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  • 1
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Cellular fatty acid-binding proteins (FABP) are a highly conserved family of proteins consisting of several subtypes, among them the mammary-derived growth inhibitor (MDGI) which is quite homologous to or even identical with the heart-type FABP (H-FABP). The FABPs and MDGI have been suggested to be involved in intracellular fatty acid metabolism and trafficking. Recently, evidence for growth and differentiation regulating properties of MDGI and H-FABP was provided. Using four affinity-purified polyclonal antibodies against bovine and human antigen preparations, the cellular localization of MDGI/H-FABP in human and mouse tissues and organs was studied. The antibodies were weakly cross-reactive with adipose tissue extracts known to lack H-FABP, but failed to react by Western blot analysis with liver-type FABP (L-FABP) and intestinal-type FABP (I-FABP). MDGI/H-FABP protein was mainly detected in myocardium, skeletal and smooth muscle fibres, lipid and/or steroid synthesising cells (adrenals, Leydig cells, sebaceous glands, lactating mammary gland) and terminally differentiated epithelia of the respiratory, intestinal and urogenital tracts. The results provide evidence that expression of H-FABP is associated with an irreversibly postmitotic and terminally differentiated status of cells. Since all the antisera employed showed spatially identical and qualitatively equal immunostaining, it is suggested that human, bovine and mouse MDGI/H-FABP proteins share highly homologous epitopes.
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  • 2
    ISSN: 1432-1246
    Keywords: Key words Occupational exposure ; Spermatozoa ; Sperm count ; Epidemiology ; Genotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Organic solvents have been suspected to exert detrimental effects on human spermiogenesis. Styrene, which is both mutagenic and neurotoxic, was selected as a suitable organic solvent for further assessment of a possible effect on semen quality and sperm DNA damage. Subjects and methods: Semen samples were collected from 23 reinforced plastics workers at the time of employment and after 6 months of styrene exposure and from 21 nonexposed farmers. Intra-individual changes in conventional semen parameters and sperm-DNA denaturation patterns were related to the internal dose of styrene exposure as measured by postshift urinary mandelic acid. Results: A statistically significant decline in sperm density was seen during styrene exposure from 63.5 to 46.0 million sperm/ml, whereas no decline was seen in the nonexposed subjects. The total sperm count was almost halved from an initial value of 175 million sperm/ejaculate. However, no relationship was apparent when the sperm parameters were related to internal levels of exposure. However, an exposure-response relationship was shown for DNA-denaturation patterns, but the numbers were small. Conclusion: A declining sperm count following styrene exposure is suggested. However, the findings of the internal and external comparisons are inconsistent, and this may be due to the high intraindividual variability of semen parameters and the limited study size but may also be attributable to a weak internal exposure gradient. Spermatogenesis may be vulnerable to styrene exposure. However, due to the small numbers these findings are only preliminary.
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  • 3
    ISSN: 1432-1246
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SF/HGF has multiple activities on target cells in culture1'5'11 14 and has been implicated in mesenchymal-epithel-ial interactions during organ development15'16. To understand the physiological role of the factor, we produced embryonic stem (ES) cells in which exon 2 of the SF/HGF gene, which ...
