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Biomedical subjects

E Meier

Publications and source records attributed to E Meier.

At least 91 records · Page 5Linked to original sources

Cognitive processing of tokens and their description in aphasia.

In a dual-reaction time task aphasics (N = 21) and right-hemisphere (RH) controls (N = 24) had to decide whether a list of features given verbally or pictorially correctly described the picture of a token. Although the error rates were extremely low, aphasics made significantly more errors than RH controls. There were no significant differences between the groups in latencies when pictures of tokens were presented; the groups differed drastically, however, when confronted with lists of features. The findings are interpreted as indicating a general deficit in the short-term storage of highly specific information.

Adolescent↗

Expression of a cDNA encoding a functional 241-kilodalton vesicular stomatitis virus RNA polymerase.

The large gene, L, of vesicular stomatitis virus (VSV), which codes for the multifunctional RNA-dependent RNA polymerase, was assembled from five overlapping cDNA clones. The sequence of the 6.4-kilobase gene of the final construct was identical to the consensus sequence reported earlier. The gene was inserted into the simian virus 40 transient expression vector pJC119. Antibodies directed against synthetic peptides corresponding to the amino and carboxyl termini of the L protein were raised in rabbits. Both antibodies specifically immunostained the cytoplasm of COS cells that had been transfected with the vector DNA. The expressed L protein was immunoprecipitated from cell extracts and it was identical in size to the L protein of the virion (241 kilodaltons). Most importantly, COS cells that expressed the recombinant L protein transcribed, replicated, and consequently complemented and rescued temperature-sensitive RNA polymerase mutants of VSV at the nonpermissive temperature. The kinetics of virus release were similar to those of a wild-type VSV infection. We conclude that the recombinant RNA polymerase protein L is indistinguishable in its size and its functions from the VSV polymerase.

Animals↗

Effects of undernutrition and thyroid state on the ontogenetic changes of D1, D2, and D3 brain-specific proteins in rat cerebellum.

Disturbances in metabolic balance brought about by alterations in thyroid state and undernutrition during early life had a marked effect on the concentrations of the brain-specific proteins, D1, D2, and D3 in the developing rat cerebellum. In normal rats, the concentrations of D1 and D3 increased and that of D2 decreased during the first 3 weeks after birth. In the hyperthyroid state a small but consistent advancement was observed in the developmental curves of these proteins. The hypothyroid state caused a marked retardation in the maturational pattern of D1 and D2 but not of D3. In undernutrition, at 6 days the concentrations of D1 and D3 proteins were higher than in controls, but thereafter the developmental increase was markedly delayed for D1 only. The concentration of D2 was normal at 6 days, but after the first week a marked retardation was observed in the maturational pattern of this protein in undernourished rats. In addition, the "anodic-immature" form of D2 predominated in 6-day-old controls, but this was gradually replaced by a "cathodic-mature" form which progressively became the dominant form of D2 in 35-day-old rat cerebellum. The developmental switch in terms of the two forms was also advanced in hyperthyroidism and retarded in thyroid deficiency and undernutrition. Furthermore, daily treatment of hypothyroid rats with physiological doses of thyroxine from birth restored the concentrations of D1 and D2 to normal, but that of D3 was increased above control levels, indicating differences between the proteins in their sensitivity to mechanisms of control by thyroid hormone. Also, the overall effects of undernutrition were markedly different from those of hypothyroidism.

Age Factors↗

Cultured neurons as model systems for biochemical and pharmacological studies on receptors for neurotransmitter amino acids.

By the use of primary cultures of neurons consisting of cerebral cortex interneurons or cerebellar granule cells it is possible to study biochemical and pharmacological aspects of receptors for GABA and glutamate. Cerebellar granule cells have been shown to express both high- and low-affinity GABA receptors. The latter ones develop, however, only when the neurons are treated with GABA or GABA receptor agonists. It is suggested that the high-affinity receptors play a role in the neurotrophic activity of GABA, whereas the low-affinity GABA receptors are involved in the mediation of the inhibitory action of GABA on evoked release of glutamate, which is the neurotransmitter in cerebellar granule cells. Also glutamate receptors have been studied with regard to the 2 types of neurons. Both cerebral cortex neurons (GABAergic) and cerebellar granule cells (glutamatergic) possess glutamate receptors, which mediate an L-glutamate-induced transmitter release. The pharmacological properties of these glutamate receptors are, however, distinctly different for the 2 types of neurons. While cerebral cortex neurons express both quisqualate-, N-methyl-D-aspartate- and kainate-receptors, the cerebellar granule cells have a receptor which is activated only by L-glutamate and L-aspartate.

