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  • 2000-2004  (26)
  • 1970-1974
  • 1930-1934
  • 1900-1904
  • 2004  (26)
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  • 2000-2004  (26)
  • 1970-1974
  • 1930-1934
  • 1900-1904
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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent data suggests that metallothioneins (MTs) are major neuroprotective proteins within the CNS. In this regard, we have recently demonstrated that MT-IIA (the major human MT-I/-II isoform) promotes neural recovery following focal cortical brain injury. To further investigate the role of MTs in cortical brain injury, MT-I/-II expression was examined in several different experimental models of cortical neuron injury. While MT-I/-II immunoreactivity was not detectable in the uninjured rat neocortex, by 4 days, following a focal cortical brain injury, MT-I/-II was found in astrocytes aligned along the injury site. At latter time points, astrocytes, at a distance up to several hundred microns from the original injury tract, were MT-I/-II immunoreactive. Induced MT-I/-II was found both within the cell body and processes. Using a cortical neuron/astrocyte co-culture model, we observed a similar MT-I/-II response following in vitro injury. Intriguingly, scratch wound injury in pure astrocyte cultures resulted in no change in MT-I/-II expression. This suggests that MT induction was specifically elicited by neuronal injury. Based upon recent reports indicating that MT-I/-II are major neuroprotective proteins within the brain, our results provide further evidence that MT-I/-II plays an important role in the cellular response to neuronal injury.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 90 (2004), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Oligodendroglial cytoplasmic inclusions composed of α-synuclein filamentous aggregates are the pathological hallmark of multiple system atrophy (MSA). We found that cortical tissue from MSA cases contains increased detergent-resistant high-molecular-weight α-synuclein species. To analyse these species, we immunopurified α-synuclein aggregates from pathological samples and examined their ultrastructures using scanning electron and atomic force microscopies. Purified aggregates consisted of bundles of filaments. After treatment with 1% sarcosine or 2% 3-[(3-cholamidopropyl) dimethyl-ammonio]-1-propanesulfonate (CHAPS) detergents, we observed frequent 30–50 nm annular particles, probably released from pathological aggregates due to the dissociation of filaments by the detergents. Antibody recognition imaging using a specific anti-α-synuclein antibody confirmed that the annular structures were positive for α-synuclein. In contrast to pathological α-synuclein, detergent treatment of recombinant α-synuclein yielded only smaller, 10–18 nm spherical particles. Our results demonstrate that detergent treatment of pathological MSA α-synuclein aggregates, but not recombinant α-synuclein, yields discrete α-synuclein-positive species with annular morphologies. The ability of the pathological α-synuclein to form annular aggregates may be an important factor contributing to the toxicity of the protein in disease that may have implications in designing therapeutic strategies aimed at detoxifying α-synuclein aggregates.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Male rat pups (21 days old) were placed on a diet deficient in n-3 polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing α-linolenic acid (α-LNA; 18 : 3n-3). After 15 weeks on a diet, [4,5-3H]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral cerebral ventricle, and the rats were killed at fixed times over a period of 60 days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by plotting log10 (DHA radioactivity) against time after tracer injection, equaled 33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in phosphatidylserine; all had a decay slope significantly greater than 0 (p 〈 0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or greater, and calculated rates of DHA loss from brain, Jout, were reduced. Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and to do so even more effectively in the face of reduced n-3 PUFA availability for only 15 weeks.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim : To assess the pharmacokinetics of alosetron, its effect on in vivo enzyme activities, and influence of demographic factors during repeated dosing.Methods : Thirty healthy men and women received 1 mg oral alosetron twice-daily for 29.5 days and a single oral dose of a metabolic probe cocktail before and on the last day of alosetron dosing. Serum alosetron concentrations were measured on days 1, 8, 15, 22 and 29. Probe-substrate and metabolite concentrations were measured after each cocktail dose.Results : Alosetron accumulation in serum was negligible. Exposure to alosetron did not alter probe-metabolite/substrate ratios associated with CYP2C19, 2E1, 2C9, or 3A4 activity, but modestly decreased those associated with CYP1A2 and N-acetyltransferase activity. Systemic exposure to alosetron was higher in women, positively correlated with age and body mass index, and negatively correlated with CYP1A2 activity. Incidence of constipation was higher in women, but not associated with alosetron concentration.Conclusions : Single dose data can reliably predict the pharmacokinetics of alosetron after repeated doses. Alosetron exhibits limited potential for inhibition of cytochrome P450-mediated metabolism. Interindividual differences in alosetron pharmacokinetics associated with demographic factors may be related to strong dependence on metabolism by CYP1A2.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK and Malden, USA : Blackwell Publishing Ltd.
