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  • 1
    ISSN: 0044-281X
    Keywords: Schlüsselwörter Rattenhirn – Streß– Glucocorticoidrezeptor – ATP-stimulierter Translokationspromoter – HSP 70 ; Key words Rat brain – glucocorticoid receptor – ATP-stimulated translocation promoter – HSP 70
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Chronic or repeated stress can induce a damage of neurons, expecially in hippocampus, by which the degree of damage differs in various species. Sapolski has reported that there is a correlation between hippocampal degeneration, disturbed feed-back reaction, and hypersecretion of glucocorticoids. The aim of this study was to investigate if the signal transmission via glucocorticoid receptors (GR) in the brain of male wistar rats of two age groups (5–6 and 17–24 months, respectively) is changed in aging and which cytoplasmic factors/modulators participate in this process. The binding of 3H-dexamethasone to cytosolic GR, the transformation, translocation, and nuclear binding of GR complexes (GRC) were studied before and after physiological stress. The influence of cytoplasmic modulators ASTP1) and HSP 701), isolated from brain cytosol and purified, and of exogenous PK C1) was also tested in parallel incubation systems. Whereas old control animals showed a higher cytosolic concentration of unoccupied GR than young ones, this was significantly reduced only in old stressed rats 60 min after stress compared to old controls. The part of transformed GRC, bound to isolated nuclei, was somewhat lower in old than in young rats before and after stress. The nuclear GRC binding could be slightly elevated by addition of ASTP and HSP 70, resp., at the heat transformation of GRC; however, by simultaneous addition of PK C it was significantly increased in both age groups. The GRC binding also rose significantly in stressed animals compared to controls, after simultaneous addition of PK C to more than double of initial assays in young animals. Purified ASTP, isolated from brain cytosol of young animals, showed higher 32P-incorporation after phosphorylation in vitro than that from old animals. The reduced phosphorylation of ASTP could be one possible cause of the retarded transformation/translocation and the reduced nuclear binding of GRC together with the restricted expression of HSP 70 and decreased PK C activity in the old rat brain.
    Notes: Zusammenfassung Chronischer bzw. wiederholter Streß kann eine Schädigung von Neuronen insbesondere im Hippocampus bewirken, wobei das Ausmaß der Schädigung bei verschiedenen Spezies unterschiedlich ist. Nach Sapolski besteht ein Zusammenhang zwischen hippocampaler Degeneration, gestörter Feedback-Reaktion und Glucocorticoid-Hypersekretion. Es sollte deshalb bei männlichen Wistar-Ratten zweier Altersgruppen (5–6 bzw. 17–24 Monate) geprüft werden, inwieweit die zelluläre Signalübertragung im Gerhirn über die Glucocorticoidrezeptoren (GR) im Alter verändert ist und welche zytoplasmatischen Faktoren/Modulatoren daran beteiligt sind. Die Bindung von 3H-Dexamethason an zytosolische GR sowie die Transformation, Translokation und Kernbindung von GR-Komplexen (GRK) wurden vor und nach physiologischem Streß untersucht. In parallelen Inkubationsansätzen wurde der Einfluß der zytoplasmatischen Modulatoren ASTP1) und HSP 701), die aus Hirnzytosol isoliert und gereinigt wurden, sowie von exogener PK C1) getestet. Während alte Kontrolltiere eine höhere zytosolische Konzentration von freien GR als junge aufwiesen, war diese 60 min nach Streß nur bei alten Tieren signifikant gegenüber den Kontrollen vermindert. Der an Zellkerne gebundene, transformierte GRK-Anteil war vor und nach Streß bei alten Tieren etwas niedriger als bei jungen. Zugabe von ASTP bzw. HSP 70 bei der Wärmetransformation der GRK erhöhte die Kernbindung leicht, jedoch bei gleichzeitiger Zugabe von PK C signifikant in beiden Altersgruppen. Bei Streßtieren war die GRK-Kernbindung gegenüber Kontrollen signifikant in beiden Gruppen erhöht, nach simultaner PK-C-Zugabe bei jungen Tieren sogar auf das Doppelte der Ausgangswerte. Gereinigter ASTP, isoliert aus dem Hirnzytosol junger Ratten, zeigte einen signifikant höheren 32P-Einbau nach Phosphorylierung in vitro als ASTP der alten Tiere. Die verminderte Phosphorylierung von ASTP könnte neben einer eingeschränkten Expression von HSP 70 und einer verminderten PK-C-Aktivität eine mögliche Ursache für die verzögerte Transformation/Translokation und verminderte Kernbindung der GRK im alten Rattenhirn sein.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Mathematical geology 28 (1996), S. 376-377 
    ISSN: 1573-8868
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Mathematics
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  • 3
    ISSN: 1573-7217
    Keywords: cicaprost ; experimental mammary tumors ; metastasis ; prostacyclin analogue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.
