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Biomedical subjects

E Meyer

Publications and source records attributed to E Meyer.

At least 91 records · Page 5Linked to original sources
PubMed1999

Enzymatic reactions in liposomes using the detergent-induced liposome loading method.

Microcompartmentalization is a crucial step in the origin of life. More than 30 years ago, Oparin et al. proposed models based on biochemical reactions taking place in so-called coacervates. Their intention was to develop systems with which semipermeable microcompartments could be established. In the present work we follow their intuition, but we use well-characterized bilayer structures instead of the poorly characterized coacervates. Liposomes from phospholipids can be used as microreactors but they exhibit only a modest permeability and, therefore, chemical reactions occurring inside these structures are depleted after a relatively short period. Here it is shown that even highly stable liposomes from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) can be used as semipermeable microreactors when treated with sodium cholate. Using this kind of mixed liposomes, we describe a biochemical reaction occurring inside the liposomes while the same reaction is prevented in the external medium. In addition, we show that this cholate-induced permeability of POPC bilayers can even be used to load macromolecules such as enzymes from the outside.

Cholates↗
PubMed1999

JNK/SAPK activity contributes to TRAIL-induced apoptosis.

We report here that JNK/SAPKs are activated by TRAIL in parallel to induction of apoptosis in human T and B cell lines. Death signaling as well as JNK/SAPK activation by TRAIL in these cells is FADD- and caspase-dependent since dominant-negative FADD or the caspase inhibitor zVAD prevented both, apoptosis and JNK/SAPK activity. JNK/SAPK activity in response to triggering of CD95 by an agonistic antibody (alphaAPO-1) was also diminished by dominant-negative FADD or zVAD. Correspondingly, a cell line resistant to alphaAPO-1-induced death exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate JNK/SAPK activity in response to TRAIL or alphaAPO-1. Inhibition of JNK/SAPK activity, by stably transfecting cells with a dominant-negative JNKK-MKK4 construct, reduced apoptosis in response to TRAIL or alphaAPO-1. Therefore, activation of JNK/SAPKs by TRAIL or alphaAPO-1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines.

Antibodies↗
PubMed1999

Ca2+ activation of hSlo K+ channel is suppressed by N-terminal GFP tag.

The human slow poke (hSlo) K+ channel was tagged with GFP (green fluorescent protein) at the N-terminus of its alpha-subunit. The fusion protein was expressed transiently in HEK293 cells; it formed functional voltage-gated channels as shown by whole cell patch-clamp measurements. However, the tag lowered the voltage dependence of gating and it suppressed the typical left-shift of gating by intracellular binding of Ca2+. The location of the GFP-tagged N-terminus was confirmed to be on the extracellular side by application of a monoclonal antibody to nonpermeabilized cells. Structural interpretations of the effects are discussed.

Calcium↗
PubMed1999

Frequency-dependent changes in cerebral metabolic rate of oxygen during activation of human visual cortex.

To test the hypothesis that brain oxidative metabolism is significantly increased upon adequate stimulation, we varied the presentation of a visual stimulus to determine the frequency at which the metabolic response would be at maximum. The authors measured regional CMR(O2) in 12 healthy normal volunteers with the ECAT EXACT HR+ (CTI/Siemens, Knoxville, TN, U.S.A.) three-dimensional whole-body positron emission tomograph (PET). In seven successive activating conditions, subjects viewed a yellow-blue annular checkerboard reversing its contrast at frequencies of 0, 1, 4, 8, 16, 32, and 50 Hz. Stimulation began 4 minutes before and continued throughout the 3-minute dynamic scan. In the baseline condition, the subjects began fixating a cross hair 30 seconds before the scan and continued to do so for the duration of the 3-minute scan. At the start of each scan, the subjects inhaled 20 mCi of (15)O-O2 in a single breath. The CMR(O2) value was calculated using a two-compartment, weighted integration method. Normalized PET images were averaged across subjects and coregistered with the subjects' magnetic resonance imaging in stereotaxic space. Mean subtracted image volumes (activation minus baseline) of CMR(O2) then were obtained and converted to z statistic volumes. The authors found a statistically significant focal change of CMR(O2) in the striate cortex (x = 9; y = -89; z = -1) that reached a maximum at 4 Hz and dropped off sharply at higher stimulus frequencies.

Administration, Inhalation↗
PubMed1998

The effect of lead in tap water on blood lead in children in a smelter town.

