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Biomedical subjects

H Arps

Publications and source records attributed to H Arps.

At least 55 records · Page 3Linked to original sources
PubMed1988

Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content.

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Forty-eight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. Local recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC.

Adult↗
PubMed1988

Effectiveness of mitoxantrone on the proliferation of cell cultures derived from malignant mesenchymal tumors of human origin.

The antiproliferative potency of mitoxantrone (MITOX) has predominantly been established for epithelial and hematologic neoplasias. In this study the effectiveness of MITOX was investigated in vitro for 6 sarcomatous human cell lines derived from 2 synovial sarcomas, a malignant schwannoma, a malignant histiocytoma, a leiomyosarcoma, and a chondrosarcoma. The examination was performed using a proliferation assay with monolayer cell cultures. The effect of MITOX was compared with that of adriamycin (ADR) and cisplatin (CDDP). For each drug at least 3 concentrations were tested which covered the therapeutically achievable range, i.e., for MITOX 0.2-0.002 micrograms/ml, for ADR 0.5-0.005 micrograms/ml, and for CDDP 5.0-0.05 micrograms/ml. Test incubations were performed for 3 days. Antiproliferative potency of the cytostatic drugs was assessed by counting the number of cells at the start and the end of the test period with and without drug addition. Furthermore the dose inhibiting cell growth to 50% of controls (ID50) was determined for MITOX. For comparison 4 cell lines from carcinomatous lesions were included in the study. MITOX inhibited proliferation rates of 4 sarcomatous tumor cell lines more intensively than ADR, and was less effective in 2 cell lines. However, these differences were not significant. In all mesenchymal cell lines tested the antiproliferative potency of MITOX was more pronounced than that of CDDP. In carcinomatous cell lines the MITOX-induced growth inhibition was similar to that found in response to administration of ADR and CDDP confirming the described effect on epithelial tumors. The study suggests that MITOX possesses a growth inhibitory potency for malignant soft tissue tumors in vitro. From these data it may be worthwhile to initiate clinical trials testing the treatment of sarcomatous lesions with MITOX.

Adolescent↗
PubMed1988

DNA cytophotometry in malignant thyroid tumors--use of different evaluation schemes for prognostic statements.

Quantitative evaluation of nuclear DNA has been found to provide information on diagnosis and prognosis in a number of malignant tumours and borderline lesions. Using 53 carcinomas of the thyroid with varying differentiation we examined the prognostic information obtained by DNA cytophotometry with respect to clinical outcome, applying three different evaluation schemes. DNA cytophotometry allowed the discrimination of euploid carcinomas with good prognosis from aneuploid tumours with bad prognosis and a generally shortened life span. However, the encapsulated variants of follicular and papillary thyroid carcinomas, with their generally excellent prognosis, exhibited DNA histograms similar to those of their widely invasive counterparts. Thus, the favourable prognosis of these minimal invasive subtypes may primarily be related to the tumours' encapsulation and cannot be ascribed to a particular DNA content. We conclude that DNA cytophotometry can provide additional prognostic information for the individual patient suffering from thyroid carcinoma and may probably lead to an individualization of the therapeutic strategies.

Adenocarcinoma↗
PubMed1988

A novel method to demonstrate parathyroid hormone binding on unfixed living target cells in culture.

We present a rapid and specific procedure that enables one to identify living target cells of peptide hormones within heterogeneous cell populations by means of morphological demonstration of ligand-receptor binding. This is exemplified using a biotinylated parathyroid hormone (PTH) analogue (biotinyl-b-PTH 1-84) which reacts with avidin-fluorescein (avidin-FITC) as a histochemical marker. The experiments revealed a fine dot-like distribution pattern of binding after 1-5 min of incubation at room temperature, changing to a more clustered pattern after 10 min of incubation. Competition of labeled and unlabeled PTH exhibited lack of staining if unlabeled PTH was applied in excess. The results suggest that the demonstrated binding sites represent specific receptors for PTH on living target cells.

Animals↗
PubMed1987

Establishment of primary cell cultures: experiences with 155 cell strains.