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  • 4
    ISSN: 1573-7373
    Keywords: glioma ; cytokine gene therapy ; interleukin-6 ; retroviral vector ; T9 glioblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell line, with a retroviral expression vector containing the human IL-6 cDNA and investigated the effects of IL-6 secretion on glioma formation in the syngeneic Fischer rat. Two subclones producing high and low levels (35 and 3.5 ng/106 cells/48 h) of IL-6 were identified and were termed T9.F/IL6/hi and T9.F/IL6/lo, respectively. Subcutaneous (SC) injection of 1×106 parental T9.F cells resulted in 100% tumor formation and progression. When 1×106 IL-6 secreting T9.F cells were injected SC, a small palpable tumor formed which sometimes regressed. In this regard, no tumors were detected after 30 days in 76% (13/17) of animals injected with T9.F/IL6/hi cells, whereas only 10% (1/10) of the rats injected with T9.F/IL6/lo cells completely rejected their tumors within this time frame. The addition of an IL-6 neutralizing antibody to the T9.F/IL6/hi SC inoculum followed by an intratumoral injection of the IL-6 neutralizing antibody, seven days later, abrogated the anti-tumor effects. Animals that rejected the IL-6 secreting tumors were 100% protected from subsequent intracranial (IC) challenges with the parental T9.F glioma as well as the original T9 glioblastoma; partially protected from an IC challenge with the unrelated, syngeneic RT-2 glioma; but were not protected from an IC challenge with the syngeneic MadB106 adenocarcinoma. When 1×104 cells were injected in the brain of naive animals, survival time was significantly increased for those rats implanted with T9.F/IL6/hi cells, but not T9.F/IL6/lo cells, as compared to animals implanted with T9.F parental cells (p=0.003). This study demonstrates that IL-6 secretion attenuates SC and IC glioma growth and SC rejection of IL-6 secreting T9.F cells induces long-term glioma immunity which is effective in the brain.
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  • 5
    ISSN: 1573-904X
    Keywords: amphotericin B ; lecithin ; emulsion ; stability ; monolayer ; low-dimensional structures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the interaction of the polyene antifungal amphotericin B with phospholipid Langmuir monolayers and to correlate with stability of phospholipid-stabilized drug emulsions. Methods. Pressure—area isotherms of mixed monolayers of amphotericin B (0–20 mol%) and different phospholipid types were recorded using conventional Langmuir trough methods. Emulsion stability of amphotericin B-containing lipid emulsions was measured using dynamic light scattering. Results. Incorporation of amphotericin B into monolayers composed of saturated phospholipids (Lipoid E80-3) had a profound effect on the shape of the isotherm. This effect was directly related to the concentration of amphotericin B in the monolayer. At high drug concentrations, the shape of the isotherms became progressively similar to that of pure DPPC, thus exhibiting regions attributable to phospholipid in different phase states. This effect on isotherm shape was not observed following incorporation of the drug into monolayers composed of the equivalent unsaturated lecithin (Lipoid E80). Conclusions. These results are interpreted as indicating the formation of an amphotericin B-phospholipid complex, resulting in phase separation within the monolayer. The extent and nature of this phase separation was dependent on both the concentration of drug in the system, and the saturation state of the phospholipid component. The relevance of these observations to the stability of amphotericin B drug emulsions stabilised by saturated and unsaturated phospholipid emulsifiers is discussed. These observations may also be relevant to the toxicity of these, and other novel amphotericin B formulations.
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  • 6
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract A experimental method to measure the fate and distribution of a variety of radionuclides under the ChemChar gasification process has been developed. The elements studied were arsenic, mercury, thorium, protactinium, uranium and neptunium. Results indicate that the ChemChar gasification system quantitatively retains these elements. In all of the cases except mercury the radiotracer was found to reside on the char matrix with small amounts (〈1%) being found downstream in the condensation trap and char filter. Mercury, presumably as vapor, was entrained and distributed in significant amounts (≈40%) to the downstream char filter and its pre-filter. A methodology was developed to account for char height differences in quantifying the radiotracer on the char prior and subsequent to gasification. These results demonstrate the efficacy of using relatively short-lived radiotracers to characterize the behavior of hazardous elements during waste treatment via gasification.
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  • 7
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The Californium User Facility for Neutron Science has been established at Oak Ridge National Laboratory (ORNL). The Californium Use Facility (CUF) is a part of the larger Californium Facility, which fabricates and stores compact252Cf neutron sources for worldwide distribution. The CUF can provide a cost-effective option for research with252Cf sources. Three projects at the CUF that demonstrate the versatility of252Cf for biological and biomedical neutron-based research are described: future establishment of a252Cf-based neutron activation analysis system, ongoing work to produce miniature high-intensity, remotely afterloaded252Cf sources for tumors therapy, and a recent experiment that irradiated living human lung cancer cells impregnated with experimental boron compounds to test their effectiveness for boron neutron capture therapy.
