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E Neumann

Publications and source records attributed to E Neumann.

At least 55 records · Page 3Linked to original sources
PubMed1997

Continued inhibitory capacity throughout adulthood: conceptual negative priming in younger and older adults.

Two negative priming experiments in older and younger adults are reported. Participants in Experiment 1, involving both positive and negative priming conditions, showed both types of priming. There were no significant differences between age groups. If anything, older participants showed more negative priming. In Experiment 2, involving only negative priming conditions, similar results were obtained. Our findings rule out possible effects of experimental conditions that episodic retrieval theorists have suggested might account for negative priming in older adults. Although our results may be consistent with an explanation of negative priming in older adults by an expansively specified theory of episodic retrieval, they are at least as consistent with the view that inhibitory processes are intact in older adults. In light of these findings, conflicting empirical results and alternative views of negative priming in older adults are examined.

Adult↗
PubMed1996

Binding of the neurotoxin fasciculin 2 to the acetylcholinesterase peripheral site drastically reduces the association and dissociation rate constants for N-methylacridinium binding to the active site.

The acetylcholinesterase (AChE) active site consists of a gorge 2 nm deep that is lined with aromatic residues. A serine residue near the base of the gorge defines an acylation site where an acyl enzyme intermediate is formed during the hydrolysis of ester substrates. Residues near the entrance to the gorge comprise a peripheral site where inhibitors like propidium and fasciculin 2, a snake neurotoxin, bind and interfere with catalysis. Like certain other cationic ligands that bind specifically to the acylation site, N-methylacridinium can still interact with the acylation site in the AChE-fasciculin 2 complex. At 310 K (37 degrees C), the equilibrium dissociation constant KL' for N-methylacridinium binding to the complex was 4.0 +/- 0.7 microM, less than an order of magnitude larger than the KL = 1.0 +/- 0.3 microM for N-methylacridinium interaction with human AChE in the absence of fasciculin 2. To assess whether fasciculin 2 can sterically block access of a ligand to the acylation site, thermodynamic and kinetic constants for the interaction of N-methylacridinium with AChE in the presence and absence of fasciculin 2 were measured by fluorescence temperature jump relaxation kinetics. During progressive titration of the enzyme with increasing concentrations of N-methylacridinium, a prominent relaxation in the 0.1-1 ms range was observed in the absence of fasciculin 2. When excess fasciculin 2 was added, the prominent relaxation shifted to the 0.3-1 s range. Estimates of total AChE concentrations, KL, or KL' from analyses of relaxation amplitudes agreed well with those from equilibrium fluorescence, confirming that the relaxations corresponded to the bimolecular reactions of interest. Further analysis of the relaxation times in the absence of fasciculin 2 gave estimates of the N-methylacridinium association rate constant k12 = 8 x 10(8) M-1 s-1 and dissociation rate constant k21 = 750 s-1 at 310 K (37 degrees C). For the AChE-fasciculin 2 complex, the corresponding constants were k12' = 1.0 x 10(5) M-1 s-1 and k21' = 0.4 s-1. Thus the rate constants decreased by more than 3 orders of magnitude when fasciculin 2 was bound, consistent with a pronounced steric blockade of N-methylacridinium ingress to and egress from the acylation site.

Acetylcholinesterase↗
PubMed1996

Electro-optics of membrane electroporation in diphenylhexatriene-doped lipid bilayer vesicles.

