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Showing papers by "Humboldt University of Berlin published in 1995"


Journal ArticleDOI
08 Jun 1995-Nature
TL;DR: A very strong direct relationship is reported between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation, indicating that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
Abstract: Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.

1,692 citations


Journal ArticleDOI
TL;DR: The fact that telomere length correlates with the final inhibition of proliferation under conditions of varied oxidative stress, while the population doubling level does not, suggests that telitere shortening provides the signal for cell cycle exit in senescence.

863 citations


Journal ArticleDOI
TL;DR: The double cubic lattice method (DCLM) is an accurate and rapid approach for computing numerically molecular surface areas and the volume and compactness of molecular assemblies and for generating dot surfaces, and is the method of choice, especially for large molecular complexes and high point densities.
Abstract: The double cubic lattice method (DCLM) is an accurate and rapid approach for computing numerically molecular surface areas (such as the solvent accessible or van der Waals surface) and the volume and compactness of molecular assemblies and for generating dot surfaces. The algorithm has no special memory requirements and can be easily implemented. The computation speed is extremely high, making interactive calculation of surfaces, volumes, and dot surfaces for systems of 1000 and more atoms possible on single-processor workstations. The algorithm can be easily parallelized. The DCLM is an algorithmic variant of the approach proposed by Shrake and Rupley (J. Mol. Biol., 79, 351–371, 1973). However, the application of two cubic lattices—one for grouping neighboring atomic centers and the other for grouping neighboring surface dots of an atom—results in a drastic reduction of central processing unit (CPU) time consumption by avoiding redundant distance checks. This is most noticeable for compact conformations. For instance, the calculation of the solvent accessible surface area of the crystal conformation of bovine pancreatic trypsin inhibitor (entry 4PTI of the Brookhaven Protein Data Bank, 362-point sphere for all 454 nonhydrogen atoms) takes less than 1 second (on a single R3000 processor of an SGI 4D/480, about 5 MFLOP). The DCLM does not depend on the spherical point distribution applied. The quality of unit sphere tesselations is discussed. We propose new ways of subdivision based on the icosahedron and dodecahedron, which achieve constantly low ratios of longest to shortest arcs over the whole frequency range. The DCLM is the method of choice, especially for large molecular complexes and high point densities. Its speed has been compared to the fastest techniques known to the authors, and it was found to be superior, especially when also taking into account the small memory requirement and the flexibility of the algorithm. The program text may be obtained on request. © 1995 by John Wiley & Sons, Inc.

805 citations


Journal ArticleDOI
TL;DR: The literature on ameloblastoma of the jaw was reviewed, including publications from 1960 to 1993, and compared to the latest larger review, published by Small and Waldron in 1955, for clarification of therapeutic approaches.
Abstract: Available literature on ameloblastoma of the jaw was reviewed, including publications from 1960 to 1993, and compared to the latest larger review, published by Small and Waldron in 1955. The average age of patients with ameloblastoma is 36 years. In developing countries ameloblastomas occur in younger patients. Men and women are equally affected. Women are 4 years younger than men when ameloblastomas first occur, and the tumours appear to be larger in females. Dominant clinical symptoms such as painless swelling and slow growth are non-characteristic. The ratio of ameloblastoma of the mandible to maxilla is 5 to 1. Ameloblastomas of the mandible occur 12 years earlier than those of the maxilla. Ameloblastomas occur most frequently in the molar region of the mandible. In Blacks, ameloblastomas occur more frequently in the anterior region of the jaws. Radiologically, 50% of ameloblastomas appear as multilocular radiolucent lesions with sharp delineation. Histologically, one-third are plexiform, one-third follicular; other variants such as acanthomatous ameloblastoma occur in older patients. Two percent of ameloblastomas are peripheral tumours. Unicystic ameloblastomas occurring in younger patients have been found in 6%. Detailed data on 345 patients with ameloblastoma were evaluated for clarification of therapeutic approaches. Chemotherapy and radiation seem to be contraindicated. Ameloblastomas of the maxilla should be treated as radically as possible, ameloblastomas of the mandible should also be treated radically. However, ameloblastomas which radiologically appear as unilocular lesions may be treated conservatively (enucleation, curettage), whenever all areas of the cystic lumen are controllable intraoperatively. Unicystic ameloblastomas occurring in patients 15 years younger than those with multisystic ameloblastoma may be treated conservatively except in cases with invasion of epithelium into the cyst wall. Different recurrence rates have been found for histological variants of the ameloblastoma. Follicular ameloblastomas appear to recur more often than the plexiform type. Unicystic ameloblastomas reveal lower recurrence rates than “non-unicystic” ameloblastomas. The peripheral type of ameloblastoma may be excised, since conservative therapy results in low recurrence rates. Postoperative follow-up is most important in the therapy of ameloblastoma, because more than 50% of all recurrences occur within 5 years postoperatively.

