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Biomedical subjects

E Meyer

Publications and source records attributed to E Meyer.

At least 127 records · Page 7Linked to original sources
PubMed1996

Hydroxyethyl cyclosporin A induces and decreases P4503A and P-glycoprotein levels in rat liver.

1. A new immunosuppressant SDZ IMM 125 (IMM), the hydroxyethyl derivative of D-serine8-cyclosporin (cyclosporin A, CSA), induced or decreased the liver P450s of rat, in particular the 3A proteins, depending on the dose and duration of exposure. Doses of 20 mg/kg/day for 2 weeks and 10 mg/kg/day for 26 weeks induced the rat liver 3A levels 2- and 1.8-fold respectively, whereas 52 weeks of 24 mg/kg/day decreased the 3A levels by 22%. High doses of IMM, 100 mg/kg/day for 26 weeks, significantly decreased the 3A levels by 56%. 2. Changes in the rate of IMM biotransformation paralleled the changes in the levels of liver 3A indicating that liver 3A levels could influence the clearance of IMM. 3. Both IMM and CSA affected liver and kidney P-glycoprotein (Pgp) levels. The increases measured after short-term treatment (20 mg/kg/day for 2 weeks) in the liver (1.8-fold) and kidney (1.3-fold) were less pronounced in the long-term studies in which liver Pgp levels were increased 1.4-fold (48 mg/kg/day for 52 weeks). At higher doses (100 mg/kg/day for 26 weeks) Pgp levels were significantly decreased. The modulation of Pgp levels by IMM did not parallel the changes in 3A levels, indicating that Pgp regulation is most likely due to a direct effect of the cyclosporin rather than a co-regulation mechanism linked to 3A or P4501A modulation. 4. Increased arachidonic metabolism to the 19- and 20-HETE metabolites, a possible mechanism of the cyclosporin-induced renal hypertension, occurred in the liver microsomes and not the kidney S9 fraction of the 2-week study, and only at very high doses (100 mg/kg/day) in the longer studies (26 weeks).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Epigenetic self-regulation of developmental excision of an internal eliminated sequence on Paramecium tetraurelia.

Differentiation of the somatic macronucleus of ciliates after sexual events involves the programmed excision of thousands of single-copy internal eliminated sequences (IESs) from the germ-line genome. We have studied two cell lines of Paramecium tetraurelia that have identical germ-line genomes but differ in their macronuclear genomes. In the IES- cell line, a 222-bp IES interrupting a coding sequence is reproducibly excised during macronuclear differentiation, whereas it is not in the IES+ cell line. In a cross between the two lines, the developmental alternative in maternally inherited, suggesting that it is epigenetically controlled by the old (prezygotic) macronucleus in each cell. Transformation of the macronucleus of both lines with plasmids carrying fragments of either version of the gene shows that the presence of the IES sequence in the old macronucleus results in retention of the IES in the new macronuclear genome of sexual progeny. This could be attributable to (1) inhibition of excision, or (2) repair of a double-strand gap left in the genomic sequence after constitutive excision of the IES, by a polymerization mechanism using a homologous IES+ template from the old macronucleus. The latter possibility is ruled out by experiments showing that modified IESs can inhibit excision without being copied in the new macronuclear genome. Possible mechanisms are discussed in the light of a quantitative analysis of excision inhibition by the maternal IES sequence.

Animals↗
PubMed1995

The neural substrates underlying word generation: a bilingual functional-imaging study.

We used positron emission tomography to investigate word generation in subjects whose first language was English but who were also proficient in French. These subjects performed three types of lexical search: rhyme generation based on phonological cues, synonym generation requiring a semantic search, and translation involving access to a semantic representation in the other language. Two control tasks required word repetition in each language. We investigated whether phonological and semantic word-generation activate similar regions and whether the same neural substrates subserve the second language as subserve the first. A series of cerebral blood flow increases, corresponding to Brodmann's areas 47, 46, 45, and 8, were observed in the left frontal cortex when the baseline repetition task was subtracted from each of the respective generation tasks. The results suggest that common neural substrates are involved in within- and across-language searches and that the left inferior frontal region is activated irrespective of whether the search is guided by phonological or semantic cues.

Acoustic Stimulation↗
PubMed1995

Microsatellite polymorphisms reveal phylogenetic relationships in primates.

