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  • 21
    ISSN: 1432-1459
    Keywords: Dementia ; Brain circulation ; Brain metabolism ; Metabolism of the brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In einer retrospektiven Studie wurde bei 115 dementen Patienten im Alter von 40 bis 83 Jahren das Verhalten der Durchblutung und des oxydativen Stoffwechsels des Gehirns unter deskriptiv-statistischen und funktionellen Aspekten untersucht und geprüft, ob das Lebensalter einen determinierenden Einfluß auf die Hirndurchblutung, die nach Kety u. Schmidt gemessen wurde, den cerebralen Sauerstoff- und Glucoseverbrauch hat. Es ergab sich bei dementen Patienten, daß 1. die Werte der Hirndurchblutung insgesamt nicht Gauß-verteilt sind. Einem offenbar Gauß-verteilten Kollektiv mit erniedrigter Durchblutung stehen mindestens zwei mit normaler bzw. erhöhter Durchblutung gegenüber. 2. der cerebrale Sauerstoffverbrauch bei Patienten mit erniedrigter Hirndurchblutung ebenfalls erniedrigt ist. Die Werte sind offenbar Gauß-verteilt. Bei Patienten mit normaler oder erhöhter Hirndurchblutung liegt keine Gauß-Verteilung des cerebralen Sauerstoffverbrauchs vor, der entweder heabgesetzt oder normal bis leicht erhöht sein kann. 3. die cerebrale Glucoseaufnahme weder bei Patienten mit erniedrigter noch bei Patienten mit normaler oder erhöhter Durchblutung eine Gauß-Verteilung aufweist. Beide Verteilungskurven sind mehrgipflig, d. h., die Glucoseaufnahme kann entweder erniedrigt, normal oder erhöht sein. 4. Die nachgewiesene Inhomogenität der Durchblutung, des Sauerstoffverbrauchs und der Glucoseaufnahme des Gehirns deutet darauf hin, daß bei der Demenz pathophysiologisch bzw. pathobiochemisch ganz unterschiedliche Schädigungsmuster vorliegen können. 5. Im vorliegenden Patientengut konnte ein Einfluß des Lebensalters auf Durchblutung und oxydativen Stoffwechsel des Gehirns bei der Demenz nicht gesichert werden.
    Notes: Summary The purpose of this retrospective study was to investigate how the blood flow and oxidative metabolism of the brain was changed in dementia and the influence of the age factor. Cerebral blood flow (CBF) was measured in 115 patients aged from 40 to 83 years by means of the Kety-Schmidt technique with the modification of Bernsmeier and Siemons. The cerebral metabolic rates of oxygen and CO2 were determined by the van Slyke method and by gaschromatography respectively and of glucose and lactate by standard enzymatic methods. All cases of dementia due to head injuries, cerebral infections, cerebral infarctions, exogenous or endogenous intoxications or circulatory diseases were excluded from this study, but no classification of the dementias was made. Statistical calculations were carried out by means of the analysis of variance for a two-way design. Cerebral blood flow did not show a normal distribution curve but was at least triphasic; CBF in demented patients was either lower than normal, normal or higher than normal. The distribution curves showed further that low cerebral blood flow of mean 32.5 ml/100 g min coincided with a low CMR oxygen of 2.50 ml/100 g min; however, CMR glucose was either low (2.50 mg/100 g min), or nearly normal (4.50 mg/100 g min) or elevated (7.50 mg/100 g min). A normal (45.0 ml/100 g min) or enhanced (62.5 ml/100 g min) CBF correlated with a CMR oxygen which was either decreased to 2.75 ml/100 g min or increased to 4.75 ml/100 g min; CMR glucose was either decreased to 1.50 mg/100 g min, or nearly normal (4.50 mg/100 g min), or was elevated to 6.50 and 10.50 mg/100 g min with respect to the peaks of the distribution curves. It is assumed that the variability of the findings with respect to the blood flow and oxidative metabolism of the brain in dementia is due to different pathophysiological and pathobiochemical disturbances in the brain. A significant influence of age on CBF and metabolism in patients with dementia was not found.