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  • 5
    ISSN: 1573-7217
    Keywords: new mammary carcinoma lines ; estradiol receptor ; stroma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two new human mammary carcinoma lines originating from surgical material were established in nude mice. According to the adopted criteria, the tumor 4049 has been classified as estradiol receptor positive and mammary carcinoma 4296 as estradiol receptor negative. Both tumors proved to be c-erbB-2 protein positive and EGF-receptor negative. In contrast to carcinoma 4296, thein vitro growth and the take rate of mammary carcinoma 4049 in nude mice seems to be dependent on stromal components. Pretreatment of mice with estradiol/peanut oil before tumor engraftment was an essential precondition for the growth of the primary tumor in nude mice. After successful establishment the tumor growth was significantly stimulated by estradiol. The growth rate of mammary carcinoma 4296 was independent of any supplementation of estradiol. The two breast tumors were characterized with regard to their growth behaviour, histology, and sensitivity to cytostatics and antihormones. They are considered suitable tumor models for the testing of antineoplastic substances and for biological experiments.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 47 (1969), S. 1241-1247 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary From theoretical points of view, therapy of the amyloidoses could be rendered possible by influencing amyloidogenic factors, inhibition of amyloid synthesis, prevention of extracellular fibrillar amyloid precipitation or lysis of amyloid deposits. In previons experiments, the effects on amyloidosis of glycocorticoids, antibiotics and chemotherapeutic agents as well as of X-rays, thymectomy and splenectomy have been studied. Among these substances and trials, the potentially effective ones exert their action either by inhibition of transscription of the genetic code or by stimulation of the R.E.S. Any relationship between immunosuppressive or adjuvant effects, respectively, and the influence on amyloid development is lacking. It is beyond doubt that remission of amyloidosis takes place in man and under experimental conditions. However, for the time being, experimental methods which could be applied therapeutically for inducing lysis of amyloid fibrils, are unknown. The interpretation of experimental results with regard to inhibition or enhancement of amyloidosis have to consider the comparability of animal and human types of this disease, and require a methodically exact quantitative estimation of amyloid deposits. Furthermore, any successfull therapy depends to a decisive degree upon the time of action of the agents used in the course of an experimental regimen as well as of human amyloidoses. All the therapeutical trials which have been attempted are certainly unspecific. Further progress can be expected by using drugs which act through inhibition of transscription of the genetic code. Any specific therapy supposes the elucidation of the etiology and the formal pathogenesis of the amyloidoses.
    Notes: Zusammenfassung Eine Therapie der Amyloidosen erscheint theoretisch durch Beeinflussung amyloidogener Faktoren, Hemmung der Amyloidsynthese, Verhinderung der extracellulären fibrillären Präcipitation oder der Auflösung bereits abgelagerten Amyloids möglich. Experimentell wurde bisher der Einfluß von Medikamenten (vor allem Glykocorticoiden, Chemotherapeutica und Antibiotica), physikalischen (Röntgenbestrahlung) und chirurgischen Maßnahmen (Thymektomie, Splenektomie) untersucht. Potentiell wirksam sind Verbindungen bzw. Eingriffe mit transskriptionshemmendem oder RES-stimulierendem Effekt. Korrelationen zu ihrer immunsuppressiven oder -steigernden Wirkung ergeben sich nicht. Eine therapeutisch verwertbare induzierte Lyse von Amyloidfibrillen ist nach den derzeitigen Erfahrungen nicht möglich, obwohl an ihrer Resorbierbarkeit kein Zweifel besteht. Bei der Auswertung und Interpretation experimenteller Ergebnisse ist die Äquivalenz tierischer und humaner Amyloidformen sowie die methodisch exakte, quantitative Erfassung von Amyloidablagerungen besonders zu berücksichtigen. Als weiterer Parameter ist der Zeitpunkt des Therapiebeginns für den Erfolg experimenteller und klinischer Behandlungsversuche von wesentlicher Bedeutung. Alle bisher geprüften Maßnahmen sind sicher unspezifischer Natur. Weitere Fortschritte sind vorerst durch den Einsatz transskriptionshemmender Verbindungen und durch Aufklärung der kausalen formalen Pathogenese der Amyloidosen zu erwarten.
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  • 7
    ISSN: 1432-1335
    Keywords: Human mammary carcinomas ; c-erbB-2 protein regulation ; Estradiol ; Antioestrogens ; Xenotransplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Attempts were made to correlate growth effects induced by oestradiol and tamoxifen with the hormonal regulation of c-erbB-2 protein in experiments in vivo. We report here the responsiveness of four xenotransplanted oestrogen-receptor(ER)-positive and four ER-negative human mammary carcinomas to oestradiol and tamoxifen. Oestradiol in a dose of 0.5 mg/kg significantly increased the growth of the ER-positive mammary carcinomas 3366, MCF-7, 4134 and 4049, but not the ER-negative tumours 4000, 4296 and MT-3. However, within the group of the ER-negative breast carcinomas the tumour 4151 ES deviates from this growth behaviour, as we could prove an estrogen induced growth. The stimulation of tumour growth by oestradiol was always accompanied by a down-regulation of c-erbB-2 protein both in the ER-positive mammary carcinomas and in the ER-negative mammary carcinoma 4151 ES. Tamoxifen significantly inhibited the growth of the ER/PR-positive mammary carcinomas 3366 and MCF-7 but not the ER-positive/PR-negative mammary carcinomas 4049 and 4134. In the group of ER-negative mammary carcinomas only the growth of the oestrogen-responsive tumour 4151 ES was significantly inhibited by tamoxifen. The inhibition of tumour growth by tamoxifen was correlated with a reversion of the oestradiol-induced down-regulation of c-erbB-2, also in the ER-negative/oestradiol-responsive mammary carcinoma 4151 ES. From our results we hypothesize that the oestrogen-dependent growth of ER-negative breast carcinoma 4151 ES could also be correlated with the oestradiol-regulated expression of c-erbB-2 protein.
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  • 8
    ISSN: 0730-2312
    Keywords: explant culture ; stimulation of DNA synthesis ; inhibition of functional differentiation ; endogenous TGFα ; arachidonic acid release ; phospholipase A2 ; metabolic inhibitors ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Epidermal growth factor (EGF) has been suggested to be involved in mammary gland development by mitogenic stimulation of the ductal and alveolar epithelium in virgin mice. The present studies demonstrate that also in late-pregnant mice EGF leads to proliferation of the ductal, ductular, and alveolar epithelium. The mitogenic effect is associated with structural and functional dedifferentiation of alveolar cells as revealed by analysis of morphology, expression of cytosolic and secretory proteins, and fatty acid synthesis. Using a combination of metabolic inhibitors, the dedifferentiating effect of EGF could be blocked while the mitogenic action was not influenced. This finding demonstrates that the signal transduction pathway leading to dedifferentiation and mitosis can be separated, and that the dedifferentiating effect of EGF is independent of its mitogenic properties, but is probably mediated by activation of the arachidonic acid-dependent pathways (cyclo- and lipoxygenase pathways). Release of arachidonic acid from the endogenous phospholipid pool was found to be an early response of the explants to EGF. Accordingly, arachidonic acid itself proved to be capable of inducing epithelial dedifferentiation but failed to stimulate proliferation. TGFα showed qualitatively similar effects as EGF but was generally a stronger agonist. It is suggested that EGF and TGFα also play a role in mammary gland physiology during pregnancy by final developing and maintanance of the lobulo-alveolar structure in the mammary gland and prevention of premature onset of lactation, and that this is mediated through the PLA2-arachidonic acid signalling cascade.
    Additional Material: 4 Ill.
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  • 9
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Antiprogestins possess a potent antitumor activity in hormone-dependent experimental breast cancer models. Though the underlying mechanism is not clear, induction of functional differentiation seems to be a major event. This study attempts to test directly for antiproliferative and differentiation promoting activities of antiprogestins on the normal mammary gland. To this end, whole organ cultures of mammary glands from estradiol/progesterone-primed virgin mice maintained in a serum-free medium with aldosterone, prolactin, insulin, and hydrocortisone were exposed to the antiprogestin ZK114043. A 4-day treatment of organ cultures led to a strong inhibition of epithelial DNA synthesis. In parallel, ZK114043 caused alveolar cells to acquire a more differentiated phenotype distinguished by secretory active alveoli composed of single cell layers with increased fat droplet accumulation and enhanced expression of the milk proteins b̃-casein and whey acidic protein (WAP). Particularly strong effects were found on the expression of mammary-derived growth inhibitor (MDGI). Both half-maximal inhibition of epithelial DNA synthesis and stimulation of MDGI mRNA expression were found at about 5 ng/ml of ZK114043. Presence in the medium of 5 m̈g/ml hydrocortisone rendered antiglucocorticoid effects of ZK114043 highly unlikely. Furthermore, prevention of action of ZK114043 by the progesterone agonist R5020 and ZK114043 stimulated expression of b̃-casein and MDGI mRNA in cultured glands of 10-week-old unprimed virgin mice suggest a progesterone receptor-mediated mechanism of antiprogestin action. Two other antiprogestins, Mifepristone and Onapristone, likewise stimulated MDGI expression. The data provide direct evidence that antiprogestins act like a differentiation factor in the normal mammary gland. © 1995 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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