647 citations


01 Jan 1995
TL;DR: The function, the mediators, and the hemodynamic mechanisms of coupling are considered and the potential interference by diet, and neurological disease is pointed out.
Abstract: The coupling of brain cell function to the vascular system is the basis for a number of functional neuroimaging methods relevant for human studies. These include methods as diverse as functional magnetic resonance imaging, positron emission tomography, single photon emission tomography, optimal intrinsic signals, as well as near infrared spectroscopy, a method that may have imaging capabilities in the near future. These methods map a specific localized brain activation through a vascular response, such as an increase in cerebral blood flow or a change in blood oxygenation. To understand these direct maps to obtain high resolution maps of localized functional brain activity, a precise knowledge of the specific underlying physiological mechanisms and methodological properties and restrictions is essential. In this article, these fundamental physiological and methodological aspects will be discussed. After reviewing how the techniques cited obtain maps of functional activity, we will discuss our current knowledge of the physiology of coupling with particular reference to the functional imaging techniques. Specifically, we will consider the function, the mediators, and the hemodynamic mechanisms of coupling and point out potential interference by diet, and neurological disease.

598 citations


Journal ArticleDOI
TL;DR: Gd-EOB-DTPA is safe and efficient for MR imaging of the liver, with no important side effects or changes in laboratory parameters.
Abstract: PURPOSE: To determine the safety, pharmacokinetics, and magnetic resonance (MR) imaging results of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) as a contrast agent for use in hepatobiliary MR imaging. MATERIALS AND METHODS: Gd-EOB-DTPA was tested at doses of 10, 25, 50, and 100 mumol per kilogram of body weight. Results of laboratory tests, clinical measurements, and pharmacokinetic data were obtained in 44 healthy volunteers in a double-blind, randomized, placebo-controlled design. MR images were obtained in another 16 healthy volunteers before and up to 6 hours after fast intravenous administration of Gd-EOB-DTPA. RESULTS: Gd-EOB-DTPA was well tolerated, with no important side effects or changes in laboratory parameters. Homogeneous enhancement of liver parenchyma was observed immediately after injection of the contrast agent. Peak liver signal intensity was noted 20 minutes after injection, followed by plateaulike enhancement over about 2 hours. The common bile duct was hype...

546 citations


Journal ArticleDOI
TL;DR: Importin 90 potentiates the effects of importin 60 on nuclear protein import, indicating that the importin complex is the physiological unit responsible for import.

495 citations


Journal ArticleDOI
TL;DR: In vitro induced LPS tolerance looks like the ex vivo LPS hyporesponsiveness of monocytes from septic patients with fatal outcome: downregulation of LPS-induced TNF-alpha and IL-10 production but not of IL-1RA secretion.
Abstract: Tolerance of monocytes/macrophages to endotoxin (lipopolysaccharide [LPS]) can be induced both in vivo and in vitro by LPS itself. Exposure to LPS, even at a very low dose, induces a downregulation of cytokine response to a second high dose LPS challenge. To learn more about the unknown mechanisms of this phenomenon, we studied the role of antiinflammatory cytokines in this process. Preculture of human peripheral blood monocytes for 24 hours with low concentrations of LPS induced hyporesponsiveness to high-dose LPS rechallenge with respect to tumor necrosis factor (TNF) alpha and interleukin (IL) 10 but not IL-1RA production. These results suggest that LPS tolerance reflects a functional switch of monocytes rather than a general LPS hyporesponsiveness. IL-10 and transforming growth factor (TGF) beta 1 showed additive effects in replacing LPS for induction of LPS hyporesponsiveness in vitro. Additionally, neutralizing anti-IL-10 and anti-TGF-beta monoclonal antibodies prevented induction of LPS tolerance. In vitro induced LPS tolerance looks like the ex vivo LPS hyporesponsiveness of monocytes from septic patients with fatal outcome: downregulation of LPS-induced TNF-alpha and IL-10 production but not of IL-1RA secretion. LPS hyporesponsiveness in septic patients was preceded by expression of IL-10 at both the mRNA and protein level. In summary, our data suggests that IL-10 and TGF-beta mediate the phenomenon of LPS tolerance in vitro and perhaps in vivo (septic patients), too.

