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Biomedical subjects

A Niendorf

Publications and source records attributed to A Niendorf.

At least 19 recordsLinked to original sources
PubMed1992

Elevated lipoprotein(a) levels in patients with acute myeloblastic leukaemia decrease after successful chemotherapeutic treatment.

Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to investigate disease-associated changes in lipid metabolism. Lipoprotein (a) [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23 mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87 and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol and HDL levels increased in all 10 and LDL in 9 cases in which complete remission was achieved. These data suggest that the catabolism of LDL-cholesterol might be even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a) level in acute myeloblastic leukaemia is influenced either directly or indirectly by the leukaemic blasts.

Adult↗
PubMed1991

Antiatherosclerotic effect of probucol in WHHL rabbits: are there plasma parameters to evaluate this effect?

Probucol has been used as a lipid-lowering agent for over 10 years. Lately it has been found that its antiatherogenic action is due mainly to its antioxidative capacity, in addition to its known lipid-lowering effect. To study the antioxidative capability of probucol and its influence on plaque development we used the animal model of the LDL-receptor-defective Watanabe heritable hyperlipidemic (WHHL) rabbit. In this study we measured all lipid values before and after probucol feeding and compared them with corresponding values in untreated controls. Probucol levels were determined, as were the physiological antioxidants alpha and gamma tocopherol (vitamin E). Thiobarbituric reactive substances were measured in plasma as a parameter for lipid peroxidation. In addition to the biochemical measurements the plaque area was analyzed macroscopically and microscopically to check the antiatherosclerotic effect and correlate it with the biochemical parameters. In four experiments we showed that probucol treatment in WHHL rabbits decreases the progression of atherosclerotic plaques by way of a combined lipid-lowering and antioxidative effect.

Animals↗
PubMed1990

Membrane vesicle formation due to acquired mitoxantrone resistance in human gastric carcinoma cell line EPG85-257.

A newly established gastric carcinoma cell line (EPG85-257P) exhibited a high sensitivity to mitoxantrone (DHAD) as determined by a monolayer proliferation assay. The concentration to inhibit cell growth to 50% of controls (IC50) was 0.0022 micrograms/ml culture medium. The cells were continuously incubated for more than 4 months in the presence of stepwise increased concentrations of DHAD, and the IC50 was increased to 0.41 micrograms/ml, i.e., 186.4-fold. This resistant variant was named EPG85-257RNOV. The EPG85-257RNOV cells became cross-resistant to Adriamycin with enhanced IC50 by 10.5-fold and to daunomycin with enhanced IC50 by 3.9-fold. No distinct resistance was observed to vinblastine, vincristine, and colchicine. Verapamil (10(-6), 4 X 10(-6) and 10(-5) M) and cyclosporin A (10(-6), 3 X 10(-6) and 10(-5) M) did not reverse DHAD resistance. As shown by immunocytochemistry (monoclonal antibodies: C219 and JSB-1) and Northern blot analysis, DHAD resistance was not associated with the appearance of the multidrug resistance (MDR)-associated (Mr 170,000) P-glycoprotein or the overexpression of P-glycoprotein mRNA. The data indicate a chemoresistance pattern unlike typical MDR (often called "atypical" MDR). The phenotypes of parent and resistant EPG85-257 cells were compared using interference contrast microscopy, electron microscopy, and immunocytochemistry. After DHAD application the following structural characteristics were found to be associated with emergence of resistance: (a) intensive formation of surface vesicles in the resistant variant. Such vesicles were almost absent in sensitive cells; (b) the vesicles contained the selecting DHAD which was visualized by its blue color; and (c) in electron microscopy the vesicles were formed by an inner and an outer double membrane, presumably derived from the plasmalemma. These observations suggest a complex cellular mechanism responsible for DHAD resistance which includes formation of membrane vesicles, vesicular drug binding, and drug compartmentalization.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Immunocytochemical differential diagnosis of adrenocortical neoplasms using the monoclonal antibody D11.

The monoclonal antibody D11 is a valuable aid in the accurate typing of adrenal tumours as, in formalin-fixed, paraffin-embedding material, strong nuclear D11 positivity was observed only in adrenocortical cells in 190 neoplasms (including 100 adrenal tumours). This pattern was demonstrated for all zona glomerulosa cells in 27 normal adrenals and for the neoplastic cells of 15 adrenocortical adenomas derived from that zone, as judged from clinically evident hyperaldosteronism. Normal cells of zona fasciculata and reticularis also showed strong diffuse D11 immunostaining and the same nuclear plus cytoplasmic D11 reactivity was evident in 15 benign and malignant adrenocortical neoplasms derived from these zones, documented by hypercortisolism. Cytoplasmic and/or nuclear D11 staining made topohistogenetic typing possible in 15 non-functioning cortical tumours. D11 immunostaining gave negative results in 50 specimens containing normal, hyperplastic and neoplastic adrenomedullary cells. In addition, absence of D11 reactivity was recorded in 4 adrenal metastases of extra-adrenal carcinomas, 5 paragangliomas, 25 primary renal carcinomas and 59 of 60 primary thyroid carcinomas. D11 immunocytochemistry allows the accurate typing of benign and malignant adrenocortical neoplasms, irrespective of histology and function. With this method, primary adrenocortical tumours can be separated from carcinomas metastatic to the adrenal gland, including secondary tumours of similar phenotype (such as renal carcinomas). By exclusion, D11 negativity provides evidence of the medullary origin of primary adrenal tumours even in the absence of clinical, structural, histochemical and conventional immunohistochemical indicators of phaeochromocytoma.

