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  • 1
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 80 (2002), S. 3367-3369 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A large low-field magnetoresistance (MR) slightly above the metal–insulator transition temperature (234 K) was observed in single-crystalline Pr0.7Pb0.3MnO3. Combining the temperature dependence of magnetization, resistance, and electron spin resonance spectra, it was suggested that phase separation occurs above the Curie temperature; ferromagnetic metallic clusters imbedding in the insulating paramagnetic matrix, and spin-polarized electron tunneling between isolated ferromagnetic clusters should be responsible for the large low-field MR observed. Undoubtedly, this observation opens a window to explore large low-field MR at high temperature, which is very important for the practical application of colossal MR effect. © 2002 American Institute of Physics.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 78 (2001), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have revealed that activation of rat striatal D1 dopamine receptors stimulates both adenylyl cyclase and phospholipase C via Gs and Gq, respectively. The differential distribution of these systems in brain supports the existence of distinct receptor systems. The present communication extends the study by examining other brain regions: hippocampus, amygdala, and frontal cortex. In membrane preparations of these brain regions, selective stimulation of D1 dopamine receptors increases the hydrolysis of phosphatidylinositol/phosphatidylinositol 4,5-biphosphate. In these brain regions, D1 dopamine receptors couple differentially to multiple Gα protein subunits. Antisera against Gαq blocks dopamine-stimulated PIP2 hydrolysis in hippocampal and in striatal membranes. The binding of [35S]GTPγS or [α-32P]GTP to Gαi was enhanced in all brain regions. Dopamine also increased the binding of [35S]GTPγS or [α-32P]GTP to Gαq in these brain regions: hippocampus = amygdala 〉 frontal cortex. However, dopamine-stimulated binding of [35S]GTPγS to Gαs only in the frontal cortex and striatum. This differential coupling profile in the brain regions was not related to a differential regional distribution of the Gα proteins. Dopamine induced increases in GTPγS binding to Gαs and Gαq was blocked by the D1 antagonist SCH23390 but not by D2 receptor antagonist l-sulpiride, suggesting that D1 dopamine receptors couple to both Gαs and Gαq proteins. Co-immunoprecipitation of Gα proteins with receptor-binding sites indicate that in the frontal cortex, D1 dopamine-binding sites are associated with both Gαs and Gαq and, in hippocampus or amygdala, D1 dopamine receptors couple solely to Gαq. The results indicate that in addition to the D1/Gs/adenylyl cyclase system, brain D1-like dopamine receptor sites activate phospholipase C through Gαq protein.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 78 (2001), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Using the inactivation of mitochondrial and cytosolic aconitases as markers of compartment-specific superoxide (O2−) production, we show that oxygen-glucose deprivation (OGD) or excitotoxin exposure produce a time-dependent inactivation of mitochondrial, but not cytosolic, aconitase in cortical cultures. To determine if mitochondrial O2− production was an important determinant in neuronal death resulting from OGD, metalloporphyrins with varying superoxide dismutase (SOD) activity were tested for their ability to protect against mitochondrial aconitase inactivation and cell death. OGD-induced mitochondrial aconitase inactivation and cell death was inhibited by manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), manganese tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) and NMDA receptor antagonists. By contrast, NMDA- or kainate (KA)-induced mitochondrial aconitase inactivation and cell death was inhibited by MnTBAP, but not MnTE-2-PyP. Moreover, both MnTBAP and MnTE-2-PyP penetrated mitochondrial fractions of cortical cells. These data suggest that mitochondrial aconitase inactivation closely correlates with subsequent neuronal death following excitotoxicity produced by OGD or NMDA/KA exposure. Assessment of biological rather biochemical antioxidant activities better predicted neuroprotection by metalloporphyrins. Moreover, antioxidants that protect oxidant-sensitive mitochondrial targets such as aconitase may be useful as therapies for disease states involving excitotoxicity.
