary databank, Intranet, fine instruments, imaging techniques) for prenatal diagnostics and fetal pathology in the Center for Perinatal Medicine at the Charité University Medical Center in Berlin, Germany. RESULTS: Our technical setup has made it possible for us to plan autopsies in such a way that rare malformations in special cases can be documented in sectional planes corresponding to the prenatal sonographic images. Before the postmortem examination the pathologist receives all the prenatal findings obtained for the fetus and is able to examine the prenatal images on a monitor. The final diagnosis in the postmortem report includes the results of modern molecular pathology, clinical-genetic examination of the fetus, cytogenetic and molecular-cytogenetic findings and postmortem x-rays. CONCLUSIONS: To be able to incorporate these various results into a final report in routine work the use of an interdisciplinary database is essential. Such a database also ensures faster and more productive interdisciplinary communication in a center of perinatal medicine.

Adult↗

Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients.

The aim of this study was to determine the extent of accumulation of lipoprotein(a) [Lp(a)] in human arterial wall and to define its potential role in atherogenesis. Biopsies routinely taken from the ascending aorta of 107 patients undergoing aortocoronary bypass surgery were analyzed for lipid and lipoprotein parameters, which were then correlated to serum values. A significant positive correlation was established between serum Lp(a) and arterial wall apolipoprotein (apo)(a) by enzyme-linked immunosorbent assay. High serum Lp(a) also led to a significant increase of apo B in the arterial wall. No significant correlation was found between apo B in serum and aortic tissue. Apo B was found to be partially linked to apo(a) in the aortic extract. Furthermore, apo(a) was found to be intact, as determined by its molecular weight in sodium dodecyl sulfate electrophoresis. This technique also revealed that the apo(a) isoform pattern of aortic homogenate was comparable to the individual serum pattern. Immunohistochemical methods demonstrated a striking colocalization of apo(a) and apo B in the arterial wall, predominantly located extracellularly. Both proteins were increased in atherosclerotic plaques. With density gradient ultracentrifugation, Lp(a)-like particles could be isolated from plaque tissue. This initial study showed that Lp(a) accumulates in the arterial wall, partly in the form of lipoprotein-like particles, therefore contributing to plaque formation and coronary heart disease.

Aorta↗

Actinomycotic inflammatory disease and misdiagnosis of ovarian cancer. A case report.

Actinomycosis in the pelvic region is an uncommon diagnosis. This infection is caused by Actinomyces israelii, a gram-positive anerobic saprophyte bacterium that is a normal inhabitant of the upper intestinal tract in humans. Pelvic actinomycosis is difficult to diagnose pre-operatively and is diagnosed, in most cases, accidentally. Actinomycosis can mimic pelvic and abdominal malignancies. A case report of a 35-year-old female patient with a fixed pelvic mass is presented and the diagnosis and treatment of pelvic actinomycotic inflammatory disease in relation to ovarian cancer are discussed. Clinicians should be aware of this rare infection to spare women potential morbidity from excessive surgical procedures.

Actinomycosis↗

Alteration of melanoma cell phenotype following in vitro culturing and exposure to cytostatic agents.

Pleiotropic drug resistance is supposed to be associated with a particular tumor cell phenotype, defined by certain plasma membrane glycolipids. Therefore we wondered how far chemosensitivity in vitro correlates with phenotypic characteristics of melanoma cells, which are known to be highly refractory to cytocidal agents. 13 monolayer cell cultures of metastatic melanoma derived from 9 patients were tested with 12 monoclonal antibodies against constitutive, differentiation- and progression-associated antigens. In parallel these primary cell cultures were subjected to a proliferation inhibition assay in the presence of dacarbazine, cis-platinum and carboplatinum. Transferring melanoma cells from original tissue-suspensions into short-term monolayer cultures caused a change in the expression of certain tumor antigens in 54% of 104 assays. In addition, the incubation of the cultivated cells with various cytostatic agents caused them to alter their phenotype in 32% of 128 assays. Irrespective of the spontaneous or induced changes in the antigen patterns, cells lacking HLA-ABC and/or HLA-DR were inhibited more markedly by cytostatic agents as compared to those other cells expressing these antigens. The data suggest, that pretherapeutic determination of tumor cell phenotype may provide clinically useful information for therapeutic decisions in patients with metastatic melanoma.

Antibodies, Monoclonal↗