Cell culture systems allow the examination of cell populations in a functional state. To simulate in vivo conditions as closely as possible freshly established cell strains are superior to permanent cell lines. Different aspects for the establishment of primary cell cultures obtained from various tissues are compared: Disintegration, culture media supplemented with basal additions, special supplements (growth factors, hormones), and attachment factors. The proliferation rates of the attained cell strains were evaluated by determination of cell doubling times. Procedures for how to obtain a relatively high plating efficiency (approx. 70% in our series of 219 attempts) of primary growth in vitro are described: (1) Mechanical disintegration is superior to enzymatic digestion. If mechanical treatment alone did not produce a sufficient number of viable cells, additional digestion with collagenase/dispase revealed a higher number of proliferating primary cultures than with trypsin. (2) Proliferation of cell cultures from normal and tumorous tissues of epithelial origin was superior in Leibovitz L 15 medium (58 of 87 (67%) cases). Cultures from mesenchymal tissues and tumors were found to have shortest cell doubling times in MEM and RPMI 1640 (16 of 23 (70%) cases). The media were supplemented with the basal additions indicated. (3) In approx. 30% of the cases special supplements like growth factors or hormones increased cell replication, although they were almost always not essential for cell growth. (4) Attachment factors only rarely contributed to the initiation of primary monolayer cultures. The application of various culture conditions does not lead to a protocol optimal for all tissues, for all probes of the same type of tumor, or for all tumor specimens of unique differentiation.

Cell Adhesion↗
PubMed1987

Effect of 1,25-dihydroxyvitamin D3 on human cancer cells in vitro.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) dependent growth and differentiation of 6 tumor cell lines has been determined by the use of the monolayer proliferation assay. Cell lines of 4 gastro-intestinal carcinomas, 1 malignant schwannoma, and 1 malignant histiocytoma have been established and characterized. Cells were incubated for 4, 7, and 11 days in the presence of 0.8 or 8 nM 1,25(OH)2D3 and for control without addition of the hormone. Proliferation rates of 1,25(OH)2D3 treated cells were compared with cell growth in the untreated controls. Five out of 6 cell lines showed a 1,25(OH)2D3 dependent growth pattern. With 8 nM 1,25(OH)2D3 they were all inhibited. With 0.8 nM, 3 of them were inhibited at any time of the test period, whereas 1 was stimulated at day 4 and inhibited at days 7 and 11. One cell line was stimulated at days 4, 7, and 11 when incubated with 0.8 nM 1,25(OH)2D3. No striking morphological changes could be observed in the presence of 1,25(OH)2D3. We conclude that 1,25(OH)2D3 dependent cells in vitro are not necessarily growth-inhibited by this compound. Thus, 1,25(OH)2D3 is not an exclusively proliferation inhibiting agent.

Antigens, Neoplasm↗
PubMed1987

Abnormal calcium distribution in human parathyroid adenomas as possible cause of primary hyperparathyroidism.

Current knowledge suggests that normal parathyroid glands and parathyroid adenomas have different sensitivities to environmental calcium. In search for morphological equivalents, 5 normal human and 10 porcine parathyroid glands, as well as 10 human parathyroid adenomas were investigated with regard to intracellular and extracellular calcium distribution. The glands were incubated for 2, 4, 6 and 20 h in tissue cultures using HAM's F10 medium with various calcium concentrations. For visualization of the calcium distribution in the tissue the method of pyroantimonate precipitation was applied. Specificity of the reaction was controlled by X-ray microanalysis. Shifts of the calcium pyroantimonate precipitates were quantitated by morphometry using an area-counting system. The results demonstrate that in normal parathyroid glands calcium precipitates are distributed randomly. Incubation of normal glands in medium with low calcium concentration (0.6 mM) provoked reduced amounts of intracellular and extracellular calcium complexes. When the incubations were performed in medium with high calcium content (2.6 mM), calcium accumulated inside parathyroid and stroma cells. In contrast to normal parathyroid glands, parathyroid adenomas fixed immediately after surgery showed an atypical calcium distribution with low amounts of intracellular and high amounts of extracellular calcium grains. The data suggest that in normal parathyroid glands the intracellular calcium concentration follows the extracellular environmental calcium concentration. Thus, calcium modulates parathyroid hormone (PTH) secretion via intracellular regulatory mechanisms. In parathyroid adenomas the calcium transport via the tumor cell membrane appears to be disturbed resulting in lowered intracellular calcium levels. This is remarkable since the environmental calcium concentration is elevated due to the hypercalcemia of primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1987

Extent and diversity of inflammatory cell infiltrates in squamous cell carcinomas and basal cell epitheliomas of the head and neck.