Animals↗

Changes in the expression of a neuronal surface protein during development of cerebellar neurones in vivo and in culture.

The expression of the neurone-specific D2 protein changes both quantitatively and qualitatively during development in vivo and in cultures of cerebellar nerve cells. The total D2 content per unit protein shows a two-fold increase in vivo from birth to postnatal day 6, after which it declines progressively to about 50% of the maximal value. This increase can be accounted for by an immature form of the protein anodic D2 being preferentially expressed at the early stages of cerebellar development. After postnatal day 9 this form gradually switches to a mature form cathodic D2. This switch can be mimicked by neuraminidase treatment, suggesting a developmental loss of sialic acid from the D2 protein. In freshly isolated cells the total D2 content per unit protein is only 30% of that in the corresponding intact tissue from 8-day-old cerebella, but it increases rapidly during the first 8 days of culture to levels similar to those of the equivalent age in vivo. The switch from anodic D2 to cathodic D2 also occurs at a faster rate in culture, probably reflecting the culture conditions that favour differentiation. The changes in the expression of D2 during development of cerebellar nerve cells in culture suggest that anodic D2 is preferentially expressed on nerve cells that are proliferating, migrating, or in the initial stages of differentiation, whereas cathodic D2 is associated with differentiated neurones. The transition between the two forms appears to occur during the formation of interneuronal contacts.

Animals↗

GABA induces functionally active low-affinity GABA receptors on cultured cerebellar granule cells.

The effect of gamma-aminobutyric acid (GABA) and its agonists muscimol and 4,5,6,7-tetrahydroisoxazolo[5-4-c]pyridin-3-ol (THIP) on the development of GABA receptors on cerebellar granule cells was studied by cultivation of the cells in media containing these substances. It was found that the presence of 50 microM GABA in the culture media led to the induction of low-affinity GABA receptors (KD 546 +/- 117 nM) in addition to the high-affinity receptors (KD 7 +/- 0.5 nM) which were present regardless of the presence of GABA in the culture media. The functional activity of the GABA receptors was tested by investigating the ability of GABA to modulate evoked glutamate release from the cells. It was found that GABA could inhibit evoked glutamate release (ED50 10 +/- 3 microM) only when the cells had been cultured in the presence of 50 microM GABA, 50 microM muscimol, or 150 microM THIP, i.e., under conditions where low-affinity GABA receptors were present on the cells. This inhibitory effect of GABA could be blocked by 120 microM bicuculline and mimicked by 50 microM muscimol or 150 microM THIP whereas 150 microM (-)-baclofen had no effect. It is concluded that GABA acting extracellularly induces formation of low-affinity receptors on cerebellar granule cells and that these receptors are necessary for mediating an inhibitory effect of GABA on evoked glutamate release. The pharmacological properties of these GABA receptors indicate that they belong to the so-called GABAA receptors.

Animals↗

Primary structure of the vesicular stomatitis virus polymerase (L) gene: evidence for a high frequency of mutations.

A consensus sequence of the polymerase (L) gene of vesicular stomatitis virus, derived from three genomic cDNA copies, is presented. This analysis completes the primary structure of the vesicular stomatitis virus genome, totaling 11,162 bases. The L gene alone spans 6,380 nucleotides and codes for a basic 2,109-amino-acid protein with a molecular weight of 241,012. Sixteen point mutations were detected among cDNA clones prepared from viral RNA of the same strain, representing direct evidence for either the high mutability of vesicular stomatitis virus, the infidelity of reverse transcription during cDNA synthesis, or a combination of both. Some mutation, if present in the viral genome, would result in the translation of incomplete L proteins. For example, two out of four cDNA copies which covered the same region of the L gene had a single-base deletion in the exact same position, whereas the other two clones did not, strongly suggesting that a subpopulation of the genomic RNA may contain this lethal mutation. These lethal mutants define a new class of defective and most likely interfering particles which are indistinguishable in size from the parental virus and can be distinguished only by direct sequencing. We suggest that because of its infidelity, the viral polymerase itself introduces mutations and because of its size, most of these mutations are localized within the polymerase gene. In persistently infected cells in which the selective pressures on the polymerase are different, some of these L gene mutations may further erode the accuracy of the polymerase and thereby lead to the increased mutation rate that is characteristic of this type of infection.

Amino Acid Sequence↗

Sites of copy choice replication involved in generation of vesicular stomatitis virus defective-interfering particle RNAs.

The copy choice model for the generation of defective interfering (DI) particles of vesicular stomatitis virus suggests that during replication the polymerase prematurely terminates, moves with the nascent daughter strand to another site on the same or a different template molecule, and resumes elongation of the nascent chain. We have analyzed the sites where premature termination or resumption of replication has occurred during the generation of the deletion DI particle LT, the snapback DI particle 011, and the panhandle DI particles T, T(L), and 611. The recombination sites were identified by comparing the nucleotide sequences of the relevant regions of these DI particle RNAs to those of the vesicular stomatitis virus L gene (Schubert et al., J. Virol. 51:505-514, 1984). Sequence homology was not detected between these sites, which rules out the existence of a general terminator or promoter sequence involved in copy choice replication. In several cases, however, premature termination or resumption of RNA replication may be favored by specific signal sequences. The sequences immediately before the start and at the end of the deletion in DI LT contain two hexanucleotides, ATCTGA and GATTGG, in a similar spacing. In these case of DI T and 611, but not of DI T(L), the end of the 5'-terminal region bears the hexanucleotide CCUCUU. This sequence is also repeated in the stem region in all three DI particle genomes. In addition, we present data that the added 3'-terminal regions of the panhandle DI particle RNAs may differ by only one base and are 46 [DI T(L) and 611] or 45 (DI T) bases long. We suggest that each site of the vesicular stomatitis virus genome has the potential to give rise to DI particle RNAs. Specific sequences, however, may modulate this process in a quantitative way, and they favor the generation of certain types of DI particle genomes like those of the panhandle type.

Base Sequence↗

Novel neuron-related regulatory mechanisms for astrocytic glutamate and GABA high affinity uptake.

The effect of conditioned media from cultures of cerebral cortical neurons and cerebellar granule cells on high affinity uptake of glutamate and GABA into cerebellar astrocytes cultured from 7-day-old rats was studied. Granule cell-conditioned media selectively enhanced GABA uptake whereas cerebral cortex neuron-conditioned media selectively enhanced glutamate uptake into these astrocytes. This selectivity was apparently restricted to cerebellar astrocytes since astrocytes cultured from cerebral cortex of 7-day-old rats exhibited a slight increase in both GABA and glutamate uptake after culture in conditioned media from both types of neurons. The results point to as yet unknown regulatory mechanisms for the development of astrocytic uptake of transmitter amino acids which may be dependent upon the regional origin of the astrocytes as well as the surrounding neuronal cell type.

Animals↗

[Transient chronic hepatitis after acute viral hepatitis A (author's transl)].

Serologic, chemical and in part bioptic follow-up investigations were done in 25 patients with acute viral hepatitis A. The disease course was completely uncomplicated in 19 patients; pathologically increased transaminases returned to normal within 3 months. Transaminases remained increased pathologically in 3 patients for 3 to 6 months. In a further 3 patients normalisation took 8 to 15 months. Two patients showed histologic changes in the early phase of the disease which were compatible with persistent or chronic active hepatitis. Cure of hepatitis appeared likely in all cases on the grounds of clinical and laboratory follow-up investigations. These investigations show that in acute viral hepatitis A prolonged disease courses and transient chronicity may occur besides the uncomplicated course.

Adult↗