Hettstedt, a city in eastern Germany with a long history of mining and smelting of non-ferrous ores, has multiple lead waste deposits and the remains of a former lead smelter and a copper-silver smelter. As part of a cross-sectional study, an analysis of lead concentrations in drinking water and in blood was undertaken to determine the impact of lead in drinking water on the internal burden of lead in children. The geometric mean of blood lead levels among children 5-14 years old was 35.0 micrograms/l with a 95% confidence interval (C.I.) of 33.4-36.7. The geometric mean of lead in the random tap water samples was 0.5 microgram/l (95% C.I., 0.5-0.6) and 0.7 microgram/l (95% C.I., 0.6-0.8) in the stagnant tap water samples. Blood lead levels were somewhat correlated with the random water measures but not the stagnant water measures (random sample: r = 0.12, P = 0.012; stagnant sample: r = 0.04, P = 0.396). After adjustment for relevant confounders, lead in drinking water (random sample) was not significantly associated with blood lead levels. Factors that were significantly associated with blood lead included gender, the city area of residence, lead in house dust, regular contact with dogs and dirtiness of the child after playing outdoors. Based on this study, lead in domestic tap water contributed little to the lead exposure of children in the lead contaminated region of Hettstedt.

Adolescent↗
PubMed1998

Population genetic diversity in relation to microsatellite heterogeneity.

Nine populations (Germans, Turks, Moroccans, Ovambos, Ugandans, Chinese, Japanese, Papuans, and Australian Aborigines) were investigated using six microsatellite systems (HumCD4, Hum F13B, HumFES/FPS, HumTH01, HumVWA, and D21S11), so-called STRs (short tandem repeats). Allele frequency data and sequencing results were used to compare the population genetic diversity among these populations. The genetic differences varied depending on the STR applied. According to the systems investigated, we defined three categories of STR microvariation: LOMs (low microvariation systems), INMs (intermediate microvariation systems), and HIMs (high microvariation systems). LOMs (STRs: CD4, FES, F13B, TH01) are characterised by a number of repeats between 5-15 and a stable repeat sequence. INMs and HIMs each showed an increasing number of repeats and additional sequence variation in the repeat motifs. The rate of new mutations was associated with the extent of microvariation. The reconstruction of phylogenetic trees led to a clustering in an early split of the African populations followed by further branching of the Asian/Melanesian and the Caucasian groups.

Africa↗
PubMed1998

Full-body interface pressure testing as a method for performance evaluation of clinical support surfaces.

A method for evaluating the performance of clinical support surfaces is required by designers in their efforts to produce better clinical support surfaces that will reduce the incidence of pressure ulcers. In this study, a Pressure Index (P(index)) is defined which is derived from an analytical equation used to evaluate the average interface pressure, the peak pressure, the magnitude of the peak pressure, and the number of peak pressures on the entire body. The type of subjects needed to represent a population of users as well as the head of bed elevations necessary to simulate clinical applications were integrated with the P(index) to create a single-value mean pressure index which can be used to evaluate any type of surface. To determine the accuracy and repeatability of the mean pressure index, three surfaces (a standard hospital innerspring, a replacement foam mattress, and a low-airloss surface) were tested and evaluated using this method. The low airloss performed the best and the standard innerspring clearly performed the worst (p < 0.0001). The method appeared to accurately and reproducibly predict the relative performance of the three surfaces in reducing pressure.

Aged↗
PubMed1998

Phylogenetic resolution of complex mutational features at Y-STR DYS390 in aboriginal Australians and Papuans.

Y-chromosomal short tandem repeats (STRs) are used for the study of male aspects of human evolution as well as for forensic applications and paternity testing. Both applications require an understanding of the underlying mutational mechanisms that create variability. We describe complex mutations at the substructured DYS390 STR locus in 97 natives of the New Guinea/Australian region. Sequencing of short alleles in these populations indicates multirepeat deletions. All samples are further characterized using the five additional Y-STR loci DYS19, DXYS156-Y, DYS391, DYS392, and DYS393. Phylogenetic analysis of the resulting haplotypes yields ethnically specific clusters predating the settlement of Australia and Papua New Guinea (although archaic Homo sapiens or Homo erectus lineages are absent). The phylogeny confirms that DYS390 violates the stepwise mutation model and demonstrates that the DYS390 locus mutates relatively rapidly and retains its variability after structural change.

Alleles↗
PubMed1998

Increased oxygen consumption in human visual cortex: response to visual stimulation.

To test whether a sufficiently complex visual stimulus causes the consumption of oxygen to rise in the human visual cortex, we used positron emission tomography (PET) to measure the cerebral metabolic rate of oxygen (CMRO2) during visual stimulation in 6 healthy normal volunteers. A yellow-blue checkerboard, reversing its contrast at a frequency of 8 Hz, was presented for a period of 7 min, beginning 4 min before the onset of a 3-min scan. In the baseline condition, subjects fixated a cross-hair from 30 s before until the end of the 3-min scan. The CMRO2 was calculated with the two-compartment weighted integration method (1). The checkerboard minus baseline subtraction yielded statistically significant increases in CMRO2 in the primary (V1) and higher order visual cortices (V4 and V5). The significant CMRO2 increases were detected in these regions in both the group average and in each individual subject.

Adult↗
PubMed1998

Homology-dependent maternal inhibition of developmental excision of internal eliminated sequences in Paramecium tetraurelia.

Thousands of single-copy internal eliminated sequences (IESs) are excised from the germ line genome of ciliates during development of the polygenomic somatic macronucleus, following sexual events. Paramecium IESs are short, noncoding elements that frequently interrupt coding sequences. No absolutely conserved sequence element, other than flanking 5'-TA-3' direct repeats, has been identified among sequenced IESs; the mechanisms of their specific recognition and precise elimination are unknown. Previous work has revealed the existence of an epigenetic control of excision. It was shown that the presence of one IES in the vegetative macronucleus results in a specific inhibition of the excision of the same element during the development of a new macronucleus, in the following sexual generation. We have assessed the generality and sequence specificity of this transnuclear maternal control by studying the effects of macronuclear transformation with 13 different IESs. We show that at least five of them can be maintained in the new macronuclear genome; sequence specificity is complete both between genes and between different IESs in the same gene. In all cases, the degree of excision inhibition correlates with the copy number of the maternal IES, but each IES shows a characteristic inhibition efficiency. Short internal IES-like segments were found to be excised from two of the IESs when excision between normal boundaries was inhibited. Available data suggest that the sequence specificity of these maternal effects is mediated by pairing interactions between homologous nucleic acids.

Animals↗
PubMed1998

Regional lumped constant differences and asymmetry in fluorine-18-FDG uptake in temporal lobe epilepsy.

UNLABELLED: To date, there has been no satisfactory explanation for the observation that interictal uptake of the glucose analog [18F]fluorodeoxyglucose (FDG) is consistently reduced in the temporal lobe ipsilateral to the seizure focus in patients with temporal lobe epilepsy. We examined the hypothesis that regional differences in tracer uptake in temporal lobe epilepsy reflect regional differences in the lumped constant (lambda). METHODS: In 9 control subjects and 10 patients with temporal lobe epilepsy, we obtained regional estimates of lambda by expressing lambda in terms of transfer coefficients for FDG and parameters which are likely to remain constant throughout both the brain and under different functional states. RESULTS: In the patients, lambda was lower in the temporal lobe ipsilateral to the epileptic focus (0.53 +/- 0.06; p < 0.005) than in the contralateral temporal lobe (0.56 +/- 0.06). Interside differences in lambda were highly correlated with asymmetry in tracer uptake. Furthermore, the use of regional estimates of lambda reduced the asymmetry in estimated rCMRglc in patients with temporal lobe epilepsy but not in controls. CONCLUSION: In these patients, a change in tracer uptake may not indicate a change in glucose consumption of corresponding magnitude, raising the possibility that in at least some patients with temporal lobe epilepsy, the term hypometabolism does not accurately describe reductions in tracer uptake.

Adult↗
PubMed1998

Signal-enhancing switched protocols to study higher-order cognitive tasks with PET.

UNLABELLED: We tested the effectiveness of a switched protocol when it is used to detect signals that result from the study of a higher-order cognitive task with PET. Using language tasks that have been studied extensively in our laboratories, we compared the signal-to-noise ratio (S/N) and statistical significance of the activation signals detected in PET images of regional cerebral blood flow (rCBF), obtained using a standard activation protocol, and of activity concentration, obtained using a switched protocol. METHODS: Four volunteers were studied with PET while they were performing synonym-generation and word-repetition tasks (activation and baseline tasks, respectively). Each volunteer had three activation/baseline and three baseline/ activation scans. Data for each scan were collected in two frames (60 and 120 sec long). During the first 60 sec, data were collected using a standard activation protocol. Subjects then switched tasks, and acquisition continued for 120 sec. Two images were obtained from each scan: an rCBF image using the first frame and an activity-concentration image using both frames. Images were transformed into Talairach space, subtracted and averaged within and across subjects. Parametric t-statistic images were generated for each protocol, and the magnitude and significance of the activation signals yielded by the two acquisition methods were compared. RESULTS: All the activation foci detected using measurements of rCBF were detected when the switched protocol was used; this protocol, in addition, yielded better S/N values. The cognitive component introduced by task-switching in switched protocols did not yield extra statistically significant foci. In single subjects, the average improvement in the signal significance from regions of activation, at a 95% confidence level, was between 6% and 25%. When scans were averaged across subjects, the switched protocol yielded improvements in signal statistical significance of up to 38%. CONCLUSION: We present evidence suggesting that switched protocols can be used to study higher-order cognitive tasks and that they yield activation foci with S/N values that are greater than those of equivalent foci detected using an rCBF protocol. Switched protocols appear to be easy to apply to the testing of higher-order cognitive functions. However, the extra cognitive requirement of switching tasks during data acquisition may be a limiting factor when switched protocols are used to study memory processes.