Using monoclonal antibodies reactive with Langerhans' cells (LCs), macrophages, and T cell subpopulations, the density and proportions of cells of the immune system of the normal oral mucosa were determined immunohistochemically, and compared with findings in oral squamous cell carcinomas (SCC) and basal cell epitheliomas (BCE). In normal oral epithelia, the dominant cell type was the LC, positive for CD 1, and expressing HLA-DR antigens (DR+). Many intraepithelial cells were lymphocytes of the suppressor/cytotoxic phenotype (CD 8+), which was also the most prominent cell type in the normal mucosal stroma. Significant differences were observed for the content of CD 8-, OKM 1-, and CD 4-positive cells in the epithelium of normal oral mucosa, SCC, and BCE, and for the amount of CD 1-positive Langerhans cells in the connective tissue of the different groups of tissues. When CD 4/CD 8 ratios were calculated, differences between SCC and BCE became most evident. A CD 4/CD 8 ratio greater 0.5 was seen to be characteristic for BCE. Thus, in contrast to the striking preponderance of suppressor/cytotoxic lymphocytes (CD 8+) in SCC, BCE showed typically almost balanced numbers of suppressor/cytotoxic (CD 8+) and helper/inducer (CD 4+) lymphocytes. This finding further underlines the biological differences recognized between these most common neoplasias of the head and neck.

Adult↗
PubMed1987

Immunoreactivity of PTH-binding in intact bovine kidney tissue and cultured cortical kidney cells indicative for specific receptors.

Localization of PTH-binding sites has been examined in intact kidney sections and cultured cells derived from bovine kidney cortex. Tissue sections were incubated with 10(-7) M bovine PTH (1-84) for 2 h, cells for 15 min, at 37 degrees C. Visualization of PTH-binding was achieved by immunocytochemistry using a carboxy-terminal specific anti-PTH antiserum (S 478). For control, cell culture incubations were performed applying competitively 10(-7) bovine PTH (1-84) and a 10-fold excess of synthetic 1-34 PTH fragment, not antigenic for S 478. This resulted in a lack of staining. PTH-binding was found in all cells of the proximal and the distal tubule, and with less intensity in the thick ascending limb of Henle's loop. In collecting ducts a PTH specific staining was also present, which was confined to single cells localized between others without PTH binding sites. No staining was seen in glomerula, the thin limb of Henle's loop, in blood vessels, and in connective tissue. The data suggest that large parts of the nephron contain PTH-binding sites, although in different amounts. This is in agreement with the numerous actions of PTH in the kidney. In the collecting segment a distinct cell-to-cell difference was disclosed indicative for different functional states or cellular heterogeneity.

Animals↗
PubMed1987

Co-localization of parathyroid hormone and secretory protein-I in bovine parathyroid glands: a double immunocytochemical study at the electron microscopical level.

Secretory protein-I (SP-I), also known as chromogranin A, is an acidic glycoprotein of unknown function that is found in large amount in the secretory granules of all endocrine and neuroendocrine cells, but not in exocrine or epithelial cells. It is cosecreted with parathyroid hormone (PTH) and by immunocytochemical staining has been reported to exist in the same subcellular structures of the gland. In the present study we have used the colloidal gold-double immunocytochemical technique at the ultrastructural level to precisely define the locales of SP-I and PTH in the bovine parathyroid cell. SP-I and PTH were co-localized to the same secretory granules. The patterns for both gold labels were diffuse ones throughout the granule and suggested that there was a general association of SP-I and PTH. There was little or no localization of the SP-I at the secretory granule membrane. The results support the concept that SP-I is responsible for stabilization of PTH within the secretory granules.

Animals↗
PubMed1986

Antigen detection by the monoclonal antibodies CA 19-9 and CA 125 in normal and tumor tissue and patients' sera.

The tumor markers CA 19-9 and CA 125 defined by the monoclonal antibodies 19-9 and OC 125 were investigated with respect to organ specificity and tumor sensitivity. Normal and tumor tissue specimens, and blood samples from 34 patients with pancreatic carcinomas, 40 with ovarian carcinomas and 39 with miscellaneous tumors were examined. CA 19-9 and CA 125 were determined by immunohistochemistry (IH) applied to sections of the tumors and adjacent normal tissues. In parallel, the antigens were measured in the patients' sera by radioimmunoassay (RIA). By means of IH CA 19-9 and CA 125 were detected in normal surface cells from many different organs. Both antigens were also found in tissue sections of various types of tumors and in the sera of the corresponding patients. Thus, organ specificity could not be demonstrated. Sensitivity of CA 19-9 was found to be high for pancreatic carcinomas, i.e., 88% of the tumors expressed the antigen shown by IH and 85% of the sera revealed concentrations above the cut-off value (greater than 37 units/ml). Evidence for CA 125 was high in ovarian carcinomas with a tissue positivity in 83% and elevated (greater than 35 units/ml) serum levels in 70% of patients. Comparing IH and RIA case by case a discrepancy was found in 14% of cases with positive IH and low serum values a vice versa. Reasons for this finding are small tumor mass not producing elevated serum levels, retention of the antigen inside the tumor cells because of defective release mechanisms demonstrable only by IH, or heterogeneity of tumors with only focal antigen expression not present in the tissue sections investigated and thus disclosable only by RIA. The relevance of immunohistochemical detection of the antigens for therapeutic planning is discussed.