456 citations


Journal ArticleDOI
TL;DR: It is demonstrated that in mild CHF patients the baroreceptor inhibitor influence on heart rate and MSNA is already markedly impaired, which may be responsible for the early sympathetic activation that occurs in the course of CHF.
Abstract: Background Baroreflex control of sympathetic activity is impaired in severe congestive heart failure (CHF), probably causing the marked sympathetic activation typical of this condition. Little information exists, however, as to whether baroreflex impairment and related sympathetic activation also occur in mild CHF. Methods and Results We studied 19 patients (age, 57.5±2.2 years, mean±SEM) with CHF in New York Heart Association (NYHA) class III or IV and with a marked reduction in left ventricular ejection fraction (LVEF, 30.1±1.5% from echocardiography) and 17 age-matched patients with CHF in NYHA class I or II and with an only slightly reduced LVEF (44.9±3.3%) that never was <40%. Seventeen age-matched healthy subjects served as control subjects. Primary measurements included beat-to-beat arterial blood pressure (with the Finapres technique), heart rate (from ECG), and postganglionic muscle sympathetic nerve activity (MSNA, from microneurography at the peroneal nerve). Measurements were performed at base...

417 citations


Journal ArticleDOI
TL;DR: Ebselen inhibits at low concentrations a number of enzymes involved in inflammation such as lipoxygenases, NO synthases, NADPH, oxidase, protein kinase C and H+/K(+)-ATPase, which may contribute to the antiinflammatory potential of ebselen.
Abstract: 1. 1. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a non-toxic seleno-organic drug with antiinflammatory, antiatherosclerotic and cytoprotective properties. 2. 2. Ebselen and some of its metabolites are effective reductants of hydroperoxides including those arising in biomembranes and lipoproteins. 3. 3. By reactions with hydroperoxides and thiols several interconversion cycles are formed which include ebselen metabolites with varying oxidation number of the selenium. 4. 4. In the presence of thiols ebselen mimics the catalytic activities of phospholipid hydroperoxide glutathione peroxidase. 5. 5. Ebselen inhibits at low concentrations a number of enzymes involved in inflammation such as lipoxygenases, NO synthases, NADPH, oxidase, protein kinase C and H+/K+-ATPase. The inhibitions are manifested on the cellular level and may contribute to the antiinflammatory potential of ebselen.

404 citations


Journal ArticleDOI
TL;DR: In this article, a behavioral theory of ultimatum bargaining based on a dynamic reasoning process is presented, where the stages specify either an intention generator and its corresponding intention filter or, as the final step, an ex post-evaluation of the actual behaviour.
Abstract: This review of ultimatum bargaining experiments concentrates on studies in which the author was actively involved. The basic game situation is either the ultimatum game or multiperiod-ultimatum bargaining. We outline a behavioral theory of ultimatum bargaining based on a dynamic reasoning process. The stages of this process specify either an intention generator and its corresponding intention filter or, as the final step, an ex post-evaluation of the actual behaviour. In our concluding remarks the merits of behavioral theories versus rational choice-explanations are elaborated.