The electric (linear) dichroisms observed in the membrane electroporation of salt-filled lipid bilayer vesicles (diameter O = 2 alpha = 0.32 micron; inside [NaCl] = 0.2 M) in isotonic aqueous 0.284 M sucrose-0.2 mM NaCl solution indicate orientation changes of the anisotropic light scattering centers (lipid head groups) and of the optical transition moments of the membrane-inserted probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Both the turbidity dichroism and DPH absorbance dichroism show peculiar features: (1) at external electric fields E > or = Esat the time course of the dichroism shows a maximum value (reversal): Esat = 4.0 (+/- 0.2) MV m-1, T = 293 K (20 degrees C), (2) this reversal value is independent of the field strength for E > or = Esat, (3) the dichroism amplitudes exhibit a maximum value Emax = 3.0 (+/- 0.5) MV m-1, (4) for the pulse duration of 10 microseconds there is one dominant visible normal mode, the relaxation rate increases up to tau-1 approximately 0.6 x 10(6) s-1 at Esat and then decreases for E > Esat. The data can be described in terms of local lipid phase transitions involving clusters Ln of n lipids in the pore edges according to the three-state scheme C<-->HO<-->HI, C being the closed bilayer state, HO the hydrophobic pore state and HI the hydrophilic or inverted pore state with rotated lipid and DPH molecules. At E > or = Esat, further transitions HO<-->HO* and HI<-->HI* are rapidly coupled to the C<-->HO transition, which is rate-limiting. The vesicle geometry conditions a cos theta dependence of the local membrane field effects relative to the E direction and the data reflect cos theta averages. The stationary induced transmembrane voltage delta phi (theta, lambda m) = -1.5 aEf(lambda m) magnitude of cos theta does not exceed the limiting value delta phi sat = -0.53 V, corresponding to the field strength Em,sat = -delta phi sat/d = 100 MV m-1 (10(3) kV cm-1), due to increasing membrane conductivity lambda m. At E = Esat, f(lambda m) = 0.55, lambda m = 0.11 mS m-1. The lipid cluster phase transition model yields an average pore radius of rp = 0.35 (+/- 0.05) nm of the assumed cylindrical pore of thickness d = 5 nm, suggesting an average cluster size of = 12 (+/- 2) lipids per pore edge. For E > Esat, the total number of DPH molecules in pore states approaches a saturation value; the fraction of DPH molecules in HI pores is 12 (+/- 2)% and that in HO pores is 48 (+/- 2)%. The percentage of membrane area P approximately (lambda m/lambda i) x 100% of conductive openings filled with the intravesicular medium of conductance lambda i = 2.2 S m-1 linearly increases from P approximately 0% (E = 1.8 MV m-1) to P = 0.017% (E = 8.5 MV m-1). Analogous estimations made by Kinosita et al. (1993) on the basis of fluorescence imaging data for sea urchin eggs give the same order of magnitude for P (0.02-0.2%). The increase in P with the field strength is collinear with the increase in concentration of HI and HI* states with the field strength, whereas the HO and HO* states exhibit a sigmoid field dependence. Therefore our data suggest that it is only the HI and HI* pore states which are conductive. It is noted that the various peculiar features of the dichroism data cannot be described by simple whole particle deformation.

Chemical Phenomena↗
PubMed1996

Calcium-mediated DNA adsorption to yeast cells and kinetics of cell transformation by electroporation.

Detailed kinetic data suggest that the direct transfer of plasmid DNA (YEp 351, 5.6 kbp, supercoiled, Mr approximately 3.5 x 10(6)) by membrane electroporation of yeast cells (Saccharomyces cerevisiae, strain AH 215) is mainly due to electrodiffusive processes. The rate-limiting step for the cell transformation, however, is a bimolecular DNA-binding interaction in the cell interior. Both the adsorption of DNA, directly measured with [32P]dCTP DNA, and the number of transformants are collinearly enhanced with increasing total concentrations [Dt] and [Cat] of DNA and of calcium, respectively. At [Cat] = 1 mM, the half-saturation or equilibrium constant is KD = 15 +/- 1 nM at 293 K (20 degrees C). The optimal transformation frequency is TFopt = 4.1 +/- 0.4 X 10(-5) if a single exponential pulse of initial field strength E0 = 4 kV cm-1 and decay time constant tauE = 45 ms is applied at [Dt] = 2.7 nM and 10(8) cells in 0.1 ml. The dependence of TF on [Cat] yields the equilibrium constants KCazero = 1.8 +/- 0.2 mM (in the absence of DNA) and K'Ca (at 2.7 nM DNA), comparable with and derived from electrophoresis data. In yeast cells, too, the appearance of a DNA molecule in its whole length in the cell interior is clearly an after-field event. At Eo = 4.0 kV cm-1 and T = 293 K, the flow coefficient of DNA through the porous membrane patches is Kto = 7.0 +/- 0.7 x 10(3)S-1 and the electrodiffusion of DNA is approximately 10 times more effective than simple diffusion: D/D0 approximately 10.3. The mean radius of these pores is rp = 0.39 +/- 0.05 nm, and the mean number of pores per cell (of size ø approximately 5.5 microns) is Np = 2.2 +/- 0.2 x 10(4). The maximal membrane area that is involved in the electrodiffusive penetration of adsorbed DNA into the outer surface of the electroporated cell membrane patches is only 0.023% of the total cell surface. The surface penetration is followed either by additional electrodiffusive or by passive (after-field) diffusive translocation of the inserted DNA into the cell interior. For practical purposes of optimal transformation efficiency, 1 mM calcium is necessary for sufficient DNA binding and the relatively long pulse duration of 20-40 ms is required to achieve efficient electrodiffusive transport across the cell wall and into the outer surface of electroporated cell membrane patches.

Adsorption↗
PubMed1996

The initiation of the muscle action potential.

The specific functional properties of the nicotinic acetylcholine receptors (AChR) and the particular oligomeric membrane organization of AChR are suggested to be the basis for the steep electrical depolarisation, required for the initiation of the postsynaptic action potentials causing muscle contraction and discharge of electric organs. The dimer (M(r) approximately 580,000) and the monomer (M(r) approximately 290,000) of the detergent-solubilized, affinity-purified AChR of Torpedo californica electrocytes exhibit different channel conductances and larger oligochannels. Patch clamp data of the dimer, reconstituted in large lipid vesicles, show that the dimer is a double-channel protein causing single-channel events of conductance G(D) = 84 +/- 6 pS at 0.11 M K+ and 0.1 mM Ca2+ at 293 K (20 degrees C). At the same ionic conditions the vesicle-reconstituted monomer, if prevented from aggregation, exhibits a channel conductance, G(M) = 42 +/- 3 pS, which is only half of that of the dimer. The dimer conductivity event thus reflects the synchronous switching of its two constituent monomeric parts. The K(+)-conductance of the reconstituted Torpedo dimer is the same, and shows the same inhibitory Ca(2+)-dependence, as that of the Torpedo AChR expressed in Xenopus laevis oocytes (Imoto et al., Nature, 324, 670-674, 1986). In terms of Ca(2+)-binding, reducing K(+)-transport, the equilibrium constant is KCa = 0.48 mM at 0.11 m K+, 20 degrees C; G0([Ca]-->0) = 98 +/- 6 pS and G infinity ([Ca]-->infinity) = 27 +/- 6 pS. The ratio G0/G infinity and an estimate of the lateral surface area of the channel vestibule yields about 16 negatively charged groups in an average distance of 1.8 nm. These negative charges cause an accumulation of K+ ions in the channel vestibule by a factor of about 4. Our results and the comparison with the oocyte data reveal that it is also the dimer which is the physiological opening-closing unit of the AChR in the oocyte membrane. The larger macrochannel events are multiples of the dimer or of the monomer conductances. The occurrence of such oligochannels from AChR protein oligomers could guarantee the steep electrical depolarisation necessary to generate the action potential by the Na(+)-channel system.

Action Potentials↗
PubMed1996

[Dorsal recumbency in dogs--a circulatory risk during surgical treatment?].

In this study, changes in hemodynamic, blood gas, and metabolic variables recorded during right lateral and dorsal recumbency in beagles anaesthetised with thiopental are presented. Other than reported in human beings, dorsal recumbency in these dogs resulted in an increase (33%) in heart rate, decrease (30%) in systolic, diastolic, and mean systemic arterial pressure, a decrease (17%) in systemic vascular resistance, and a decrease in both right (31%) and left (39%) ventricular work in comparison with lateral recumbency. Furthermore, mixed-venous PO2, oxygen saturation and respiratory quotient were lower in dorsal than in lateral recumbency while O2 consumption and lipolysis were increased in the former. The changes presented may have been caused by beta-adrenergic stimulation in dorsal recumbency. It needs to be studied if capillary perfusion can be maintained adequately during surgery in dorsal recumbency or if this predisposes to cardiovascular shock.

Anesthetics, Intravenous↗
PubMed1994

High efficacy of the German multicenter ALL (GMALL) protocol for treatment of adult acute lymphoblastic leukemia (ALL)--a single-institution study.

Sixty-one consecutive patients with acute lymphoblastic leukemia (ALL) (B-ALL excluded) were treated with the protocol described by Hoelzer et al. [15]. The complete remission (CR) rate was 85% (52/61 patients). Three patients died during induction therapy; six patients were refractory to treatment. The median duration of continuous complete remission (CCR), disease-free survival (DFS), and overall survival was 41.5, 41.4, and 40.8 months, respectively. At 5 years the probability of CCR was 49%, of DFS 43.5%, and of overall survival 41.6%. In the univariate analysis older age (> 35 years, p = 0.01), bcr-abl positivity (p = 0.007), and time to CR (> 4 weeks, p = 0.05) were significantly unfavorable prognostic factors. In the multivariate analysis only age (p = 0.006) and time to CR (p = 0.02) remained significant. Thus, our data confirm the high efficacy of this treatment regimen with regard to CR rate and remission duration.

Adolescent↗
PubMed1994

Astrocytoma with a unique telomere association.

Many primary pediatric brain tumors are characterized by nonrandom cytogenetic abnormalities involving specific structural rearrangements and loss or gain of specific chromosomes. We describe a low-grade cerebellar astrocytoma with telomeric association of chromosomes 18 and 21 in a 7-year old girl. The nonrandom telomeric association of these chromosomes represents a unique cytogenetic finding in this type of pediatric brain tumor.

Astrocytoma↗
PubMed1994

Dip patch clamp currents suggest electrodiffusive transport of the polyelectrolyte DNA through lipid bilayers.

Planar lipid bilayers formed from monolayers of diphytanoyl lecithin (DPhL) were found to interact with plasmid DNA (5.6 kbp; M(r) = 3.7 x 10(6)) leading to an increase in the conductance of the membrane. The association of DNA with a lipid bilayer greatly facilitates the transport of the small ions of the main salt KCl. The appearance of long-lived current levels, for instance, of 27.6 pA at Vm = +60 mV membrane voltage, where the actual contact (adsorption) is electrophoretically enhanced, suggests a locally conductive DNA/lipid interaction zone where parts of the DNA strand may be transiently inserted in the bilayer, leaving other parts of the DNA probably protruding out from the outer surface of the bilayer. At Vm = -60 mV, where DNA can be electrophoretically moved away from the membrane, the membrane current is practically zero. This current asymmetry is initially also observed at higher voltages, for instance at 200 mV. However, if the voltage sign (Vm = +200 mV) is changed after a transient positive current (approximately 15 pA) was observed, there is also now (at Vm = -200 mV) a finite negative current at the negative membrane voltage. Thus, it appears that at Vm = +200 mV the adsorbed parts of the polyelectrolyte DNA are not only transiently inserted in, but actually also electrophoretically pulled through, the porous zones onto the other membrane side leaving the bilayer structure basically intact. These data provide direct electric evidence for the electrophoretic transport of a highly charged and hydrated macromolecule, probably together with the associated gegen-ions, through the thin hydrophobic film of the lipid bilayer.

Diffusion↗
PubMed1994

Control by pulse parameters of electric field-mediated gene transfer in mammalian cells.

Electric field-mediated gene transfer in mammalian cells (electrotransformation) depends on the pulsing conditions (field intensity, pulse duration, number of pulses). The effect of these parameters was systematically investigated using the transient expression of the chloramphenicol acetyltransferase and the beta-galactosidase activities in Chinese hamster ovary cells. Pulsing conditions inducing reversible permeabilization of the cell plasma membrane are not sufficient to induce gene transfer. The plasmid must be present during the electric pulse if it is to be transferred across the membrane into the cytoplasm. Only the localized part of the cell membrane brought to the permeabilized state by the external field is competent. Pulse duration plays a key role in the magnitude of the transfer. The field induces a complex reaction between the membrane and the plasmid that is accumulated at the cell interface by electrophoretic forces. This leads to an insertion of the plasmid, which can then cross the membrane.

Animals↗
PubMed1994

The occurrence of IgA pemphigus foliaceus without neutrophilic infiltration.

A 70-year-old woman with pemphigus foliaceus is reported. Direct immunofluorescence performed on perilesional skin revealed deposits of IgA, C3 and lambda chains in the intercellular substance of the upper stratum spinosum. Indirect immunofluorescence demonstrated serum antibodies of the IgA class against the intercellular region of the upper epidermis at an initial titre of 1:2560. Histological studies, performed together with immunofluorescence, revealed an absence of a distinct neutrophil infiltrate either in the epidermis or dermis, contrary to the findings in cases with intra-epidermal IgA deposits reported previously.

Aged↗
PubMed1993

Cytogenetic analysis of 109 pediatric central nervous system tumors.

Reports of cytogenetic abnormalities in pediatric central nervous system (CNS) tumors are important for collection and comparison of large numbers of karyotypes of primary CNS neoplasms to produce statistically significant correlations. We report cytogenetic results of 119 samples of pediatric CNS tumors from 109 patients. Tumors included 33 low-grade astrocytomas, 18 high-grade astrocytomas, 14 gangliogliomas, 13 ependymomas, 17 primitive neuroectodermal tumors (PNET), three choroid plexus papillomas and carcinomas, and a miscellaneous group of 20 rare primary CNS tumors and metastases. In each group, cytogenetic results were correlated with histologic subtype and survival. The study indicated specific chromosome abnormalities in different groups of tumors. Low-grade astrocytomas showed mostly numeric abnormalities with gains of chromosome 7, high-grade astrocytomas showed differences from karyotypic changes observed in adults in lacking double minutes (dmin) and monosomy 10. The ependymoma group showed the largest proportion of abnormal karyotypes with frequent involvement of chromosome 6 and 16. Chromosome 6 was the single most common abnormal chromosome in this study, closely followed by chromosomes 1 and 11. Pediatric CNS neoplasms differ from adult tumors cytogenetically as well as histologically and biologically.

