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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The motor signs of Parkinson's disease have been partly attributed to an overinhibition of the external globus pallidus (GP) that results from hyperactivity of striatopallidal GABA/enkephalinergic neurons. The goals of this study were to measure basal levels of extracellular fluid GABA in the GP of normal cats, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian cats and cats spontaneously recovered from MPTP-induced parkinsonism, and to examine the effects of opioid receptor activation on potassium (K+)-evoked GABA release in the GP in these animals. Basal GP GABA levels were increased 75% from normal in parkinsonian animals 1 week after MPTP administration and returned to control levels in recovered animals 6 weeks afterMPTP administration. No significant differences were observed in K+-evoked GABA release across conditions. The opioid receptor agonist [D-Ala2]-Met-Enkephalinamide (DALA) significantly attenuated K+-evoked GABA release in the GP of MPTP-treated symptomatic and recovered cats, but had no significant effect on GABA release in normal animals. These data show that basal GP GABA levels are elevated coincident with expression of parkinsonian signs and return to normal in animals that have functionally compensated for a nigrostriatal lesion. DALA-induced inhibition of pallidal GABA release after a dopamine-depleting lesion, suggests that enkephalin may attenuate GABA release in the GP specifically after striatal dopamine loss.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 641 (1992), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    International journal of thermophysics 11 (1990), S. 889-896 
    ISSN: 1572-9567
    Keywords: binary mixtures ; ethane ; fugacity ; hydrogen mixtures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The fugacity coefficients of hydrogen in binary mixtures with ethane were measured. Data were taken using an experimental chamber which is divided into two regions by a semipermeable membrane through which hydrogen, but not ethane, can penetrate. The measurement of the gas pressures inside and outside the membrane gives the hydrogen component fugacity at a given temperature, binary mixture mole fraction, and mixture pressure. In this paper, results are reported at mixture pressures of 5.25, 6.97, 10.21, and 13.47 MPa. In each case, the temperature of the mixture was maintained at an average value of 130°C (403.15 K). The general qualitative features of the data are discussed, and comparisons are made with predictions obtained from the Redlich-Kwong and Peng-Robinson equations of state.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    International journal of thermophysics 8 (1987), S. 437-447 
    ISSN: 1572-9567
    Keywords: ethane ; fugacity ; hydrogen ; mixtures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The fugacity coefficients of hydrogen in binary mixtures with ethane were measured using a physical equilibrium technique. This technique involves the use of an experimental chamber which is divided into two regions by a semipermeable membrane through which hydrogen, but not ethane, can penetrate. Measurement of the gas pressures inside and outside of the membrane allows a direct measurement of the hydrogen component fugacity coefficient at a given temperature and binary-mixture mole fraction. In this paper, results are reported at 101, 116, 141, 151, 160, and 190°C. In each case the total pressure of the mixture was maintained at 3.41 MPa. The qualitative features of the measurements are discussed and comparisons are made with predictions obtained from the Redlich-Kwong, Peng-Robinson, and extended corresponding-states models.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    International journal of thermophysics 9 (1988), S. 525-534 
    ISSN: 1572-9567
    Keywords: carbon monoxide ; fugacity ; hydrogen mixtures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The fugacity coefficients of hydrogen in binary mixtures with carbon monoxide were measured using a physical equilibrium technique. This technique involves the use of an experimental chamber which is divided into two regions by a semipermeable membrane through which hydrogen, but not carbon monoxide, can penetrate. Measurement of the gas pressures inside and outside of the membrane allows a direct measurement of the hydrogen component fugacity at a given temperature and binary mixture mole fraction. In this paper, results are reported at 130, 160, and 190°C. In each case, the total pressure of the mixture was maintained at a nominal value of 3.39 MPa. The general qualitative features of the data are discussed, and comparisons are made with predictions obtained from the Redlich-Kwong, Peng-Robinson-Soave, and extended corresponding-state models.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 539-548 
    ISSN: 0021-9304
    Keywords: cytokine delivery via covalent binding ; tissue repair ; biomaterials ; collagen ; transforming growth factor β ; polyethylene glycol ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To overcome rapid diffusion and clearance from the implant site and to increase stability, recombinant transforming growth factor β2 (TGF-β2) was covalently bound to injectable bovine dermal fibrillar collagen (FC) and its activity compared to admixed TGF-β2. Covalent binding was achieved in a two-step procedure: First, TGF-β2 was reacted with the difunctional polyethylene glycol (PEG) linker, and then the PEG-attached TGF-β2 (PEG-TGF-β2) was bound to the fibrillar collagen (FC-PEG-TGF-β2). Initial binding of TGF-β2 to difunctional succinimidyl glutarate (D-SG-PEG) or succinimidyl propionate polyethylene glycol (D-SE-PEG) linkers was completed after reacting for 8 or 10 min as monitored by reverse-phase high-performance liquid chromatography. After reaction with injectable fibrillar collagen, extraction of unbound PEG-TGF-β2 and Western blot analysis, using a TGF-β specific antibody, demonstrated that at least 85% of the TGF-β2 was bound to the fibrillar collagen. The activity of PEG-TGF-β2 was fully stable in phosphate-buffered saline at 4°C and 37°C for at least up to 4 weeks. Unmodified TGF-β2 mixed with fibrillar collagen was completely inactivated after 1 week of incubation, as measured by the mink lung epithelial cell (Mv1Lu) growth inhibition assay. Formulations of FC-PEG-TGF-β2 containing 40 μg/mL TGF-β2 were implanted subcutaneously into rats and analyzed after days 7, 21, and 42. All TGF-β2-containing formulations showed the TGF-β typical fibroblastic response at the day 7 time point. Covalent binding of TGF-β2 to collagen with both difunctional PEG crosslinkers resulted in a significantly stronger and longer-lasting TGF-β2 response than that observed with admixed formulations of collagen and TGF-β. The TGF-β response with FC-PEG-TGF-β2 lasted up to day 42 but was not seen after day 7 for TGF-β2 admixed to FC. These findings clearly demonstrate that TGF-β2 remains fully active after being covalently bound to collagen via difunctional PEG. In addition, covalent binding potentiates and prolongs in vivo TGF-β responses and stabilizes the TGF-β in vitro. Results suggest that this method of formulation could be useful to stabilize and deliver similar peptide growth factors or biologically active agents. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 539-548, 1998.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Letters Edition 13 (1975), S. 215-219 
    ISSN: 0360-6384
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2015-11-11
    Description: Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis , the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo ; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis , A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 9
    Publication Date: 2015-12-29
    Description: Pneumonic plague represents the most severe form of disease caused by Yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. The Y. pestis outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by Y. pestis in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A 2 activities of Prdx6. In addition, we found that infection with wild-type Y. pestis reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with pla Y. pestis , suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or pla Y. pestis , Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function in vitro and reduce Prdx6 levels in vivo , the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 10
    Publication Date: 2016-03-11
    Description: Evidence shows that factor VIII (FVIII) ectopically expressed in platelets (2bF8) is therapeutic in FVIII null mice even with anti-FVIII inhibitory antibodies (inhibitors). If current efforts to generate platelets in vitro succeed, genetically manipulated platelets containing FVIII may be used therapeutically in hemophilia A patients with inhibitors. One important concern is the immunogenicity of platelet-derived FVIII. To address this concern, we infused 2bF8 transgenic (2bF8 Tg ) platelets into naïve FVIII null mice weekly for 8 weeks. No anti-FVIII antibodies were detected in the infused animals during the study course. We then explored whether platelet-derived FVIII is immunogenic in FVIII null mice with inhibitors. The 2bF8 Tg platelets were transfused into rhF8-primed FVIII null mice, resulting in no augmentation of anti-FVIII antibodies. To investigate whether preconditioning affects the immune response, animals were sublethally irradiated and subsequently transfused with 2bF8 Tg platelets. No anti-FVIII antibodies were detected in the recipients after platelet infusions. Following further challenge with rhF8, the inhibitor titer in this group was significantly lower than in naïve FVIII null mice utilizing the same immunization protocol. Thus, our data demonstrate that infusion of platelets containing FVIII triggers neither primary nor memory anti-FVIII immune response in FVIII null mice and that sublethal irradiation plus 2bF8 Tg platelet infusion suppresses anti-FVIII immune response in FVIII null mice.
    Keywords: Thrombosis and Hemostasis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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