Journal ArticleDOI
TL;DR: A free-air CO2 enrichment (FACE) experiment was conducted at Maricopa, Arizona, on wheat from December 1992 through May 1993 as mentioned in this paper, where the FACE apparatus maintained the CO2 concentration, [CO2], at 550 μmol mol−1 across four replicate 25m-diameter circular plots under natural conditions in an open field.
Abstract: A free-air CO2 enrichment (FACE) experiment was conducted at Maricopa, Arizona, on wheat from December 1992 through May 1993. The FACE apparatus maintained the CO2 concentration, [CO2], at 550 μmol mol−1 across four replicate 25-m-diameter circular plots under natural conditions in an open field. Four matching Control plots at ambient [CO2] (about 370 μmol mol−1) were also installed in the field. In addition to the two levels of [CO2], there were ample (Wet) and limiting (Dry) levels of water supplied through a subsurface drip irrigation system in a strip, split-plot design. Measurements were made of net radiation, Rn; soil heat flux, Go; soil temperature; foliage or surface temperature; air dry and wet bulb temperatures; and wind speed. Sensible heat flux, H, was calculated from the wind and temperature measurements. Latent heat flux, λET, and evapotranspiration, ET, were determined as the residual in the energy balance. The FACE treatment reduced daily total Rn by an average 4%. Daily FACE sensible heat flux, H, was higher in the FACE plots. Daily latent heat flux, λET, and evapotranspiration, ET, were consistently lower in the FACE plots than in the Control plots for most of the growing season, about 8% on the average. Net canopy photosynthesis was stimulated by an average 19 and 44% in the Wet and Dry plots, respectively, by elevated [CO2] for most of the growing season. No significant acclimation or down regulation was observed. There was little above-ground growth response to elevated [CO2] early in the season when temperatures were cool. Then, as temperatures warmed into spring, the FACE plants grew about 20% more than the Control plants at ambient [CO2], as shown by above-ground biomass accumulation. Root biomass accumulation was also stimulated about 20%. In May the FACE plants matured and senesced about a week earlier than the Controls in the Wet plots. The FACE plants averaged 0.6 °C warmer than the Controls from February through April in the well-watered plots, and we speculate that this temperature rise contributed to the earlier maturity. Because of the acceleration of senescence, there was a shortening of the duration of grain filling, and consequently, there was a narrowing of the final biomass and yield differences. The 20% mid-season growth advantage of FACE shrunk to about an 8% yield advantage in the Wet plots, while the yield differences between FACE and Control remained at about 20% in the Dry plots.

Journal Article
TL;DR: The study demonstrated differential phenotypic activity of various NAT2 genes and gives a solid basis for clinical and molecular-epidemiological investigations.
Abstract: The polymorphic arylamine N-acetyltransferase (NAT2; EC 2.3.1.5) is supposed to be a susceptibility factor for several drug side effects and certain malignancies. A group of 844 unrelated German subjects was genotyped for their acetylation type, and 563 of them were also phenotyped. Seven mutations of the NAT2 gene were evaluated by allele-specific PCR (mutation 341C to T) and PCR-RFLP for mutations at nt positions 191, 282, 481, 590, 803, and 857. From the mutation pattern eight different alleles, including the wild type coding for rapid acetylation and seven alleles coding for slow phenotype, were determined. Four hundred ninety-seven subjects had a genotype of slow acetylation (58.9%; 95% confidence limits 55.5%-62.2%). Phenotypic acetylation capacity was expressed as the ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after caffeine intake. Some 6.7% of the cases deviated in genotype and phenotype, but sequencing DNA of these probands revealed no new mutations. Furthermore, linkage pattern of the mutations was always confirmed, as tested in 533 subjects. In vivo acetylation capacity of homozygous wild-type subjects (NAT2*4/*4) was significantly higher than in heterozygous genotypes (P = .001). All mutant alleles showed low in vivo acetylation capacities, including the previously not-yet-defined alleles *5A, *5C, and *13. Moreover, distinct slow genotypes differed significantly among each other, as reflected in lower acetylation capacity of *6A, *7B, and *13 alleles than the group of *5 alleles. The study demonstrated differential phenotypic activity of various NAT2 genes and gives a solid basis for clinical and molecular-epidemiological investigations.

Journal ArticleDOI
TL;DR: A two-mass model of vocal-fold vibrations is analyzed with methods from nonlinear dynamics and it is shown that a sufficiently large tension imbalance of the left and right vocal fold induces bifurcations to subharmonic regimes, toroidal oscillations, and chaos.
Abstract: A two-mass model of vocal-fold vibrations is analyzed with methods from nonlinear dynamics. Bifurcations are located in parameter planes of physiological interest (subglottal pressure, stiffness of the folds). It is shown that a sufficiently large tension imbalance of the left and right vocal fold induces bifurcations to subharmonic regimes, toroidal oscillations, and chaos. The corresponding attractors are characterized by phase portraits, spectra, and next-maximum maps. The relevance of these simulations for voice disorders such as laryngeal paralysis is discussed.