Adenoma↗
PubMed1990

Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries.

Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n = 74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.

Adolescent↗
PubMed1990

Lipoprotein(a) in the arterial wall.

We compared CHD patients with healthy blood donors to confirm the role of Lp(a) as an independent risk factor. More important, we performed biochemical and immunohistochemical studies to evaluate the potential mechanism by which Lp(a) causes CHD. We measured the Lp(a) concentration in comparison with other lipoprotein parameters in fresh human arterial wall biopsies and, in autopsy tissue, we localized apo (a) and apo B, as well as fibrin, with immunohistochemical methods in different vessel areas. Density gradient ultracentrifugation was used to analyse lipoprotein fractions isolated from human arterial wall. Lp(a) accumulates in the intima, preferentially in plaque areas, dependent on the serum Lp(a) level. Most of the Lp(a) can be located extracellularly, but apo(a) can also be detected in foam cells. A strong co-localization has been observed for apo(a) and apo B; only a few areas containing only apo B were detected. Moreover, a striking co-localization for apo(a) and fibrin was found. The possibilities for the pathways by which Lp(a) enters the arterial wall and accumulates extracellularly are discussed on the basis of the present data and recent data published by other groups.

Aorta↗
PubMed1990

[Leu-M1, CEA and intermediate filament proteins in histochemical differential diagnosis of malignant pleural mesothelioma].

The differential diagnosis "pleuramesothelioma" vs "metastatic adenocarcinoma" can mostly not be decided clearly by conventional histological methods in malignant pleuraneoplasias. Leu-M1 is employed in immunhistochemical diagnosis of lymphomas in Hodgkin's disease but it also reacts with adenocarcinoma cells. Pleuramesotheliomas are Leu-M1 negative. Intermediary filament proteins, CEA and Leu-M1 are important "markers" in the diagnosis of malignant pleuraneoplasias. 25 pleura biopsies of malignant pleura processes were subjected to immunhistochemical examination.

Adenocarcinoma↗
PubMed1989

[Individualization of chemotherapy through in vitro predictive determination of the cytostatic sensitivity of malignant tumors].

An in-vitro test was developed for predicting the efficacy of anti-tumour chemotherapy. Cell cultures were grown from freshly removed tumours and it was then demonstrated by DNA cytophotometry and immuno-cyto-chemistry whether the growing tumour cells corresponded to those of the original tumour cells. Several cytostatic agents were then tested for their efficacy of inhibiting growth at clinically customary dosage. Growing cell cultures were established in 306 of 413 submitted tumours (74%). They responded quite differently to the various drugs that were tried. The clinical course in 94 cases was observed for minimally four and a mean of eight months to obtain an in-vitro to in-vivo correlation of response, with 178 individual correlations. A discrepancy was recorded in 16% of cases, a false-positive in-vitro sensitivity result was 3.6 times more frequently associated with an in vivo resistance than the reverse. Concordance between test results and clinical tumour response occurred in 84%. The monolayer proliferation assay correctly indicated resistance in 93.8%, sensitivity in 72.8%.

Antineoplastic Agents↗
PubMed1989

Effect of continuous vs intermittent application of 3-OH-tamoxifen or tamoxifen on the proliferation of the human breast cancer cell line MCF-7 M1.

The antiproliferative potency of 5 x 10(-7) M tamoxifen (TAM) and 3-hydroxytamoxifen (3-OH-TAM) was investigated during continuous (8 days) or intermittent (2 h every 2nd or 3rd day, respectively) application to the oestrogen-receptor-positive, estradiol-sensitive human mammary carcinoma cell line MCF-7 M1, a variant of MCF-7 wild type. Growth modulation was evaluated in parallel by counting cells and by measuring DNA content. Continuous incubation resulted in a growth inhibition to 21.8 +/- 3.2% by 3-OH-TAM and to 39.5 +/- 4.8% by TAM when compared with control cultures defined as 100%. Intermittent addition induced a growth reduction to 23.0 +/- 2.1% by 3-OH-TAM and to 41.2 +/- 2.4% by TAM in relation to 100% controls. Addition of 3-OH-TAM for 2 h only at day 1 resulted in an inhibition to 70.3 +/- 3.2%, again in relation to 100% controls. When TAM was administered once for 2 h at day 1 it induced an inhibition to 79.0 +/- 4.9% at day 8. The in vitro results indicate that (a) at 5 x 10(-7) M 3-OH-TAM has a better antiproliferative effectiveness than TAM, (b) the intermittent application is as effective as continuous application (no significant difference), and (c) the addition once a week reveals only a slight growth reduction after 8 days of culture. Application of the long-living TAM results in continuously high serum concentrations, which have been shown to create resistant cell clones. Compared to TAM the 3-OH metabolite has a considerably shorter half-life and its application in vivo reveals rise and fall of its serum concentrations. Since the presented data demonstrate that 3-OH-TAM is more potent than TAM and that the intermittent application is as effective as the continuous form, interval therapy with 3-OH-TAM may slow down the process of acquiring resistance to antioestrogens.

Breast Neoplasms↗
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↗