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previously a distinct D1-like dopamine receptor (DAR) that selectively couples to phospholipase C/phosphatidylinositol (PLC/PI) was proposed. However, lack of a selective agonist has limited efforts aimed at characterizing this receptor. We characterized the in vitro and in vivo effects of SKF83959 in regulating PI metabolism. SKF83959 stimulates (EC50, 8 µm) phosphatidylinositol 4,5-biphosphate hydrolysis in membranes of frontal cortex (FC) but not in membranes from PC12 cells expressing classical D1A DARs. Stimulation of FC PI metabolism was attenuated by the D1 antagonist, SCH23390, indicating that SKF83959 activates a D1-like DAR. The PI-linked DAR is located in hippocampus, cerebellum, striatum and FC. Most significantly, administration of SKF83959 induced accumulations of IP3 in striatum and hippocampus. In contrast to other D1 DAR agonists, SKF83959 did not increase cAMP production in brain or in D1A DAR-expressing PC12 cell membranes. However, SKF83959 inhibited cAMP elevation elicited by the D1A DAR agonist, SKF81297, indicating that the compound is an antagonist of the classical D1A DAR. Lastly, we demonstrated that SKF83959 enhances [35S]guanosine 5′-O-(3-thiotriphosphate) binding to membrane Gαq and Gαi proteins, suggesting that PI stimulation is mediated by activation of these guanine nucleotide-binding regulatory proteins. Results indicate that SKF83959 is a selective agonist for the PI-linked D1-like DAR, providing a unique tool for investigating the functions of this brain D1 DAR subtype.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 31 (2004), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The 5-HT2A receptor belongs to the G-protein superfamily. It plays an important role in vascular regulation.2. Previous reports in the UK have indicated that there is an association of the T102C genetic polymorphism of the 5-HT2A receptor with hypertension, but no studies have been made on the T102C genetic polymorphism in Chinese hypertensive patients. In the present study, we investigated the T102C genetic polymorphism of 5-HT2A receptors in Chinese hypertensive patients to determine whether there is an association of this polymorphism with hypertension in Chinese.3. The present study was conducted on 198 hypertensive patients and 164 healthy controls. Polymerase chain reaction–restriction fragment length polymorphism was used to identify the T102C genetic polymorphism of the 5-HT2A receptor.4. In the present study, the C allele frequency of the 5-HT2A receptor genetic polymorphism was 0.343 in hypertensive patients, which was not significantly different to that in healthy controls (0.393; χ2 = 1.922; P = 0.166; odds ratio = 0.807, 95% confidence interval 0.596–1.093). In addition, no gender differences were observed.5. In conclusion, to our knowledge, this is the first report on the T102C genetic polymorphism of the 5-HT2A receptor in Chinese hypertensive patients. We find that no correlation exists between the T102C genetic polymorphism and hypertension, which affords useful information on the pathogenesis of hypertension in the Chinese population.
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Journal of cutaneous pathology 31 (2004), S. 0 
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers.Methods:  Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed.Results:  Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p ≤ 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p ≤ 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = −0.4, p = 0.0001). Skp2 cytoplasmic labeling index of 〉20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis.Conclusions:  Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Journal of cutaneous pathology 30 (2003), S. 0 
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Lichen aureus is localized variant of persistent pigmented purpuric dermatitis that typically affects the legs and can be associated with delayed hypersensitivity reactions or vascular abnormalities. Plasma cell vulvitis (Zoon's vulvitis) is a rare condition that frequently contains hemosiderin deposits and is suspected to be a mucosal reaction pattern due to variety of insults, most often local irritation or trauma.Case Report:  A 50-year-old female with longstanding complaints of spotting, vulvar dryness, irritation, and dyspareunia presented with circumscribed, purpuric, erythematous vulvar patches. Past estrogen cream treatment evoked symptoms of discomfort. On biopsy, siderophages and extravasated red blood cells were found in conjunction with a lichenoid, lymphocyte and plasma cell infiltrate, and dilated dermal and intraepithelial vessels.Conclusions:  Reported herein is an unusual vulvar dermatosis that is best classified as a localized variant of persistent pigmented dermatosis (lichen aureus) but overlaps clinically and histologically with Zoon's vulvitis. This constellation of findings may represent a site-specific mucosal reaction to an erosive process that could either be inflammatory (hypersensitivity reaction) and/or traumatic in nature.
