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Biomedical subjects

H Schöler

Publications and source records attributed to H Schöler.

13 recordsLinked to original sources

[Validated diagnostics for dysgrammatism].

BACKGROUND: Non-standardized procedures are used to evaluate, in particular, grammatical performance in most German institutions performing diagnostic procedures on children with impaired speech and language development. This makes a comparison of results difficult. METHODS: We studied 181 boys and 72 girls aged between 5 and 6 years using four subtests of IDIS additionally to the routine procedure. Results were compared to the "degree of dysgrammatism" determined from the traditional evaluation based on expert rating. RESULTS: The new procedure is able to divide the children into groups with normal speech and language ability, with deficits accessible to a traditional logopedic treatment, and with severe speech and language impairment that necessitates intensive treatment. DISCUSSION: The proposed tests allow an accurate evaluation of grammatical performance instead of subjective estimates.

Articulation Disorders↗

[Are the language skills of our children declining? Results based on the examinations at school enrollment of the years 1999 to 2004 in Münster].

The physical examinations at school enrollment of the years 1999 to 2004 were subjected to comparative analysis to help clarify whether children's language performance at enrollment has significantly decreased in recent years or not. This question has indeed been a matter of public debate for some time. Furthermore, potential influencing factors, in particular social environment, were to be examined as regards their effects on language performance. The results indicate that the children's performance level has not significantly decreased over the six-year period of observation. Instead, rather an increase can be observed over this period of time. If, nevertheless, more and more and, in particular, more significant language deficits continue to be observed, one explanation for this may be seen in a changing assessment of children's needs for therapy or remedial education. The performance level of children who were recommended therapy or means of remedial education in 2004 is significantly higher than that of children for whom such recommendations were given in 1999 or 2000. Perhaps an increased sensitivity for those performance areas where performance levels are found to be deficient should be postulated, and, consequently, a more differentiated assessment of diagnostic findings should be assumed. The results of the examinations once again demonstrate the enormous influence that social factors have on language performance. Children growing up in a less advantaged social environment tend to achieve significantly lower performance marks in language tests than children from more privileged social environments. Also the duration of kindergarten education appears to be relevant to children's language performance: children who have visited institutions of preschool-education for three or more years achieve higher performance marks than children who have spent no ore only little time in these institutions. When seen against the background of circa one in four children with a migration background (around 8% of persons of the same age in Münster's population) having unsatisfactory knowledge of German at school enrollment, there appear to be efficient prevention measures available here.

Child↗

[Diagnosis and differentiation of children with language development disorders. What role can be attributed to intelligence?].

BACKGROUND: Specific language impairment (SLI) is defined as a developmental disorder in which language comprehension and the child's ability to use expressive spoken language is markedly below the appropriate level for his or her mental age. The intelligence of SLI children is in the normal range, while their language abilities are impaired. "Normal intelligence", the defining feature of SLI is questioned in this study. PATIENTS AND METHODS: Using IDIS (an inventory of diagnostic information in language impairment), we examined 138 children aged 5 and 6 years with severe language impairment; 108 SLI and 30 LI children. Various indicators of speech and language such as articulation, the ability to discriminate sounds, lexicon, grammar and pragmatic abilities but also auditory and visual perception, auditory and visual memory, fine and gross motor function were assessed. RESULTS: The performance of the SLI children was significantly higher in most of the tests than that of the LI children. Factor analysis showed that the two groups also differed in the structure of performance. Auditory short-term memory was reduced in most children irrespective of intelligence. CONCLUSIONS: We propose the retention of the differentiation of subgroups of developmental speech and language disorders depending on the level of intelligence.

Child↗

[On the diagnostics of structural deficits in dyslexia in clinical work: relationship between different achievement indicators].

