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  • 1
    Electronic Resource
    Electronic Resource
    In vitro biotransformation of estradiol by explant cultures of murine mammary tissues (1989)
    Springer
    Breast cancer research and treatment 13 (1989), S. 173-181 
    Details
    ISSN: 1573-7217
    Keywords: estradiol metabolism ; mammary tissue ; explant culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vivo experiments have demonstrated a correlation between the extent of 16α-hydroxylation of estradiol and incidence of mammary cancer. The ability of mammary ductal epithelium (MDE), the site for neoplastic transformation, to metabolize estradiol or to accumulate estradiol metabolites has not been unequivocally established. Using a newly developed mammary explant culture system and a radiometric assay, we have compared the site-specific metabolism of estradiol (E2) by the C-17-oxidation and C-16α-hydroxylation pathways in mouse tissues that differ in relative risk for mammary cancer. A comparison between MDE (target tissue) and liver (nontarget tissue) from NFS (low risk) and C3H/ouj (high risk) mice revealed that: a) increase in C-17-oxidation was similar in MDE and liver from the two strains, and b) while C-16α-hydroxylation was similar in liver from the two strains (p = 0.5, n.s.), it was increased 4-fold in the MDE from the high risk C3H/ouj strain relative to that from the low risk NFS strain (p = 0.001). Furthermore,in vivo administration of progesterone resulted in modulation of cell proliferation as well as of E2 metabolism in mammary explant cultures. The effect of progesterone depended upon the presence of the MtV-2 proviral gene. This study demonstrates that mammary explants can extrahepatically metabolize estradiol. The specific risk-related increase in C-16α-hydroxylation suggests that intrinsic metabolic ability of the target tissue leading to the formation of 16α-hydroxyestrone from estradiol may be a determinant in the relative risk for developing mammary cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01806529
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  • 2
    Electronic Resource
    Electronic Resource
    Online control of d-tubocurarine induced muscle relaxation: A simulation study (1983)
    Springer
    Medical & biological engineering & computing 21 (1983), S. 710-717 
    Details
    ISSN: 1741-0444
    Keywords: Control ; Identification ; Least squares ; Muscle relaxants ; Simulation ; State estimation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract A self-tuning algorithm is presented for the online control of muscle relaxation. Although some patient parameters were fixed at a mean value determined by offline analysis of patient data, certain parameters have been explicitly identified online. In addition the patient states are estimated and are used by a novel controller to bring an unrelaxed patient to some desired level of paralysis and maintain it. Simulations show that a twitch depression of 80% can be achieved in less than 20 min using d-tubocurarine without excessive overdosage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02464034
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Online parameter estimation and control of d-tubocurarine-induced muscle relaxation (1985)
    Springer
    Medical & biological engineering & computing 23 (1985), S. 556-564 
    Details
    ISSN: 1741-0444
    Keywords: Control ; Least squares ; Muscle relaxants ; Neuromuscular blockade ; Parameter estimation ; Simulation ; State estimation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract An existing algorithm designed to control d-tubocurarine-induced muscle relaxation in humans has been evaluated in 38 clinical trials on patients undergoing upper and lower abdominal surgery. The data captured during these trials were used to perform offline analysis of the algorithm reported on here, by which the correct functioning of the algorthm was established and its efficacy rated. It is shown that, for practical purposes, the average controller performance is close to the theoretical limit which can be achieved for this drug. The use of online parameter estimation makes precise initialisation of the controller less critical than would be the case with a fixed control low. In the trials undertaken, an average time of 12 min was needed to reach the chosen set point and excessive overshoot was avoided in every case. With a setpoint for the single twitch response of 20 per cent of the control height, the average drug consumption for the first hour of operation was 0·38 mg kg−1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02455310
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  • 4
    Electronic Resource
    Electronic Resource
    Molecular and endocrine biomarkers in non-involved breats: Relevance to cancer chemoprevention (1992)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 50 (1992), S. 161-169 
    Details
    ISSN: 0730-2312
    Keywords: chemoprevention ; in vitro models ; estradiol metabolism ; intermediate biomarker ; mammary preneoplasia ; Ras p21 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The animal models for chemoprevention of breast cancer have provided important experimental systems to evaluate the efficacy of tumor suppression by dietary macro-and micronutrients. In the initiation/promotion cascade, early occurring premalignant changes constitute less extensively examined aspects of disease progression. Molecular, endocrine and cellular biomarkers may provide clinically relevant endpoints for prevention of breast cancer that focus on downregulation of preneoplastic transformation. In vitro models derived from non-involved murine and human mammary tissues are utilized to identify molecular, endocrine and cellular markers that are perturbed in response to such diverse initiators as viruses and chemical carcinogens. This upregulation was manifested as persistant Ras p21-GTP binding, altered C16α/C2 hydroxylation of estradiol, and hyperplasia preceding tumorigenesis. Prototypic chemopreventive agents such as n-3 polyunsaturated fatty acids, retinoids, and indole-3-carbinol were capable of downregulating all of the preneoplastic markers perturbed by initiators. Experimental modulation of these biomarkers in murine and human mammary tissue prior to the expression of a fully transformed tumorigenic phenotype is suggestive of their potential clinical application in chemopreventive intervention for breast cancer. © 1992 Wiley-Liss, Inc. © 1992 Wiley-Liss, Inc.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240501128
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    Paper (German National Licenses)
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