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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: TGFβ1 is a multipotent secreted cytokine that plays a pivotal role in wound healing. Previously, both positive and negative effects of TGFβ1 on cutaneous wound healing have been reported. The mechanisms underlying these effects of TGFβ1 remain to be elucidated. In the present study, we used a mouse model to examine the effects of cutaneous wound healing, wherein the latent form of TGFβ1 is constitutively expressed in basal keratinocytes of the mouse epidermis, targeted by the keratin 5 promoter (K5.TGFβ1). In wild-type mice with 6-mm full thickness excisional cutaneous wounds, TGFβ1 protein levels were elevated immediately after wounding, and reached a peak level on day 3 postwounding, which was 3–5-fold higher than that in the nonwounded skin, and sharply declined afterward. This elevated expression pattern suggests that only transient TGFβ1 overexpression is required for normal wound healing. In contrast, K5.TGFβ1 mice with prolonged TGFβ1 transgene expression at the level equivalent to the above peak level in wild-type mice exhibited a significant delay in healing of 6-mm full thickness excisional wounds when compared to wild-type mice. Histological analysis of wounds revealed delayed reepithelialization, increased inflammation and prolonged granular tissue accumulation in K5.TGFβ1wt mice. Immunohistochemistry analysis revealed excessive leukocyte infiltration in transgenic wounds when compared to wild-type wounds. Understandably, the accumulation of leukocytes was also accompanied by increased expression of inflammatory cytokines, chemokines, angiogenic factors and fibrotic factors as determined by qRT-PCR analysis. Although the above factors override the growth inhibitory effect of TGFβ1 on epidermal proliferation away from the wound edge, proliferation at the leading edge of the migrating keratinocytes was reduced in transgenic skin compared to the nontransgenic skin, evident by PCNA staining. Keratinocyte proliferation was also reduced in vitro when assessed by H3-thymidine incorporation. To assess the direct effect of TGFβ1 on keratinocyte migration, we performed an in vitro migration assay and found that K5.TGFβ1 keratinocytes had delayed migration when compared with wild-type cells. Our study suggests that prolonged TGFβ1 expression in keratinocytes delays cutaneous wound healing by excessive inflammation, coupled to a direct inhibitory effect on keratinocyte proliferation and migration.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Previous study has shown that cholecystokinin (CCK) octapeptide (CCK-8) suppressed the binding of opioid receptors to the universal opioid agonist [3H]etorphine. In the present study, highly selective tritium-labeled agonists for the μ- {[tyrosyl-3,5-3H][d-Ala2,MePhe4,Gly-ol5]enkephalin ([3H]DAGO)}, δ- {[tyrosyl-3,5-3H][d-Pen2,5]enkephalin ([3H]DPDPE)}, and k- ([3H]U69,593) opioid receptors were used to clarify which type(s) of opioid receptor in rat brain homogenates is suppressed by CCK-8. In the competition experiments, CCK-8 suppressed the binding of [3H]DAGO and [3H]U69,593 but not that of [3H]DPDPE to the respective opioid receptor. This effect was blocked by the CCK antagonist proglumide at 1 μmol/L. In the saturation experiments. CCK-8 at concentrations of 0.1 nmol/L to 1 μmol/L decreased the Bmax of [3H]DAGO binding sites without affecting the KD; on the other hand, CCK-8 increased the KD of [3H]U69,593 binding without changing the Bmax. The results suggest that CCK-8 inhibits the binding of μ- and K-opioid receptors via the activation of CCK receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 83 (1985), S. 4554-4561 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: A three variable thermokinetic model of ignition is devised to describe the gas-phase oxidation of hydrocarbons in CSTR. For a single set of thermokinetic parameters, the model displays steady states, bistability, cool flame oscillation, simple ignition oscillation, and complex ignition-cool flame oscillations, when the reactant pressure P and vessel temperature T0 are varied as control parameters. The predicted P-T0 state diagram compares fairly well with the experimental finding for the system of acetaldehyde/oxygen. The model also predicts interesting bifurcation sequences of complex periodic states. The proposed skeleton model is justified qualitatively by considering detailed kinetics in the oxidation of acetaldehyde.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 28 (2001), S. 165-168 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The β-catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine. c-Myc a downstream target of β-catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro. To determine the role of c-Myc in epidermal stem cells in ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillan Magazines Ltd.
    Nature 398 (1999), S. 708-713 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The p53 tumour suppressor is a transcription factor that regulates the progression of the cell through its cycle and cell death (apoptosis) in response to environmental stimuli such as DNA damage and hypoxia. Even though p53 modulates these critical cellular processes, mice that lack p53 are ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Communications in mathematical physics 131 (1990), S. 317-332 
    ISSN: 1432-0916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Physics
    Notes: Abstract The Newhouse phenomenon of infinitely many coexisting periodic attractors is studied in its simplest form. One shows that the corresponding parameter set (the Newhouse set)J N has a strictly positive Hausdorff dimension. This result is stronger than that of Tedeschini-Lalli and Yorke [Commun. Math. Phys.106, 635 (1986)] concerning the Lebesgue measure of the Newhouse set; and is complementary to our knowledge on the topological properties ofJ N, namely it is a residual set, hence uncountable and everywhere dense in a parameter interval.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 279-287 
    ISSN: 1432-1335
    Keywords: Carcinogenesis ; Tumor promotion ; protein kinase C ; Mouse epidermis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the current study, the protein kinase C (PKC) isozymes present in mouse epidermis have been identified using immunological and chromatographic methods. Six PKC isozymes, PKCα, PKCβ, PKCγ, PKCδ, PKCε, and PKCζ, were identified in unfractionated epidermal preparations by protein immunoblotting. The subcellular distribution and presence of these isozymes was further verified by hydroxyapatite (HA) chromatography with the exception of PKEε, which could not be detected following HA chromatography. The five PKC isozymes recovered following HA chromatography were detected in both epidermal cytosol and particulate fractions, although PKCδ was found in a much higher proportion relative to the other PKC isozymes in the particulate fraction using histone H1 as the substrate. The biochemical properties of the epidermal PKC isozymes partially purified by HA chromatography agreed with those reported for other tissues and further supported their immunological identification in epidermal preparations. The activities of HA chromatography peaks corresponding to PKCα, PKCβ, and PKCγ were found to be dependent on both Ca2+ and phosphatidylserine (PtdSer), whereas, the activities of HA peaks corresponding to PKCδ and PKCζ were Ca2+-independent but PtdSer-dependent. The HA peak corresponding to PKCγ also displayed a characteristic biphasic modulation by arachidonic acid (activation at low, inactivation at high concentrations) and inactivation by preincubation with PtdSer. PKCζ activity was also characteristic, in that it was dependent on PtdSer and was not increased by the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate. Some differences in substrate specificity were also observed between the epidermal PKC isozymes. The presence of multiple isozymes of PKC in mouse epidermis suggests that the different isozymes may play distinct roles in signal transduction and tumor promotion in this tissue.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of computational neuroscience 5 (1998), S. 53-69 
    ISSN: 1573-6873
    Keywords: sleep spindle rhythm ; thalamus ; GABAB receptor ; wavefront velocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Medicine , Physics
    Notes: Abstract A reduction method is used to analyze a spatially structured network model of inhibitory neurons. This network model displays wave propagation of postinhibitory rebound activity, which depends on GABAB synaptic interactions among the neurons. The reduced model allows explicit solutions for the wavefronts and their velocity as a function of various parameters, such as the synaptic coupling strength. These predictions are shown to agree well with the numerical simulations of the conductance-based biophysical model.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of computational neuroscience 5 (1998), S. 383-405 
    ISSN: 1573-6873
    Keywords: working memory ; prefrontal cortex ; bistability ; network attractor dynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Medicine , Physics
    Notes: Abstract We report a computer simulation of the visuospatial delayed-response experiments of Funahashi et al. (1989), using a firing-rate model that combines intrinsic cellular bistability with the recurrent local network architecture of the neocortex. In our model, the visuospatial working memory is stored in the form of a continuum of network activity profiles that coexist with a spontaneous activity state. These neuronal firing patterns provide a population code for the cue position in a graded manner. We show that neuronal persistent activity and tuning curves of delay-period activity (memory fields) can be generated by an excitatory feedback circuit and recurrent synaptic inhibition. However, if the memory fields are constructed solely by network mechanisms, noise may induce a random drift over time in the encoded cue position, so that the working memory storage becomes unreliable. Furthermore, a “distraction” stimulus presented during the delay period produces a systematic shift in the encoded cue position. We found that the working memory performance can be rendered robust against noise and distraction stimuli if single neurons are endowed with cellular bistability (presumably due to intrinsic ion channel mechanisms) that is conditional and realized only with sustained synaptic inputs from the recurrent network. We discuss how cellular bistability at the single cell level may be detected by analysis of spike trains recorded during delay-period activity and how local modulation of intrinsic cell properties and/or synaptic transmission can alter the memory fields of individual neurons in the prefrontal cortex.
    Type of Medium: Electronic Resource
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