We amplified, via PCR, DNA segments from intron 1 of the tyrosine hydroxylase gene (TH01) and intron 40 of the von Willebrand factor gene (VWA) in ten nonhuman primate genera. In humans both introns contain polymorphic microsatellites with tetrameric repeats. Compared to the allelic ranges in human populations relatively short repeat arrays could be detected for the nonhuman primates typed, presumably reflecting an ancient precursor state at both microsatellite loci. Furthermore, our results provide evidence for an association of the average number of repeats present in different primate genera and their divergence time from man. DNA sequencing of VWA orthologues revealed a relatively high variability in the arrangement of repeats in the 5'-repeat arrays, the generation of which could probably be explained by polar mutational events.

Animals↗
PubMed1995

Population study of 3 STR loci in the Basque Country (northern Spain).

The tetrameric STRs, HUMTH01, HUMVWA31A and HUMFES/FPS, were studied in a population from the Basque Country (northern Spain) for their frequency distribution and applicability to identity and paternity testing. All systems conformed to Hardy-Weinberg equilibrium; pairwise comparisons demonstrated the allelic independence between loci, and furthermore, all systems seemed to be in agreement with expectations from the Stepwise Mutation Model (SMM) of the mutation-drift theory, which indicates the homogeneity of the population and suggests a replication slippage mechanism as a possible model for generating alleles. A comparison with other population groups appeared to indicate that frequencies are well conserved in Caucasians, but differ from other racial groups. The calculated parameters "a priori probability of exclusion" (PEX) and "index of discrimination" (ID), show the informativeness of these loci for the determination of identity and relatedness of individuals.

Alleles↗
PubMed1995

Phenotype differences of STRs in 7 human populations.

A maximum of 6 STR systems (TH01, VWA, ACTBP2, FES, F13B, D21S11) was investigated in 7 human populations (Germans, Turks, Moroccans, Japanese, Chinese, Papuans, Ovambos). In each population no deviations from Hardy-Weinberg equilibrium were observed. Out of each population the phenotypes of 50 individuals (comprising 3 to 6 STRs) were randomly selected. Based on the phenotype frequencies interpopulation comparisons were carried out using the frequencies of each other population. Within major ethnic groups only minor differences in phenotype frequencies were found. Between major ethnic groups differences of up to several orders of magnitude could be observed. The most discriminative STRs for interpopulation comparisons were TH01, FES and F13B.

China↗
PubMed1995

HumFES/FPS and HumF13B: Turkish and German population data.

The allele distribution of two STRs has been investigated in two populations, i.e. Turks (n = 203/200) and Germans (n = 414/402). The Turkish population showed 11 alleles in HumFES/FPS and 6 alleles in HumF13B while the German population had 9 (FES) and 8 (F13B) alleles respectively. Although the frequency profiles looked quite similar in both populations, there exist significant differences mainly due to alleles 8 and 10 (F13B) and allele 12 (FES). Four variant alleles have been sequenced and are described. Investigation of 368 (FES)/372 (F13B) meioses revealed no new mutations.

DNA↗
PubMed1995

Functional PET scanning in the preoperative assessment of cerebral arteriovenous malformations.

We have evaluated positron emission tomography (PET) scanning during sensory stimulation or during the performance of auditory, visually based or expressive language tasks (activation PET scanning) to determine its reliability in establishing the relationships of cerebral arteriovenous malformations (AVMs) to the ambient cortex in 10 patients. Five patients with a central AVM underwent activation PET scanning combined with three-dimensional MRI during vibrotactile stimulation of the contralateral hand, and 5 patients with AVMs in or around speech areas were similarly scanned during a language task. Vibrotactile stimulation identified the post-central gyrus, establishing the relationship of the AVM to the central region. The results of language activation were specific to the modality (visual, auditory, articulate) on which the task was based. Sensory PET activation scanning is reliable in identifying the pre- and post-central gyri and useful in assessing AVMs in and around the central region. A greater understanding of results in normal controls for specific visual, auditory, and expressive language tasks is necessary before language activation PET scanning can be confidently applied to clinical cases.

Brain↗
PubMed1995

Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers.

OBJECTIVE: The authors tested the prediction of temporal cortex activation during experimentally induced anxiety by using positron emission tomography and the [15O]H2O bolus-subtraction method to determine regional cerebral blood flow (CBF) changes in normal volunteers challenged with a bolus injection of cholecystokinin tetrapeptide (CCK4). METHOD: Eight right-handed healthy subjects (five male, three female; mean age, 26.4 years) underwent four 60-second [15O]H2O scans separated by 15-minute intervals; each scan followed an intravenous bolus injection of either saline (placebo) or CCK4 (50 micrograms). Each subject received CCK4 once, as the first or second bolus, in a random-order, placebo-controlled, double-blind fashion. Two of the three placebo conditions were nominally identical, and the remaining placebo was used to control for anticipatory anxiety. Magnetic resonance imaging scans were obtained for subsequent anatomical correlation of blood flow changes. RESULTS: CCK4, but not placebo, elicited a marked anxiogenic response, reflected by robust increases in subjective anxiety ratings and heart rate. CCK4-induced anxiety was associated with 1) robust and bilateral increases in extracerebral blood flow in the vicinity of the superficial temporal artery territory and 2) CBF increases in the anterior cingulate gyrus, the claustrum-insular-amygdala region, and the cerebellar vermis. CONCLUSIONS: Some of the temporopolar cortex CBF activation peaks previously reported in humans in association with drug- and non-drug-induced anxiety, as well as the increase in regional CBF in the claustrum-insular-amygdala region, may be of vascular and/or muscular origin.