Journal ArticleDOI
TL;DR: It is concluded that TNF-alpha is involved in the up-regulation of its antagonist IL-10, and shows remarkable homology to the mouse IL- 10 promoter in regions that have been associated with transcriptional regulation, including a cAMP responsive element which could explain the cAMP-mediated effects.
Abstract: It is well established that endotoxin [lipopolysacharide (LPS)] induces pro-inflammatory cytokine production in monocytes, which is followed by secretion of the anti-inflammatory cytokine, IL-10. IL-10 down-regulates inflammatory response [tumor necrosis factor (TNF)-alpha, IL-1, IL-6, IL-8] as well as IL-10 synthesis itself. We wondered whether pro-inflammatory cytokines such as TNF-alpha may be involved in the regulation of human IL-10 synthesis. TNF-alpha induced de novo IL-10 mRNA expression in a dose-dependent manner but no IL-10 protein in human peripheral blood mononuclear cells. Furthermore, LPS-induced IL-10 gene and protein expression was significantly inhibited by neutralizing anti-TNF-alpha mAb. On the basis of these results, we conclude that TNF-alpha is involved in the up-regulation of its antagonist IL-10. Paradoxically, drugs that effectively inhibit expression of TNF-alpha via the elevation of intracellular cAMP level (iloprost, pentoxifylline, prostaglandin E2 and N6,2-O-dibutyryl cAMP) augmented the endotoxin-induced IL-10 synthesis at both protein and mRNA levels. In order to provide a basis for the analysis of the transcriptional regulation of the human IL-10 gene, we isolated a fragment of the human IL-10 gene containing 1308 bp of the 5' non-coding sequence. It shows remarkable homology to the mouse IL-10 promoter in regions that have been associated with transcriptional regulation, including a cAMP responsive element which could explain the cAMP-mediated effects. The lack of a NF-kappa B-like binding site in the human sequence suggests a NF-kappa B-independent mechanism of TNF-alpha-induced IL-10 gene activation.(ABSTRACT TRUNCATED AT 250 WORDS)


Journal ArticleDOI
TL;DR: In this paper, the evolutionary approach is applied to a game model whose sequential decision process allows for reciprocal behavior and it is shown that mutants established with incentives to reciprocate are more effective, measured in terms of (reproductive) success.
Abstract: Reciprocal behavior means that recipients of harm respond in kind, that is by harming the other. We try to explain why such a behavior may be rational, although the damage cannot be prevented anymore. Our main approach is the one of evolutionary stability, i.e. we will show that mutants established with incentives to reciprocate are more effective, measured in terms of (reproductive) success. The evolutionary approach is applied to a game model whose sequential decision process allows for reciprocal behavior. We allow for complete and incomplete information about reciprocal incentives. Other ways to generalize our analysis are studied only for the case of complete information.

Journal ArticleDOI
TL;DR: In this paper, the low energy effective Lagrangian of N = 2 heterotic string vacua at the classical and quantum level is studied. And the couplings of the vector multiplets are uniquely determined at the tree level, while the loop corrections are severely constrained by exact discrete symmetries of the string vacuum.

Book ChapterDOI
01 Jan 1995
TL;DR: “Projection Pursuit” (PP) stands for a class of exploratory projection techniques that contains methods designed for analyzing high dimensional data using low-dimensional projections.
Abstract: “Projection Pursuit” (PP) stands for a class of exploratory projection techniques. This class contains methods designed for analyzing high dimensional data using low-dimensional projections. The main idea is to describe “interesting” projections by maximizing an objective function or projection pursuit index.

Journal ArticleDOI
TL;DR: It is suggested that the binding of the 11 S regulator to any of the proteasome preparations markedly changed both the quality and quantity of peptides produced.

Journal ArticleDOI
TL;DR: A tomographical scheme is proposed to infer the quantum states of finite-dimensional systems from experiments and a new discrete Wigner formalism is developed.
Abstract: A tomographical scheme is proposed to infer the quantum states of finite--dimensional systems from experiments. For this a new discrete Wigner formalism is developed.

