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- influenza virus ; virion RNA segments ; oligonucleotide mapping ; gene reassortment (1)
- o-Chlorobenzylidene malononitrile (1)
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Es wird argumentiert, daß bei der Prüfung der Homgenität von Zentren in mehrfaktoriellen Multicenter-Studien vor allem entscheidend ist, daß sich die Zentren in den faktoriellen Variablen nicht unterscheiden, deren Effekte in der späteren Auswertung interpretiert werden sollen. Dazu wird folgendes Procedere vorgeschlagen: (1) überprüfe, ob in allen Zentren die Randomisierungsbedingungen eingehalten wurden, (2) überprüfe, ob die Zentren homogen bezogen auf die eingebrachten Schichtvariablen (z.B. Geschlecht, Indikation) sind und (3) überprüfe, ob die Zentren homogen sind bezogen auf die Wechselwirkungen zwischen den eingebrachten faktoriellen Variablen. Es wird gezeigt, daß vor allem Forderung (3) für die Interpretationsfähigkeit der Ergebnisse von entscheidender Bedeutung ist. Möglichkeiten der statistischen Prüfung dieser Voraussetzungen werden an einem Beispiel aus der klinischen Prüfung eines Psychopharmakons vorgestellt.
No abstract available.
Neoplasia in Xiphophorus can be classified into: a) a Jarge group triggered by carcinogens; b) a large group triggered by promoters; and c) a small group that develops "spontaneously" according to Mendelian Jaw. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Interpopulational arid interracial hybridization is the most effective process that Ieads to disintegration of the protective gene systems. Environmental factors may complete disintegration in somatic cells and thus may trigger neoplasia. The applications of the findings on Xiphophorus to humans are discussed.
The psychological and physiological effects of a socially oriented sensitivity training were evaluated. It is shown that decreased physical distance as well as increased intimacy yields high activation, both in psychological measures (experienced stress) and in pulse frequences. One result (highly significant and replicated in other experiments) was paradoxical: when Ss had to caress the face of a heterosexual vis-a-vis, they reported high experienced stress, but pulse frequences dropped rapidely below the resting pulse. Some suggestions are made to explain these findings. The question arises whether an autonomic somatic process, induced by social Stimulation, but independent of the cognitive coping is responsible for these results.
Summary (Social Situations as Experimental Conditions in Psychopharmacology): To reduce a great variability of drug effects in healthy subjects, stress conditions are used often in pharmacopsychology. However, empirical results show that the desired stress effects are failing. This paper suggests to realize social stress Situations as interactions between subjects, expecting higher challenging effects than experimentator-subject-interactions, usually used in experimental designs. Two experimental studies are reported: the call-upsituation and the group-therapy situation. The experimental effects were measured by changes of pulse-frequencies. The results indicate that in the two situations high and low dosages of tranquilizing drugs lead to comparable (and so predictable) effects only, if a Situation is high challenging for the experimental subjects. The call-up situation, which proves performance, challenges male subjects highly. The emotional or social competence demanding group-therapy situation is a high challenging situation for warnen. It is concluded that no situation is stressing a person generally. Depending from personality characteristics, differential stressor effects appear. Consequences for experiments in pharmacopsychology are discussed.
Neoplasia in Xiphophorus can be classified into a) a large group that is triggered by carcinogens; b) a large group triggered by promoters; c) a small group that develops "spontaneously" following interpopulational and interracial hybridizations; and d) a small group that develops "spontaneously" following germ line mutation. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Hybridization is the most effective process that leads to disintegration of the protection gene systems. Environmental factors may complete disintegration and thus may trigger neoplasia. It is discussed whether the findings on Xiphophorus may also apply to humans.
no abstract available
Das Sila-Dimetacrin (3a), ein Sila-Analogon des Psychopharmakons Dimetacrin (2), und sein N,N-Diethylderivat 3 b sowie sein 3-Chlorderivat 3 c wurden, von den o-Halogenanilinen 4 a- c ausgehend, über die teilweise unbekannten Stufen 5 a- c bis 10a- d synthetisiert, in ihren Eigenschaften beschrieben und in ihrer Struktur über Elementaranalysen, \(^1\)H-NMR- und Massenspektren sichergestellt. Die Synthese des Zwischenproduktes Bis(2-bromphenyl)amin (9a) konnte optimiert werden.
Die Organophosphorsäureester la-4a und ihre Sila-Analoga lb-4b des Typs R\(^1\)R\(^2\)P(O)( p-OC\(_6\)H\(_4\)ElMe\(_3\)) (EI = C, Si) wurden synthetisiert. Die Kohlenstoff-Verbindungen 1 a- 4a zeigen hinsichtlich ihrer Anticholinesterase-Aktivität die gleichen Struktur-Wirkungs-Beziehungen wie die Silicium-Verbindungen 1 b- 4 b. Letztere sind jeweils wirksamer als die entsprechenden C-Analoga.
Lack of covalent binding to rat liver DNA of the hypolipidemic drugs clofibrate and fenofibrate
(1981)
\(^{14}\)C-Labelled clofibric acid and fenofibric acid were administered p.o. to 200 g male and female rats. After 10 h, liver nuclear DNA and protein were isolated and the radioactivity was determined. Binding to protein was clearly measurable whereas no binding to DNA could be detected from any drug. A comparison of the Iimit of detection of such DNA binding with well-known chemical carcinogens revealed that the known hepatocarcinogenicity of clofibrate cannot be based upon an initiating, DNA damaging, mode of action but must be due to other, nongenotoxic, mechanisms such as peroxisome proliferation, hepatomegaly, or cytotoxicity due to protein binding. The risk assessment in man and the interpretation of the carcinogenicity data for rodents are discussed.