Adult↗
PubMed1997

Obligatory role of the LIFG in synonym generation: evidence from PET and cortical stimulation.

We report results from a patient in whom we obtained converging evidence from positron emission tomography (PET) and intraoperative stimulation mapping to support a one-way dissociation between the functional areas involved in word repetition and synonym generation. Intraoperative stimulation mapping interfered with synonym generation but did not disturb word repetition at the same left inferior frontal site at which a cerebral blood flow (CBF) increase had been observed for a synonym generation task. The results for this single subject suggest that the functional areas involved in different aspects of linguistic processing are dissociable and that specific disruption under conditions of cortical stimulation can be correlated with the brain regions identified via PET as the most active during performance of a specific task.

Adult↗
PubMed1997

Prevalence of intestinal parasites in the human population of León, Nicaragua.

Intestinal parasites appear to be prevalent in Nicaragua, which motivated a more extensive prevalence study in which socioeconomic conditions such as degree of crowding, quality of water supply, type of floor and disposal of excretion, were considered. The study was performed on 1267 stool samples from about 8% of the citizens of the city of León. The overall prevalence of intestinal pathogenic parasites among the 1267 individuals was found to be 47.2%. The prevalence of Entamoeba histolytica/dispar was 18.6% followed by Giardia (15.9%) and Ascaris (13.4%). Other helminths such as hookworms and Strongyloides sp. were found at very low rates. Giardia, in contrast to worm infections, was prevalent already in children under 5 years of age. E. histolytica/dispar increased with age and remained high. Of 595 individuals with intestinal parasites 81% were living in 'poor' conditions and in 13 clusters of households, a lower prevalence of parasites was seen in households characterised as having good socioeconomic conditions. However, several variables appear to be important in determining the prevalence of the individual intestinal protozoa and helminths encountered.

Animals↗
PubMed1997

The internal burden of lead among children in a smelter town--a small area analysis.

Hettstedt, a city in former East Germany with a history of mining and smelting of nonferrous ores, has multiple lead waste deposits and the remains of a former lead and copper-silver smelter. A small-area analysis of lead concentrations in blood and in household dust was undertaken in a cross-sectional study to determine if children living near the sources had particularly high burdens of lead. The overall geometric mean of the region was 38.0 micrograms Pb/liter blood with a 95% confidence interval (CI) of 36.5-39.5. The burden of lead among children living in the region containing the lead tailings piles and adjacent smelters was almost twice as high (77.4 micrograms Pb/liter blood; 95% CI 65.0-92.0). It decreased in the areas farther northeast from the smelter. Lead levels in the children residing in areas southwest of the smelters were not appreciably elevated. The same pattern was found in house dust lead concentrations. This analysis helped target areas where follow-up is needed and found that not only distance from lead sources, but also meteorological factors played an important role in lead exposure.

Adolescent↗
PubMed1997

STR analysis on perforating FMJ bullets and a new VWA variant allele.

In three separate shooting incidents involving multiple gunshots, two FMJ bullets and one bullet fragment found at the scene (one from each case) were investigated for the presence of biological material from the victim after perforation. The surface of the missiles, which did not show obvious tissue traces when examined under a macroscope, was swabbed. PCR typing of up to five STR loci was performed on the small amounts of DNA extracted, which were seen below the detection limit of the slot blot quantification in one case. Nevertheless, individualisation of cellular material from the perforating projectiles was successful in each of the three cases presented. Consequently, identification of the victim wounded by a perforating bullet can reliably be achieved if contamination or removal of evidentiary material by improper handling is prevented. This technique is especially useful in cases where more than one person has fired a gun because the bullet carrying DNA can be linked to the firearm by investigation with a comparison microscope. As a by-product of this investigation, a variant allele 14 (14+4) at the VWA locus was detected.

Alleles↗