Showing papers by "University of Cologne published in 1996"
TL;DR: A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation, where only mutants binding antigen with high affinity survive to become memory cells.
Abstract: Each antibody-producing B cell makes antibodies of unique specificity, reflecting a series of ordered gene rearrangements which must be successfully performed if the cell is to survive. A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation. Here only mutants binding antigen with high affinity survive to become memory cells. Cells expressing autoreactive receptors are counter-selected at both stages. This stringent positive and negative selection allows the generation and diversification of cells while rigorously controlling their specificity.
1,705 citations
TL;DR: It is concluded that ASA physical status classification was a predictor of postoperative outcome using both univariate analysis and calculation of the odds ratio of the risk of developing a postoperative complication by means of a logistic regression model.
Abstract: In a prospective study of 6301 surgical patients in a university hospital, we examined the strength of association between ASA physical status classification and perioperative risk factors, and postoperative outcome, using both univariate analysis and calculation of the odds ratio of the risk of developing a postoperative complication by means of a logistic regression model. Univariate analysis showed a significant correlation (P
884 citations
TL;DR: These studies demonstrate that β-polymerase functions specifically in base-excision repair in vivo, and establishes embryonic fibroblast cell lines homozygous for a deletion mutation in the gene encoding DNA polymerase-β.
Abstract: Synthesis of DNA by DNA polymerase-beta is distributive on single-stranded DNA templates, but short DNA gaps with a 5' PO4 in the gap are filled processively to completion. In vitro studies have suggested a role of beta-polymerase in different types of DNA repair. However, the significance of these studies to the in vivo role of beta-polymerase has remained unclear. Because genetic studies are essential for determining the physiological role of a gene, we established embryonic fibroblast cell lines homozygous for a deletion mutation in the gene encoding DNA polymerase-beta. Extracts from these cell lines were found to be defective in uracil-initiated base-excision repair. The beta-polymerase-deleted cells are normal in viability and growth characteristics, although they exhibit increased sensitivity to monofunctional DNA-alkylating agents, but not to other DNA-damaging agents. Both the deficiency in base-excision repair and hypersensitivity to DNA-alkylating agents are rescued following stable transfection with a wild-type beta-polymerase minitransgene. These studies demonstrate that beta-polymerase functions specifically in base-excision repair in vivo.
811 citations
TL;DR: Results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.
Abstract: We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using H2 15O positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e.,, subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal lobes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.
802 citations
TL;DR: Analysis of HRS cells micromanipulated from infiltrated tissue sections of 10 primary HD patients for rearranged V genes suggests that the HRS cell precursors reside inside GCs, have acquired crippling mutations that prevent antigenic selection, but escape apoptosis through some transforming event.
Abstract: In Hodgkin's disease (HD), the Hodgkin and Reed-Sternberg (HRS) cells represent only a minute population in the diseased tissue. The investigation of lineage derivation and clonal origin of these cells has yielded conflicting results. We have analyzed HRS cells micromanipulated from infiltrated tissue sections of 10 primary HD patients for rearranged V genes, extending a previous study. Clonally related rearrangements were found in nine cases, indicating that HRS cells represent a dominant clone of B lineage-derived cells in at least a large fraction of cases of HD. Rearranged VH genes from HRS cells carried a high load of somatic mutation, indicating that HRS cells are derived from germinal center (GC) cells or their progeny. Stop codons in some in-frame V gene rearrangements suggest that the HRS cell precursors reside inside GCs, have acquired crippling mutations that prevent antigenic selection, but escape apoptosis through some transforming event.
719 citations
TL;DR: It is reported that, in mice deficient for the β7 integrin subfamily of adhesion molecules, the formation of the GALT is severely impaired, probably due to a failure of β7–/– lymphocytes to arrest and adhere to the vasculature at the site of transmigration into the Galt.
Abstract: Immune defence against pathogens entering the gut is accomplished by lymphocytes in the gut-associated lymphoid tissue (GALT), a major compartment of the immune system. The GALT, comprising Peyer's patches, lamina propria lymphocytes and intra-epithelial lymphocytes of the intestine, is populated by lymphocytes that migrate there from the vasculature. Here we report that, in mice deficient for the beta7 integrin subfamily of adhesion molecules, the formation of the GALT is severely impaired. This is probably due to a failure of beta7-/- lymphocytes to arrest and adhere to the vasculature at the site of transmigration into the GALT.