The aim of this study was to determine whether o-chlorobenzylidene malononitrile ( CS) exhibits any genotoxic activity towards Salmonella or mammalian DNA in vivo. CS was synthesized with a [\(^{14}\)C]-label at the benzylic carbon atom. It was administered i. p. at a dose level of 13 mg/kg (1 mCi/kg) to young adult male rats. Liverand kidney DNA was isolated after 8, 25, and 75 h. The radioactivity was at (liver, 8 and 75 h) or below (all other samples) the limit of detection of 3 dpm. Therefore, a possible binding of CS to DNA is at least 10\(^5\) times lower than that of the strong hepatocarcinogen aflatoxin B1, and 4,000 times lower than that of vinyl chloride. In contrast to this lack of DNA binding, but in agreement with the chemical reactivity of CS, a binding to nuclear proteins could be detected with specific activities ranging between 50 and 121 dpm/mg for liver and between 3 and 41 dpm/mg for kidney. Protein binding could well be responsible for its pronounced cytotoxic effects. Cs was also tested in the Ames Salmonella/microsome assay. Strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100 were used with or without pre-incubation. Only with strain TA 100 and only without pre-incubation, a doubling of the number of revertants was detectable at the highest dose Ievels used, 1,000 and 2,000 !lg CS per plate. With pre-incubation of TA 100 with CS, a slight increase of the number of revertants was seen at 100 and 500 !lg per plate, and a subsequent fall below control values at 1,000 J.tg. A check for the number of surviving bacteria revealed a strong bacteriotoxicity of the higher doses of es so that the calculated mutation frequencies, i.e., the oumber of revertants per number of surviving bacteria, increased with doses up to 500 !J.g. This toxicity could be counteracted in part by the addition of increasing amounts of rat liver microsomes. In the view of these results, and taking into account the rare and low exposure of man, it is concluded that CS will not create a risk for the induction of point mutations or of carcinogenic processes mediated by DNA binding.
No abstract available
The distribution of lipofuscin in the perikarya of Purkin je cells of vermal and hemispheric lobules has been determined quantitatively in 7 rats, 30-38 months old, by the point-counting method. On the basis of morphologically and statistically significant differences a pigmentarchitectonics of the cerebellar cortex is established. The Purkinje cells of lobule VIa (Larsell 1952) are extremely lipofuscin-rich. The Purkinje cells of the hemispheres, lobules V, Vlb + c and VII contain considerable amounts of a finely granular lipofuscin, the Purkinje cells of lobules I-III and VIII- IXa a globular type of lipofuscin. The Purkinje cells of sublobule XI d c and X are lipofuscin-poor cells. Three types of lipofuscin ha ve been identified in the light microscope.
Prostacyclin (PGI2) induced a dose-dependent decrease in blood pressure with slight increases in heart rate and body temperature, when administered at the doses of 0.1-100 ~g into the lateral cerebral ventricle (i.c.v.) of the urethane-anaesthetised rat. When the same doses were administered intravenously, both the blood pressure and heart rate decreased. Central pretreatment wib~ sodiurn meclofenamate (1 mg/rat i.c.v.) antagonised the central hypotensive effect of PGI2 but i.c.v. pretreatrnent of the rats with indomethacin (1 mg/rat) failed to affect the PGI 2-induced hypotension. Central pretreatment with two histamine H2-receptor antagonists, cimetidine (500 ~g/rat i.c.v.) or metiamide (488 ~g/rat i.c.v.), antagonised the blood pressure lowering effect of 0.1 ~g dose of PGI2 but failed to affect the hypotension induced by higher PGI2 doses. Therefore the main central hypotensive effect of PGI2 seems not to be associated with the stimulation of histamine H2 -receptors in the brain. The hypotensive effect of i.c.v. administered PGI2 appears to be due to an action upon the central nervous system rather than to a leakage into the peripheral circulation. This assurnption is supported by the fact that sodiurn meclofenamate i.c.v. antagonised the effect of PGI 2. In addition, the chronotropic response to i.c.v. PGI2 was opposite to that induced by intravenous administration. The results also suggest that there may be differences in the mode of action between sodiurn meclofenamate and indomethacin.
No abstract available
No abstract available
Theoretische Analysen zum Problem des Recht-Schreibens weisen darauf hin, daß weniger Intelligenzmerkmale als vielmehr Gedächtnis'eistungen bei dem Erwerb der Schriftsprache von Bedeutung sind. Daraus folgt, daß für die Prüfwörter in normierten Rechtschreibtests zumindest hinreichende Vorkommensfrequenz gewährleistet sein sollte. Diese Frage wird in der vorliegenden Untersuchung am Beispiel des Allgemeinen Schulleistungstests überprüft: für die ausgewählten Klassenstufen kann gezeigt INerden, daß die Vorkommenshäufigkeit der PrüfWÖfter nicht ausreicht und damit wenig geeignet ist, um die tatsächliche Rechtschreibfertigkeit zu erfassen. Der Vergleich mit mehreren eng am Curriculum orientierten Diktatproben kann gleichzeitig die Schwierigkeiten verdeutlichen, die dann entstehen, wenn zuverlässige Bestimmungen der individuellen Rechtschreibkompetenz vorgenommen werden sollen.