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Biomedical subjects

E Neumann

Publications and source records attributed to E Neumann.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

Behavior problems and adaptive functioning in children with mild and severe closed head injury.

Assessed behavior problems and adaptive functioning in children with mild or severe closed head injuries, on average more than 2 years postaccident. To ensure that any problems detected in the present study were not merely preexisting problems, potential subjects were excluded if there was a history of preexisting CNS damage, significant developmental delay, or behavior problems. Children with severe head injuries had an excessive rate of behavior problems and impaired adaptive functioning. Children with mild head injuries also had an excessive rate of behavior problems (comparable to that of children with severe head injuries) but did not have impaired adaptive functioning. Results are discussed in terms of six alternative ways brain injury and behavior problems can be related functionally.

Activities of Daily Living

Recurrent corneal oedema following late migration of intraocular glass.

This is a report of very late complications following intraocular penetration of numerous fragments of glass as a result of a test tube explosion. Fifteen years after the initial injury glass splinters began to migrate from the vitreous into the anterior chamber, causing acute episodes of corneal oedema. Four such episodes occurred over the past nine years, the corneal oedema each time disappearing within a few days following surgical extraction of the glass splinters. The literature on intraocular glass and its movement within the eye is reviewed.

Adolescent

The nematocyst extract of Hydra attenuata causes single channel events in lipid bilayers.

The nematocyst extract of Hydra attenuata causes single conductance events in reconstituted planar lipid membranes as well as in inside-out patches derived from liposomes. The smallest single channel conductance level of the toxins is 110 pS. The conductance levels increase stepwise with time up to 2000 pS. These large conductance jumps indicate channel cooperativity. If the membrane-voltage is changed from positive to negative values, the single channel events become undefined and noisy, indicating major reorganizations of the proteins which form the channels. The molecular properties of the ionophoric component(s) of the nematocyst extract may help explain the observed macroscopic effects, such as hemolysis of human erythrocytes, after addition of the nematocyst extract.

Animals

[Semi-invasive measurement of pulmonary pressure as a method of evaluating cardiac function in hypertension and ischemic heart disease. Experience at Charité Hospital for more than 20 years].

Since 1969, microcatheterization (floating catheterization) of the pulmonary artery has systematically been used at the Hospital Charité in Berlin for measuring (indirectly) the left ventricular filling pressure. That seemed especially be justified in patients in whom conventional catheterization was not needed. Noninvasive techniques had not been available. Since then, our interest was focused on the hypertensive heart, earlier under the aspect of early discovering and influencing heart insufficiency, later concerning a developing myocardial ischemia, in relationship to left ventricular hypertrophy. At the Charité more than 1,000 microcatheterizations in more than 400 hypertensive cases have been performed, mostly in combination with nuclear-cardiological measurements. The rate of complications was found minimal. Thus, cardiac function could be characterized hemodynamically, at rest and even under ergometric load. Special programmes served the acute application of drugs for diagnostic or therapeutic reasons. In the meantime a longterm study could also be finished by using hemodynamic measurements, starting with hygienic means and followed by a antihypertensive basis therapy, in newly detected hypertensives. That included repeated catheterizations of the pulmonary artery.

Catheterization, Peripheral

Miscibility of octyl glucoside-phosphatidylcholine micellar solutions. Partition of the nicotinic acetylcholine receptor into the surfactant-rich phase.

Phospholipid phosphatidylcholines (PC) and the nonionic detergent octyl glucoside (OG) were found to form a miscibility gap in aqueous solution at a molar ratio [OC]T/[PC]T=2.6-2.4. This ratio is just below the critical ratio for the formation of vesicles. At [PC] greater than 1.3 g/l the transition from micelles to vesicles is not direct but via a surfactant-rich phase (SRP). The various stability regions are summarized in a phase diagram. Though the partition coefficient gamma=[Db]/[Dw] increases markedly with temperature, the critical ratio for the phase separation R(c) is biased to higher detergent concentrations. This behaviour can be explained by increased motion of the hydrocarbon moiety at higher temperatures. The different phases are investigated by light microscopy, nuclear magnetic resonance and thin-layer chromatography. The miscibility gap of PC/OG is compared to the lamellar phase of Triton X-114; the miscibility gap has implications for membrane protein reconstitution and can be used for membrane protein purification. The Torpedo californica nicotinic acetylcholine receptor (n-AcChR) was found to partition into the SRP.

Animals

Miniature fiber-optic pattern-reversal stimulator for determination of the visual evoked potential threshold; comparison with Snellen acuity.

In this report we recommend the estimation of visual acuity by detection of the visual evoked potential (VEP) threshold, defined by the smallest visual angle of a constant check size that evokes potentials. This approach was implemented using a fiber-optic pattern-reversal stimulator placed at measured, increasing distances from the examined eye. Snellen visual acuity as determined in 113 subjects was correlated with the VEP detection threshold. A highly significant correlation was found between visual acuity and the threshold visual angle of check size in subjects whose vision was impaired due to opacity in ocular media. For any given visual acuity a somewhat wide range of threshold check sizes, typically 5-10 min of arc was observed. Technical difficulties that need to be overcome to improve these results are discussed.

Adult

Effects of gentamycin and chloramphenicol on the transparency of cultured rat lenses.

The effect of the antibiotics gentamycin and chloramphenicol on lens opacity was studied in an organ culture system. Opacity was monitored by split laser beam. Both antibiotics enhanced the onset of opacity in the cultured lenses under a variety of conditions. For instance, treatment with 5.0 mg/ml gentamycin for 60 min caused initial opacity after 4.8 +/- 1.3 days as opposed to untreated lenses at which initial opacity appeared after 18.1 +/- 2.99 days. Exposure to 20 mg/ml chloramphenicol for 60 min caused initial opacity after 4.6 +/- 1.51 days. Continuous exposure to penicillin and streptomycin (0.1 mg/ml each) did not enhance the onset of opacity.

Age Factors

[Differential therapy of myocardial ischemia in females].

Peripheral perfusion abnormalities are considered a possible reason for myocardial ischemia in the absence of visible coronary artery stenoses. In 85 women (age: 41-58 years, mean age: 46 +/- 8) with pathological exercise ECG (precordial mapping: 50 leads), hemodynamic studies were performed without medication, after sublingual nitroglycerin (NTG, 0.8 mg), sublingual Nifedipin (N, 30 mg), and intravenous Dipyridamol (D, 0.5 mg/kg). Eighteen women showed normal coronary arteries and a normal myocardial perfusion (group I), 21 an impaired perfusion due to coronary stenoses (Group II), and 46 women a reduced perfusion without visible changes (Group III). Reference methods were measurement of pulmonary artery pressure, 201-TI-scintigraphy, and coronary angiography. In group II, enddiastolic and endsystolic left ventricular volume (EDV, ESV) as well as enddiastolic pulmonary artery pressure (pAd) were increased, the ejection fraction (EF) was reduced, and cardiac output (CO) was normal. In group III, ESV, EDV, EF, and CO were significantly reduced, while pAd increased. In group II, N led to a normalization of ESV, EDV, EF, and pAd. In group III, NTG led to a reduction of pAd and EDV, and concomitantly to a further reduction of the already low CO. In both groups the reduction of ST-segment depressions after NTG was significant. N led to a moderate reduction of pAd and ST-segment depression, but to an increase of CO in both groups. D exhibited a comparable effect in group III. In group II an increase of ST-segment changes and of pAd with unchanged CO was observed. With regard to longterm treatment of women in group III, N and D seemed to be more efficacious than nitrates due to a beneficial effect on cardiac output.

Administration, Sublingual