BACKGROUND: The aim of the study is to research the relationship between different indicators used in the diagnosis of reading and writing disabilities in clinical work. METHODS: In addition to being tested for intelligence and writing ability, a total of 141 children in second and fourth grade were submitted to tests assessing their ability for speech intelligibility in noise, dichotic listening, phoneme discrimination, as well as auditory short-term memory for digits and non-words. In a partial sample of 40 children with average intelligence manifesting at least a standard deviation between their ability to write and their IQ a regression analysis was introduced to assess the predictive power of applied indicators for writing ability. RESULTS: Next to IQ testing, phoneme analysis as used in the Heidelberg Test of Phoneme Discrimination accorded for the variance in writing ability. However, the relationship between these indicators proved to be most important for the beginning of learning the written language. CONCLUSIONS: The diagnostic procedures used in clinical work are critically evaluated whereby the tests to assess speech intelligibility in noise and dichotic listening, as well as short-term memory appear to be clinically relevant too, however a standardized procedure and age-relevant norms are still needed.

Age Factors↗

[Initial examination for school attendance in Mannheim: language development at initial school entry level].

INTRODUCTION: In autumn 2001 the initial examination for school attendance in Mannheim has been fundamentally reorganised. The individual examination elements had been widely standardized, the results can be evaluated by regions and a diagnosis for the early detection of legasthenia has been developed. METHODS: The testing involved repeating sentences, numbers and artificial words. This has been developed by the Pedagogical University Heidelberg. In pre-examinations in Heidelberg the results relate significantly to the subsequent results in reading and writing. PROBANDS: A total of 2,744 children (46.1% girls, 53.9% boys) aged of 5 to 7 years was seen. 71.5% of the children were German nationality. Most non-German nationalities were Turkish (15.4%) and Italian (3.6%) children. Besides the nationality the mother tongue has been also recorded. More than 96% of the children had been attending a kindergarten. For judgement of the social strata the frequency of social welfare receivers has been recorded. RESULTS: The testing results are significantly influenced by the native language and the social strata of the children. The results of children with German as native language are above those of non-Germans. Within the migrant children there are significant differences between the several nationalities. Children from a lower social strata achieved lower results. A positive effect to the language development is attributed to the attendance of a kindergarten. CONCLUSION: These results are the basis for language- and general health supporting projects in Mannheim. For the examination for school attendance in the current year the diagnostic for language development has been extended by some more aspects.

Child↗

The onset of germ cell migration in the mouse embryo.

Mouse primordial germ cells (PGCs) are specified between embryonic day 6.5 (E6.5) and E7.5, when they have been visualized as an alkaline phosphatase-positive (AP+) cell population in the developing allantois. By E8.5, they are embedded in the hind-gut epithelium. Previous experiments have suggested different sites for PGCs' origin, and it is unclear how they reach the gut epithelium. We have used transgenic mice expressing GFP under a truncated Oct4 promoter to visualize living PGCs. We find GFP+/AP+ cells in the posterior end of the primitive streak as a dispersed population of cells actively migrating into the allantois, and directly into the adjacent embryonic endoderm. Time-lapse analysis shows these cells to be actively migratory from the time they exit the primitive streak.

Alkaline Phosphatase↗

Expression pattern of Oct-4 in preimplantation embryos of different species.

POU transcription factors are involved in transcriptional regulation during early embryonic development and cell differentiation. Oct-4, a member of this family, has been shown to be under strict regulation during murine development. The expression of Oct-4 correlates with the undifferentiated cell phenotype of the mouse preimplantation embryo. In this study, expression of a gene construct consisting of selected parts of the region upstream from the murine Oct-4 gene as promoter/enhancer, enhanced green fluorescent protein (EGFP) as reporter and the five exons of the murine Oct-4 gene (GOF18-delta PE EGFP) was evaluated in murine, porcine, and bovine preimplantation embryos. For comparison, expression of the endogenous Oct-4 gene was also analyzed in all three species by immunocytochemistry. The transgene construct was microinjected into zygotes cultured in vitro to various developmental stages. The EGFP fluorescence was visualized in developing embryos by excitation with blue light at different days following microinjection and showed similar expression patterns in all three species. Most embryos displayed a mosaic pattern of transgene expression. The EGFP fluorescence was not restricted to the inner cell mass (ICM) but was also seen in trophoblastic cells. An affinity-purified polyclonal antibody specific to Oct-4 was used for immunocytochemical analysis of in vivo- and in vitro-derived bovine and porcine blastocysts and also of in vivo-derived murine blastocysts. In the in vivo-derived murine embryos, Oct-4 protein was detectable in the ICM but not the trophectoderm, whereas in porcine and bovine blastocysts, derived in vivo or in vitro, Oct-4 protein was detected in both the ICM and the trophectoderm. Thus, in the two large animal species, Oct-4 expression from the endogenous gene was clearly not restricted to the pluripotent cells of the early embryo. These results show that Oct-4 regulation differs between these species and that the presence of Oct-4 protein may not be sufficient for selection of undifferentiated cell lines in domestic animals.

