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Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is. suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologaus recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.
1.2-Dioxetanes, very reactive and high energy molecules. are involved as labile intermediates in dioxygenase- activated aerobic metabolism and in physiological processes. Various toxico1ogica1 tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonucleasesensitive sites, most of them are FPG protein-sensitive base modifications (8-hydroxyguanine, fonnamidopyrimidines). Pyrimidinedimersand sites ofbase loss (AP sites) which were probed by UV endonuclease and exonuclease 111 are minor lesions in this system. While the alky1-substituted dioxetanes do not show any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetanes such as benzofuran and furocoumarin dioxetanes are strongly mutagenic in S. typhimurium strain TA I 00. DNA adducts formed with an intermediary alkyJating agent appear to be responsible for the mutagenic activity of benzofuran dioxetane. We assume that the benzofuran epoxides, generated in situ from benzofuran dioxetanes by deoxygenation are the ultimate mutagens of the latter. since benzofuran epoxides are highly mutagenic in the S. typhimurium strain TAIOO and they form DNA adducts. as detected by the 212Ppostlabelling technique. Our results imply that the type of D NA darnage promoted by dioxetanes is dependent on the structural feature of dioxetanes. Furthermore, the direct photochemical DNA darnage by energy transfer. i.e., pyrimidine dimers, plays a minor role in the genotoxicity of dioxetanes. Instead, photooxidation dominates in isolated DNA. while radical darnage and alkylation prevail in the cellular system.
Humanfoamy virus (HFV) is a retrovirus encoding structural genes and, like human immunodeficiency virus and human T ceU leukemia virus I, several anciUary reading frames collectively termed the belgenes. We have previously shown that HFV transgenic mice develop an encephalopathy with neuronal loss in hippocampus and cerebral cortex. We have now raised and characterized rabbit antisera to various recombinant portions of gag, pot, env, and bel-I, the viraltransactivator. Immunoreactivity for gag and bel-I was observed in nuclei and processes of hippocampal and cortical neurons before the onset of morphological lesions and correlated with the appearance of HFV mRNA. Astrocyte-derived multinucleated giant ceUs containing HFV proteins were present in the brain oftransgenic mice coexpressingfuU- length HFV genes but not in mice expressing truncated gag and env, suggesting that these genes contain afusogenic domain. Expression of fuU-length structural genes decreased the life expectancy oftransgenic mice, implying an a4Juvant rolefor these proteins in HFV-induced brain damage. (Am] Pathol 1993, 142:1061-1072)
Quantification of the peripheral nerve myelin glycoprotein PO and antibodies to PO is difficult due to insolubility of PO in physiological solutions. We have overcome this problern by using the water-soluble recombinant form of the extracellular domain of PO (PO-ED) and describe newly developed assays which allow detection and quantitation of PO and antibodies to PO, in serum and cerebraspinal fluid (CSF). These sensitive and specific assays based on the ELISA technique were used to study humoral immune responses to PO during experimental autoimmune ("allergic") neuritis (EAN). In order to establish these tests, monoclonal antiborlies to different epitopes of rodent and human PO-ED were produced. A two-antibody sandwich-ELISA allowing quantitation of PO Oower detection Iimit of 0.5 ngjml or 30 fmoljml) and an antibody-capture ELISA (lower detection Iimit 1 ng specific antibody jml) to detect antiborlies to PO in serum and CSF were developed. EAN was induced in rats by active immunization with bovine myelin or the neuritogenic protein P2 or by adoptive transfer using P2 specific CD4 positive T cells. Serum and CSF were assayed for the presence of PO-ED and antibodies to PO-ED or P2. Antibodies to PO-ED were detected during active myelin-induced EAN, but not during P2-induced or adaptive transfer EAN. The anti-PO-ED antibodies in the CSF showed a correJation with disease activity. In contrast, in the same model antibodies to P2 persisted long after the disease ceased. No soluble PO-Iike fragments could be found in serum or CSF during any of the three types of EAN. We conclude that PO may be a B-eeil epitope in EAN. These findings warrant a screen for antibodies to PO-ED in human immune neuropathies.