Adult↗
PubMed1995

Human liver cytochrome P4503A biotransformation of the cyclosporin derivative SDZ IMM 125.

In humans, cytochrome P4503A (CYP3A) is the major cytochrome P450 gene family that metabolizes SDZ IMM 125 (IMM) to its primary metabolites. Human liver microsomes could be used for this study, because the metabolite profile matched that found in human blood. The apparent affinity (KM) of IMM for the cytochrome P450 proteins (5.1 +/- 1.8 microM) is similar to that of cyclosporin A (CSA). CSA competitively inhibited the metabolism of IMM, increasing the KM 2- and 4.6-fold in the presence of 4 and 10 microM CSA, respectively (Ki 3.8 +/- 1.1 microM). Ketoconazole exhibited competitive inhibition kinetics toward IMM biotransformation, increasing the KM of IMM 1.8-fold at 0.5 microM ketoconazole and 3.5-fold at 1 microM ketoconazole, with no effect on Vmax (Ki of 0.5 +/- 0.4 microM). These results indicate that both CSA and ketoconazole would cause drug interactions, interfering with the biotransformation of IMM. The metabolism of IMM was also greatly inhibited (approximately 80%) by the CYP3A suicide substrate triacetyloleandomycin and a CYP3A inhibitory antibody, indicating the involvement of CYP3A proteins in the biotransformation of IMM. Confirmation of CYP3A4 involvement in the formation of the three primary IMM metabolites was demonstrated with recombinant cells expressing human CYP3A4. Therefore, compounds interacting with CYP3A proteins are expected to cause drug-drug interactions (i.e. the antimycotics ketoconazole and clotrimazole, the steroids ethinylestradiol and testosterone, the ergots, the calcium channel blocker nifedipine, and the immunosuppressants FK-506 and rapamycin).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Purtscher's retinopathy].

A 20-year-old soldier trapped under a minibus for 90 minutes sustained a crush injury to his chest and a maxillofacial fracture. 2 days later he complained of decreased visual acuity in both eyes. Funduscopy revealed Purtscher's retinopathy. The traumatologist should be aware of this type of indirect eye injury, and should request ophthalmological assessment and follow-up in such patients.

Adult↗
PubMed1994

Left putaminal activation when speaking a second language: evidence from PET.

The neural representation of the languages of the polyglot speaker has been highly controversial. We used positron emission tomography (PET) to investigate whether production in a second language (L2) involves the same neural substrates as that of a first language (L1) in normal bilingual subjects who learned L2 after the age of 5 years. Comparison of cerebral blood flow (CBF) when repeating words in L2 and repeating words in L1 yielded only a single significant CBF change: an increase in the left putamen. We hypothesize that this region plays a specific role for articulation in L2. The role of the putamen in articulation is supported by foreign accent syndrome (FAS), which can occur after left putaminal damage. The increased articulatory demands imposed by speaking a second language may require complex motor control for speech production in L2.

Adult↗
PubMed1994

N5-carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli.

Conversion of aminoimidazole ribonucleotide (AIR) to 4-carboxyaminoimidazole ribonucleotide (CAIR) in Escherichia coli requires two proteins, PurE and PurK, previously thought to be subunits of a single enzyme, AIR carboxylase. Past studies revealing an ATP requirement for this reaction (Meyer et al., 1992), in conjunction with present studies, reveal that PurE and PurK possess independent catalytic activities. PurK is shown, by NMR spectroscopy, to catalyze the conversion of AIR in the presence of HCO3- and ATP to ADP, P(i), and the carbamate of AIR (designated N5-CAIR). PurE has been shown by NMR spectroscopy and kinetic analysis, to catalyze the reversible conversion of N5-CAIR and CAIR. N5-CAIR has a half-life of 0.9 min at pH 7.8 and 30 degrees C. Thus, two new enzymatic activities and a new intermediate have been discovered in the de novo purine biosynthetic pathway of E. coli.

Adenosine Diphosphate↗