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Biomedical subjects

B Wegmann

Publications and source records attributed to B Wegmann.

11 recordsLinked to original sources

[Prenatal ultrasonography in Switzerland--a repersentative national survey] .

BACKGROUND: The cost-effectiveness ratio of routine ultrasound during pregnancy has been debated for years. However, there is a lack of population based data concerning both costs and benefit. AIM: Population based survey of ultrasound examinations (US) during pregnancy in Switzerland with respect to quantity, indications and results; estimation of total costs, the proportion paid by health insurance and the costs for routine US. METHOD: During a representative week all certified physicians and obstetrical out-patient departments in Switzerland were asked to participate in an anonymous questionnaire based national survey on the use of ultrasound during pregnancy. RESULTS: With 62.9% of the physicians and 90.6% of the out-patient departments participating a total of 6455 questionnaires were returned. On average, 4.6 US were done per pregnancy or about 520,000 scans per year. At a mean price of $ 50 per scan total costs equalied $ 26 million a year. $ 19.5 million were covered by health insurance and the rest was not billed by the physicians. The indication for the scan was a medical problem in 48%, a routine scan in 36.9% of cases a first and a second trimester scan is paid for and in 15.1% reassurance of either the women or the physician. Abnormal results were found in 40.7% of medical indications, in 15% of routine scans and in 12.6% of reassurance cases. CONCLUSION: The considerable number of scans done for reasons of reassurance and not changed for does support our hypothesis that ultrasound during pregnancy has become a tool to routinely check the general state of the fetus comparable to the stethoscope of the general practitioner. One in seven US yielded a pathological result. Maximal cost savings for the health insurance amount to about 9 million a year. This amount has to be balanced by the health benefit, respectively if routine US were abolished.

Cost-Benefit Analysis↗

Transfection of human insulin-like growth factor-binding protein 3 gene inhibits cell growth and tumorigenicity: a cell culture model for lung cancer.

IGF-I and IGF-II are potent mitogens, postulated to exert autocrine/paracrine effects on growth regulation in human lung cancer. Their proliferative effects are modulated by IGF-binding proteins (IGFBPs), which are found in conditioned medium (CM) of lung cancer cell lines. The biological role of the IGFBPs, which are ontogenetically and hormonally regulated, is not fully understood. Both inhibitory and stimulatory effects on cell growth have been demonstrated. Exogenous IGFBP-3 has been consistently shown to block IGF action, inhibiting cell growth in vitro. In order to evaluate the action of endogenously produced IGFBP-3 on cell growth in lung cancer, we stably transfected the non-small cell lung cancer cell line NCI-H23 with human IGFBP-3 cDNA (resulting in NCI-H23 pOPI3/BP-3) or with the vector pOPI3CAT as control (resulting in NCI-H23 pOPI3CAT). RT-PCR confirmed expression of IGFBP-3-specific mRNA in NCI-H23 pOPI3/BP-3, but not in N! CI-H23 or NCI-H23 pOPI3CAT. Western ligand blot and Western immunoblot analysis of CMs yielded strong signals of the characteristic 40-44 kDa human IGFBP-3 protein in NCI-H23 pOPI3/BP-3. An IGFBP-3 ELISA demonstrated a 20-fold increase in IGFBP-3 protein expression in NCI-H23 pOPI3/BP-3 as compared with NCI-H23. The growth of NCI-H23 pOPI3/BP-3 in serum-containing medium was significantly slower (1.7-fold) than that of NCI-H23 or the vector-transfected control NCI-H23 pOPI3CAT. While the proliferation rate of parental and vector-transfected cells could be stimulated by IGF-I, IGF-II, IGF-I analog Long R(3) IGF-I or insulin, that of NCI-H23 pOPI3/BP-3 could not. Xenotransplantation in nude mice resulted in marked tumor growth after the injection of NCI-H23 or NCI-H23 pOPI3CAT, but absent or minimal growth for the IGFBP-3-transfected cell line. These data suggest that IGFBP-3 is a potent inhibitor of cell growth in human lung cancer c! ell lines and may impair tumorigenicity in vivo.

Animals↗

Envelope and long terminal repeat sequences of an infectious murine leukemia virus from a human SCLC cell line: implications for gene transfer.

Development of methods for gene transfer into specific cell types or tissues is important for experimental research as well as clinical therapeutical approaches. We report here the cloning and characterization of the envelope (env) gene and the U3 region of a retrovirus from an infected human Small Cell Lung Cancer (SCLC) cell line. The replication of this murine retrovirus is also fully supported by other lung cancer cell lines of different histological origin. We present evidence that a long terminal repeat (LTR)-beta-galactosidase (beta-Gal) reporter construct performed as well as an analogous cytomegalovirus (CMV) promoter beta-Gal construct in the human lung epithelial cell line A549 and in the human larynx carcinoma cell line HEp2.

Amino Acid Sequence↗

Neural network models and the visual cortex: the missing link between orientation selectivity and the natural environment.

Orientation selectivity is a basic property of neurones in the visual cortex of higher vertebrates. Such neurones can be seen to act as 'feature detectors', which provide an efficient cortical representation of the outside world. More recently, the removal of correlations between the signals of cortical neurones has been suggested as suitable theoretical concept for explaining the development of receptive fields. Corresponding neural network simulations yielded oriented 'receptive field' structures resembling those observed by neurophysiologists. The findings suggest that the 'decorrelation approach' can provide a causal relationship between characteristics of the physical world and brain function. However, we were able to reveal a basic deficit of the decorrelation approach which we illustrate by the construction of two artificial 'worlds', a 'Gaussian' one and an 'orientation-only' one. We show that, according to the decorrelation approach, oriented environmental features would be neither necessary nor sufficient for the development of oriented receptive fields. Thus the link between environmental structure and cortical orientation selectivity still awaits a theoretical explanation.