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  • 22
    ISSN: 1432-1750
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Journal of ornithology 27 (1879), S. 1-83 
    ISSN: 1439-0361
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 24
    ISSN: 1437-1596
    Keywords: Key words Short tandem repeats ; Y chromosome ; Population analysis ; Mutation rate ; Y haplotype ; analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract A multicenter study has been carried out to characterize 13 polymorphic short tandem repeat (STR) systems located on the male specific part of the human Y chromosome (DYS19, DYS288, DYS385, DYS388, DYS389I/II, DYS390, DYS391, DYS392, DYS393, YCAI, YCAII, YCAIII, DXYS156Y). Amplification parameters and electrophoresis protocols including multiplex approaches were compiled. The typing of non-recombining Y loci with uniparental inheritance requires special attention to population substructuring due to prevalent male lineages. To assess the extent of these subheterogeneities up to 3825 unrelated males were typed in up to 48 population samples for the respective loci. A consistent repeat based nomenclature for most of the loci has been introduced. Moreover we have estimated the average mutation rate for DYS19 in 626 confirmed father-son pairs as 3.2 × 10–3 (95% confidence interval limits of 0.00041–0.00677), a value which can also be expected for other Y-STR loci with similar repeat structure. Recommendations are given for the forensic application of a basic set of 7 STRs (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) for standard Y-haplotyping in forensic and paternity casework. We recommend further the inclusion of the highly polymorphic bilocal Y-STRs DYS385, YCAII, YCAIII for a nearly complete individualisation of almost any given unrelated male individual. Together, these results suggest that Y-STR loci are useful markers to identify males and male lineages in forensic practice.
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  • 25
    ISSN: 1437-1596
    Keywords: Key words Y chromosome ; Haplotypes ; Evolution ; Population studies ; Genetic affinities ; STR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract By means of a multicenter study, a large number of males have been characterized for Y-chromosome specific short tandem repeats (STRs) or microsatellites. A complete summary of the allele frequency distributions for these Y-STRs is presented in the Appendix. This manuscript describes in more detail some of the population genetic and evolutionary aspects for a restricted set of seven chromosome Y STRs in a selected number of population samples. For all the chromosome Y STRs markedly different region-specific allele frequency distributions were observed, also when closely related populations were compared. Haplotype analyses using AMOVA showed that when four different European male groups (Germans, Dutch, Swiss, Italians) were compared, less than 10% of the total genetic variability was due to differences between these populations. Nevertheless, these pairwise comparisons revealed significant differences between most population pairs. Assuming a step-wise mutation model and a mutation frequency of 0.21%, it was estimated that chromosome Y STR-based evolutionary lines of descent can be reliably inferred over a time-span of only 1950 generations (or about 49000 years). This reduces the reliability of the inference of population affinities to a historical, rather than evolutionary time scale. This is best illustrated by the construction of a human evolutionary tree based on chromosome Y STRs in which most of the branches connect in a markedly different way compared with trees based on classical protein polymorphisms and/or mtDNA sequence variation. Thus, the chromosome Y STRs seem to be very useful in comparing closely related populations which cannot probably be separated by e.g. autosomal STRs. However, in order to be used in an evolutionary context they need to be combined with more stable Y-polymorphisms e.g. base-substitutions.
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  • 26
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurology 235 (1988), S. 143-148 
    ISSN: 1432-1459
    Keywords: Dementia of Alzheimer type ; Brain blood flow ; Oxidative metabolism ; Amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Global cerebral blood flow, oxidative brain metabolism, and the cerebral arteriovenous differences of amino acids and ammonia were studied in 20 clinically diagnosed patients with early-onset dementia of Alzheimer type (DAT). Eleven healthy age-matched subjects and 15 healthy young volunteers served as controls. The most prominent abnormality in patients with early-onset DAT was a 44% reduction in the cerebral metabolic rate of glucose and a fourfold increase of lactate production, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were found not to be altered. The cerebral amino-N balance substantially changed in patients with early-onset DAT, showing a massive loss of amino acids and ammonia from the brain, which was indicative of excess protein catabolism due to cell degeneration in the acutely diseased brain. The abnormality found in glucose metabolism may suggest a perturbed control of glycolytic breakdown of glucose and its first oxidation step at the pyruvate dehydrogenase complex level, this thus being of pivotal significance in early-onset DAT.
