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Biomedical subjects

S Harth

Publications and source records attributed to S Harth.

At least 19 recordsLinked to original sources

[Evidence based treatment of executive dysfunction].

The therapy of executive functions plays an essential role for the functional outcome and the social reintegration. Nevertheless there is a lack of cognitive oriented and evidence-based therapy programs. The purpose of our review is the classification of the present evaluation studies with regard of the principles of evidence based medicine (EbM) and of the content. Besides the EbM criteria the number of participants, the kind and number of interventions, the types of etiology and the standardisation and quality of the outcome parameters are measured. By that, an assessment should be possible, which interventions are successful for what types of dysexecutive syndrome. The present studies belong to three different types of therapy: at first, a therapy form focussing on manipulation and modification of the environment, second, a therapy form using behaviour management and a third form, which is based on practise and cognitive interventions. The heterogeneity of the therapy forms makes different types of evaluation necessary. The evaluation studies reach different classes of evidence. While the cognitive therapy forms reach comparable high evidence classes, the evaluation studies about behaviour management--mostly present as single case studies with individual outcome parameter--reach only low evidence classes. Final, we discuss, which therapy forms are effective using the strong evaluation criteria and at which point further conceptual task and further research is useful.

Cognitive Behavioral Therapy↗

Molecular structure of the multifunctional fatty acid synthetase gene of Brevibacterium ammoniagenes: its sequence of catalytic domains is formally consistent with a head-to-tail fusion of the two yeast genes FAS1 and FAS2.

The Brevibacterium ammoniagenes fatty acid synthetase (FAS) gene was isolated from a series of overlapping clones by both immunological and plaque hybridization screening of two independent gene libraries. From the isolated DNA a contiguous segment of 10,549 bp was sequenced in both directions. The sequenced DNA contained a very long (9312 nucleotides) open reading frame coding for a protein of 3104 amino acids and with a molecular mass of 327,466 daltons. Based on characteristic sequence motifs known from other FAS systems, seven different FAS active centres were identified at distinct locations within the polypeptide chain. Only one component enzyme, the 3-hydroxydecanoyl beta, gamma-dehydratase, has not yet been localized definitively within the gene. Translation is presumed to start from a GUG triplet located 25 nucleotides downstream of the transcriptional initiation site. There is a canonical Shine-Dalgarno sequence just before this start codon. Comparison of the B. ammoniagenes FAS sequence with those of other known fatty acid synthetases revealed a particularly high degree of similarity to the products of the two yeast genes, FAS1 and FAS2 (30% identical and 46% identical plus closely related amino acids). This similarity extends over the entire length of the genes and involves not only the primary sequences of individual component enzymes but also their sequential order within the multifunctional proteins. These data, together with those on the structure of other fatty acid synthetases, are interpreted in terms of a contribution of both primary structure and subunit cooperation to a conserved topology of functional domains common to all type I FAS complexes.

Amino Acid Sequence↗

Preventive dental health practices of non-institutionalized Down syndrome children: a controlled study.

Although Down syndrome children are known to be greatly predisposed to periodontal disease when compared with normal children, the preventive dental health practices of non-institutionalized Down syndrome children have not been well reported. This questionnaire study of 25 Down syndrome children aged 1-14 years compared with 25 normal control children showed that Down syndrome children have poorer dental health practices compared with normal children. Significantly greater numbers of Down syndrome children were weaned from the bottle at greater than 18 months of age (56% vs 24%, p less than 0.05) or had taken a bottle to bed (40% vs 12%, p less than 0.05), indicating their increased risk for the development of nursing bottle caries. In addition, Down syndrome children were receiving less help during tooth brushing (60% vs 84%, p less than 0.05), were older when they first visited the dentist, and less likely to be taking regular fluoride supplements. These results indicate that Down syndrome children are further disadvantaged by poor preventive dental health practices and should be targeted for increased preventive dental care.

Adolescent↗

Elastofibroma dorsi: CT, MR and pathologic study in a new case.

As reported before elastofibroma dorsi is a rare benign tumor of elastic connective tissue with typical clinical and suggestive radiological features. We evaluated the CT and MR characteristics of this periscapular lesion in a new case, before and after contrast enhancement, and tried to determine in how far the nature and extent of the tumor can be predicted.

Back↗

Metabolism and function of gangliosides in developing neurons.