Seven monoclonal antibodies were raised against the immunoglobulin-like extracellular domain of PO (POED), the major protein of peripheral nervous system myelin. Mice were immunized with purified recombinant rat PO-ED. After fusion, 7 clones (POI-P07) recognizing either recombinant, rat, mouse, or human PO-ED were selected by ELlS A and were characterized by Western blot, immunohistochemistry, and a competition assay. Antibodies belonged to the IgG or IgM class, and P04-P07, reacted with PO in fresh-frozen and paraffin-embedded sections of human or rat peripheral nerve, but not with myelin proteins of the central nervous system of either species. Epitope specificity of the antibodies was determined by a competition enzyme-linked immunosorbent assay (ELISA) and a direct ELlS A using short synthetic peptides spanning the entire extracellular domain of PO. These assays showed that POl and P02 exhibiting the same reaction pattern in Western blot and immunohistochemistry reacted with different distant epitopes of PO. Furthermore, the monoclonal antibodies P05 and P06 recognized 2 different epitopes in close proximity within the neuritogenic extracellular sequence of PO. This panel of monoclonal antibodies, each binding to a different epitope of the extracellular domain of PO, will be useful for in vitro and in vivo studies designed to explore the role of PO during myelination and in demyelinating diseases of the peripheral nervous system.
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.
In this paper, we present results on the first MBE growth of HgSe. The influence of the GaAs substrate temperature as well as the Hg and Se fluxes on the growth and the electrical properties has been investigated. It has been found that the growth rate is very low at substrate temperatures above 120°C. At 120°C and at lower temperatures, the growth rate is appreciably higher. The sticking coefficient of Se seems to depend inversely on the Hg/Se flux ratio. Epitaxial growth could be maintained at 70°C with Hg/Se flux ratios between lOO and ISO, and at 160°C between 280 and 450. The electron mobilities of these HgSe epilayers at room temperature decrease from a maximum value of 8.2 x 10^3 cm2 /V' s with increasing electron concentration. The concentration was found to be between 6xlO^17 and 1.6x10^19 cm- 3 at room temperature. Rocking curves from X-ray diffraction measurements of the better epilayers have a full width at half maximum of 5S0 arc sec.
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.
The molecular beam epitaxially growth of (001) Hg\(_{1-x}\) Cd\(_z\) Te-HgTe superlattices has been systematically investigated. The well width as well as the period were determined directly by X-ray diffraction. This was accomphshed for the well width by exploiting the high reflectivity from HgTe and the low reflectivity from CdTe for the (002) Bragg reflection. Knowing the well and barrier thicknesses we have been able to set an upper limit on the aver~ge composition of the barriers, Xl, by annealing the superlattice and then measuring the composition of the. resultmg alloy. Xb was shown to decrease exponentially with decreasing barrier width. Xb is appreciably smaller m. narrow barriers due to the increased significance of interdiffusion in the Hg\(_{1-x}\)Cd\(_x\) Te/HgTe interface in narrow barriers. The experimentally determined optical absorption coefficient for these superlattices is compared WIth theoretical calculations. The absorption coefficient was determined from transmission and reflection spectra at 300, 77 and 5 K. Using the thickness and composition of the barriers and wells, and an interface width due to interdiffusion, the complex refractive index is calculated and compared with the experimental absorption coefficient. The envelope function method based on an 8 x 8 second order k . p band model was used to calculate the superlattice states. These results when inserted into Kubo's formula, yield the dynamic conductivity for interband transitions. The experimental and theoretical values for the absorption coefficient using no adjustable parameters are in good agreement for most of the investigated superlattices. Furthermore the agreement for the higher energetic interband transitions is much worse if values for the barrier composition, which are appreciably different than the experimentally determined values, are used. The infrared photoluminescence was investigated at temperatures from 4.2 to 300 K. Pronounced photoluminescence was observed for all superlattices in this temperature range.
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.