Journal ArticleDOI
TL;DR: There exists, however, no obvious correlation between the observed changes in hydrolytic activities against short fluorogenic peptides and the changes in dual cleavage site usage within the 25‐mer polypeptide substrate.
Abstract: The 20S proteasome is the enzyme complex responsible for the processing of antigens bound by major histocompatibility complex class I molecules. The role of the interferon-gamma (IFN-gamma)-inducible proteasome subunits LMP2 and LMP7 in this process is, however, still controversial. We have studied the effects of IFN-gamma-independent LMP incorporation on the quality of peptides processed from the murine cytomegalovirus IE pp89 25-mer polypeptide substrate through dual cleavages by 20S proteasomes. The incorporation of a single LMP subunit or both LMP2 and LMP7 induces changes in 20S proteasome subunit stoichiometry, alters its cleavage site preference and in consequence, the quality of the generated peptides. When the several hydrolytic activities are tested with short fluorogenic peptide substrates, the Vmax, S0.5 (Km), or both values of 20S proteasomes are altered, depending on the combination of LMP. There exists, however, no obvious correlation between the observed changes in hydrolytic activities against short fluorogenic peptides and the changes in dual cleavage site usage within the 25-mer polypeptide substrate. As judged from the calculated Hill coefficients, the presence of both LMP subunits induces a drastic increase in positive cooperativity between the proteasome subunits.

Journal ArticleDOI
TL;DR: Contrast-enhanced MR imaging allows detection of sacroiliitis in early stages of back pain, and significantly different degrees of enhancement related to the patients' degree of pain were clearly detected.
Abstract: PURPOSE: To investigate the diagnostic value of gadolinium-enhanced magnetic resonance (MR) imaging in the detection of early sacroiliitis. MATERIALS AND METHODS: Of 125 patients with back pain, 72 had inflammatory back pain and had a diagnosis of spondylarthropathy; the other 53 patients had other mostly mechanical causes of back pain and served as the control group. The 72 patients with spondyloarthropathy were further subdivided into two groups according to established radiographic criteria for ankylosing spondylitis. While group 2 patients (n = 36) with a diagnosis of ankylosing spondylitis had definite radiographic changes in the sacroiliac joints, group 1 patients (n = 36) with undifferentiated spondylarthropathy had no such findings. RESULTS: While no contrast enhancement was found in normal sacroiliac joints, significantly different degrees of enhancement (P < .05) related to the patients' degree of pain were clearly detected in both groups of patients with spondyloarthropathy. Contrary to the mos...

Journal ArticleDOI
TL;DR: It is believed that postoperative radiation therapy alone cannot be advocated as a adjuvant therapy following curative resection of squamous cell carcinoma of the esophagus.
Abstract: Postoperative radiation therapy following curative resection of squamous cell carcinoma of the esophagus was investigated in a prospective randomized study. A group of 33 patients received postoperative radiation therapy and were compared to a control group of 35 patients treated by surgery alone. No statistically significant differences were noted between the two treatment groups concerning overall and disease-free survival rates. Postoperative irradiation significantly increased the incidence of fibrotic strictures of the esophagogastric or esophagocolonic anastomoses and caused a delayed recovery of patients quality of life. Based on these results, we believe that postoperative radiation therapy alone cannot be advocated as a adjuvant therapy following curative resection of squamous cell carcinoma of the esophagus.

Journal ArticleDOI
TL;DR: In this article, beam splitting, amplification and heterodyning are used to measure the Wigner function of a single light mode in optical homodyne tomography, where the WIGNer function is reconstructed from measured quadrature distributions.