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  • 27
    Electronic Resource
    Electronic Resource
    Springer
    European archives of psychiatry and clinical neuroscience 212 (1969), S. 321-328 
    ISSN: 1433-8491
    Keywords: Organic Psychoses ; EEG-Changes ; Disturbances of Cerebral Metabolism ; Cerebral Blood-Flow ; Lack of Correlations ; Organisches Psychosyndrom ; EEG-Veränderungen ; Störungen des Hirnstoffwechsels ; Cerebrale Durchblutung ; Mangelnde Korrelation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 20 Patienten mit dem psychopathologischen Bild eines organischen Psychosyndroms wurden die EEGs mit den Werten von Hirndurchblutung und Hirnstoffwechsel verglichen. Dabei war eine auffallende Koincidenz in 4 Fällen zwischen normalem EEG und erniedrigtem Glucoseoxydationsquotienten (GOQ) als Hinweis auf einen cerebralen Glucosemangel sowie in 3 Fällen zwischen relativ flachem EEG und erhöhtem GOQ bei stark erhöhtem Glucoseverbrauch festzustellen. Sowohl bei Minderung der Hirndurchblutung wie auch bei normaler oder sogar erhöhter Durchblutungsgröße konnten pathologische EEGs beobachtet werden. Auch die in dieser Studie erfaßten Hirnstoffwechselgrößen wie Milchsäureproduktion, cerebraler O2-Verbrauch und Glucoseaufnahme konnten nicht in eine eindeutige Beziehung zum EEG gebracht werden. Es muß deshalb angenommen werden, daß entweder die Summe von pathologischen Hirnstoffwechselwerten einschließlich Hirndurchblutung eine EEG-Veränderung verursachen oder daß die hier angegebenen Untersuchungsmethoden nicht ausreichend sind, den eigentlichen pathologischen Vorgang der EEG-Veränderung zu erfassen.
    Notes: Summary 20 patients showing psychopathological features of an organic psychosyndrome were investigated and the EEGs, blood-flow and metabolism of the brain were compared. In 4 cases the coinciding of normal EEG and lower quotients of glucose oxidation was considered as an indication of diminished glucose in the brain. 3 cases had a flat EEG and increased glucose oxidation. Pathological EEGs were observed during diminished cerebral blood-flow as well as with normal or increased blood-flow. Other metabolic alterations, e.g. lactic acid production, O2-consumption and glucose uptake showed no clear correlation with the EEG. It is concluded that either the sum of pathological metabolic disturbances plus altered cerebral blood-flow cause EEG-changes or that the methods used were not sufficient to determine the pathological mechanisms causing the EEG-changes.
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  • 28
    ISSN: 1435-1463
    Keywords: Glucose utilization ; dementia of Alzheimer type ; late-onset ; brain insulin ; insulin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Global cerebral blood flow and the cerebral metabolic rates of oxygen, CO2, glucose and lactate were studied in 11 patients aged 61–78 years who had been clinically diagnosed as suffering from incipient late-onset dementia of the Alzheimer type (DAT), and in 7 patients aged 66–83 years, in whom advanced late-onset DAT had been diagnosed, using the Kety-Schmidt technique. In incipient late-onset DAT, the predominant abnormality was a 45% reduction in cerebral glucose utilization, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were diminished by only 17% and 18%, respectively. A severe imbalance between oxygen utilization and glucose utilization thus became obvious. In contrast, in advanced stages of late-onset DAT, this imbalance between oxygen and glucose utilization rates in the brain became smaller and smaller, and cerebral blood flow diminished markedly; these biological brain parameters finally all settled down at between 55% and 65% of the corresponding control values. The predominant abnormality in brain glucose utilization in incipient late-onset DAT may be associated with an impairment of its control mechanism(s), which are assumed to be either an influence of brain insulin action, or brain insulin receptor function, or both.
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  • 29
    ISSN: 1573-7276
    Keywords: experimental metastasis ; heat shock proteins ; hydroxyurea ; stress response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment of tumor cells with hydroxyurea (HU) has been shown to increase the experimental metastatic potential of these cells. We have previously described the induction of stress proteins (antioxidants) by in B16 murine melanoma cells and their relationship to the metastatic process. We have now investigated the induction by HU of another set of stress proteins, the heat shock proteins, and their role in experi-mental metastasis. HU markedly increased the cellular content of heat shock protein (hsp) 27 but not hsp 90, 72/73, or 60 as measured by immunoblotting. The induction of hsp27 protein was preceded specific increase in hsp27 mRNA. Furthermore, HU-treated cells were more thermotolerant. To investigate the functional role of hsp27, human hsp27 cDNA was constitutively overexpressed in B16 cells at seen in HU-treated cells. In separate experiments, we induced a global increase in hsps by heat shock. Neither the hsp27 transfectants nor the heat-shocked cells demonstrated an increase in their experimental metastatic capacity. We conclude that hsp27 protein is increased by HU by the specific induction of hsp27 mRNA in B16 melanoma cells but increased hsp27 protein is not responsible for the increase in experimental metastasis. Since high levels of hsp27 are associated with metastatic disease in breast and ovarian cancers, but not in our experimental system, the functional role of hsp27 in metastasis requires further study. © Rapid Science 1998
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  • 30
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; hsp27 ; topoisomerase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIα and β were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract
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