Murine epidermal Langerhans cells (LC) have been demonstrated to stimulate a vigorous T cell response to Leishmania major, a cause of human cutaneous leishmaniasis. It was therefore of interest to analyze whether LC can take up viable parasites. Epidermal cells were obtained from mouse ear skin for incubation with L. major and subsequent detection of intracellular parasites by cytochemistry. Freshly isolated LC, but not cultured LC, phagocytosed L. major and the uptake was inhibited by antibodies to the complement receptor type 3. Electron microscopic studies revealed the presence of viable amastigotes within Le. Moreover, with double-Iabeling techniques, L. major-containing LC could also be detected in infected skin. The results demonstrate that LC can internalize L. major. Since the number of organisms per infected LC remained consistently low, the prime task of LC may not be the promotion of parasite spreading but the presentation of L. major antigen to T cells and, thus, the regulation of the cellular immunity during cutaneous leishmaniasis.
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.
In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus
(1993)
The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.
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The question addressed was whether Stimulation of cell proliferation could be responsible for tumor induction in the torestornach by styrene 7,8-oxide (SO). Male F344 rats were treated for 4 weeks with 0, 137,275, and 550 mglkg SO by p.o. gavage 3 times/week. Positive controls received 0, 0.5, I, and 2% butylated hydroxyanisole (BHA) in the diet for 4 weeks. Twenty-four h before termination of the experlment, the rats were implanted s.c. with an osmotic minipump deliverlog S-bromo-2'-deoxyuri· dine (BrdU). Cell proliferation in the forestomach was assessed by immunohistochemistry for BrdU incorporated into DNA. Cell number/mm section length and fraction of replicating cells (labeling Index) were determined in 3 domains of the forestomach, the saccus caecus, the midregion, and the prefundic region. With the exception of the prefundic reglon of the low-dose SO group, a significant increase of the labeling index was found in all regions both with SO and BHA. Rats treated with BHA showed, in addition, a dose-dependent increase in number and size of hyperplastic lesions. This was most pronounced in the prefundic region where carcinomas were reported to be localized. In this region, the number of dividing cells/mm section length was increased up to 17-fold. With SO, only marginal morphological changes were occasionally observed, despite the fact that the respective long-term treatment bad been reported to result in a higher carcinoma incidence than treatment with BHA. It ls concluded that the rate of replicating cells alone, numerically expressed by the labeling Index, is an lnsufficient tool for interpretlog the role of cell division in carcinogenesis. It is postulated that SO and BHA induce forestomach tumors via different mechanisms. While hyperplasia in the prefundic region most likely dominates the carcinogenicity of BHA, a mechanism combining marginal genotoxicity with strong promotion by increased cell proliferation appears to be involved in the tumorigenic action of SO.
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.
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.
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.
In order to develop all-fish expression vectors for microinjection into fertilized fish eggs, we have prepared the following cunstructs: rainbow trout metallothionein a/b and the gilthead seabream growth hormone cDNA (ptMTa-gbsGHcDNA, ptMTb-gsbGHcDNA), carp ß-actin gilthead seabream GH cDNA (pcAßgsbGHcDNA). The inducible metallothionein promoters a and b were cloned from rainbow trout, and the constitutive promoter ß-actin was isolated from carp. The metallothionein promoters were cloned by using the PCR technique. The tMTa contains 430 bp, while the tMTb contains 260 bp (Hong et al. 1992). These two promoters were introduced to pGEM-3Z containing the GH cDNA of Sparus aurata to form ptMTa-gsbGH and ptMTb-gsbGH, respectively. The carp cytoplasmic ß-actin gene was chosen as a source for isolating strong constitutive regulatory sequences. One of these regulatory sequences in pUC118 was Iigated to GH cDNA of S. aurata to form the pcAß-gsbGHcDNA. Expression of the constructs containing the metallothionein promoters was tested in fish cell culture and was found tobe induced effectively by zinc. The ptMTa gsb-GH cDNA construct was microinjected into fertilized carp eggs, and integration in the genome of carp was detected in the DNA isolated from fins at the age of two months.