Animals↗

Taube nuss is a novel gene essential for the survival of pluripotent cells of early mouse embryos.

The cells of the inner cell mass constitute the pluripotent cell population of the early embryo. They have the potential to form all of the tissues of the embryo proper and some extra-embryonic tissues. They can be considered a transient stem cell population for the whole of the embryo, and stem cells maintaining the same capacity can be isolated from these cells. We have isolated, characterised and mutated a novel gene, taube nuss (Tbn), that is essential for the survival of this important cell population. The taube nuss protein sequence (TBN) was highly conserved between human, mouse, Xenopus laevis, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana, particularly in a domain that is not present in any published proteins, showing that TBN is the founding member of a completely new class of proteins with an important function in development. The Tbn gene was expressed ubiquitously as early as E2. 5 and throughout embryonic development. It was also expressed in adult brain with slightly higher levels in the hippocampus. The Tbn mutant embryos developed normally to the blastocyst stage and contained inner cell masses. They hatched from the zonae pellucidae, implanted and induced decidual reactions, but failed to develop beyond E4.0. At this time the trophoblast cells were viable, but inner cell masses were not detectable. At E3.75, massive TUNEL-positive DNA degradation and chromatin condensation were visible within the inner cell masses, whereas the cell membranes where intact. Caspase 3 was expressed in these cells. In vitro, the inner cell mass of mutant embryos failed to proliferate and died after a short period in culture. These results indicate that the novel protein, taube nuss, is necessary for the survival of the inner cell mass cells and that inner cell mass cells died of apoptosis in the absence of the taube nuss protein. As cell pruning by apoptosis is a recognised developmental process at this stage of development, the taube nuss protein may be one of the factors regulating the extent of programmed cell death at this time point.

Amino Acid Sequence↗

Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.

Oct4 is a mammalian POU transcription factor expressed by early embryo cells and germ cells. We report that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo. Oct4-deficient embryos develop to the blastocyst stage, but the inner cell mass cells are not pluripotent. Instead, they are restricted to differentiation along the extraembryonic trophoblast lineage. Furthermore, in the absence of a true inner cell mass, trophoblast proliferation is not maintained in Oct4-/- embryos. Expansion of trophoblast precursors is restored, however, by an Oct4 target gene product, fibroblast growth factor-4. Therefore, Oct4 also determines paracrine growth factor signaling from stem cells to the trophectoderm.

Animals↗

Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation.

The POU transcription factor Oct-4 is expressed in early mouse embryogenesis and in pluripotent ES and EC stem cell lines. After gastrulation in the embryo, Oct-4 expression is confined to the germline. The present study provides evidence that Oct-4 undergoes downregulation during oogenesis and spermatogenesis, coincident with entry into meiosis. Furthermore, analysis of maturation stages of oocytes showed that Oct-4 is upregulated de novo in the final stages of meiotic prophase I in female germ cells. These data suggest that Oct-4 downregulation in germ cells in both sexes might represent one of the molecular triggers involved in the commitment to meiosis. The upregulation of Oct-4 in oocytes at the completion of the prophase I of meiotic division further suggests a specific involvement of this transcription factor in oocyte growth or the acquisition of meiotic competence.

Animals↗

A mouse model for hereditary thyroid dysgenesis and cleft palate.