Journal ArticleDOI
TL;DR: In CA1 as well as in CA3 cells, the kinetic and pharmacological properties of IA and IK remained stable during postnatal development, however, the contribution of IAand IK to the whole cell current varied with age.
Abstract: 1. The properties of voltage-gated potassium currents were studied in acutely isolated rat hippocampal pyramidal cells from area CA1 and CA3 at postnatal ages of day 6-8, 9-14, and 26-29 (P6-8, P9-14, and P26-29) with the use of the whole cell version of the patch-clamp technique. 2. The outward current pattern of all cells under investigation could be separated in a fast transient A current (IA) and a delayed rectifier-like current (IK). 3. In both preparations, IA activated and inactivated rapidly. Vh describing steady-state inactivation was -84.5 mV in CA3 cells and -85.5 mV in CA1 cells. The activation behavior was characterized by Vh = -23.8 mV in CA3 cells and -27.2 mV in CA1 cells. The removal of inactivation was monoexponential both in CA1 and CA3 neurons with time constants of 32.1 and 28.5 ms, respectively. IA was insensitive to tetraethylammonium (TEA), dendrotoxin (300 nM), and mast cell degranulating peptide (200 nM), but could be blocked with 5 mM 4-aminopyridine (4-AP) by approximately 80%. In both preparations, A currents did not depend on Ca2+ influx. 4. Delayed rectifier currents (IK) in CA1 and CA3 pyramidal neurons decayed along a double exponential time course. Steady-state inactivation was described by Vh = -79.5 mV in CA3 cells and -76.0 mV in CA1 cells. The activation curves were characterized by midpoints of -3.8 mV in CA3 cells and of -1.4 mV in CA1 cells. The removal of inactivation was monoexponential in CA1 and CA3 neurons with time constants of 210.3 and 202.4 ms, respectively. All kinetic properties were identical for the differentially decaying components of IK. In CA1 cells IK was blocked by TEA at +30 mV with an IC50 of 0.98 mM. In CA3 cells the corresponding IC50 value was 1.05 mM. About 20% of IK were insensitive to TEA. IK was partially blocked by approximately 30% with 100 microM 4-AP. Mast cell degranulating peptide (100-200 nM) and dendrotoxin (50-300 nM) had no effect on IK. 6. Perfusion of charybdotoxin (30 nM), Cd2+ (300 microM), La3+ (10 microM), or Ca(2+)-free solutions resulted in the isolation of a small noninactivating outward current component. Around 10% of IK appeared to be Ca2+ dependent in CA1 neurons. In CA3 pyramidal cells Ca(2+)-dependent outward currents seemed to be somewhat larger with approximately 20%. 7. In CA1 as well as in CA3 cells, the kinetic and pharmacological properties of IA and IK remained stable during postnatal development. However, the contribution of IA and IK to the whole cell current varied with age. IA was more prominent in CA1 cells of age group P6-8 than in age-matched CA3 cells. CA3 cells had smaller A currents and larger delayed rectifier currents than CA1 pyramidal cells. Current densities of IA and IK were analyzed during development to assess changes in the expression of these currents. With increasing postnatal age, the expression of IA was downregulated in both preparations. This effect was more pronounced in CA3 than in CA1 cells. In contrast, IK was upregulated during the same developmental period. This increase in the expression of IK was with approximately 300% much larger in CA1 cells than in CA3 cells with only approximately 50%.

Journal ArticleDOI
TL;DR: Lucigenin-enhanced CL is a promising tool to study ROS production continuously from the in vivo brain of experimental animals and brain slices, and it is concluded that the CL signal most likely derives from the intracellular production of superoxide.
Abstract: Using online in vivo chemiluminescence (CL), we studied for the first time continuously the production of reactive oxygen species (ROS) after global cerebral ischemia and the relationship of ROS production to CBF. In anesthetized rats equipped with a closed cranial window, the CL enhancer, lucigenin (1 mM), was superfused onto the brain topically. CL was measured through the cranial window with a cooled photomultiplier, and CBF was measured simultaneously with laser-Doppler flowmetry. Reperfusion after 10 min (n = 8) of global cerebral ischemia led to a CL peak to 188 +/- 77% (baseline = 100%) within 10 +/- 4 min. After 2 h of reperfusion, CL had returned to 102 +/- 28%. Reperfusion after 20 min (n = 8) of ischemia increased CL to 225 +/- 48% within 12 +/- 3 min. After 2 h, CL was still increased (150 +/- 44%, p < 0.05 compared with 10 min of ischemia). CL after 10 min of ischemia was neither affected by brain topical free CuZn-superoxide dismutase (SOD) (100 U/ml, n = 3) nor by i.v. administration of free CuZn-SOD (104 U/kg, followed by 104 U/kg/h, n = 3). The CBF hyperfusion peak on reperfusion preceded the CL peak in all experiments by several minutes. In additional in vitro experiments we investigated the source of CL: Intracellular loading of lucigenin was demonstrated in cultured CNS cells, and a very similar pattern of CL as in the in vivo preparation after ischemia developed in rat brain slices after 15 min of hypoxia, which was unaffected by free CuZn-SOD (100 U/ml) but strongly attenuated by liposome-entrapped CuZn-SOD. We conclude that lucigenin-enhanced CL is a promising tool to study ROS production continuously from the in vivo brain of experimental animals and brain slices, and that the CL signal most likely derives from the intracellular production of superoxide. The production of ROS is preceded by reperfusion, is burst-like, and is dependent on the duration of the ischemic interval.