Environment↗

Nuclear localization of insulin-like growth factor binding protein 3 in a lung cancer cell line.

Considerable evidence exists that lung cancer cell lines produce large amounts of insulin-like growth factor-binding proteins (IGFBPs). In addition, these cells are subject to an autocrine or paracrine growth control by insulin-like growth factors (IGFs). We now demonstrate by immunocytochemistry with IGFBP-3 antibodies that nuclei of a lung cancer cell line distinctly immunostain for IGFBP-3. This finding led us to investigate in more detail the localization of this protein that, to date, had only been known to occur extracellularly. Ligand blotting revealed that purified nuclear extracts contain a 43,000-Da IGFBP which can bind [I125]IGF-I. By Western blot this protein was identified as IGFBP-3. Thus, our data are consistent with the results of a previous structural study predicting a nuclear localization for IGFBP-3. Moreover, our findings raise the possibility that nuclear IGFBP-3 is functional and involved in the pathogenesis of lung cancer.

Blotting, Western↗

Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer.

Female gender is a significant independent favorable prognostic factor in lung cancer. To study the possible role of sex hormones in lung cancer, the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry, ligand-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation, NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in 13 and androgen receptor in 12 out of 17 cases examined; sex-steroid-receptor expression was virtually absent in SCLC cell lines. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochemistry. Among patients with primary lung-cancer sex-steroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of 16 cases, vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. Immunohistology is a feasible method of studying steroid-receptor expression in lung cancer.

Base Sequence↗

Expression of vitamin D receptor in lung cancer.

The active metabolite of vitamin D 1,25-dihydroxycholecalciferol is a hormone-like agent that regulates cell differentiation and proliferation. Various vitamin D derivatives have been shown to induce differentiation in neoplastic cells. The prerequisite for any hormone action is the presence of its receptor. We studied the expression of vitamin D receptor in human lung cancer cell lines and in primary lung cancer tissue. Employing the polymerase chain reaction, 10 out of 11 cell lines stemming from small-cell lung cancer and 15 out of 15 cell lines stemming from non-small-cell lung cancer demonstrated vitamin D receptor expression. An immunohistochemical analysis, using a specific monoclonal antibody, demonstrated vitamin D receptor protein expression in 31 out of 117 (26%) primary small-cell lung cancer cases tested. Positive cells exhibited a nuclear reaction pattern. Twenty-one out of 37 primary non-small-cell lung cancer cases, particularly adenocarcinomas (9/14) and squamous-cell carcinomas (10/15), exhibited vitamin D receptor. Results indicate that a subset of lung cancer cases may be susceptible to the differentiating effects of vitamin D analogues.

Base Sequence↗

Production of insulin-like growth factor binding proteins by human ovarian carcinoma cells.

Cells of the human ovarian carcinoma lines EFO-21, EFO-27, MFO-35 and MFO-36 secrete binding proteins for insulin-like growth factors (IGFBPs) into their culture media. By sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and ligand blotting, seven groups of IGFBPs with molecular masses of 25, 30 (doublet), 34, 37, 40, 45, and 50 kDa were observed, depending on the cell line under investigation. By Northern blot analyses using cDNAs or oligonucleotides specific for the six types of IGFBP (IGFBP-1 to IGFBP-6), mRNA for all IGFBPs tested except for IGFBP-1 could be detected in the ovarian carcinoma cell extracts. In detail, analysis of EFO-21 protein products by SDS-PAGE yielded IGFBPs of 25, 34, and 50 kDa; extracts of EFO-21 cells contained mRNAs for IGFBP-2, -3, -4, and -6. EFO-27 cells produced IGFBPs of 40 kDa and 45 kDa as determined by SDS-PAGE, and mRNAs for IGFBP-3, -4, and -6 were detected. In the conditioned medium of MFO-35 cells, IGFBPs of 25, 30 (doublet), 34, 37, 40, and 45 kDa were observed by SDS-PAGE, while mRNAs for the five proteins IGFBP-2 to IGFBP-6 were found. MFO-36 cells produced IGFBPs of 34 kDa and 50 kDa as determined by SDS-PAGE, and the cells expressed mRNAs for IGFBP-2, -3, -4, and -6. In relation to published molecular mass data of the known IGFBPs, the size of the secreted proteins could be correlated to the mRNA patterns expressed by the ovarian carcinoma cells. It is concluded that ovarian carcinoma cells frequently express IGFBP-3, -4, and -6 and, to a lesser extent, IGFBP-2; the expression of IGFBP-5 appears as a rather rare event, while IGFBP-1 was not found to be expressed in ovarian carcinoma cells.

Carrier Proteins↗

Differential expression of insulin-like growth factor binding proteins in human non-small cell lung cancer cell lines.

The possible expression and secretion of insulin-like growth factor binding proteins (IGFBPs) by non-small cell lung cancer (NSCLC) cell lines was investigated and compared with possible IGFBP expression by primary NSCLC tumours. Cells growing under serum-free conditions released binding proteins with apparent molecular masses of 26-43 kD when analysed by a ligand blotting method under non-reducing conditions. Additionally, northern blot analysis of total RNA from NSCLC cell lines and tumours was performed using cDNAs coding for each of IGFBP-1, IGFBP-2, and IGFBP-3. This analysis revealed expression of all three mRNAs to varying degrees by all cell lines. In contrast all primary tumours analysed expressed predominantly IGFBP-2 and IGFBP-3 and none showed any evident expression of IGFBP-1. Both NSCLC cell lines and tumours synthesise IGFBPs but the pattern of expression differs significantly between cell lines and primary tumours.

Blotting, Northern↗

Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines.

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.

Carcinoma, Non-Small-Cell Lung↗