533 citations
TL;DR: It is concluded that these loci constitute a gene complex, for which the name epidermal differentiation complex is proposed, since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidersmal structural proteins.
501 citations
01 Jun 1996
493 citations
470 citations
TL;DR: Marked regional differences in density and rate-dependent properties of the transient outward current exist in subendocardial and subepicardial layers in human left ventricular myocardium, causing transmural electrical gradients that are important for normal and pathological electrical behavior of the human heart.
Abstract: Background Recordings of outward currents in human ventricular myocytes revealed the presence of a large calcium-insensitive transient outward current. This current has been suggested to contribute significantly to regional electrophysiological heterogeneity in myocardial cells and tissue of several animal species and to cause electrical gradients across the ventricular wall. Methods and Results The patch-clamp technique was used to record action potentials and outward currents in myocytes enzymatically isolated from thin subepicardial and subendocardial layers of human nonfailing and failing left ventricle. In all subepicardial cells studied, a calcium-insensitive transient outward current (Ito1) could be recorded with large density (10.6±1.08 pA/pF at 40 mV), whereas current density of Ito1 in subendocardial cells was fourfold smaller (2.63±0.31 pA/pF, P<.0001, nonfailing myocardium). In failing hearts, the density of Ito1 was significantly smaller in subepicardial cells (7.81±0.53 pA/pF, P=.012) but no...
455 citations
TL;DR: PKC-βI and PKC-βII play an important role in B cell activation and may be functionally linked to Bruton's tyrosine kinase in antigen receptor-mediated signal transduction.
Abstract: Cross-linking of the antigen receptor on lymphocytes by antigens or antibodies to the receptor results in activation of enzymes of the protein kinase C (PKC) family. Mice homozygous for a targeted disruption of the gene encoding the PKC-βI and PKC-βII isoforms develop an immunodeficiency characterized by impaired humoral immune responses and reduced cellular responses of B cells, which is similar to X-linked immunodeficiency in mice. Thus PKC-βI and PKC-βII play an important role in B cell activation and may be functionally linked to Bruton's tyrosine kinase in antigen receptor-mediated signal transduction.
TL;DR: A simple two-lane cellular automaton based upon the single-lane CA introduced by Nagel and Schreckenberg is examined, pointing out important parameters defining the shape of the fundamental diagram and investigating the importance of stochastic elements with respect to real life traffic.
Abstract: We examine a simple two-lane cellular automaton based upon the single-lane CA introduced by Nagel and Schreckenberg. We point out important parameters defining the shape of the fundamental diagram. Moreover we investigate the importance of stochastic elements with respect to real life traffic.
TL;DR: The International Society of Ocular Trauma, the United States Eye Injury Registry, the American Academy of Ophthalmology, the Hungarian Eye injury registry, the Vetreous Society, and the Retina Society as discussed by the authors developed a classification based on the authors' extensive personal experience.
TL;DR: It is reported that the Drosophila gene serpent (srp) encodes the previously described GATA factor ABF, which implies that some aspects of the molecular mechanisms underlying blood cell development as well as endodermal differentiation are early acquisitions of metazoan evolution and may be common to most higher animals.
Abstract: In vertebrates, transcriptional regulators of the GATA family appear to have a conserved function in differentiation and organ development. GATA-1, -2 and -3 are required for different aspects of hematopoiesis, while GATA-4, -5 and -6 are expressed in various organs of endodermal origin, such as intestine and liver, and are implicated in endodermal differentiation. Here we report that the Drosophila gene serpent (srp) encodes the previously described GATA factor ABF. The multiple functions of srp in Drosophila suggest that it is an ortholog of the entire vertebrate Gata family. srp is required for the differentiation and morphogenesis of the endodermal gut. Here we show that it is also essential for Drosophila hematopoiesis and for the formation of the fat body, the insect organ analogous to the liver. These findings imply that some aspects of the molecular mechanisms underlying blood cell development as well as endodermal differentiation are early acquisitions of metazoan evolution and may be common to most higher animals.
TL;DR: A UDP-galactose ceramide galactosyltransferase (CGT) null mutant mouse with CNS and PNS myelin completely depleted of GalC and derived sGalC is generated and severe dysmyelinosis leads to death of the cgt-/- mouse at the end of the myelination period.