Previous experiments have shown that the addition of a mixture of gangliosides to the growth medium induced morphological changes in primary neuronal cultures, producing especially a trophic effect and a sprouting of neurites (neuritogenesis). The study reported here examined the changes of some biochemical parameters that paralleled the morphological modifications of cultured neurons from chick brain hemispheres treated with gangliosides. Neurons cultured from 3 to 7 days in the presence of various concentrations of a purified mixture or of single-species of gangliosides (GM1, GD1a, GT1b) revealed that these glycolipids were easily incorporated into the cells as a function of their exogenous concentrations. Incubation of neurons with N-acetyl-D-[U-14C]mannosamine showed a final labeling of all endogenous cellular and exogenous incorporated gangliosides; however, the radioactivity recovered decreased as a function of the number of sialic acid units of the exogenously added gangliosides. The treatment of neuronal cells from 3 to 7 days in culture with a mixture of 10(-8) M and 10(-5) M gangliosides led to the following observations on some neurochemical parameters: no effect on the influx of choline and dopamine; no effect on the spontaneous choline efflux, whereas the K+-provoked one is abolished; decrease of the spontaneous and K+-stimulated release of dopamine; no effect on the spontaneous release of GABA for 10(-8) M gangliosides but an increase of both spontaneous and K+-provoked release for 10(-5) M gangliosides. The data suggest that the possible insertion of gangliosides into the neuronal membranes may imply structural modifications that may influence enzymatic activities, neurotransmitter transport, and finally, some nerve cell mechanisms.

Animals↗

Ectoglycosyltransferase activities at the surface of cultured neurons.

Glycosyltransferase activities (ectogalactosyl, ectofucosyl and ectosialyl) were studied at the external surface of exclusively neuronal cultures. An appropriate methodology gave the possibility to eliminate sources of errors due to the hydrolysis of nucleotide sugar substrates or due to cellular uptake of free sugars. Ovomucoid and asialofetuin coupled to Sepharose and Ultrogel beads were used as exogenous substrate to circumvent possible substrates pinocytosis. Ectoglycosyltransferase activities were studied as function of protein concentration, incubation time and amount of bead coupled exogenous acceptors. The data show that these enzymes are present at the external surface of the neuronal membrane; their possible role in cell - cell interactions is suggested.

Animals↗

Neuraminidase in calf retinal outer segment membranes.

An enzyme catalyzing the hydrolysis of sialic acid (N-acetylneuraminic acid: NeuNAc)-containing glycoconjugates has been found in bovine retinal rod outer segment (ROS) membranes. The enzymatic activity is optimal at pH 4.0 and is stimulated by 0.15% Triton X-100. Total activity was determined by the release of NeuNac from endogenous and exogenous substrates (GD1a). The ROS enzyme preferentially hydrolyses the ROS gangliosides, possibly because they are more accessible than the glycoproteins as substrates for the neuraminidase. Release of NeuNAc from gangliosides leads to important changes in the ganglioside patterns; whereas the amounts of GM1 increased throughout the incubation, the levels of polysialogangliosides GT1b and GD3 diminished owing to their rapid hydrolysis. The finding that gangliosides are hydrolysed more extensively than glycoproteins suggests that endogenous ROS gangliosides may be the principal source of metabolically available sialic acid in ROS. It was also observed that the activity of ROS neuraminidase is not affected by illumination of the membranes.

Animals↗

[Existence of UDP galactose: galactosyltransferase activity at the external surface of cultured neurons].

The existence of UDP-galactose:galactosyltransferase activities at the external surface of cultured neurons from chick embryo hemispheres, was demonstrated. [14C]-galactose was transferred upon cellular substrates present on the neuronal surface and upon exogenous substrates (ovomucoïd) bound to Sepharose beads. The activity of ectogalactosyltransferase was not due to a leakage of intracellular enzymes into the incubation medium nor to an intracellular enzymatic activity utilizing [14C]-galactose obtained from the hydrolysis of UDP-[14C]-galactose. Kinetics of these ectogalactosyltransferases were analysed. The results support the hypothesis of a communication and/or interaction among the nerve cell surfaces via glycoconjugates or their biosynthetic enzymes.

Animals↗

Gangliosides in various brain areas of three inbred strains of mice.

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p less than 0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri- and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.

Animals↗

Possible role of sialocompounds in the uptake of choline into synaptosomes and nerve cell cultures.

Incubation of primary nerve cell cultures and of crude synaptosomal preparations with neuraminidase released sialic acid from both gangliosides and sialoglycoproteins. After this treatment, the pattern of ganglioside distribution was severely modified with a decrease of polysialogangliosides (GD1b, GT1b, Gt1L, GQ1) and a dramatic increase in monosialoganglioside GM1. The choline influx into neuraminidase treated cells and organelles was reduced by 30--50% but the efflux was unmodified. In particular the high affinity mechanism of choline uptake disappeared and the low affinity mechanism was modified in both cases. The disappearance of the high affinity uptake mechanism was not followed by a decreased acetylcholine synthesis as it should be if the current theories on choline uptake and acetylcholine synthesis are correct. Our present data thus confirm our previous hypothesis that choline metabolism regulates choline uptake rather than the other way round as is suggested by the theories most widely accepted at present. Choline uptake was unaffected by pretreatment of cells and organelles with tetanus toxin suggesting that the effect of neuraminidase on the choline uptake were either mediated through glycoproteins or through gangliosides other than those which bind to tetanus toxin (GD1b and GT1b). Several speculative models for explaining the effect of neuraminidase on choline uptake are proposed.

Animals↗

Topographic distribution of enzymes synthesizing phosphatidylcholine and phosphatidylethanolamine in chicken brain microsomes.

The localization of phosphatidylethanolamine and phosphatidylcholine biosynthetic enzymes within the transverse plane of chicken brain microsomes was investigated by using proteases (trypsin and pronase) and neuraminidase. Treatment of intact microsomes with the proteases inactivated the phosphocholine transferase completely and the ethanolamine phosphotransferase only slightly. This latter enzyme was, however, completely inactivated when deoxycholate-treated microsomes were exposed to proteases. Treatment of intact microsomes with neuraminidase had no effect on both phosphotransferases, although 65% of the sialic acid of sialoglycoproteins and 37% of that of gangliosides were removed. With deoxycholate-disrupted microsomes nearly all sialic acid from the sialoglycoproteins and about 70% of that of gangliosides were released. In parallel, the phosphoethanolamine transferase was 90% inactivated. It is suggested that phosphocholine transferase is localized on the outer face of the microsomal vesicle, whereas the phosphoethanolamine transferase could be a sialoglycoprotein, possibly situated on the inner face of the vesicle, or perhaps a transmembrane protein.

Animals↗

[Role of sialo compounds in choline uptake by synaptosomes].

Two kinetic mechanisms are responsible for the uptake of choline in Rat brain synaptosomal fractions with different affinity towards the substrate (high affinity mechanism: Km 5.1 microM, Vmax 44 pmol/mg prot/min.; low affinity mechanism: 35.7 microM, Vmax 286 pmol/mg prot/min). The treatment of synaptosomal fractions with neuraminidase (15 min. at 37 degrees C) followed by 1 min. incubation with various concentrations of [14C] choline reduces the uptake in parallel with the disappearance of the high affinity mechanism (Km 202.2 microM, Vmax 119 pmol/mg prot/min.), without influencing the synthesis of acetylcholine.

Acetylcholine↗

Biosynthesis of galactocerebrosides and glucocerebrosides in glial cell lines.

UDP-galactose:ceramide galactosyltransferase (CGalT, EC 2.4.1.45) and UDP-glucose:ceramide glucosyltransferase (CGlcT, EC 2.4.1.80) were determined in the glial cell lines G26-20, G26-24, C6, and C6TK-. The enzymatic assay for CGalT in cultured glial cells was complicated by a rapid conversion of UDP-galactose to UDP-glucose, due to the elevated UDP-galactose-4'-epimerase activity in certain glial cell clones. It seems that mechanisms regulating UDP-galactose-4'-epimerase activity and levels of UDP sugars in the glial cell lines differ from those in brain tissue. Compared with the maximum activity of CGalT in the myelinating rat brain, the enzyme activities in the oligodendroglioma clonal cell lines G26-20 and G26-24 were 16-30 times lower. On the other hand, CGalT levels in G26-20 and G26-24 cells were comparable to the values found in young rat brain before myelination starts. No CGalT activity could be detected in C6 or C6TK- cells by the method used in this study, whereas CGlcT activity was found in all glial cell lines tested and its levels were close to the values observed in the young rat brain.

Animals↗