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  • 8
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The devR-devS two-component system of Mycobacterium tuberculosis was identified earlier and partially characterized in our laboratory. A devR::kan mutant of M. tuberculosis was constructed by allelic exchange. The devR mutant strain showed reduced cell-to-cell adherence in comparison to the parental strain in laboratory culture media. This phenotype was reversed on complementation with a wild-type copy of devR. The devR mutant and parental strains grew at equivalent rates within human monocytes either in the absence or in the presence of lymphocytic cells. The expression of DevR was not modulated upon entry of M. tuberculosis into human monocytes. However, guinea pigs infected with the mutant strain showed a significant decrease in gross lesions in lung, liver and spleen; only mild pathological changes in liver and lung; and a nearly 3 log lower bacterial burden in spleen compared to guinea pigs infected with the parental strain. Our results suggest that DevR is required for virulence in guinea pigs but is not essential for entry, survival and multiplication of M. tuberculosis within human monocytes in vitro. The attenuation in virulence of the devR mutant in guinea pigs together with DevR-DevS being a bona fide signal transduction system indicates that DevR plays a critical and regulatory role in the adaptation and survival of M. tuberculosis within tissues.
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Despite the convenience of self-pollination (selfing) in flowering plants , the detrimental effects of inbreeding that follow repeated selfing have promoted strong natural selection for mating systems that ensure successful cross-fertilization (outcrossing). Here we describe a mechanism ...
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  • 10
    ISSN: 1432-0851
    Keywords: Key words Intracellular cytokine pattern ; Th1/Th2 cell ; Tc1/Tc2 cell ; Acute lymphoblastic leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: During an ongoing immune response, cytokines produced by T helper types 1 (Th1) and 2 (Th2) together with T cytotoxic types 1 (Tc1) and 2 (Tc2) are critical to the effectiveness of that response. Dysregulated expansion of one or the other subset may contribute to the impaired function of the T-cell-mediated immune system in cancer patients. In the present study we have investigated whether such dysregulation might exist in children with acute lymphoblastic leukemia (ALL). Methods: We analyzed 61 blood samples from 45 children with B cell precursor ALL and 16 healthy children. Interleukin(IL)-2, IL-4, and interferon γ (IFNγ) production of their respective purified CD4+ and CD8+ T cells were assessed at the single-cell level by intracellular-cytokine-staining flow cytometry. Results: At the time of diagnosis, IL-2-producing cell populations in CD4+ and CD8+ T cells were reduced below the normal range in 31 of 44 (70.5%) and 23 of 38 (60.5%) cases respectively. Similarly, IFNγ-producing cell populations in CD4+ and CD8+ T cells decreased in 17 of 44 (38.6%) and 18 of 38 (47.4%) cases respectively. Conversely cell populations capable of IL-4 production in CD4+ and CD8+ T cell subsets were increased in 13 of 30 (43.3%) and 15 of 30 (50.0%) cases respectively. Therefore, the Th1-to-Th2 and Tc1-to-Tc2 ratios (1.6 ± 2.2 and 7.7 ± 6.7 respectively) were significantly lower in peripheral blood T cells of ALL patients (n = 30) than those (6.0 ± 2.9 and 20.1 ± 10.3 respectively) in 15 healthy controls (P 〈 0.0001). Although both CD45RA+/CD4+ and CD45RA+/CD8+ cells significantly increased in 43 ALL patients (P 〈 0.05), there existed no apparent correlation between CD45 isoform expression and cytokine (IL-2 and IFNγ) production. Interestingly, the ability to produce both IL-2 and IFNγ was recovered in 8 cases examined, after complete remission had been achieved. Conclusion: These observations suggest that, in both CD4+ and CD8+ T cells of ALL patients, there is a dysregulation in the functionality of Th1 (Tc1) and Th2 (Tc2) cells with a gross reduction of Th1 (Tc1) cell populations and an expansion in Th2 (Tc2).
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