Abstract: The lipid bilayer of the myelin membrane of the central nervous system (CNS) and the peripheral nervous system (PNS) contains the oligodendrocyte- and Schwann cell-specific glycosphingolipids galactocerebrosides (GalC) and GalC-derived sulfatides (sGalC). We have generated a UDP-galactose ceramide galactosyltransferase (CGT) null mutant mouse (cgt-/-) with CNS and PNS myelin completely depleted of GalC and derived sGalC. Oligodendrocytes and Schwann cells are unable to restore the structure and function of these galactosphingolipids to maintain the insulator function of the membrane bilayer. The velocity of nerve conduction of homozygous cgt-/- mice is reduced to that of unmyelinated axons. This indicates a severely altered ion permeability of the lipid bilayer. GalC and sGalC are essential for the unperturbed lipid bilayer of the myelin membrane of CNS and PNS. The severe dysmyelinosis leads to death of the cgt-/- mouse at the end of the myelination period.
TL;DR: A mouse mutant that lacks most of the Ig-α cytoplasmic tail exhibits only a small impairment in early B cell development but a severe block in the generation of the peripheral B cell pool, revealing a checkpoint in B cell maturation that ensures the expression of a functional BCR on mature B cells.
Abstract: The immunoglobulin alpha (Ig-alpha)-Ig-beta heterodimer is the signaling component of the antigen receptor complex on B cells (BCR) and B cell progenitors (pre-BCR). A mouse mutant that lacks most of the Ig-alpha cytoplasmic tail exhibits only a small impairment in early B cell development but a severe block in the generation of the peripheral B cell pool, revealing a checkpoint in B cell maturation that ensures the expression of a functional BCR on mature B cells. B cells that do develop demonstrate a differential dependence on Ig-alpha signaling in antibody responses such that a signaling-competent Ig-alpha appears to be critical for the response to T-independent, but not T-dependent, antigens.
TL;DR: In this paper, a prospective study of 2266 cancer patients, assessed localisations, aetiologies and pathophysiological mechanisms of the pain syndromes, and found that 30% of the patients presented with 1, 39% with 2 and 31% with 3 or more distinct pain disorders.
Abstract: Although pain assessment is a vital preliminary step towards the satisfactory control of cancer pain, data on the prevalence of different pain syndromes are rare. In a prospective study of 2266 cancer patients, we assessed localisations, aetiologies and pathophysiological mechanisms of the pain syndromes. Thirty percent of the patients presented with 1, 39% with 2 and 31% with 3 or more distinct pain syndromes. The majority of patients had pain caused by cancer (85%) or antineoplastic treatment (17%); 9% had pain related to cancer disease and 9% due to aetiologies unrelated to cancer. Pain could be classified as originating from nociceptors in bone (35%), soft tissue (45%) or visceral structures (33%) or otherwise as of an neuropathic origin (34%). In most patients, pain syndromes were located in the lower back (36%), abdominal region (27%), thoracic region (23%), lower limbs (21%), head (17%) and pelvic region (15%). The main pain syndrome was also coded according to the IASP Classification of Chronic Pain. Regions and systems affected by the main pain syndrome showed large variation depending on the site of cancer origin, whereas temporal characteristics, intensity and aetiology were not markedly influenced by the cancer site. The variety of pain syndromes evaluated in our patients confirms the importance of comprehensive pain assessment prior to treatment.
TL;DR: In this article, the systematics and fragmentation of the M1 Scissors Mode in even-even rare earth and actinide nuclei, its deformation dependence and saturation behavior, the existence of the Scissors mode in odd deformed nuclei and 2 + ⊗ 3 − two-phonon E1 excitations in N =82 isotones and Z =50 isotopes.
TL;DR: In CD5-deficient mice, B-1 cells responded to mIgM crosslinking by developing a resistance to apoptosis and entering the cell cycle, indicating the B cell receptor-mediated signaling is negatively regulated by CD5 in normal B- 1 cells.
Abstract: A subset of B lymphocytes present primarily in the peritoneal and pleural cavities is defined by the expression of CD5 and is elevated in autoimmune diseases. Upon signaling through membrane immunoglobulin M (mIgM), splenic B lymphocytes (B-2) proliferate, whereas peritoneal B cells (B-1) undergo apoptosis. However, in CD5-deficient mice, B-1 cells responded to mIgM crosslinking by developing a resistance to apoptosis and entering the cell cycle. In wild-type B-1 cells, prevention of association between CD5 and mIgM rescued their growth response to mIgM crosslinking. Thus the B cell receptor-mediated signaling is negatively regulated by CD5 in normal B-1 cells.