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  • 8
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of protein gene product 9.5 (PGP) and ubiquitin in the spermatozoa and epithelial cells in the different regions of the rat duetus epididymidis (proximal caput, distal caput, corpus and cauda) was studied by Western blotting analyses and electron microscopical immunogold labelling. Western blotting analyses showed that the PGP immunoreactive band was very intense in the caput and cauda epididymidis and almost irrelevant in the corpus, while the ubiquitin immunoreactive band was intense in the distal caput and cauda. No ubiquitin immunoreactive band was observed in the proximal caput and only a very weak band was seen in the corpus. The results of electron microscopical immunogold labelling varied from one epididymal region to another. The proximal caput epididymidis presented immunoreaction to PGP in the rough endoplasmic reticulum, cytosol, mitochondria and microvilli of most principal cells, and in the cytosol, rough endoplasmic reticulum and mitochondria of most basal cells. No ubiquitin immunoreaction was observed in this epididymal region. In the distal caput epididymidis, PGP immunoreactivity was detected in some principal and basal cells in the same intracellular locations as described in the proximal caput. In this region, ubiquitin immunoreactivity appears in the apical cytosol and mitochondria of principal cells. The corpus epididymidis showed no immunoreaction to PGP or ubiquitin. In the cauda epididymidis, immunostaining to PGP was observed in most clear cells and in isolated principal cells. The intracellular location of PGP in both cell types was the cytosol, mitochondria and microvilli. Ubiquitin immunoreactivity was detected in the perinuclear cytosol and mitochondria — but not in the digestive vacuoles — of some clear cells. Scanty ubiquitin immunolabelling was also found in the microvilli, cytosol and mitochondria of some principal cells. The head of the spermatozoa present in the ductal lumen in all epididymal regions immunoreacted intensely to PGP. Ubiquitin was detected in the intermediate piece and residual cytoplasm of intraluminal spermatozoa present in the corpus and cauda epididymidis. These findings suggest that a non-ubiquitinated PGP irnrnunoreactive protein is secreted by the principal cells in caput epididymidis and binds the spermatozoon heads. It is possible that the clear cells of the cauda epididymidis secrete the ubiquitin that binds to spermatozoon tail.
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  • 9
    ISSN: 1615-5947
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 10
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of protein gene product 9.5 (PGP) and ubiquitin in the spermatozoa and epithelial cells in the different regions of the rat duetus epididymidis (proximal caput, distal caput, corpus and cauda) was studied by Western blotting analyses and electron microscopical immunogold labelling. Western blotting analyses showed that the PGP immunoreactive band was very intense in the caput and cauda epididymidis and almost irrelevant in the corpus, while the ubiquitin immunoreactive band was intense in the distal caput and cauda. No ubiquitin immunoreactive band was observed in the proximal caput and only a very weak band was seen in the corpus. The results of electron microscopical immunogold labelling varied from one epididymal region to another. The proximal caput epididymidis presented immunoreaction to PGP in the rough endoplasmic reticulum, cytosol, mitochondria and microvilli of most principal cells, and in the cytosol, rough endoplasmic reticulum and mitochondria of most basal cells. No ubiquitin immunoreaction was observed in this epididymal region. In the distal caput epididymidis, PGP immunoreactivity was detected in some principal and basal cells in the same intracellular locations as described in the proximal caput. In this region, ubiquitin immunoreactivity appears in the apical cytosol and mitochondria of principal cells. The corpus epididymidis showed no immunoreaction to PGP or ubiquitin. In the cauda epididymidis, immunostaining to PGP was observed in most clear cells and in isolated principal cells. The intracellular location of PGP in both cell types was the cytosol, mitochondria and microvilli. Ubiquitin immunoreactivity was detected in the perinuclear cytosol and mitochondria — but not in the digestive vacuoles — of some clear cells. Scanty ubiquitin immunolabelling was also found in the microvilli, cytosol and mitochondria of some principal cells. The head of the spermatozoa present in the ductal lumen in all epididymal regions immunoreacted intensely to PGP. Ubiquitin was detected in the intermediate piece and residual cytoplasm of intraluminal spermatozoa present in the corpus and cauda epididymidis. These findings suggest that a non-ubiquitinated PGP irnrnunoreactive protein is secreted by the principal cells in caput epididymidis and binds the spermatozoon heads. It is possible that the clear cells of the cauda epididymidis secrete the ubiquitin that binds to spermatozoon tail.
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