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- influenza virus ; virion RNA segments ; oligonucleotide mapping ; gene reassortment (1)
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- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (1)
No abstract available.
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.
Die Tricarbonyl(germacy~lopentadien)eisen-Komplexe VI-X werden durch Umsetzung der Germacyclopentadiene I-V niit Fe(CO)\(_5\) dargestellt. In l,l-Dialkyl- und -Diaryl-l-gemiacyclopentadien-Komplexen kann die Ge-C( exo )-Bindung durch verschiedene Elementhaloge~de gespalten werden, wobei die I-Halogen-l-germacyclopentadien-Komplexe XII, XIII, XV-XVII gebildet werden. Eine Entkomplexierung des Komplexes XI tritt bei der Reaktion mit Me\(_3\)NO oder TiCl\(_4\) ein. Das Tricarbonyl(l-chlor-l-germacyclopentadien)eisen XII reagiert mit AgF, NaJ, NaOMe und LiAIH\(_4\) zu den Komplexen XIXXXII. Das German XXII kann mit CCl\(_4)\ in XII überführt werden. Die Tricarbonyleisen-Komplexe XI, XII, XVI, XVII und XIX reagieren photochemisch mit Trimethylphosphan zu den Dicarbonyl(trimethylphosphan)-Komplexen XXIII-XXVII. Die Kristallstruktur des Tricarbonyl(l-exo-fluor-1-endo-methyl-2,3,4,5-tetraphenyl-1-germacyclopentadien)eisen wird beschrieben.
The GVHRIL foHowing transplantation of small intestine are different from those found after bone marrow transplantation or spleen cell injections in that they show a remarka ble, significant prevalence of lesions within the intestinal mucosa. These findings are consistent with the observation that jntestinal lymphocytes newly formed in mesenteric lymph nodes predominantly home in on the intestine again.& The degree of histologic alteration within different tissues indicates that the graft and the host may survive the lesions of the lymphatic tissues, whereas the severe intestinal lesions following GVHR may easily cause death of the recipient. With regard to clinical sman bowel transplantation two statements can be made: (l) GVHRIL play a significant role in small bowel trans~ plantation. (2) To minimize their biologic importance, a selective elimination of the graft's Jymph nodes by irradiation or surgical resection should be considered in view of the remarkable difference between GVHRIL in lymph nodes and in the graft's intestinal wall itself.
No abstract available
Die Struktur von Tetramethylammoniumchloropentacarbonylwolframat wurde rontgenographisch aue Einkristalldaten bestimmt. Die Verbindung kristallisiert mit vier Formeleinheiten in del' monoklinen Elementarzelle (Raumgruppe P2Jc) folgender Dimensionen: a = 1111,3(4) pm, b = 1110,3(4) pm, c = 1204,1(3) pm, f3 = 99,63(3)°, V = 1464,8 . 106 pm' (R = 0,028). Das Anion besitzt annahernd C4v·Symmetrie mit d(W -C(ois» = 203 pm, d(WC( trans» = 197 pm, d(W-Cl) = 256,6 pm. Zwischen Kation undAnion treten keine ungewohnliche Kontakte auf.
No abstract available
Comparisons ofrelative lengths oflampbrush loops, nascent RNP transcripts and hnRNA molecules from oocytes of amphibia with different C-values show that there is an increasing trend in loop, and transcriptional unit, length with increase in genome size but no increasing trend with respect to RN A contour length.The formation of duplex regions and circles in RNP fibrils indicates that RNA processing may occur within the nascent fibrils. The hnRNA molecules from oocytes of the various amphibia readily form intermolecular duplex structures. These complementary sequences have a low kinetic complexity and are transcribed from highly repetitive sequences distributed throughout the genome. Their possible function is considered.
Electron microscope preparations of lampbrush chromosomes from oocytes of Pleurodeles waltl;; have revealed a new class of tandemly repeated genes. These genes are highly active, as judged by the close spacing of nascent transcripts. They occur in clusters of >100 copies and are transcribed in units containing roughly 940 base pairs of DNA that are separated by nontranscribed spacers of an estimated DNA content of 2,410 base pairs. The size and the pattern of arrangement of these transcription units can not be correlated with any of the repetitious genes so far described.
A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis
(1981)
The amplified, extrachromosomal nucleoli of Xenopus oocytes contain a meshwork of -4-nm-thick filaments, which are densely coiled into higher-order fibrils of diameter 30-40 nm and are resistant to treatment with high- and low-salt concentrations, nucleases (DNase I, pancreatic RNase, micrococcal nuclease), sulfhydryl agents, and various nonionic detergents. This filamentous "skeleton" has been prepared from manually isolated nuclear contents and nucleoli as weil as from nucleoli isolated by fluorescence-activated particle sorting. The nucleolar skeletons are observed in light and electron microscopy and are characterized by ravels of filaments that are especially densely packed in the nucleolar cortex. DNA as weil as RNA are not constituents of this structure, and precursors to ribosomal RNAs are completely removed from the extraction-resistant filaments by treatment with high-salt buffer or RN ase. Fractions of isolated nucleolar skeletons show specific enrichment of an acidic major protein of 145,000 mol wt and an apparent pi value of -6.15, accompanied in some preparations by various amounts of minor proteins. The demonstration of this skeletal structure in "free" extrachromosomal nucleoli excludes the problem of contaminations by nonnucleolar material such as perinucleolar heterochromatin normally encountered in studies of nucleoli from somatic cells. It is suggested that this insoluble protein filament complex forms a skeleton specific to the nucleolus proper that is different from other extraction-resistant components of the nucleus such as matrix and lamina and is involved in the spatial organization of the nucleolar chromatin and its transcriptional products. In studies of the organization of the interphase nucleus, considerable progress has been made in the elucidation of the arrangement of chromatin components and transcriptional products. However, relatively little is known about the composition and function of another category of nuclear structures, the nonnucleoproteinaceous architectural components that are insoluble in solutions of low and high ionic strength, despite numerous studies dedicated to this problem. Such structures include (a) the nuclear envelope and its pore complexes (I, 15, 18, 23, 37, 41), (b) a peripheral layer of insoluble protein ("lamina"; I, 15, 22, 23, 59), (e) certain skeletal proteins related to the chromosome "scaffold" described by Laemmli and coworkers (see references 2 and 3), and (d) ill-defined tangles of fibrillar structures of the nuclear interior that are collectively described as residual "matrix" (6, 21 ; for reviews, see references THE JOURNAL OF CEll BrOlOGY . VOlUME 90 AUGUST 1981 289-299 © The RockefeIler University Press · 0021 -9525/ 81 / 08/ 0289/ 11 $1 .00 4 and 12). The latter, preparatively
Antibodies directed against RNA polymerase II (B) from Drosophila melanogaster were obtained from rabbit sera and, as monoclonal immunoglobulins, from mouse hybridomas and shown to cross-react with the amphibian enzyme protein. Localization by indirect immunofluorescence microscopy revealed the association of this enzyme with chromatin of interphase nuclei of amphibian cells and its absence in nucleoli. Purified immunoglobulins were microinjected in to nuclei ofliving vitellogenic oocytes of Ple1lrodeles waltlii and X enopus laevis and their effects on transcriptional processes were monitored by biochemical and light and electron microscopic stud ies. RNA polymerase II antibodies from rabbit sera caused a rapid and almost complete release of nascent transcripts from the chromatin axis of the loops of lampbrush chromosomes, followed by collapse of the loops and their retraction on the main chromosome axis. Monoclonal murine antibodies to the Iarge RNA polymerase II subunits also inhibited transcription in chromosome Ioops but appeared to inhibit initiation rather than elongation events. Activities of class land III RNA polymerases were not significantly affected by injection of antibodies to polymerase II, indicating immunological differences between the three RNA polymerases. The potential value of the in vitro test system described , as a very sensitive assay for detecting proteins involved in transcription in living cells, is discussed. 1
Nonnucleolar chromatin from interphase nuclei of Physarum polycephalum plasmodia occurs in two different structural configurations as seen in electron microscopic spread preparations. While the majority of the chromatin is devoid of nascent ribonucleoprotein (RNP) fibrils and compacted into nucleosomal particles, a minor proportion (10- 20%) is organized differently and reveals a smooth contour. It is this form of smooth chromatin which is rich in transcription units (mean length: 1.36±0.21 11m). Only occasionally are solitary nascent RNP fibrils observed which are associated with beaded strands of chromatin. In transcribed smooth chromatin nucleosomal particles are not only absent from the transcription units but also from their nontranscribed flan king regions, indicating that this special structural aspect is not merely a direct consequence of the transcriptional process. The existence of ca. 10- 20% of Physarum chromatin in the smoothly contoured form is discussed in relation to reports of a preferential digestibility of a similar proportion of Physarum chromatin by DNAse I (Jalouzot et al. , 1980) and to the altered configuration of "peak A" chromatin subunits after micrococcal nuclease digestion (Johnson et al., 1978a, b).
The influenza virus H1N1 (the A/USSR/90/77 strain) that reappeared in 1977 after the H1N1 influenza viruses had disappeared from the human population, is compared with the A/FM/1/47 and the A/FW/1/50 influenza viruses by the method of oligonucleotide mapping of individual segments of the viral RNAs. Seven genes of the A/USSR/90/77 virus appear to be very similar to the corresponding genes of the A/FW/1/50 virus, whereas the gene coding for the M protein displays considerable homology to the corresponding gene of the A/FM/1/47 virus. The data demonstrate that the A/USSR/90/77 strain is a recombinant virus.
Barley stripe mosaic virus (BSMV) RNA which was previously reported to contain poly(A) sequences (Agranovsky et al., 1978) can be specifically esterified with tyrosine in vitro in the presence of an aminoacyl-tRNA synthetase fraction from wheat embryos. All the three RNA components of the BSMV strain with a three-component genome (Norwich) and both RNA components of a two-component strain (Russian) can be tyrosylated. The poly(A)-containing (bound to oligo(dT)-cellulose) and poly(A)-deficient(not bound to oligo(dT)-cellulose) fractions of BSMV RNA display a similar amino acidaccepting ability. The nucleotide sequence which accepts tyrosine is coupled with the intact genomic polyadenylated BSMV RNA. The viral RNA isolated after sucrose density gradient centrifugation under drastic denaturing conditions retains its aminoacylating activity, which suggests that this activity is not due to the presence in a BSMV RNA preparation of a tyrosine tRNA associated with BSMV RNA. Inhibition of aminoacylation of the 3’-oxidized (treated with sodium metaperiodate) BSMV RNA suggests that the tyrosine-accepting structure is localized at the 3’ terminus of BSMV RNA molecules. It is shown that segments of different lengths obtained upon random fragmentation can be tyrosylated. The 3’-terminal (tyrosine-accepting) poly(A)+ segments can be isolated. The shortest segments of viral RNA capable of being aminoacylated [i.e., containing both tRNA-like structure and poly(A)] consists of approximately 150-200 nucleotides. The analysis of the oligonucleotides derived from individual BSMV RNA components labeled with 32P at the 3’ end revealed two types of 3’-terminal sequences different from poly(A). It is suggested that a poly(A) sequence is intercalated between a 3’-terminal tyrosineaccepting structure and the 5’-terminal portion of poly(A)+ BSMV RNA.
No abstract available