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It is shown that the rate of convergence in the von Mises conditions of extreme value theory determines the distance of the underlying distribution function F from a generalized Pareto distribution. The distance is measured in terms of the pertaining densities with the limit being ultimately attained if and only if F is ultimately a generalized Pareto distribution. Consequently, the rate of convergence of the extremes in an lid sample, whether in terms of the distribution of the largest order statistics or of corresponding empirical truncated point processes, is determined by the rate of convergence in the von Mises condition. We prove that the converse is also true.
1 We studied the effect of temperature on the binding to rat heart \(M_2\) muscarinic receptors of antagonists related to the carbon/silicon pairs pridinol/sila-pridinol and diphenidol/sila-diphenidol (including three germanium compounds) and six structurally related pairs of enantiomers [(R)- and (S)-procyclidine, (R)- and (S)-trihexyphenidyl, (R)- and (S)-tricyclamol, (R)- and (S)-trihexyphenidyl methiodide, (R)- and (S)-hexahydro-diphenidol and (R)- and (S)-hexbutinol]. Binding affinities were determined in competition experiments using \([^3H]\)-N-methyl-scopolamine chloride as radioligand. The reference drugs were scopolamine and N-methyl-scopolamine bromide.
2 The affinity of the antagonists either increased or decreased with temperature, van 't Hoff plots were linear in the 278–310°K temperature range. Binding of all antagonists was entropy driven. Enthalpy changes varied from large negative values (down to \(−29 kJ mol^{−1}\)) to large positive values (up to \(+ 30 kJ mol^{−1}\)).
3 (R)-configurated drugs had a 10 to 100 fold greater affinity for \(M_2\) receptors than the corresponding (S)-enantiomers. Enthalpy and entropy changes of the respective enantiomers were different but no consistent pattern was observed.
4 When silanols \((R_3SiOH)\) were compared to carbinols \((R_3COH)\), the affinity increase caused by C/Si exchange varied between 3 and 10 fold for achiral drugs but was negligible in the case of chiral drugs. Silanols induced more favourable enthalpy and less favourable entropy changes than the corresponding carbinols when binding. Organogermanium compounds \((R_4Ge)\) when compared to their silicon counterparts (R4Si) showed no significant difference in affinity as well as in enthalpy and entropy changes.
5 Exchange of a cyclohexyl by a phenyl moiety was associated with an increase or a decrease in drug affinity (depending on the absolute configuration in the case of chiral drugs) and generally also with a more favourable enthalpy change and a less favourable entropy change of drug binding.
6 Replacement of a pyrrolidino by a piperidino group and increasing the length of the alkylene chain bridging the amino group and the central carbon or silicon atom were associated with either an increase or a decrease of entropy and enthalpy changes of drug binding. However, there was no clear correlation between these structural variations and the thermodynamic effects.
7 Taken together, these results suggest that hydrogen bond-forming OH groups and, to a lesser extent, polarizable phenyl groups contribute significantly to the thermodynamics of interactions between these classes of muscarinic antagonists and \(M_2\) muscarinic receptors.
Transforming growth factor \(\beta\) (TGF-\(\beta\)) has a growth-inhibitory effect on numerous different cell types of the immune system, including T lymphocytes. We show in this study that the inhibitory action of TGF-\(\beta\) on T lymphocytes is accompanied by a block of interleukin 2 (IL-2) gene expression which is mediated, at least in part, by inhibition of IL-2 promoter/enhancer activity. The functional analysis of cis-regulatory (protoenhancer) elements of the IL-2 enhancer/promoter region showed that the most TGF-\(\beta\)-responsive element maps to its so-called upstream promoter site. The proto-enhancer activity of the upstream promoter site element is also inhibited by cyclosporin A. The upstream promoter site DNA harbors two noncanonical, closely linked binding sequences for octamer and AP-1-like factors. Both sites are involved in the establishment of IL-2 enhancer activity. Since the activity of genuine octamer sites but not that of AP-1-binding sites is also impaired by TGF-\(\beta\) and cyclosporin A in E14 T lymphoma cells, we conclude that both immunosuppressives interfere with the activity but not the DNA binding of octamer factors in T lymphocytes.
Phenotypic and functional changes in lymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIVmac 32H. Animals preimmunized with keyhole limpet hemocyanin (KLH) were sacrificed l, 3, 6, 12, and 24 weeks post infection. Subset composition and function of lymphocytes from blood, spleen, lymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4 + CD8 + immature thymocytes, and a relative increase in both CD4 + and CD8 + mature subsets was observed. Infectious virus was readily recovered from homogenates of lymph node and spleen, but not of thymus tissue. Interestingly, however, virus was detected in thymocytes from all infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible cell line.
No abstract available
We report on the growth of the compound semiconductor MgTe as weil as the ternary alloy Cd\(_{l-x}\)Mg, Te by molecular hcam cpitaxy. This is to our knowkdgc thc first time that this material has heen grown by any epitaxial technique. Bulk MgTe, which is hygroscopic, has a band gap of 3.0 eV and crystallizcs usually in thc wurtzite structure. Pseudomorphic films were grown on zincblende Cd Te suhstrates for a MgTe thickness helow a critical layer thickncss of approximately 500 nm. In addition, Cd\(_{l_x}\),Mg\(_x\)Te epilayers were grown with a Mg concentration between 0 and 68%, which corresponds to a band gap betwcen 1.5 and 2.5 eV at room temperature. The crystalline quality of thc layers is comparabk to CdTc thin films as long as they are fully strained. The lauice constant of zincblende MgTe is slightly smaller than that of CdTe, and the lattice mismatch is as low as O.7%. In addition highly n-type CdMgTe layers were fabricatcd by hromine doping. The tunability of the band gap as weil as the rather good laUice match with CdTc makes the matcrial interesting for optoelectronic device applications for the entire visible range.