No abstract available
No abstract available
Streßbewältigung
(1993)
No abstract available
No abstract available
Parkinson und Demenz
(1993)
Auf der Delegierten-Konferenz der dPV in Hannover waren eine Reihe von Fragen wr Demenz im Zusammenhang mit dem Morbus Parkinson gestellt worden, zu denen hier Stellung genommen werden soll. Die Fragen und Antworten sind jeweil mit einem ? für die Fragen und einem ! für die Antworten gekennzeichnet.
The muscarinic receptor mediating vasodilation of resistance vessels in the rat isolated, constant-pressure perfused kidney (preconstriction by w- 7 M cirazoline) was characterized by subtype-preferring agonists and se]ective antagonists. The agonists produced vasodi1ation with the fol1owing rank order of potency: arecaidine propargy] ester (APE) > 5-methylfurtrethonium = methacholine = oxotremorine > (S)-aceclidine > arecaidine 2-butyne-1,4-diyl bisester > 4-Cl-McN-A-343 = (R)-nipecotic acid ethyl ester = N-ethyl-guvacine propargyl ester- (R)-aceclidine = (S)-nipecotic acid ethyl ester > McN-A-343. Agonist-induced vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as weH as agonist potencies at smooth muscle muscarinic M\(_3\) receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-Nmethylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol - hexahydro-sila-difenidol > pirenzepine - p-fluorohexahydro- sila-difenidol- himbacine- AF-DX 384- AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M\(_3\) receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M\(_1\) and M\(_2\) receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M\(_3\) receptors.
Reliable prediction of the isotropic hyperfine coupling constant A\(_{iso}\) is still a difficult task for ab initio calculations. Strang dependence on the method employed for its ca1culation has been found. Within a CI ansatz A\(_{iso}\) is considerably affected by the excitation classes taken into account within the CI calculation. In the present work the influence of various excitation classes on A\(_{iso}\) is examined. Calculations including all single, double, triple and a large part of the quadruple excitations are performed and the individual effects of the excitation classes are studied. It is found that the surprisingly good agreement found for S-CI treatments is due to large error cancellations. The importance of higher than double excitations arises from their indirect influence on the single excitations.
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.
No abstract available
No abstract available
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.
No abstract available
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.
'lbe mouse skin tumor model was used to investigate whether the Ievel of DNA 8dducts and/or the rate of cell division in the epidermis are indicators of the risk of cancer formation for an individual in an outbred animal popul8tion. A high risk was considered to be reftected by 8 short latency period for the 8ppearance of 8 papilloma. Fernale NMRI mice were treated twice weekly with 2.5 nmol 7 ,12-dimethylbenz[a]antbracene (DMBA) and 3 nmoi12-0-tetradecanoylphorbol-13- 8cetate (TPA) and the appearance of papillomas was registered. The first papilloma 8ppeared after 7.5 weeks. After 17 weeks, when 12 of 14 mice bad 8t least one papilloma, an osmotic minipump deliverlog 5-bromo-2'deoxyuridine (BrdU) was implanted into eacb mouse for 24 h. The mice were killed after 24 h ~d the epidermis was analyzed for D:MBA-nucleotide 8dducts by 32p.postlabeling, for the cell number per unit skin length, and for the labeling index for DNA synthesls. Unexpectedly, D:MBA-nucleotide 8dduct Ievels were highest in those anima1s wbich showed the Iongest latency periods. Adduct Ievels were negatively correlated with the 18beling index, indicating that dilution of adducts by cell division was a predominant factor in determining average adduct concentrations. Individual tumor-latency time was not corTelated with either cell ntunber or labeling index. This could be due to the fact that the measurements only provided 8veraged data and gave no infonnation on the specific situation in clones of premalignant cells. Under the conditions of tbis assay, therefore, neither DNA adduct Ievels nor information on the average kinetics of cell division bad a predidive value for the individual amcer risk withln a group of outbred animals receiving the same treatment
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.
No abstract available.
No abstract available.
Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate II p 13 Wilms' tumor gene, WTI, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome II allele encompassing the WTI gene. Analysis of the remaining WTI allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WTI polypeptide as a transcriptional regulator.
A novel technique for independent and simultaneous labeling of two antigens expressed on individual cells (referred to as mixed labeling) is presented. The staining procedure combined three-step (streptavidin-biotin) immunogold-silver staining with three-step immunoenzymatic labeling. To ensure both high specificity and high sensitivity, particular emphasis was placed on designing a protocol that avoids immunological crossreactivity between the antibody reagents and overlapping of the final color products. Two examples for usage of this mixed labeling technique are described: lymphocyte subpopulations were identified in inflammatory lesions of human skin and infected host cells were characterized in the skin of mice infected with the obligatory intracellular parasite Leishmania major, a cause of human cutaneous leishmaniasis.
Der vorliegende Beitrag faßt den derzeitigen Stand der Untersuchungen von Hangrutschungen im Bereich der Frankenhöhe, die im Rahmen des EPOCH-Programmes durchgeführt wurden, zusammen. Nach einer Inventarisierung der regionalen Rutschungsereignisse wird die Rutschung bei Obergailnau in einer geomorphologischen Detailkartierung vorgestellt. Für die Auslösung der Rutschung kommen mehrere Faktoren in Betracht: neben einer erhöhten Rutschungsanfälligkeit aufgrund der geologisch-tektonischen Verhältnisse muß v.a. auch eine Einflußnahme durch die Landnutzung mit berücksichtigt werden. Dazu zählen Steinbrucharbeiten in unmittelbarer Nähe der Rutschung, aber auch Wasserbaumaßnahmen am Schloßberg. In diesem potentielllabilisierten Gebiet kam es nach überdurchschnittlichen Niederschlägen Anfang 1958 zu einer Überschreitung der Belastungsgrenze des Hanges, die sich in einer großflächigen Rutschung äußerte. Die weiteren Untersuchungen sollen zeigen, ob sich die für Obergailnau herausgestellten Faktorenkomplexe im regionalen Rahmen verifizieren lassen.
S fimbrial adbesins (Sfa), which are able to recognize sialic acid-containing receptors on eukaryotic cells, are produced by Escherichia coli strains causing urinary tract infections or newbom meningitis. We recently described tbe cloning and molecular cbaracterization of a determinant, termed sftJI, from the chromosome of an E. coli urinary tract infection strain. Herewe present data conceming a S fimbria-specific gene duster, designated sfall, of an E. coli newbom meningitis strain. Like tbe Sfal complex, Sfall consists of tbe major subunit protein SfaA (16 kDa) and the minor subunit proteins SfaG (17 kDa), SfaS (15 kDa), and SfaH (29 kDa). The genes encoding tbe subunit proteins of Sfall were identified and sequenced. Their protein sequences were calculated from the DNA sequences and compared with tbose of the Sfal complex subunits. Altbough the sequences ofthe two major SfaA subunits ditf'ered markedly, tbe sequences ofthe minor subunits sbowed only a few amino acid exchanges (SfaG, SfaH) or were completely identical (SfaS). The introduction of a site-specific mutation into the gene sfaSII and subsequent analysis of an SfaS-negative clone indicated that sfaSII codes for the sialic acid-specific adhesin of tbe meninigitis isolate. These data were confirmed by tbe isolation and characterization of tbe SfaSII protein and the determination of its N-terminal amino acid sequence. The identity between the sialic acid-specific adhesins of Sfal and Sfall revealed that difl'erences between the two Sfa complexes with respect to tbeir capacities to agglutinate erythrocytes must result from sequence alterations of subunit proteins other tban SfaS.
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.
Vorwort (Das Kind (1993) 14)
(1993)
No abstract available
Vorwort (Das Kind (1993) 13)
(1993)
No abstract available
No abstract available
No abstract available.
No abstract available
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.
Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family
(1993)
The combined use of qualitative and quantitative analysis of I I p I 3 polymorphic markers tagether with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to I I p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible (or recurrence of del( I I )(p 13p 14) in the family: an insertion of band I I p 13-p 14 carrying the genes for predisposition to Wilms' tumor, WT I, and for aniridia, AN2, into the long arm of chromosome I I in II q 13-q 1<4. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del( II )(p 13). Two of these women gave birth to children carrying a deleted chromosome II. most likely resulting from the loss of the I I p 13 band inserted in I I q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide Variation in clinical expression. One child, with the karyotype 46,XY,del(ll)(pllpl4), presented the full-blown WAGR syndrome with anlridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del( I I )(p I 3), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WTI gene can result in similar genital and kidney abnormalities.
Neurogenic inflammation is evoked by neuropeptides released from primary afferent terminals and,
presumably, by other secondarily released inflammatory mediators. This study examines whether prostaglandins might participate in the development of neurogenic inflammation in humans and whether cyclooxygenase inhibitors have any anti-inflammatory effect on this type of inflammation. In healthy volunteers, neurogenic inflammation was elicited by epicutaneously applied capsaicin (1 %), after systemic pretreatment with acetylsalicylic acid, or topically applied indomethacin compared to pretreatment with saline or vehicle, respectively. The extent of neurogenic inflammation was quantified by planimetry of visible flare size and recording the increase of superficial cutaneous blood flow (SCBF) with a laser Doppler flowmeter. Capsaicin-induced flare sizes and outside SCBF (both representing neurogenically evoked inflammation) were unaffected by acetylsalicylic acid or indomethacin. Only the capsaicin-induced increase; of inside SCBF was attenuated by local pretreatment with indomethacin, reflecting the participation of prostaglandins in the inflammatory response of those areas which were in direct contact with capsaicin.
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.
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.
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.
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.
no abstract available
No abstract available.
Vorhersage und Erkenntnis
(1993)
No abstract available.
No abstract available.
No abstract available
The human foamy virus (HFV) bel-l transactivator protein was expressed in insect cells by a recombinant baculovirus. For the generation of the recombinant baculovirus, Acbel-1, the bel-l gene of an HFV mutant was used, that bears truncations in the bel-l overlapping bel-2 open reading frame. Acbel-1 infected Sf9 cells produced high amounts of recombinant protein of the same electrophoretic mobility (36 kD) as bel-l expressed in mammalian cells. The baculovirus expressed bel-l proteinwas readily identified by a polyclonal rabbit serum directed against bel-1 in immunoblot assay. As in mammalian cells, bel-l was predominantly localized to the nucleus of Acbel-1 infected insect cells. The baculovirus expressed bel-1 proteinwill be of use to determine the action of this novel viral transactivator more precisely.
The silver carp (Hypophthalmichthys molitrix) growth hormone (GH) genewas isolated and sequenced following amplification from genomic DNA by the polymerase chain reaction. The gene spans a region of approx. 2.5 kb nucleotides (nt) and consists of five exons. The sequence predicts a polypeptide of 210 amino acids (aa) including a putative signal peptide of 22 hydrophobic aa residues. The arrangement of exons and introns is identical to the GH genes of common carp, grass carp, and very similar to mammals and birds, but quite different from that for the GH genes of tilapia and salmonids. The silver carp GH gene shares a high homology at the nt and aa Ievels with those of grass carp (95.3% nt, 99.5% aa) and of common carp (81% nt, 95.7% aa).
The promoter of the rainbow trout metallothionein B gene ( tMTb) was isolated from genomic DNA by the polymerase chain reaction (PCR ), fused to the bacterial chloramphenicol acetyltransferase (CAT) genein an expression vector, and functionally analyzed in one human cellline and four fish celllines. This promoter exhibited an extremely low basal expression in all celllines and was zincand cadmium-inducible except in the fish melanoma cell line where the promoter was completely inactive. The metal-induced expression patterns were cellline-specific. In general the fish promoter was more species- and cell type-specific than its human counterpart. In a transient assay it was functional in developing embryos of the medaka ( Oryzias /atipes). These properties make this promoter suitable for inducible, tissue-specific expression of transgenes and for in vivo studies of gene function and regulation.