TL;DR: The tetrameric Lac repressor can bind simultaneously to twolacoperators on the same DNA molecule, thereby including the formation of a DNA loop, and repression increased significantly with decreasing inter-operator DNA length, indicating that the local Lac repression concentration at O1 is crucial for tight repression.
TL;DR: The increased expression of the Na(+)-Ca2+ exchanger molecules could be of functional relevance for the modulation of cardiac contractility by agents that increase the intracellular Na+ concentration.
Abstract: Background The present study aimed at investigating the expression of the Na+-Ca2+ exchanger and its functional role in human failing myocardium. Methods and Results Na+-Ca2+ exchanger mRNA and protein levels were examined in nonfailing (NF, n=8) and failing human myocardium (New York Heart Association functional class IV) with idiopathic dilated cardiomyopathy (DCM, n=8) or ischemic heart disease (ICM, n=6). The inotropic effect of the Na+ channel activator BDF 9148 was determined in electrically driven left ventricular papillary muscle strip preparations (1 Hz, 37°C) from nonfailing (n=8) and failing (n=8) human hearts. Na+-Ca2+ exchanger mRNA levels were significantly increased, by 79% (P<.001) in DCM and by 58% (P<.01) in ICM compared with NF; protein levels increased by 36% (P<.001) and by 20% (P<.05), respectively. BDF 9148 increased the force of contraction concentration dependently, with a similar maximal effect in NYHA class IV and NF, but was more potent in NYHA class IV as demonstrated by a sig...
TL;DR: In this paper, a heuristic approach for the dynamic multilevel multiitem lotsizing problem in general product structures with multiple constrained resources and setup times is proposed with the help of Lagrangean relaxation.
Abstract: In this paper a heuristic approach for the dynamic multilevel multiitem lotsizing problem in general product structures with multiple constrained resources and setup times is proposed. With the help of Lagrangean relaxation the capacitated multilevel multiitem lotsizing problem is decomposed into several uncapacitated single-item lotsizing problems. From the solutions of these single-item problems lower bounds on the minimum objective function value are derived. Upper bounds are generated by means of a heuristic finite scheduling procedure. The quality of the approach is tested with reference to various problem groups of differing sizes.
TL;DR: This work provides definitions for the terms commonly used in eye trauma and creates a logical system of injury types and it can be reasonably expected that the system will ultimately become the standardized international language of ocular trauma.
Abstract: • Background: No internationally standardized classification of ocular trauma terminology has existed heretofore. Despite a growing interest in eye injuries, the absence of a common language continues to impede both clinical care and research. • Methods: A classification was initially developed based on the authors' extensive personal experience. It then underwent repeated reviews over a 3-year period by international ophthalmic specialists. Written and oral suggestions from respondents in 19 countries and from selected ocular trauma experts were considered and incorporated. • Results: By always using the entire globe as the tissue of reference, the new classification is unambiguous, consistent, simple, and comprehensive. It provides definitions for the terms commonly used in eye trauma and creates a logical system of injury types. • Conclusion: In addition to widespread international acceptance by professionals, the new classification has been endorsed by the International Society of Ocular Trauma, the United States Eye Injury Registry, the American Academy of Ophthalmology, the Hungarian Eye injury Registry, the Vetreous Society, and the Retina Society. It can be reasonably expected that the system will ultimately become the standardized international language of ocular trauma.
TL;DR: LC for inflamed gallbladder has a higher conversion rate than LC for routine symptomatic gallbladders and if successfully performed, it has definite benefit for the patient in terms of better postoperative recovery, and the risk of CBD injury is significantly higher.
Abstract: p < 0.0001). Significantly more adhesions (20% versus 8%), more blood loss (48% versus 19%), a higher incidence of bile spillage (28% versus 12%), and lost stones (19% versus 8%) were encountered in patients with acute cholecystitis. Common bile duct (CBD) injuries were also more frequent in that group (5.5% versus 0.2%;p = 0.005). The rate of conversion to open surgery was higher than with routine LCs (13% versus 4%). There were two deaths in the routine LC group and none in the acutely inflamed group. There was no difference in postoperative pain intensity or postoperative fatigue according to visual analog scale measurements. Patients with acute cholecystitis stayed only 1 day longer (median 4 days versus 3 days) in hospital. The quality of life scores indicate return to almost normal values by the 14th postoperative day. Long-term follow-up (1–3 years) did not reveal any delayed clinical adverse effects. In summary, LC for inflamed gallbladders has a higher conversion rate than LC for routine symptomatic gallbladders. If successfully performed, it has definite benefit for the patient in terms of better postoperative recovery. The trade-off is that the risk of CBD injury is significantly higher.