A semiempirical model is presented that correlates the broadening of the absorption edge with both transitions below the energy gap and with transitions by the Kane band model. This model correctly fits both the absorption and luminescence spectra of narrow-gap (Hg,Cd)Te samples that have been grown by the traveling heater method as well as by molecular-beam epitaxy. The accuracy of the band-gap determination is enhanced by this model.
In somatic cells DNA topoisomerase II (topo II) is thought to be involved in the domain Organization of the genome by anchoring the basis of chromatin loops to a chromosomal scafFold. Lampbrush chromosomes of am-phibian oocytes directly display this radial loop Organization in cytological preparations. In order to find out whether topo II may play a role in the Organization of these meiotic chromosomes, we performed immunofluorescence studies using antibodies against Xenopus topo II. Our results indicate that topo II is apparently absent from lampbrush chromosomes and is hence unlikely to act as a "fastener" of the numerous lateral chromosomal loops. Topo II was, however, enriched in the amplified nucleoli of Xenopus oocytes.
During a study of the nutritional requirements of clinical isolates of Escherichia coli, we found that 21 (7.0%) of 301 strains required nicotinamide to grow in minimal medium. The nicotinamide- requiring strains were present in 16 (15.8%) of 101 cultures of urine from young women with acute cystitis, in 5 (5.0%) of 100 stool specimens from healthy adults, and in none of 100 blood samples from adult patients with bacteremia. Most of the strains belonged to serogroup OI8:KI:H7, were hemolytic, possessed type I fimbriae, and exhibited similar patterns of antibiotic susceptibility. Two of the urinary isolates expressed S fimbriae, and all 16 urinary isolates contained the s/aS homologue gene on their chromosomes. One of the stool isolates contained the s/aS gene. The urinary isolates closely resembled a large clone of E. coli that is reportedly associated with neonatal meningitis and sepsis. It may be possible to detect this and related clones by their requirement for nicotinamide and to screen strains for S fimbriae by relatively inexpensive hemagglutination methods, including the use of avian PI antigens to detect mannose- resistant, non-P-fimbriated E. coli; the agglutination of bovine erythrocytes; and the use of bovine mucin to detect sialyl galactosides in S fimbriae.
In distance geometry problems and many other applications, we are faced with the optimization of high-dimensional quadratic functions subject to linear equality constraints. A new approach is presented that projects the constraints, preserving sparsity properties of the original quadratic form such that well-known preconditioning techniques for the conjugate gradient method remain applicable. Very-largescale cell placement problems in chip design have been solved successfully with diagonal and incomplete Cholesky preconditioning. Numerical results produced by a FORTRAN 77 program illustrate the good behaviour of the algorithm.
No abstract available
CNTF is a cytosolic molecule expressed postnatally in myelinating Schwann cells and in a subpopulation of astrocytes. Although CNTF administration prevents lesion-mediated and genetically determined motor neuron degeneration, its physiological function remained elusive. Here it is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength.
The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation ofCNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyteenriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-gamma. CNTF mRNA levels were down-regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed.
Die Kupfer-Zink-Lagerstätte von Kupferberg-Neufang im Bereich der Münchberger Deckenstruktur besteht aus einem etwa 4 km langen Zug einzelner stratiformer Vererzungslinsen, der in NW-SE-Richtung vom anchimetamorphen Paläozoikum "Bayerischer" Faziesentwicklung in die Prasinit-Phyllit-Serie hinüberzieht. Bisherige lagerstättenkundliche Untersuchimgen interpretierten die gesamte Lagerstätte als einheitliche, submarin-exhalativ entstandene stratiforme Bildung in Zusammenhang mit ordovizischem basischem Vulkanismus, der in den Rahmengesteinen der Lagerstätte durch die Diabase der anchimetamorphen Randschieferserie bzw. die Prasinite der Prasinit-Phyllit-Serie dokumentiert ist. Diese Vorstellung steht jedoch in deutlichem Widerspruch zu den Ergebnissen neuerer geochemischer und biostratigraphischer Untersuchungen, die für die Diabase und Prasinite eine völlig unterschiedliche Zusammensetzung ergaben und die zeigten, daß die Prasinit-Phyllit-Serie schon im Oberproterozoikum, die erzführenden Schichten im anchimetamorphen Paläozoikum aber erst im Unterdevon sedimentiert wurden. Für eine Klärung der Situation sind weitere Untersuchungen im Bereich der Lagerstätte erforderlich.
In this paper, convex approximation methods, suclt as CONLIN, the method of moving asymptotes (MMA) and a stabilized version of MMA (Sequential Convex Programming), are discussed with respect to their convergence behaviour. In an extensive numerical study they are :finally compared with other well-known optimization methods at 72 examples of sizing problems.
The surface sublimation of Cd and Te atoms from the zinc blende (111)A CdTe surface has been investigated in detail by reflection high energy electron diffraction and x-ray photoelectron spectroscopy. These experiments verify that Te is much easier to evaporate than Cd. The experimental value for the Te activation energy from a Te stabilized (111)A CdTe surface is 1.41 ±0.1O eV, which is apparently inconsistent with recent theoretical results.
We have investigated oxygen on CdTe substrates by means of x-ray photoelectron spectroscopy (XPS) and reflection high-energy electron diffraction (RHEED). A Te oxide layer that was at least 15 A thick was found on the surface of as-delivered CdTe substrates that were mechanically polished. This oxide is not easily evaporated at temperatures lower than 350°C. Furthermore, heating in air, which further oxidizes the CdTe layer, should be avoided. Etching with HCI acid (15% HCl) for at least 20 s and then rinsing with de-ionized water reduces the Te oxide layer on the surface down to 4% of a monoatomic layer. However, according to XPS measurements of the 0 Is peak, 20%-30% of a monoatomic layer of oxygen remains on the surface, which can be eliminated by heating at temperatures ranging between 300 and 340 cC. The RHEED patterns for a molecular beam epitaxially (MBE)-grown CdTe film on a (lOO) CdTe substrate with approximately one monoatomic layer of oxidized Te on the surface lose the characteristics of the normal RHEED pattems for a MBE-grown CdTe film on an oxygen-free CdTe substrate.
Molecular beam epitaxially grown short period (001) Hg\(_{1_x}\)Cd\(_x\)Te-HgTe superlattices have been systematically investigated. Several narrow well widths were chosen, e.g., 30, 35 and 40 Å, and the barrier widths were varied between 24 and 90 Å for a particular well width. Both the well width and the total period were determined directly by means of x-ray diffraction. The well width was determined by exploiting the high reflectivity from HgTe and the low reflectivity from CdTe for the (002) Bragg reflection. Knowing the well and barrier widths we have been able to set an upper limit on the average Cd concentration of the barriers, \(\overline x_b\), by annealing several superlattices and then measuring the composition of the resulting alloy. \(\overline x_b\) was shown to decrease exponentially with decreasing barrier width. The structure of a very short period superlattice, i.e., 31.4 Å, was also investigated by transmission electron microscopy, corroborating the x-ray diffraction results.
Infrared photoconductor fabricated with HgTe/CdTe superlattice grown by molecular beam epitaxy
(1993)
An infrared photoconductor fabricated with a HgTe/CdTe superlattice grown on a GaAs substrate by molecular beam epitaxy is described here for the first time. The growth procedure, device fabrication, and measurement results are described. The results show that the device has relatively high uniformity and 1000 K black-body detectivity 2.4 X 10\(^9\) cm Hz\(^{1/2}\) W\(^{-1}\) . The photoconductivity decay method was used for determining carrier lifetime of the HgTe/CdTe superlattice, the measured lifetime is 12\(\mu\)s at 77 K, which is the longest lifetime ever reported for HgTe/CdTe superlattices and we believe that the increase of lifetime is mainly due to the reduction of dimensions.
A route to 2S,5S-and 2R,5S-hydroxypipecolic acid is presented, starting with the enantiopure 5S-5-hydroxy-piperidone 7. The key step of this reaction sequence is the chemoselsctive methylenation of the amide carbonyl group of 8 with dimethyltitanocene 9 to 10. The transformation of the exocyclic enecarbamate double bond to the carboxylic acid group is best accomplished via hydroboration/oxidation to the alcohol 11a,b. Separation and oxidation of the dlastereomers 11a,b, to 148. and 14b, and hydrolysis furnishes the diastereomeric pipecolic acids 15a and 15b in enantiopure form.
The karyotype of D. elongatus was investigated by means of C-banding, silver staining, and mithramycinand quinacrine fluorescent staining. The diploid chromosome number is 2n = 50. C-banding shows pericentromerically localized constitutive heterochromatin in every chromosome. Two of the chromosome pairs carry two telomeric nucleolus organizer regions each. No heteromorphic sex chromosomes were found.
Es wird ein Krankheitsbild negativistischer Katatonie nach Leonhard mit nachweislichem Beginn in der frühen Kindheit beschrieben. Dieses zeichnet sich durch Negativismus, negativistische Erregungen mit (Auto)aggressivität und triebhaften Durchbrüchen aus. Die expressive Sprachentwicklung fehlt oder sie bleibt auf dem erreichten Entwicklungsstand stehen. Die körperliche Gesamtreifung ist retardiert. Zumeist nicht als frühkindliche Katatonien erkannt, werden diese Krankheiten fälschlich als "Schwachsinn bei frühkindlichem Hirnschaden" oder unspezifisch als "tiefgreifende Entwicklungsstörung" (DSM III-R, ICD 10) diagnostiziert.
Anhand von drei exemplarischen fällen wird. das Krankheitsbild der selbstquälerischen Depression, eine Form der reinen Depressionen Leonhards, dargestellt. Im Zentrum stehen die Ideen der Selbsterniedrigung und Selbstentwertung und der sich daran entwickelnde ängstlich-depressive Affekt. Charakteristisch ist auch die Angst um die nächsten Angehörigen. In ihren Selbstanklagen erwarten und fordern die Patienten für sich die schrecklichsten Strafen. Diese wenigen Leitsymptome kehren in jeder Krankheitsphase gleichförmig wieder. Andere depressive Symptome wie Denkhemmung und psychomotorische Hemmung treten dagegen völlig in den Hintergrund. Der Krankheitsverlauf ist streng monopolar. Die Dauer der Krankheitsphasen wurde von Leonhard mit durchschnittlich 5,8 Monaten angegeben. Sie betrug bei unseren Patienten durchschnittlich 4,1 Monate. Das klinische Erscheinungsbild ist durch moderne Behandlungsstrategien nicht wesentlich zu beeinflussen. Eine familiäre Belastung mit affektiven Psychosen findet sich nur sehr selten.
The thymus in SIV infection
(1993)
no abstract available
When bovine or human growth hormones (GH) were injected into 6 months old (about 10 g) gilthead seabream, the growth rate of the fish, as measured by changes in their weight, increased by only about 15% compared with the saline-injected control. No effect or even slight inhibition of the growth rate was obtained when chicken or porcine GHs were injected. In a preliminary experiment, it was found that injection ofthe native GH increased the growth rate ofthe fish by about 20% after treatment for only 2 weeks. An expression vector, using the pRE1 plasmid and transformation into MZl cells, produced the gilthead seabream GH, providing a supply for further experiments on the effect of the homologaus GH on growth. Two reporter genes, ß-galactosidase (lacZ) and melanoma oncogene of Xiphophorus (mrk YY), were microinjected into fertilized eggs of S. aurata. Expression of these two genes could be demonstrated in 2-day-old embryos, the lacZ gene by staining of its enzymatic product, and the mrk YY gene by its phenotypic expression.
Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behaviour and access to the females. In general social dominance requires large investments which in turn may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups due to the difficulties of determining paternity by classical methods using non-molecular markers. DNA fingerprinting overcomes these problems offering the possibility to determine genetic relationships and mating patterns within larger groups. Using this approach we have recently shown (Schartl et al., 1993) that in the poeciliid fish Limia perugiae in small mating groups the dominant male has 100% mating success, while in larger groups its contribution to the offspring unexpectedly drops to zero. The reproductive failure under such social conditions is explained by the inability of the ex-male to protect all the females simultaneously against mating attempts of his numerous subordinate competitors.
Legionella pneumophila, the causative agent of Legionnaires' disease is a facultative intracellular bacterium, which in the course of human infection multiplies in lung macrophages predominantly manifesting as pneumonia. The natural habitat of Legionella is found in sweet water reservoirs and man-made water systems. Virulent L. pneumophila spontaneously convert to an avirulent status at a high frequency. Genetic approaches have led to the identification of various L. pneumophila genes. The mip (macrophage infectivity potentiator) determinant remains at present the sole established virulence factor. The Mip protein exhibits activity of a peptidyl prolyl cis trans isomerase (PPiase), an enzyme which is able to bind the immunosuppressant FK506 and is involved in protein folding. The recently cloned major outer membrane protein (MOMP) could play a role in the uptake of legionellae by macrophages. Cellular models are useful in studying the intracellular replication of legionellae in eukaryotic cells. Human celllines and protozoan models are appropriate for this purpose. By using U 937 macrophage-like cells and Acanthamoeba castellanii as hosts, we could discriminate virulent and avirulent L. pneumophila variants since only the virulent strain was capable of intracellular growth at 37 oc. By using these systems we further demonstrated that a hemolytic factor cloned and characterized in our laboratory, legiolysin (lly), had no influence on the intracellular growth of L. pneumophila.
Die Arbeit geht von der allgemeinen Feststellung aus, daß die Repräsentation von Wissen der Reduktion des Aufwandes von zu erwartenden Informationsverarbeitungsprozessen dient. Es werden verschiedene Anforderungen an die menschliche Informationsverarbeitung betrachtet, und es wird jeweils gefragt, welche Eigenschaften die Wissensrepräsentation haben muß, um diesen Anforderungen zu genügen. Im einzelnen werden die Objektwahrnehmung, die anschauliche Vorstellungstätigkeit, die Aufmerksamkeitssteuerung, die Erkennung semantischer Relationen, die Handlungskontrolle und der Erwerb von Wortbedeutungen betrachtet. Es wird die Schlußfolgerung gezogen, daß eine Repräsentation in diskreten symbolischen Einheiten der Dynamik der Wissensnutzung unter den verschiedenen Anforderungen wenig gerecht wird. Es scheint naheliegender, Wissen direkt in Handlungseinheiten zu repräsentieren. Solche Einheiten sollten Informationen über einzelne Handlungen mit Informationen über Situationskontexte verbinden, in denen die Handlungen erfolgreich verwendet worden sind. Die Vorteile einer solchen handlungsorientierten Wissensrepräsentation werden diskutiert.
S fimbriae are able to recognize receptor molecules containing sialic acid and are produced by pathogenic E. coli strains causing urinary tract infection and menigitis. In order to characterize the corresponding genetic determinant, termed S fimbrial adhesin ( sfa) gene duster, we have cloned the S-specific genes from a urinary pathogen and from a meningitis isolate. Nine genes are involved in the production of S fimbriae, two of these, sfaB and sfaC code for regulatory proteins being necessary for the expression of S fimbriae. Two promoters, PB and Pc, are located in front of these genes. Transcription of the sfa determinant is influenced by activation of the promotersvia SfaB and SfaC, the action of the H-NS protein and an RNaseE-specific mRNA processing. In addition, a third promoter, P A• located in front of the major subunit gene sfaA, can be activated under special circumstances. Four genes of the sfa determinant code for the subunit-specific proteins, SfaA (16 kda), SfaG (17 kda), SfaS (14 kda) and SfaH (29 kda). It was demonstrated that the protein SfaA is the major subunit protein while SfaS is identical to the sialic-acid-specific adhesin of S fimbriae. The introduction of specific mutations into sfaS revealed that a region of six amino acids of the adhesin which includes two lysine and one arginine residues is involved in the receptor specific interaction of S fimbriae. Additionally, it has been shown that SfaS is necessary for the induction of fimbriation while SfaH plays a role in the stringency of binding of S fimbriae to erythrocytes.
An antibody against the NDH-K subunit of the NAD(P)H-dehydrogenase from the cyanobacterium Synechocystis sp. PCC6803 was used to isolate a subcomplex ofthe enzyme from Triton X-lOO solubilized total membranes by immunoaffinity chromatography. The isolated subcomplex consisted of seven major polypeptides with molecular masses of 43, 27, 24, 21, 18, 14 and 7 kDa. The amino-terminal amino acid sequences of the polypeptides were determined. By comparing the sequences with the amino acid sequences deduced from DNA. three proteins were identified as NDH-H (43 kDa). NDH-K (27 kDa) and NDH-J (24 kDa). A fourth subunit (NDH-J, 21 kDa) was identified by Western blot analysis with an NDH-J antibody.
The plastid genomes of higher plants contain eleven reading frames (ndhA-K) that are homologous to genes encoding subunits of the mitochondrial NADH-ubiquinone-oxidoreductase (complex I). The carboxyterminal end of the NDH-H subunit from rice (Oryza sativa L.) was expressed as a fusion protein in Escherichia coli and antibodies against the fusion protein were generated in rabbits. The antibody was used to study the expression of NDH-H, and the following results were obtained: (i) NDH-H is expressed in mono- and dicotyledonous plants, (ii) NDH-H is localized on the stroma lamellae of the thylakoid membrane and (iii) NDH-H is expressed in etioplasts. Together with the finding that two other ndh genes (ndhI and ndhK) are expressed in plastids, these results point to the existence of an NAD(P)H-plastoquinone-oxidoreductase on the thylakoid membrane. The possible function of the enzyme in plastids is discussed and it is suggested that it works in balancing the ATP/ADP and the NADPH/NADP ratios during changing external (i.e. light) or internal (i.e. ATP and NADPH demands of biosynthetic pathways of the plastid) conditions.
We examined the potential role of fibroblast growth factor 5 (FGF-5) as a target-derived trophic factor for spinal motoneurons. Northern analysis of total RNA from rat skeletal muscle revealed an FGF-5 mRNA transcript both during the period of embryonic motoneuron death and in the adult. Recombinant human FGF-5 supported the survival of highly enriched cultures of embryonic chick motoneurons. Significant proportions of the motoneuron survival activity of rat skeletal muscle extracts could be immunoprecipitated using an antiserum to FGF-5. The immunoprecipitable activity was present in soluble and matrix-bound forms in embryonic muscle, but bound exclusively to the extracellular matrix in adult muscle. These results, along with the secretory nature of FGF-5, suggest that FGF-5 may act as a target-derived trophic factor for motoneurons.
Motoneurons played an essential role in establishing the concept of target-mediated support of innervating neurons. However, it took several decades until molecules were identined which trophically support motoneurons in vitro and in vivo. The most potent molecule identined so far is ciliary neurotrophic factor (CNTF). It is expressed as a cytosolic molecule in myelinating Schwann cells rather than in skeletal muscle in the postnatal period and therefore does not qualify as a target-derived neurotrophic factor regulating motoneuron survival during embryonic development. However, the inactivation of CNTF by gene targeting experiments results in progressive atrophy and degeneration of motoneurons, demonstrating that CNTF plays an essential role as a maintenance factor for motoneurons postnatally. Secretory molecules which are expressed in skeletal muscle during embryonic development and which support motoneurons in culture and partially also in vivo include members of the NGF gene family (BDNF, NT-3, NT-4/S) , FGF-S, IGF-I, and UF. The evaluation of the physiological importance of these molecules is under investigation.
The survival and functional maintenance of spinal motoneurons, both during the period of developmental cell death and in adulthood, have been shown to be dependent on trophic factors. In vitro experiments have previously been used to identify several survival factors for motoneurons, including CNTF, UF, and members of the neurotrophin, FGF, and IGF gene families. Some of these factors have also been shown to be active in vivo, either on chick motoneurons during embryonic development or on lesioned facial and spinal motoneurons of the newborn rat. Here we demonstrate that lesioned newborn rat facial motoneurons can be rescued by NT-4/5, IGF-I, and UF. Furthermore, in contrast to chick motoneurons, the survival of isolated embryonic rat motoneurons can be maintained by the neurotrophins BDNF, NT-3, and NT-4/5. IGF-I and FGF-5 were also active in this system, each supporting more than 50% of the originally plated neurons. The responsiveness of motoneurons to multiple factors in vitro and in vivo suggests that motoneuron survival and function are regulated by the coordinated actions of members of different gene families.
We showed previously that oligodendrocytes and their precursors require continuous signalling by protein trophic factors to avoid programmed cell death in culture. Here we show that three classes of such trophic factors promote oligodendrocyte survival in vitro: (1) insulin and insulin-like growth factors (IGFs), (2) neurotrophins, particularly neurotrophin-3 (NT -3), and (3) ciliary-neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and interleukin 6 (IL-6). A single factor, or combinations of factors within the same class, promote only short-term survival of oligodendrocytes and their precursors, while combinations of factors from different classes promote survival additively. Long-term survival of oligodendrocytes in vitro requires at least one factor from each class, suggesting that multiple signals may be required for long-term oligodendrocyte survival in vivo. We also show that CNTF promotes oligodendrocyte survival in vivo, that platelet-derived growth factor (PDGF) can promote the survival of oligodendrocyte precursors in vitro by acting on a novel, very high affinity PDGF receptor, and that, in addition to its effect on survival, NT-3 is a potent mitogen for oligodendrocyte precursor cells.
Available data on the occurrence and expression of somatic histone HI during oogenesis and early embryogenesis of Xenopus laevis are contradictory. In particular the reported presence of a large storage pool of histone HIA in oocytes is difficult to reconcile with the high transcriptional activity of all gene classes in this specific cell type. In the present study we have used polyclonal antibodies raised against somatic Xenopus histone HI (HIA and HIA/B) for combined immunoblotting experiments to quantitate HI pools and immunolocalization studies to visualize chromosome- bound HI. Both approaches failed to detect soluble or chromosomal histone HI in vitellogenic oocytes, eggs, and cleavage-stage embryos up to early blastula. In addition, chromatin assembled in Xenopus egg extract was also negative for histone HI as revealed by immunofluorescence microscopy. Lampbrush chromosomes not only lacked histone HI but also the previously identified histone HI-like B4 protein (Smith et al., 1988, Genes Dev. 2,1284-1295). In contrast, chromosomes of eggs and early embryos fluoresced brightly with anti-B4 antibodies. Our results lend further support to the view that histone HI expression is developmentally regulated during Xenopus oogenesis and embryogenesis similar to what is known from other species.
Signal transduction via receptors for N-formylmethionyl peptide chemoattractants (FPR) on human neutrophils is a highly regulated process. It involves direct interaction of receptors with heterotrimeric G-proteins and may be under thc control of cytoskeletal clemcnts. Evidencc exists suggesting that thc cytoskeleton and/or the membrane ske1eton determines the distribution of FPR in the plane of the plasma membrane, thus controlling FPR accessibility to different protcins in functionally distinct membrane domains. In desensitized cells, FPR are restricted to domains which are depleted of G proteins but enriched in cytoskeletal proteins such as actin and fodrin. Thus, the G protein signal transduction partners of FPR become inacccssible to the agonist-occupied receptor, preventing cell activation. We are investigating the molecular basis for the interaction of FPR with the membrane skeleton, and our results suggest that FPR, and possibly other receptors, may directly bind to cytoskeletal proteins such as actin.
In 55 chronic DSM I11 -R schi zophre nics the occurrence of obstetr ic complica ti ons (OCs) was investigated us ing the famili al/sporael ic strategy and Leonhard's unsystemati c/systematic distin ction. The overa ll frequency and severity of OCs elid not differ be tween patie nts anel controls. A sub-sample of patients, whose genetic ri sk was supposed to be high in both class ification systems (d iagnos is 01' unsystematic anel fa mili al sc hizophre ni a), had s igni ficantly fewer OCs than controls on the Lewis anel Murray scale (P < 0.05). With reference to previous reports of inc reased morta lity rates in the offspring of schizop hre nics, high genetic risk and addition al perinatal stressors may in crease perin atal mortality. In contrast, pat ie nts whose genetic ri sk was sllpposed to be low in both systems (di agnos is of systematic and sporadic sc hizophrenia) showed a trend to an increased freqllency of OCs in the Fuchs scale. In the context of the recently reported highl y signi ficantly increased rate of matern al infections dllring midgestation in these pati e nts, it was supposed th at perin atal complications may be of so me ae tio logical importance in sc hizophrenics with low genetic ri sk.
Diethylstilbestrol alters the morphology and calcium levels of growth cones of PC12 cells in vitro
(1993)
Diethylstilbestrol (DES) is a synthetic estrogen with carcinogenic properties. DES is known to alter cytoskeletal components, including the organization of actin stress fibres in C6 rat glioma cells. ln a test of the hypothesis that DES disrupts actin Filaments of growth cones in neuron-like cells, DES-induced changes in filopodial lengths were quantified in rat pheochromocytoma (PC12) cells in vitro. DES significantly altered growth cone morphology, with collapse of growth cone filopodia and neurite retraction invariably occurring at a concentration of 10 MikroM. At 5 MikroM DES, transient reductions in total filopodiallengths occurred. At DES concentrations of 0.1 nM and 1 nM, reductions in total filopodiallengths occurred in a fraction of growth cones. Evidence exists which shows that growth cone activity and morphology are intimately linked to Ieveis of intracellular, free calcium and that DES increases such levels. Measurements of free intracellular calcium levels by fluorescence microscopy, at times concurrent with the DES-induced reduction in total filopodial lengths, showed that calcium levels were indeed significantly increased by 10 MirkoM DES. Labelling of filamentaus actin (f-actin) with FITC-phalloidin showed that the f-actin distribution in growth cones exposed to DES could not be differentiated from the distribution found in spontaneously retracting growth cones. Tagether with evidence which showed that growth cone motility was not affected, the results are taken to indicate that DES, rather than acting directly on the cytoskeleton, exerts its effects indirectly, by a calcium-induced destabilization of actin filaments in the growth cone.
No abstract available.
No abstract available.
No abstract available.
No abstract available.
Autolyzed, antigen-extracted, allogeneic (AAA) bone was prepared from human cortical bone and its morphologic, biomechanical, and osteoinductive properlies were compared with untreated (frozen) as well as lyophilized human bone. Scanning electron microscopy revealed removal of inprganic calcium phosphates and persistence of shrunken collagen fibrils on the surface of AAA bone matrix. Biomechanical testing of differently prepared bone samples showed that lyophilization increased both the modulus of elasticity (P < .00001) and the compressive strength (P < .00001 ). Depending on the depth of decalcification in the preparation of AAA bone, both measured values decreased in rehydrated AAA bone compared with untreated bone {P < .00001 ). Completely demineralized and rehydrated AAA bone was soft, flexible, and showed very little compressive strength. Differences in biomechanical behavior between samples drilled longitudinally or perpendicularly to the diaphyseal bone axis were observed. Xenogeneic human bone samples were implanted in muscle pouches of Sprague-Dawley rats for 6 weeks. AAA bone implants showed chondrogenesis and osteogenesis in 50% of the cases, while untreated or lyophilized bone implants induced no new cartilage or bone formation. As decalcification exposed xenogeneic organic matrix components, AAA bone implants provoked the highest inflammatory reaction. When AAA bone samples were implanted in immunosuppressed rats, the inflammatory reaction was suppressed and 94o/o of the implants showed endochondral bone formation. The chondroinductivity of the bone samples also was tested in vitro using neonatal rat muscle tissue to avoid interference with inflammatory cells and secreted cytokines. In this assay, 68°/o of AAA bone samples induced chondroneogenesis, while untreated as weil as lyophilized bone samples failed to induce any cartilage formation. The results clearly dernonstrafe that AAA bone has osteoinductive properties. Biomechanical stability of AAA bone implants depends on the degree of demineralization. Thus, they can be prepared in an appropriate manner for different indications in oral and maxillofacial surgery.
Wben irradiated at 360 nm, furocoumarins with a hydroperoxide group in a side chain effciently give rise to a type of DNA damage that can best be explained by a photoinduced generation of hydroxyl radicals from the excited pbotosensitizers. The observed DNA damage profiles, i.e. the ratios of single-strand breaks, sites of base loss (AP sites) and base modifications sensitive to fonnamidopyrimidine-DNA glycosylase (FPG protein) and endonuclease m, are similar to the DNA damage profile produced by hydroxyl radicals generated by lonizing radiation or by xanthine and xanthine oxidase in the presence of Fe(III)-EDTA. No such damage is observed with the corresponding furocoumarin alcohols or in the absence of near-UV radiation. The damage caused by the photo-excited hydroperoxides is not influenced by superoxide dismutase (SOD) or catalase or by D2O as solvent. The presence of t-butanol, however, reduces both the formation of single-strand breaks and of base odifications sensitive to FPG protein. The cytotoxicity caused by one of the hydroperoxides in L5178Y mome lymphoma cells is found to be dependent on the near-UV irradiation and to be much higher than that of the corresponding alcohol. Therefore the new type of photoinduced damage occurs inside cells. Intercalating photosensitizers with an attached hydroperoxide group might represent a novel and versatile class of DNA damaging agents, e.g. for phototherapy.
In Xiphophorus melanoma formation has been attributed by classical genetic findings to the overexpression of a cellular oncogene (Tu) due to elimination of the corresponding regulatory gene locus in hybrids. We have attempted to elucidate this phenomenon on the molecular biological level. Studies on the structure and expression of known proto-oncogenes revealed that several of these genes, especially the c-src gene of Xiphophorus, may act as effectors in establishing the neoplastic phenotype of the melanoma cells . However, these genes appear more to participate in secondary steps of tumorigenesis. Another gene, being termed Xmrk, which represents obviously a so far unknown proto-oncogene but with a cons iderably high similarity to the epidermal growth-factorreceptor gene, was mapped to the Tu-containing region of the chromosome. This gene shows features with respect to its structure and expression that seem to justify it to be regarded as a candidate for a gene involved in the primary processes leading to neoplastic transformation of pigment cells in Xiphophorus.
An improved 32P-postlabelling assay for detection and quantitation of styrene 7,8-oxide-DNA adducts
(1993)
Using DNA modified with [7-3H]styrene 7,8-oxide (SO) in vitro we have standardized the 32P-postlabelling assay for detecting SO-DNA adducts. Nuclease P 1-enriched adducts were 32P-labelled and purified by high-salt ( 4.0 M ammonium formate, pH 6.1} C1s reverse-phase TLC. After elution from the layer with 2-butoxyethanol:H20 (4:6), adducts were separated by two-dimensional PEI cellulose TLC in non-urea solvents (2.0 M ammonium formate, pH 3.5, and 2.7 M sodium phosphate, pH 5.6). One major, three minor and several trace adducts were detected. The efficiency of the kinase reaction depended on the ATP concentration. Use of standard labelling conditions (['Y· 32P]ATP, <3000 Ci/mmol; <2 Mikromol) resulted in poor ( 4-7%) adduct recovery. An ATP concentration of 40 Mikromol, however, increased the labeJling efficiency by a factor of 5-8 (35-55% based on 3H-SO labelied DNA). The results indicate that the new separation technique is suitable for the relatively polar SO-DNA adducts and that high labelling efficiency can be achieved.
[7-3H)Styrene 7,8-oxide was administered by oral gavage to male CD rats at a dose of 1.3 mg/kg. After 4 h, the forestomach was excised, DNA was isolated, purified to constant specific radioactivity and degraded nzymatically to the 3 '-nucleotides. Highperformance liquid chromatography fractions with the normal nucleotides contained most of the radiolabel, but a minute level of adduct label was also detccted. Using the units of the covalent binding index (micromoles adduct per mole DNA nucleotide)/(millimole chemical administered per kilogram body weight), a DNA binding potency of 1.0 was derived. A comparison of the covalent binding indices and carcinogenic potencies of other genotoxic forestarnach carcinogens showed that the tumorigenic activity of styrene oxide is unlikely to be purely genotoxic. Therefore, styrene oxide was compared with 3-tbutylhydroxyanisole (BHA) with respect to stimulation of cell proliferation in the forestomach. Male Fischer 344 rats were treated for four weeks at three dose levels of styrene oxide (0, 137, 275 and 550 mg/kg, three times per week by oral gavage) and BHA (0, 0.5, 1 and 2% in the diet); the highest doses had been reported to result in 84% and 22% carcinomas in the forestomach, respectively. Cell proliferation was assessed by incorporation of bromodeoxyuridine into DNA and immunohistochemical analysis. An increase in the lablling indexwas found in a11 treated animals. In the prefundic region of the forestomach, the labeHing index increased significantly, from 42% (controls) to 54% with styrene oxide and from 41 to 55% with BHA. Rats treated with BHA also had severe hyperplastic lesions in the prefundic region, i.e., at the location of BHA-induced forestomach carcinomas. The number of cells per millimetre of section length was increased up to 19 fold. Hyperplastic lesions were not seen with styrene oxide, despite the higher tumour incidence reported with this compound. We conclude that the carcinogenicity of styrene oxide to the forestomach most probably involves a mechanism in which marginal genotoxicity is combined with promotion by increased cell proliferation.
Known mutagens and carcinogens in the dict were compiled and the risk of cancer was estimated on the basis of average exposure Ievels in Switzerland and carcinogenic potencies from rodent bioassays. The analysis showed that, except for a1cohol, the sum of all known dietary carcinogens could only explain a few percent of the cancer deaths attributed by epidemiologists to dietary factors. The discrepancy was explained by a "carcinogenicity" of excess macronutrients. This hypothesis was based on an evaluation of dietary restriction experiments in rats and mice, where a dramatic reducing effect on spontaneaus tumour formation was seen. From these experiments, a "carcinogenic potency" was deduced for food in excess (TD50 approximately 16 g/kg per day). Ovemutrition in Switzerland was converted into excess food intake and the cancer risk estimated on the basis ofthe TD50 value. The resulting risk of60,000 cases per one million lives wou1d aJlow to explain by overnutrition almost all "diet-related" cancer deaths in humans.
This paper reports on a longitudinal study dealing with the development of literacy in young children. A total of 163 children were first tested during their last year in kindergarten using a variety of tasks that tapped phonological processing, memory capacity, early literacy, and intelligence. Children's ward decoding, reading comprehension, and spelling skills were assessed in elementary school several years later. As a main result, all of the predictor domains had a significant impact on the acquisition of literacy in elementary school, although the contribution of each domain differed as a function of the criterion measure. An attempt to identify children-at-risk using a kindergarten screening test provided encouraging results. Nonetheless, it was shown that whereas group predictions of reading and spelling performance can be quite accurate, the individual prognosis of school problems is far from perfect.
Im vorliegenden Beitrag wird der Versuch gemacht, neuere Befunde der kognitiven Psychologie, insbesondere der Expertiseforschung, zur Entwicklung außergewöhnlicher Fertigkeiten und Kenntnisse auf den Bereich des Sports zu übertragen und damit deren Generalisierungsmöglichkeiten zu prüfen. In einem ersten Schritt werden dabei die Grundannahmen der traditionellen fähigkeitsorientierten Leistungsprognose mit denen der neueren Expertiseforschung verglichen und im Hinblick auf ihre empirische Bewährung untersucht. Der zweite Schritt besteht darin, daß mögliche Parallelen zwischen der Entwicklung kognitiver und sportlicher Expertise aufgezeigt und an Fallbeispielen demonstriert werden. Dies leitet zum Schwerpunkt des vorliegenden Beitrags über, der in einer Reanalyse von Daten besteht, die im Rahmen einer fünfjährigen Längsschnittstudie an jugendlichen deutschen Tennistalenten gewonnen wurden (vgl. Rieder, Krahl, Sommer, Weicker & Weiss, 1983). Da in dieser Untersuchung sowohl Daten zur Entwicklung allgemeiner motorischer Basisfähigkeiten wie auch zur Entwicklung sportartspezifischer Fertigkeiten erhoben worden waren, ließ sich die Bedeutsamkeit dieser beiden Komponenten für den sportlichen Erfolg relativ genau bestimmen. Weiterhin waren Informationen zu Hintergrundmerkmalen wie z.B. der elterlichen Unterstützung, der Trainingsintensität sowie Merkmalen der Motivation und Konzentration verfügbar, von denen anzunehmen war, daß sie zusätzlich dazu geeignet sein sollten, individuelle Unterschiede in den beobachteten Entwicklungsverläufen zu erklären.
No abstract available
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No abstract available
The relation between hypochondriacal attitudes, thermal pain threshold, and attentional bias toward pain was examined in a non-clinical population (N = 28). Attentional bias was operationalized with a concentration-performance test, which subjects performed while connected to a pain stimulator. Subjects were informed that they would receive a painful stimulus during the second part of the test, while the first part was introduced as pain-free. The pain stimulus was never applied during the test phase. The expectancy of a forthcoming pain stimulus reduced the performance of high hypochondriacal subjects in both parts of the test. Low hypochondriacal subjects, on the other hand, displayed significantly better performance in the first, pain-free compared to the second, pain-related part of the test. Thermal pain thresholds were assessed at four measuring sites (thenar, neck, collar-bone, abdomen), but no relations with hypochondriasis sum scores and locus of pain stimulation were found. A stepwise multiple regression of pain threshold by individual Illness Attitude Scales (IAS) led to 66% of the variance being explained by the scales ‘concern about pain’, ‘worry about illness’, and ‘disease phobia’. Results are discussed in terms of amplifying somatic style, preoccupation with or attentional bias toward bodily symptoms, and experimental induction of a hypochondriacal state.
Effects of smoking on thermal pain threshold in deprived and minimally-deprived habitual smokers
(1993)
This study examined the antinociceptive effects of smoking in nine habitual smokers under deprived (12 h) and minimally-deprived (< 30min) conditions. Pain threshold for thermal stimuli, heart rate, blood pressure and ratings of mood, arousal, dominance and well-being were assessed before and after smoking a cigarette. Overall, smoking affected all measured variables in the expected direction, leading to increased physiological activity, elevated pain threshold and improved mood. However, most of these effects depended on the deprivation status of the subjects, such that smoking after deprivation increased pain threshold whereas smoking after minimal deprivation did not. Pain threshold before smoking was the same for both groups. Deprived subjects had lower pre-smoke diastolic blood pressure, heart rate, and arousal levels, which rose to equal minimally-deprived subjects scores after smoking.
Vorwort (Das Kind (1993) 14)
(1993)
No abstract available
Vorwort (Das Kind (1993) 13)
(1993)
No abstract available
Implizites oder unbewußtes Lernen soll sich nach vorliegenden Berichten dadurch auszeichnen, daß es beiläufig geschieht, daß es aufmerksamkeitsunabhängig ist und daß seine Resultate nicht bewußt werden. Nach Meinung einiger Autoren handelt es sich um eine Urform des Lernens, die vielfachen unbewußten Abhängigkeiten menschlichen Verhaltens von verborgenen Reizstrukturen zugrunde liegt. Eine kritische Durchsicht der Befunde zeigt, daß keines der besonderen Merkmale unbewußten Lernens überzeugend belegt ist. Es liegen auch keine differenzierten Überlegungen zu den Mechanismen unbewußten Lernens vor. Es wird die Vermutung begründet, daß den untersuchten Lernvorgängen möglicherweise ein elementares Bedürfnis nach zuverlässiger Antizipation von Verhaltenskonsequenzen zugrunde liegt. Simulationen, die eine solche Spekulation unterstützen, werden diskutiert und noch zu lösende Probleme aufgezeigt.