Adolescent↗
PubMed1993

Does inhibition spread in a manner analogous to spreading activation?

Two experiments explored limited capacity inhibitory selective attention processes in working memory. Experiment 1 used a modified Sternberg-type 'short-term memory scanning' task, where both irrelevant and relevant memory-set words were included to see if an inhibitory fan effect operated on lexical associates of the should-be-ignored (irrelevant) words. Experiment 2 used a 'negative priming' task, where a target letter to be named was flanked by one, two, or three distractor letters to see if an inhibitory fan effect operated on the should-be-ignored letters. Results from both experiments supported the existence of a limited capacity spreading inhibition counterpart to spreading activation. The findings were discussed in terms of a model recently proposed by Neumann and DeSchepper (1991; 1992) in which two selective attention subprocesses (one excitatory and one inhibitory) in the brain each maximise opposed functions within their respective resource limitations in working memory.

Analysis of Variance↗
PubMed1992

Functional reconstitution of the nicotinic acetylcholine receptor by CHAPS dialysis depends on the concentrations of salt, lipid, and protein.

The detergent CHAPS was found to be the preferable surfactant for the efficient purification and reconstitution of the Torpedo californica nicotinic acetylcholine receptor (AChR). The main result is that the incorporation of the AChR proteins into lipid vesicles by CHAPS dialysis was strongly dependent on the salt and protein concentrations. As monitored by sucrose gradients, by electron microscopy, and by agonist-induced lithium ion flux, the best reconstitution yields were obtained in 0.5 M NaCl at a protein concentration of 0.5 g/L and in 0.84 M NaCl at 0.15 g/L protein. Electron micrographs of receptor molecules, which were incorporated into vesicles, showed single, nonaggregated dimer (M(r) = 580,000) and monomer (M(r) = 290,000) species. CHAPS dialysis at NaCl concentrations less than 0.5 M largely reduced the receptor incorporation concomitant with protein aggregation. Electron micrographs of these preparations revealed large protein sheets or ribbons not incorporated into vesicles. The analysis of static and dynamic light scattering demonstrated that the detergent-solubilized AChR molecules aggregate at low lipid contents (less than or equal to 500 phospholipids/AChR dimer), independent of the salt concentration. AChR proteins eluted from an affinity column with a solution containing 8 mM CHAPS (but no added lipid) still contained 130 +/- 34 tightly bound phospholipids per dimer. The aggregates (about 10 dimers on the average) could be dissociated by readdition of lipid and, interestingly, also by increasing the CHAPS concentration up to 15 mM. This value is much higher than the CMC of CHAPS = 4.0 +/- 0.4 mM, which was determined by surface tension measurements. The data clearly suggest protein-micelle interactions in addition to the association of monomeric detergents with proteins. Furthermore, the concentration of the (free) monomeric CHAPS at the vesicle-micelle transformation in 0.5 M NaCl ([Dw]c = 3.65 mM) was higher than in 50 mM NaCl ([Dw]c = 2.8 mM). However, it is suggested that the main effect of high salt concentrations during the reconstitution process is an increase of the fusion (rate) of the ternary protein/lipid/CHAPS complexes with mixed micelles or with vesicular structures, similar to the salt-dependent fusion of vesicles.

Animals↗
PubMed1991

Structural heterogeneity of membrane receptors and GTP-binding proteins and its functional consequences for signal transduction.

Recent information obtained, mainly by recombinant cDNA technology, on structural heterogeneity of hormone and transmitter receptors, of GTP-binding proteins (G-proteins) and, especially, of G-protein-linked receptors is reviewed and the implications of structural heterogeneity for diversity of hormone and transmitter actions is discussed. For the future, three-dimensional structural analysis of membrane proteins participating in signal transmission and transduction pathways is needed in order to understand the molecular basis of allosteric regulatory mechanisms governing the interactions between these proteins including hysteretic properties and cell-cybernetic aspects.

Acetylcholine↗
PubMed1991

Costs and benefits of target activation and distractor inhibition in selective attention.

Three experiments examined the relative contributions of positive and negative priming in a selective attention task. A typical trial consisted of a briefly presented letter display containing a red target letter and a distractor letter of another color. This prime display was followed by another similar letter display (the probe). When the red target letters were identical in both displays, facilitation from identity repetition priming was obtained. When the unattended letter from the prime display became the probe target letter, response times were delayed, that is, a negative priming effect was found. Other combinations of target and distractor letters were manipulated to examine the relative influences of positive and negative priming. Results support the hypothesis that selective attention involves a selective inhibition mechanism and suggest that this inhibitory mechanism can be as influential as its excitatory counterpart.

Attention↗