Journal ArticleDOI
TL;DR: An additive-free, stringently controlled diet provides a simple means of diagnosing and treating the majority of patients with chronic urticaria, and shows complete remission on diet and lasting improvement in all but one of the remaining patients on diet.
Abstract: In chronic urticaria, the possible pathogenetic role of pseudoallergic reactions to food has been repeatedly discussed, but stringent prospective studies regarding their clinical significance are not available. All patients with chronic urticaria and/or angioedema hospitalized at the department of dermatology during a period of 2 years were therefore included in a prospective study. Patients (n = 64) were screened for common causes of urticaria and then evaluated for possible benefits of a stringently controlled pseudoallergen-free diet. Double-blind, placebo-controlled oral provocation tests with food additives were performed on those patients benefitting from diet. In 73% of patients, symptoms ceased or were greatly reduced within 2 weeks on diet, although only 19% of them responded to individual pseudoallergens on provocation tests. Of the remaining patients, 11% responded to treatment of an associated inflammatory disease, and in 16%, no cause of the urticaria was ascertained. Follow-up at 6 months after hospitalization showed complete remission on diet in 46% and lasting improvement in all but one of the remaining patients on diet. An additive-free, stringently controlled diet thus provides a simple means of diagnosing and treating the majority of patients with chronic urticaria.

Journal ArticleDOI
TL;DR: Perforant path inputs activated prominent and effective disynaptic inhibition of CA1 cells, which has significance for the output of hippocampal processing during normal behaviour and also under pathological conditions.
Abstract: 1. The perforant path projection from layer III of the entorhinal cortex to CA1 of the hippocampus was studied within a hippocampal-entorhinal combined slice preparation. We prevented contamination from the other main hippocampal pathways by removal of CA3 and the dentate gyrus. 2. Initially the projection was mapped using field potential recordings that suggested an excitatory sink in stratum lacunosum moleculare with an associated source in stratum pyramidale. 3. However, recording intracellularly from CA1 cells, stimulation of the perforant path produced prominent fast GABAA and slow GABAB IPSPs often preceded by small EPSPs. In a small number of cells we observed EPSPs only. 4. CNQX blocked excitatory and inhibitory responses. This indicated the presence of an intervening excitatory synapse between the inhibitory interneurone and the pyramidal cell. 5. Focal bicuculline applications revealed that the major site of GABAA inhibitory input was to stratum radiatum of CA1. 6. The inhibition activated by the perforant path was very effective at reducing simultaneously activated Schaffer collateral mediated EPSPs and suprathreshold-stimulated action potentials. 7. Blockade of fast inhibition increased excitability and enhanced slow inhibition. Both increases relied upon the activation of NMDA receptors. 8. Perforant path inputs activated prominent and effective disynaptic inhibition of CA1 cells. This has significance for the output of hippocampal processing during normal behaviour and also under pathological conditions.

Journal ArticleDOI
TL;DR: NIRS is a promising approach for studying changes in Hb oxygenation during brain activation in physiological aging and supports the hypothesis of an age-dependent decline in the activation-induced local increase in [HbO2].
Abstract: We used near-infrared spectroscopy (NIRS) to study noninvasively the influence of aging on changes in the local concentration of oxygenated hemoglobin ([HbO2]), reduced hemoglobin ([HbR]), and total hemoglobin ([HbT] = [HbR] + [HbO2]) during activation of brain function. Young subjects (n = 12; age, 28 +/- 4 years) performing calculation tasks showed an increase in [HbO2] [mean (arbitrary units) +/- SD, 2.36 +/- 1.07] and [HbT] (2.24 +/- 1.13) in the frontal cortex, while [HbR] (-0.11 +/- 0.48) decreased. Elderly subjects (n = 17; age, 52 +/- 10 years) showed a significantly lower mean increase (p < 0.05) in [HbO2] and [HbT] levels (1.21 +/- 1.38 and 0.72 +/- 1.41, respectively). Regression analysis supports the hypothesis of an age-dependent decline in the activation-induced local increase in [HbO2] (y = -0.241x + 20.062; r = -0.431, p < 0.05) as well as [HbT] (y = -0.346x + 22.496; r = -0.568, p < 0.05). We conclude that NIRS is a promising approach for studying changes in Hb oxygenation during brain activation in physiological aging.