Alteration of thyroid gland morphogenesis (thyroid dysgenesis) is a frequent human malformation. Among the one in three to four thousand newborns in which congenital hypothyroidism is detected, 80% have either an ectopic, small and sublingual thyroid, or have no thyroid tissue. Most of these cases appear sporadically, although a few cases of recurring familial thyroid dysgenesis have been described. The lack of evidence for hereditary thyroid dysgenesis may be due to the severity of the hypothyroid phenotype. Neonatal screening and early thyroid hormone therapy have eliminated most of the clinical consequences of hypothyroidism such that the heritability of this condition may become apparent in the near future. We have recently cloned cDNA encoding a forkhead domain-containing transcription factor, TTF-2, and have located the position of the gene, designated Titf2, to mouse chromosome 4 (ref. 3). Titf2 is expressed in the developing thyroid, in most of the foregut endoderm and in craniopharyngeal ectoderm, including Rathke's pouch. Expression of Titf2 in thyroid cell precursors is down-regulated as they cease migration, suggesting that this factor is involved in the process of thyroid gland morphogenesis. Here we show that Titf2-null mutant mice exhibit cleft palate and either a sublingual or completely absent thyroid gland. Thus, mutation of Titf2-/- results in neonatal hypothyroidism that shows similarity to thyroid dysgenesis in humans.

Animals↗

The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain.

The POU transcription factor Oct-4 is expressed in totipotent and pluripotent cells of the early mouse embryo and the germ cell lineage. Transactivation capacities of regions flanking the DNA binding domain of Oct-4 were analyzed in undifferentiated and differentiated cell lines. The amino- and carboxy-terminal regions (N domain and C domain) fused to the Gal4 DNA binding domain both functioned as transactivation domains in all cell lines tested. However, the C domain failed to activate transcription in some cell lines in the context of the native protein. The underlying regulatory mechanism appears to involve the POU domain of Oct-4 and can discriminate between different POU domains, since constructs in which the C domain was instead fused to the POU domain of Pit-1 were again equally active in all cell lines. These results indicate that the C domain is subject to cell-type-specific regulation mediated by the Oct-4 POU domain. Phosphopeptide analysis revealed that the cell-type-specific difference of C-domain activity correlates with a difference in Oct-4 phosphorylation status. Since Oct-4 is expressed in a variety of distinct cell types during murine embryogenesis, these results suggest an additional regulatory mechanism for determining Oct-4 function in rapidly changing cell types during development.

3T3 Cells↗

Nuclear factors binding specific sequences within the immunoglobulin enhancer interact differentially with other enhancer elements.

The mouse immunoglobulin heavy chain (IgH) enhancer represents a cis essential control element that confers lymphoid-specific expression. Based on in vivo and in vitro competition experiments, as well as on in vivo dimethylsulfate (DMS) protection experiments, it has been inferred that cellular factors interact in trans with IgH enhancer sequences. In addition, transcription is stimulated in vitro by up to one order of magnitude in the presence of IgH enhancer sequences on an appropriate template. Thus, at least some of these factors have to be present in nuclear extracts. To examine the factors interacting with this lymphoid-specific enhancer in more detail we compared the binding pattern of nuclear factors present in B-cell, T-cell and HeLa cell extracts. We demonstrate here, using the DNase I and DMS protection methods, the specific interaction of three different nuclear factors with the central PstI--EcoRI fragment of the IgH enhancer. This fragment has previously been suggested to retain the major enhancing activity. Surprisingly, no or only minor differences were discovered when the footprints obtained with B-cell extracts were compared with those obtained with HeLa cell and T-cell extracts. Intriguingly, two factors binding specifically to different sequences of the IgH enhancer are shared by polyoma as well as Moloney sarcoma virus (MSV) and lymphotropic papova virus (LPV) enhancer, respectively. All three of these enhancer elements exhibit altered cell type specificities. This indicates the utilization of similar or identical factors for transcriptional enhancement in different cell types. A cassette model consisting of different factor binding sites will be discussed.

B-Lymphocytes↗