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.
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.
When human neutrophils become desensitized to formyl peptide chemoattractants, the receptors (FPR) for these peptides are converted to a high affinity, GTP-insensitive form that is associated with the Triton X-1 00- insoluble membrane skeleton from surface membrane domains. These domains are actin and fodrin-rich, but G protein-depfeted suggesting that FPR shuttling between G protein-enriched and depleted domains may control signal transduction. Todetermine the molecular basis for FPR interaction with the membrane skeleton, neutrophil subcellular fractions were screened for molecules that could bind photoaffinity-radioiodinated FPR solubilized in Triton X-1 00. These receptors showed a propensity to bind to a 41- to43-kDa proteinband on nitrocelluloseoverlays of SOS-PAGE-separated cytosol and plasma membrane fractions of neutrophils. This binding, as weil as FPR binding to purified neutrophil actin, was inhibited 50% by 0.6 \(\mu\)M free neutrophil cytosolic actin. Addition of greater than 1 \(\mu\)M G-actin to crude or lectin-purified Triton X-1 00 extracts of FPR from neutrophil membranes increased the sedimentationrate of a significant fraction of FPR two to three fold as measured by velocity sedimentation in Triton X-1 00-containing linear sucrose density gradients. Addition of anti-actin antibodies to FPR extracts caused a concentration-dependent immunoprecipitation of at least 65% of the FPR. More than 40% of the immunoprecipitated FPR was specifically retained on protein A affinity matrices. Membrane actin was stabilized to alkaline washing when membranes were photoaffinity labeled. Conversely, when purified neutrophil cytosolic actinwas added to membranes or their digitonin extracts, after prior depletion of actin by an alkaline membrane wash, photoaffinity labeling of FPR was increased two- to fourfold with an EC\(_{50}\) of approximately 0.1 \(\mu\)M actin. We conclude that FPR from human neutrophils may interact with actin in membranes to form Triton X-1 00-stable physical complexes. These complexes can accept additional G-actin monomers to form higher order molecular complexes. Formation of FPR-actin complexes in the neutrophil may play a role in the regulation of chemoattractantinduced activation or actin polymerization.
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.
No abstract available
No abstract available
Some chromosomes in transformed rat cells and somatic cell hybrids fail to display the presence of kinetochore proteins as detected by antikinetochore antibodies. Suchchromosomes (K- Chromosomes) may constitute a novel mechanism for the genesis of aneuploidy. Wehave analyzed primary~ immortalized and malignant marnmalian cells for the presence of kinetochore proteins and micronuclei. Our resuJts suggest a correlation of the K- chromosome and micronucleus frequency with the variability in chromosome number. Upon in situ hybridization with the minor satellite and alpha satellite sequences some Kchromosomes showed a signal. This indicates that the observed lack of kinetocbores is not necessarily due to a lack of centromeric DNA. We conclude that dislocated K- chromosomes may become incorporated into micronuclei which are prone to loss. Such events would be associated with the generation of aneuploidy.
No abstract available
Konzentration ist ein psychologisches Konstrukt, das hochkomplexe Interaktions-Situations-Phänomene bezeichnet. Die hohe Komplexität läßt unmittelbare Folgerungen für therapeutische Maßnahmen nicht zu und enthält spezielle Probleme der Validität bei niedrigen Leistungswerten in Tests. Die Diagnose von Konzentrationsproblemen dient nicht selten Lehrern, Schülern und Eltern als Entlastung. Dabeiführen oberflächliche Analysen oft zu Mißverständnissen und Fehldiagnosen. Bei solchen Diagnosen werden dann Konzentration, Interesse, Motivation, Belastbarkeit, "aus dem Felde gehen" und "auswandern" konfundiert. Ohne eine sorgfältige und möglichst umfassende Analyse der Aufmerksamkeitssituation können Maßnahmen zur Beseitigung oder Reduktion der Schwierigkeiten nicht effektiv ausgewählt werden.
No abstract available
No abstract available