    Creativity and innovation management 13 (2004), S. 0 
    ISSN: 1467-8691
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Economics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Addiction 99 (2004), S. 0 
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Regeneration of the adult central nervous system may require recapitulation of developmental events and therefore involve the re-expression of developmentally significant proteins. We have investigated whether the L1 cell adhesion molecule, and its binding partner, the ezrin-radixin-moesin (ERM) proteins are involved in the neuronal regenerative response to injury. Hippocampal and cortical neurons were cultured in vitro on either an L1 substrate or poly-L-lysine, and ERM and other neuronal proteins were localized immunocytochemically both developmentally and following neurite transection of neurons maintained in long-term culture. Activated ERM was localized to growth cones up to 7 days in vitro but relatively mature cultures (21 days in vitro) were devoid of active ERM proteins. However, ERM proteins were localized to the growth cones of sprouting neuronal processes that formed several hours after neurite transection. In addition, the L1 substrate, relative to poly-L-lysine, resulted in significantly longer regenerative neurites, as well as larger growth cones with more filopodia. Furthermore, neurons derived from the cortex formed significantly longer post-injury neurite sprouts at 6 h post-injury than hippocampal derived neurons grown on both substrates. We have demonstrated that L1 and the ERM proteins are involved in the neuronal response to injury, and that neurons derived from the hippocampus and cortex may have different post-injury regenerative neurite sprouting abilities.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  To examine whether need–service matching in addiction treatment leads to improvements in drug use, and whether treatment duration mediates those improvements.Design, participants, measurements  This analysis utilizes prospective data from a US cohort of addiction treatment patients who reported service needs beyond core rehabilitative services (n = 3103). ‘Drug use improvement’ is the difference between the patient's peak drug use frequency (in days per month) in the year before intake and in the year after treatment. Overall and primary use of the major illicit drugs (heroin, powder or crack cocaine and marijuana) are considered separately. ‘Need–service match’ means that a patient rated a service as important at intake and reported its receipt during treatment. ‘Percentage of needs matched’ indicates the proportion of five service domains (medical, mental health, family, vocational and housing) so matched.Findings  In mixed regression models controlling for multiple factors, a greater percentage of needs matched tended to improve primary (β = 0.028, P = 0.09) and overall (β = 0.049, P = 0.05) drug use in the follow-up year. Exclusion of treatment duration as a covariate doubled the magnitude of these coefficients. The benefits of matching were concentrated among the half of patients reporting needs in four to five rather than one to three domains, and were strongest among patients in long-term residential facilities. Addressing vocational and housing needs exerted the greatest effects.Conclusions  Matching comprehensive services to needs is a useful addiction treatment practice, especially for high-need patients. Treatment duration might partially mediate its effect.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  The aim of this study is to investigate suspected behavioral autarcesis. Autarcesis refers to a mechanism of non-specific shielding from or immunity to infection or disease. Here, suspecting that some facets of the adolescent behavioral repertoire (ABR) might shield youths from early drug involvement, we studied recent-onset occurrence of first chances to try a drug and first actual drug use, expressed as a function of five observed ABR dimensions: religious, socializing, sports-related, gender socialization, and home-based activities.Design and participants  Nationally representative samples of school-attending youths were drawn in Panama, the five Spanish heritage countries of Central America and the Dominican Republic (n = 12 797).Measurements  Drug involvement and ABR were assessed via anonymous self-administered questionnaires.Findings  A religious activity dimension and a separate sports dimension were associated inversely with recent onset of adolescent drug experiences, and a socializing activity dimension was related to an increased occurrence of these experiences. For example, for each unit increase of the religious activity dimension of the ABR, there was an associated reduced occurrence of the first chance to try tobacco (OR = 0.75, 95% CI: 0.63–0.90, P = 0.002). Adolescents at higher levels of sports activities and home-based activities were less likely to experience recent-onset actual use of marijuana (OR = 0.45, 95% CI: 0.30–0.67, P 〈 0.001; OR = 0.56, 95% CI: 0.32–0.99, P = 0.048, respectively).Conclusions  The study evidence lends some support for behavioral autarcesis. Manipulation of selected ABR dimensions might help prevent or reduce adolescent drug involvement, enhancing autarcesis as a protective mechanism.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York : Cambridge University Press
    Church history 73 (2004), S. 444-444 
    ISSN: 0009-6407
    Source: Cambridge Journals Digital Archives
    Topics: History , Theology and Religious Studies
    Type of Medium: Electronic Resource
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