Antibodies, Monoclonal↗
PubMed1986

Pancreatic endocrine carcinoma with ectopic PTH-production and paraneoplastic hypercalcaemia.

In a case of pancreatic endocrine carcinoma hypercalcaemia without bone metastases and normal parathyroid glands prompted our suspicion that there was paraneoplastic production of an osteoclast activating substance by the tumour tissue. This view was further confirmed by bone histology. Immunohistology post mortem revealed the production of PTH in the primary tumour and a liver metastasis. The usefulness of immunohistology in detecting paraneoplastic secretion of hormonal substances is discussed.

Cytoplasmic Granules↗
PubMed1986

Nuclear DNA content of borderline tumors of the ovary: correlation with histology and significance for prognosis.

Scanning-DNA cytophotometry was applied to Feulgen stained sections of 22 borderline tumors of the ovary (BOT). The DNA content was related to conventional histology. In 11 cases clinical follow up for more than 5 years was available. The DNA measurements disclosed two subgroups in the group of BOT. One showed a nuclear DNA content not exceeding tetraploidy (4c) indicating proliferative activity without malignant change and a second one exhibited DNA values higher than 4c indicating malignant transformation. Correlation of histological evaluation with the DNA content revealed a good agreement in 15 cases. However, a discrepancy was found in 7 cases: either the histological evaluation aroused suspicion for malignant potential but the histogram showed DNA values not higher than 4c (n = 4), or histology showed well differentiated lesions with an atypical histogram (n = 3). Clinical monitoring revealed no recurrence or tumor spread in all but one case of the group of lesions with DNA values up to 4c, whereas in the group with atypical DNA histograms (DNA values greater than 4c) relapse appeared in 6 out of 7 cases. The results suggest that DNA analysis has prognostic significance for BOT.

Cell Nucleus↗
PubMed1986

[Alloplastic replacement of the anterior cruciate ligament by a polytetrafluoroethylene ligament. Animal experiment study].

4 sheep knees received an implant of polytetrafluorethylene. 18 month after implantation the clinical and histological investigation showed two cases of anterior instability and rupture of parts of the prosthesis. We sw severe degenerative lesions intraarticular with chronic inflammation characterized by the proliferation of immature fibroblasts, the accumulation of macrophages and the formation of multinucleated giant cells. The transfer of our results to the human knee is discussed.

Animals↗
PubMed1986

Visualization of binding sites for bovine parathyroid hormone (PTH 1-84) on cultured kidney cells with a biotinyl-b-PTH (1-84) antagonist.

Parathyroid hormone (PTH) receptors have been found in a subpopulation of kidney cells. In this report, we investigated the feasibility of techniques that apply a partial antagonist of PTH conjugated to biotin to localize receptors cytochemically on bovine kidney cortical cells in monolayer culture at the light microscopic level. Biotinylated bovine PTH (1-84) (biotinyl-PTH) was bound to the cultured cells for 1-30 min at 37 degrees C in the amounts of 10(-5) -10(-10) M. In a different set of experiments, the cells were also exposed to a solution containing 10(-6) M biotinylated PTH and an excess of unlabeled PTH, insulin, adrenocorticotropin, or calcitonin for 10 and 30 min at 37 degrees C to test the specificity of the binding. The cells were then fixed in 2.5% glutaraldehyde and stained with the avidin-biotin peroxidase complex (ABC) technique. Diffuse labeling was evident on 30% of the cells in 10 min with concentrations of biotinyl-PTH as low as 10(-8) M. The stain was diffuse, but more intense after 1-10 min in higher concentrations (10(-6) M). If a 15-1500-fold excess of unlabeled PTH was added to the biotinyl-PTH, no staining was observed. The other peptides (insulin, ACTH or calcitonin) had no effect on binding. Longer times in biotinyl-PTH (10(-6) M for 10-30 min) resulted in intense patches of label on the cells resembling caps (in addition to the pale diffuse label). The percentage of labeled cells in the monolayer (30%) did not change with time. These studies show that a partial antagonist of PTH can be used as a cytochemical probe for specific PTH receptors in a subpopulation of cultured cortical kidney cells.

Animals↗
PubMed1986

[Cell receptors].

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Adenylyl Cyclases↗