TL;DR: In this article, the authors present high resolution images and spectra toward 21 H 2 O maser sources in the vicinity of ultracompact (UC) HII regions.
Abstract: In this paper we present high resolution images and spectra toward 21 H 2 O maser sources in the vicinity of ultracompact (UC) HII regions. This survey provides the basis for future studies with milli–arcsecond resolution, utilizing very long baseline interferometry (VLBI) techniques. Emission from the masing transition of interstellar H 2 O is observed in the close vicinity of UC HII regions with a median angular distance of and a median linear projected distance of pc from the continuum peak. We find that for UC HII regions with cometary morphology the water maser emission is located in front of the cometary arc whereas for non-cometary UC HII regions the water masers are often observed projected onto the contours of the ionized gas. Due to the large median distance of the water masers from the I-front of the UC HII region, it is unlikely, that the water masers are formed in the shocked layer of warm molecular gas in the interface between the ionized gas of the UC HII region and surrounding molecular gas which is predicted by the Bow Shock theory of UC HII regions. A comparison with maps in the NH 3 inversion transitions shows that in at least 7 cases, the water masers are associated with hot ( T K), dense ( n (Hcm -3 ) molecular clumps. For the UC HII regions G5.89-0.38 and G45.07+0.13 we find spatial and velocity correspondence between water masers and outflowing molecular gas. It is thus likely, that for these sources the H 2 O masers are taking part in the bipolar outflow.
TL;DR: The resulting phenotypes are discussed on the basis of the recently published structure of the Lac repression core complexed with the inducer IPTG and a model of the dimeric Lac repressor built by homology modelling from the X-ray structure ofThe purine repressor-corepressor-operator complex.
TL;DR: Observations support the speculation that the induced HSP72 plays some beneficial role in this protection mechanism, and support the proposed model of tolerance acquisition for ischemia-reperfusion injury by stress preconditioning.
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TL;DR: In this paper, it was shown that the Dirac equation in a non-inertial frame can be used to predict general relativity in a Riemann-Cartan spacetime with torsion and curvature.
Abstract: We give a short outline, in Sec.\ 2, of the historical development of the gauge idea as applied to internal ($U(1),\, SU(2),\dots$) and external ($R^4,\,SO(1,3),\dots$) symmetries and stress the fundamental importance of the corresponding conserved currents. In Sec.\ 3, experimental results with neutron interferometers in the gravitational field of the earth, as inter- preted by means of the equivalence principle, can be predicted by means of the Dirac equation in an accelerated and rotating reference frame. Using the Dirac equation in such a non-inertial frame, we describe how in a gauge- theoretical approach (see Table 1) the Einstein-Cartan theory, residing in a Riemann-Cartan spacetime encompassing torsion and curvature, arises as the simplest gravitational theory. This is set in contrast to the Einsteinian approach yielding general relativity in a Riemannian spacetime. In Secs.\ 4 and 5 we consider the conserved energy-momentum current of matter and gauge the associated translation subgroup. The Einsteinian teleparallelism theory which emerges is shown to be equivalent, for spinless matter and for electromagnetism, to general relativity. Having successfully gauged the translations, it is straightforward to gauge the four-dimensional affine group $R^4 \semidirect GL(4,R)$ or its Poincare subgroup $R^4\semidirect SO(1,3)$. We briefly report on these results in Sec.\ 6 (metric-affine geometry) and in Sec.\ 7 (metric-affine field equations (\ref{zeroth}, \ref{first}, \ref{second})). Finally, in Sec.\ 8, we collect some models, currently under discussion, which bring life into the metric-affine gauge framework developed.
TL;DR: In this article, the authors presented an estimate of the bulk Earth S-content which is based on the volatility of S in the solar nebula and the general depletion of volatile elements in meteorites and in the Earth.
TL;DR: The nestin-cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes.