Showing papers by "University of Tübingen published in 1994"
TL;DR: In this article, the influence of surface point defects on the electronic structure of stoichiometric CeO2 surfaces was studied by means of detection angle-dependent XPS, UPS and HREELS.
597 citations
TL;DR: These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts.
Abstract: The decay of excitatory postsynaptic currents in central neurons mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors is likely to be shaped either by receptor desensitization or by offset after removal of glutamate from the synaptic cleft. Native AMPA receptors show desensitization time constants of 1 to about 10 milliseconds, but the underlying molecular determinants of these large differences are unknown. Cloned AMPA receptors carrying the "flop" splice variants of glutamate receptor subtype C (GluR-C) and GluR-D are shown to have desensitization time constants of around 1 millisecond, whereas those with the "flip" variants are about four times slower. Cerebellar granule cells switch their expression of GluR-D splice variants from mostly flip forms in early stages to predominantly flop forms in the adult rat brain. These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts.
582 citations
407 citations
TL;DR: In this article, the structure and function of tight junctions in primary cultures of bovine brain endothelial cells using quantitative freeze-fracture electron microscopy, and ion and inulin permeability.
Abstract: Tight junctions between endothelial cells of brain capillaries are the most important structural elements of the blood-brain barrier. Cultured brain endothelial cells are known to loose tight junction-dependent blood-brain barrier characteristics such as macromolecular impermeability and high electrical resistance. We have directly analyzed the structure and function of tight junctions in primary cultures of bovine brain endothelial cells using quantitative freeze-fracture electron microscopy, and ion and inulin permeability. The complexity of tight junctions, defined as the number of branch points per unit length of tight junctional strands, decreased 5 hours after culture but thereafter remained almost constant. In contrast, the association of tight junction particles with the cytoplasmic leaflet of the endothelial membrane bilayer (P-face) decreased continuously with a major drop between 16 hours and 24 hours. The complexity of tight junctions could be increased by elevation of intracellular cAMP levels while phorbol esters had the opposite effect. On the other hand, the P-face association of tight junction particles was enhanced by elevation of cAMP levels and by coculture of endothelial cells with astrocytes or exposure to astrocyte-conditioned medium. The latter effect on P-face association was induced by astrocytes but not fibroblasts. Elevation of cAMP levels together with astrocyte-conditioned medium synergistically increased transendothelial electrical resistance and decreased inulin permeability of primary cultures, thus confirming the effects on tight junction structure and barrier function. P-face association of tight junction particles in brain endothelial cells may therefore be a critical feature of blood-brain barrier function that can be specifically modulated by astrocytes and cAMP levels. Our results suggest an important functional role for the cytoplasmic anchorage of tight junction particles for brain endothelial barrier function in particular and probably paracellular permeability in general.
377 citations
TL;DR: Observed alterations provide evidence for extensive plastic reorganization in the adult human cortex following nervous system injury, but they are not a sufficient cause of the phantom phenomenon termed 'facial remapping'.
Abstract: MAGNETIC source imaging revealed that the topographic representation in the somatosensory cortex of the face area in upper extremity amputees was shifted an average of 1.5 cm toward the area that would normally receive input from the now absent nerves supplying the hand and fingers. Observed alterat
355 citations
TL;DR: It is shown by angle-resolved x-ray photoelectron spectroscopy that cavitands derived from resorcin[4]arenes provided with four dialkylsulfide chains form stable monolayers on gold surfaces that are well organized by self-assembly.
Abstract: It is shown by angle-resolved x-ray photoelectron spectroscopy that cavitands derived from resorcin[4]arenes provided with four dialkylsulfide chains form stable monolayers on gold surfaces that are well organized by self-assembly. The cavitand headgroups at the surface of the resorcin[4]arene monolayer act as molecular recognition sites for small organic molecules with remarkable selectivity for perchloroethylene (C(2)Cl(4)). Comparative thermal desorption experiments indicate binding sites with high interaction energies of C(2)Cl(4) at the surface of the resorcin[4]arene monolayers. Fast and reversible "host-guest" interactions were found by the monitoring of extremely small mass changes (in the nanogram range) with a quartz microbalance oscillator provided with gold electrodes coated by resorcin[4]arene monolayers.
311 citations
Journal Article•
TL;DR: For many indications, APC has replaced the Nd:YAG-laser, which was formerly used widely in the authors' unit, and shows remarkable advantages in nearly all applications.
Abstract: Argon plasma coagulation (APC) is a new mode of non-contact electrocoagulation in which current is applied to tissues by means of ionised argon gas (argon plasma). In open surgery, APC is used for the haemostasis of superficial, diffuse haemorrhages from parenchymatous organs and for the devitalization of various tissues. Experimental studies have shown the superiority of APC to standard electrocoagulation modes and surgical techniques due to its efficiency and limited tissue traumatisation. After developing and designing special probes which can be applied through flexible endoscopes and after testing these in in vitro studies, we have been able to utilise APC in both the gastrointestinal tract and the tracheobronchial system. From June, 1991 to September, 1992, 102 patients were treated endoscopically in 189 sessions with APC in the upper and lower gastrointestinal tract as well as in the respiratory system. The indications were malignant and benign tumours, diffuse haemorrhages of various origins and sites, tissue overgrowth after stent implantation, tissue remnants after endoscopic adenomectomy, and the conditioning of fistulas prior to fibrin sealing. In all cases, APC in flexible endoscopy was highly effective and easy to perform, with advantages over standard electrocoagulation. No problems or complications were observed. The limited depth of tissue coagulation (2-3 mm) with concomitant, efficient tissue coagulation allows application even in critical areas where there is risk of perforation, such as the duodenum or colon. For many indications, APC has replaced the Nd:YAG-laser, which was formerly used widely in our unit, Except for vaporisation of extended tumours, the APC shows remarkable advantages in nearly all applications.(ABSTRACT TRUNCATED AT 250 WORDS)
311 citations
TL;DR: Except in corrections greater than 6 diopters, complications after PRK are rare and assuming an appropriate patient selection, PRK may be considered a relatively safe procedure compared with other refractive procedures.
294 citations
TL;DR: It is concluded that neurons in the cochlear root nuclei most likely provide the auditory input to PnC neurons that is required to elicit the ASR, implying that the elementary acoustic startle circuit is composed of only three central relay stations and thus appears to be organized more simply than assumed.
Abstract: The mammalian acoustic startle response (ASR) is a relatively simple motor response that can be elicited by sudden and loud acoustic stimuli The ASR shows several forms of plasticity, such as habituation, sensitization, and prepulse inhibition, thereby making it an interesting model for studying the underlying neuronal mechanisms Among the neurons that compose the elementary startle circuit are giant neurons in the caudal pontine reticular nucleus (PnC), which may be good candidates for analyzing the neuronal basis of mammalian behavior In a first step of this study, we employed retrograde and anterograde tracing techniques to identify the possible sources of input and the efferent targets of these neurons In a second step, we performed intracellular recordings in vivo, followed by subsequent injections of HRP for morphological identification, thereby investigating whether characteristic features of the ASR are reflected by physiological properties of giant PnC neurons Our observations demonstrate convergent, bilateral input from several auditory brainstem nuclei to the PnC, predominantly originating from neurons in the cochlear nuclear complex and the superior olivary complex Almost no input neurons were found in the nuclei of the lateral lemniscus As the relatively long neuronal response latencies in several of these auditory nuclei appear to be incompatible with the primary ASR, we conclude that neurons in the cochlear root nuclei most likely provide the auditory input to PnC neurons that is required to elicit the ASR The giant PnC neurons have a remarkable number of physiological features supporting the hypothesis that they may be a neural correlate of the ASR: (1) they receive short-latency auditory input, (2) they have high firing thresholds and broad frequency tuning, (3) they are sensitive to changes in stimulus rise time and to paired-pulse stimulation, (4) repetitive acoustic stimulation results in habituation of their response, and (5) amygdaloid activity enhances their response to acoustic stimuli Anterograde tracing showed that most giant PnC neurons are reticulospinal cells Axon collaterals and terminal arbors were found in the reticular formation as well as in cranial and spinal motoneuron pools The results of this study indicate that giant PnC neurons form a sensorimotor interface between the cochlear nuclear complex and cranial and spinal motoneurons This neuronal pathway implies that the elementary acoustic startle circuit is composed of only three central relay stations and thus appears to be organized more simply than assumed in the past
288 citations
TL;DR: The present results support the hypothesis that the essential aspect leading to neglect in brain-damaged patients is a disturbance of those cortical structures that are crucial for transforming the sensory input coordinates from the peripheral sensory organs--here the retina, neck muscle spindles and cupulae--into an egocentric, body-centred coordinate frame of reference.
Abstract: Three patients with a right, predominantly parietal lesion and marked left-sided neglect without visual field defects were asked to direct a laser point to the position which they felt to lie exactly 'straight ahead' of their bodies' orientation. Whereas in both light and darkness, the subjective body orientation was close to the objective body position in the control groups, the three neglect patients localized the body's sagittal midplane approximately 15 degrees to the right of the objective orientation. No relevant differences of 'straight ahead' were found between the neglect patients and controls in the vertical plane. The neglect patients' horizontal displacement of sagittal midplane to the right could be compensated for either by neck muscle vibration or by caloric vestibular stimulation on the left side. When vestibular stimulation was combined with neck muscle vibration, the horizontal deviation linearly combined by adding or neutralizing the effects observed when both types of stimulation were applied exclusively in the control groups as well as in the neglect patients. Moreover, data analysis revealed that the neglect patients' ipsilesionally displaced subjective body orientation does not result from a disturbed primary perception or disturbed transmission of the vestibular or proprioceptive input from the periphery. The present results support the hypothesis that the essential aspect leading to neglect in brain-damaged patients is a disturbance of those cortical structures that are crucial for transforming the sensory input coordinates from the peripheral sensory organs--here the retina, neck muscle spindles and cupulae--into an egocentric, body-centred coordinate frame of reference. In neglect patients the coordinate transformation seems to work with a systematic error and deviation of the spatial reference frame to the ipsilesional side leading to a corresponding displacement of subjective localization of body orientation. It can be concluded further that neck muscle proprioception and vestibular stimulation directly interact in contributing to the subject's mental representation of space. The data suggest that the afferent information from these different input channels is used simultaneously for computing egocentric, body-centred coordinates that allow us to determine our body position in space.
282 citations
TL;DR: Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.
Abstract: Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, alpha 1-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.
TL;DR: It is concluded that color duplex sonography of cervical arteries is potentially a practical method for estimating total cerebral blood flow and may be ideally suited for bedside and follow-up examinations of the critically ill patient.
Abstract: To noninvasively estimate cerebral blood flow volume, a prospective study of color duplex sonography of the common, external, and internal carotid arteries and vertebral arteries of healthy adults was done. Cerebral blood flow was calculated with the sum of flow volumes in the internal carotid and vertebral arteries of both sides.
Using a 7.0-MHz linear transducer of a computed sonography system, cervical arteries of 48 volunteers (23 women, 25 men; mean age, 35 +/- 12 years) were examined. We measured angle-corrected time-averaged velocities and the diameter of the vessels and calculated the flow volumes of all arteries. In addition, peak systolic, maximum end-diastolic, and time-averaged maximum velocities and the resistance, pulsatility, and spectral broadening indexes were determined. Furthermore, we analyzed the side-to-side difference, age dependence, and long-term reproducibility of these parameters.
The mean +/- SD values of flow volumes in the common, internal, and external carotid and vertebral arteries were 470 +/- 120, 265 +/- 62, 160 +/- 66, and 85 +/- 33 mL/min on either side, respectively. Total cerebral blood flow was 701 +/- 104 mL/min (corresponding to 54 +/- 8 mL/100 g per minute), with no variation in age or sex. Long-term reproducibility of cerebral blood flow and flow volumes in all vessels was significant (P < .01).
We conclude that color duplex sonography of cervical arteries is potentially a practical method for estimating total cerebral blood flow. This noninvasive technique may be ideally suited for bedside and follow-up examinations of the critically ill patient. In future studies it should be compared with established radionuclide techniques.
TL;DR: This article finds strongly depressed production of interferon gamma (in response to mitogen or endotoxin) following strenuous exercise, and the potential significance of cytokine modulation for exercise-related immunological problems is discussed.
Abstract: Several groups have now investigated the cytokine response to strenuous exercise. In this article we try to summarize known data on this topic. Significant, albeit mild increases in plasma levels of the monokines IL-1, TNF-alpha, IL-6, and of soluble IL-2 receptor have been reported following strenuous exercise. Increased excretion of cytokines after exercise can also be shown in the urine of athletes. Modulation of cytokine release by strenuous exercise can also be demonstrated using in vitro cell cultures. Several authors have shown an increase in endotoxin-stimulated monokine release following exercise. In contrast, using whole blood cultures we found strongly depressed production of interferon gamma (in response to mitogen or endotoxin) following strenuous exercise. The potential significance of cytokine modulation for exercise-related immunological problems is discussed.
TL;DR: The CARE-LASS system provides a reliable and sensitive method to measure cell-mediated cytotoxicity in major histocompatibility complex (MHC) class I and MHC class II restricted cytotoxic T lymphocyte (CTL) assays as well as lymphokine activated killer (LAK) mediated cytot toxicity.
TL;DR: The results indicate surprisingly clear patterns, although not quite as clear as with natural class I ligands, and the relative motif symmetry suggests the possibility of bidirectional binding of peptides in the class II groove.
Abstract: We have approached the problem of MHC class II ligand motifs by pool sequencing natural peptides eluted from HLA-DR, DQ, and DP molecules. The results indicate surprisingly clear patterns, although not quite as clear as with natural class I ligands. The most striking feature is a highly dominant Proline at position 2. We interpret this to be a consequence of aminopeptidase N-like activity in processing. Another general aspect is the existence of three to four hydrophobic or aromatic anchors, whereby the first and the last are separated by five to eight residues. The peptide motifs for HLA-DR1, DR5, DQ7, and DPw4 are allele-specific and differ by spacing and occupancy of anchors. The anchors tend to be flanked by clusters of charged residues, and small residues, especially Ala, are frequent in the motif centers. These detailed motifs allow one to interpret most previous (DR-) motifs as fitting one or more of the anchors or conserved clusters. The relative motif symmetry suggests the possibility of bidirectional binding of peptides in the class II groove.
TL;DR: Serum levels of IGF‐I and IGFBP‐3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion, but the Individual ratios between serum levels in acromegalic and healthy adults have not been described previously.
Abstract: Summary
OBJECTIVE Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-l/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion. However, the Individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously.
METHODS AND MATERIALS We studied this ratio In 198 healthy adults and In 56 acromegalic patients, grouped according to their serum GH levels (group I GH 10mLU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination.
RESULTS In healthy adults serum levels of IGF-I and IGFBP-3 decreased with Increasing age (r =−0.52 and r=−0.34, respectively, P< 0.0001). In addition, the molar IGF-l/IGFBP-3 ratio declined with increasing age (r =−0.44, P – 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7–97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SOS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 ± 240μ/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-l/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001).
CONCLUSION We demonstrated a decreasing molar IGF-l/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels In the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and Is dependent on GH levels.
TL;DR: The results indicate that the lexicons of the left and right hemisphere can "collaborate" rather than inhibit each other or act independently when processing the same linguistic stimuli.
TL;DR: Vio de-epoxidase, like plastocyanin, is mobile within the thylakoid lumen at neutral pH values which occur under in-vivo conditions in the dark, corroborate the assumption of a transmembrane opposite location of the two enzymes of the xanthophyll cycle.
Abstract: The formation of zeaxanthin (Zea) from violaxanthin (Vio) in chloroplasts of leaves and algae upon strong illumination is currently suggested to play a role in the photoprotection of plants. Properties and location of the enzyme Vio de-epoxidase, which is responsible for the transformation of Vio to Zea, were studied using thylakoid membrane vesicles isolated from leaves of Spinacia oleracea L. Without using detergents a repeated freeze-thaw treatment of thylakoid vesicles was sufficient to release the enzyme into the medium. With the same procedure the mobile electron carrier plastocyanin, known to occur in the thylakoid lumen, was also released. The enzyme was demonstrated by its activity in the supernatant of the pelleted thylakoid vesicles in the presence of the added substrates Vio and ascorbic acid, as well as by staining of the released proteins after polyacrylamide gel electrophoresis. The release of the deepoxidase from the vesicles was pH-dependent, declined below pH 6.5 and ceased in the pH range around 5, which corresponds to the pH optimum of the enzyme activity. By using thylakoid vesicles isolated from pre-illuminated and therefore Zea-containing leaves the release by freeze-thaw cycles of both the de-epoxidase and plastocyanin was diminished compared with the dark control. However, the reason for this effect was not the Zea content but an unknown effect of the illumination on the thylakoid membrane properties. The de-epoxidase collected at pH 7 was able to re-bind to thylakoid membranes at pH 5.5 and to transform intrinsic Vio to Zea in the presence of ascorbate. The isolated de-epoxidase, as well as the endogenous membrane-bound de-epoxidase, was inhibited by dithiothreitol. From these results it is concluded that Vio de-epoxidase, like plastocyanin, is mobile within the thylakoid lumen at neutral pH values which occur under in-vivo conditions in the dark. However, upon strong illumination, when the lumen pH drops (pH < 6.5) due to the formation of a proton gradient, the properties of the de-epoxidase are altered and the enzyme becomes tightly bound to the membrane (in contrast to plastocyanin) thus gaining access to its substrate Vio. These findings corroborate the assumption of a transmembrane opposite location of the two enzymes of the xanthophyll cycle, the ascorbate-dependent Vio deepoxidase at the lumenal side and the NADPH-dependent Zea epoxidase at the stromal side. Indications in favour of a location of Vio within the lipid bilayer of the thylakoid membrane and of a binding of the active deepoxidase to these areas are discussed.
TL;DR: The effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM is investigated in a double-blind, placebo-controlled study.
TL;DR: A noninvasive behaviorally unbiased method for baroreceptor stimulation is described and the application of this method to measurement ofbaroreceptor-mediated attenuation of pain perception and of the Achilles tendon reflex is applied.
Abstract: Activating the arterial baroreceptors blunts pain sensation and produces other forms of central nervous system inhibition in animals. These effects may be important to blood pressure regulation but have not been rigorously verified in humans. We describe (i) a noninvasive behaviorally unbiased method for baroreceptor stimulation and (ii) the application of this method to measurement of baroreceptor-mediated attenuation of pain perception and of the Achilles tendon reflex. The findings are relevant to basic mechanisms of blood pressure stabilization and cardiovascular reactivity and may also have implications for noncompliance with antihypertensive medications and for the pathophysiology of essential hypertension.
TL;DR: MRI and IBZM-SPECT provide in vivo evidence for combined basal ganglia and pontocerebellar involvement in almost all patients in this series.
Abstract: Sixteen patients with a clinical diagnosis of probable multiple system atrophy (MSA) were examined clinically by MRI and by 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT). The clinical records of another 16 patients were also analysed retrospectively. On the basis of their clinical presentation, patients were subdivided into those with prominent parkinsonism (MSA-P, n = 11) and those with prominent cerebellar ataxia (MSA-C, n = 21). Autonomic symptoms were present in all patients and preceded the onset of motor symptoms in 63% of patients. Calculated median lifetime and the median time to become wheelchair bound after onset of disease were significantly shorter for MSA-P than for MSA-C (lifetime: 4.0 v 9.1 years; wheelchair: 3.1 vs 5.0 years) suggesting a better prognosis for cerebellar patients. A significant loss of striatal dopamine receptors (below 2 SD threshold) was detected by IBZM-SPECT in 63% of the patients (56% below 2.5 SD threshold). There was no difference between patients with MSA-C and those with MSA-P in the proportion with significant receptor loss and the extent of dopamine receptor loss. Planimetric MRI evaluation showed cerebellar and brainstem atrophy in both groups. Atrophy was more pronounced in patients with MSA-C than in those with MSA-P. Pontocerebellar hyperintensities and putaminal hypointensities on T2 weighted MRI were found in both groups. Pontocerebellar signal abnormalities were more pronounced in MSA-C than in MSA-P, whereas the rating scores for area but not for intensity of putaminal abnormalities were higher in MSA-P. MRI and IBZM-SPECT provide in vivo evidence for combined basal ganglia and pontocerebellar involvement in almost all patients in this series.
Journal Article•
TL;DR: Because HLA-DR15 Dw2 is associated with susceptibility to develop multiple sclerosis, the delineation of ligand motifs of the two DR2 alleles may help to study the interaction between potential autoantigenic peptides and these molecules in the future.
Abstract: Antigenic peptides are presented to CD4+ T cells by MHC class II molecules via a highly polymorphic peptide-binding groove. The two HLA-DR alleles isotypically expressed on HLA-DR15Dw2-positive cells, DRB1*1501 (DR2b) and DRB5*0101 (DR2a) molecules, show a number of differences in polymorphic residues of the beta-chain, including the Gly-Val-dimorphism at position beta 86. Therefore, different requirements for interaction of peptides with these alleles must be expected. In this study, naturally processed self-peptides were eluted from purified HLA-DR15Dw2 molecules and related to DRB1*1501 or DRB5*0101 molecules by binding assays. An alignment of self-peptides and foreign peptides allowed the delineation of putative anchor motifs. N- and C-terminally truncated and alanine-substituted derivatives of the DR15Dw2 restricted myelin basic protein epitope MBP(85-105) confirmed their validity. Thus, DRB5*0101 requires a bulky hydrophobic residue (F or Y) at position i as a primary anchor, and Q or an aliphatic residue, such as V, I, or M, at position i + 3; positively charged residues at positions i + 7 and i + 8 are secondary anchors. For DRB1*1501, a nonaromatic, hydrophobic anchor (L, V, or I) at position i is supplemented by a bulky hydrophobic residue (F or Y) at position i + 3 as primary anchor; an additional hydrophobic side chain represented by M, I, V, or F occurs at position i + 6. Therefore, MBP(85-105) seems to contain two MHC interaction sites for DRB1*1501 and DRB5*0101, respectively, that may contribute to its immunodominance. Because HLA-DR15 Dw2 is associated with susceptibility to develop multiple sclerosis, the delineation of ligand motifs of the two DR2 alleles may help to study the interaction between potential autoantigenic peptides and these molecules in the future.
TL;DR: It is suggested that the source of augmented No-Go P300s is a generator involved with sensorimotor inhibition, and the mechanism of P300 waves and evidence linking these waves with inhibition in other task arrangements is discussed.
TL;DR: For the in vivo activity of CYP2D6, genetic determinants prevail over environmental factors, and smoking, use of oral contraceptive steroids, caffeine consumption, or gender had no influence on sparteine metabolism.
Abstract: The impact of gender, use of oral contraceptive steroids (OCS), coffee consumption and of smoking on the metabolism of sparteine, caffeine, and paracetamol was studied in 194 randomly selected subjects (98 male and 95 female). Thirty-eight of the male volunteers were cigarette smokers, 40 of the female subjects were smokers and/or users of OCS. The metabolic ratio of sparteine oxidation (MRs) showed a trimodal distribution. 7.7% of the subjects had a MRs > 20 and thus were poor metabolizers (PMs). Within the extensive metabolizer (EM) subjects, a distinct subgroup accounting for 11% was observed with 20 > MRs > 1.2. Six of the 15 phenotypical PMs were heterozygous EMs by genotyping. This indicates the existence of one or several CYP2D6 mutations which cannot be identified by the currently employed genotyping methods. In each subgroup, i.e. smokers/OCS and non-smokers/non-OCS, the cumulative frequency distribution of the heterozygous (wt/B) phenotype caused a shift to higher MRs compared with the wild-type homozygotes (wt/wt). Thus, for the in vivo activity of CYP2D6, genetic determinants prevail over environmental factors. Smoking, use of oral contraceptive steroids, caffeine consumption, or gender had no influence on sparteine metabolism. The distribution of the paracetamol glucuronide/paracetamol metabolic ratio appeared to be unimodal although skewed. Glucuronidation capacity was clearly affected by gender, OCS use and smoking. It was higher in male than in female subjects. Male smokers had the highest, and female non-smokers/non-OCS users the lowest metabolic ratio. CYP1A2 activity, as determined by a caffeine metabolic ratio ((AFMU + 1X + 1U)/1, 7U), was multimodally distributed and was clearly increased in smokers. It was significantly correlated to paracetamol glucoronidation in male heavy smokers (r=0.85), suggesting an element of co-regulation of CYP1A2 and of paracetamol conjugating UDP-glucuronosyltransferase isozymes, including UGTI.6.
TL;DR: Comparing the affinities of the neuropeptide Y analogs to Y1 and Y2 receptors significant differences were found for the two binding sites, which suggests a different active conformation of neuropeptic Y at the two subtypes of receptors.
Abstract: The synthesis of more than fifty 36-residue oligopeptide analogs of neuropeptide Y (NPY) and their affinity to human Y1 and Y2 receptors is described. Each amino acid of the natural sequence was replaced by L-alanine, the four alanine residues at position 12, 14, 18 and 23 were replaced by glycine. Additional residues were exchanged to closely related ones in order to characterize the prerequisites for binding. A combination of automated single and multiple peptide synthesis using fluoren-9-ylmethoxycarbonyl/tert-butoxy strategy was applied. The purified peptides were characterized by electrospray mass spectrometry, analytical HPLC and amino acid analysis. Binding was investigated by displacement of 125I-labelled neuropeptide Y from human neuroblastoma cell lines SK-N-MC and SMS-KAN. Whereas Pro2 and the integrity of the neuropeptide Y loop is important for the binding to the Y1 receptor, exchanges within the C-terminal helix affect the affinity to the Y2 receptor. The C-terminal pentapeptide amide is important for both receptors and probably represents the binding site. However, Arg33 and Arg35 may not be exchanged by L-alanine in the Y1 system, whereas Arg35 and Tyr36 are the most susceptible residues in the Y2 system. In order to distinguish between conformational effects and direct hormone/receptor interaction via the side chains of neuropeptide Y, circular dichroic studies of the alanine-containing peptides were performed and structure affinity relationships are discussed. Comparing the affinities of the neuropeptide Y analogs to Y1 and Y2 receptors significant differences were found for the two binding sites, which suggests a different active conformation of neuropeptide Y at the two subtypes of receptors. Using molecular dynamics calculations, two distinct conformations were identified which are in good agreement with the data obtained by structure/affinity investigations.
TL;DR: In this paper, the authors present path-integral attempts to derive effective meson-baryon Lagrangians out of QCD or QCD-motivated quark models.
TL;DR: In animals that received a peripheral nerve (PN) graft after ONS, RGCs with regenerating axons were identified by FG application to the graft at 14 and 21 days, and data suggest that regenerative axons in PN grafts derive specifically from GAP-43 reexpressing R GCs.
Abstract: SUMMARY Retinal ganglion ceHs (RGCs) in rats were retrogradely labeled with the fluorescent tracer Fluorogold (FG) and subjected to GAP-43 and c-JUN immunocytochemistry to identify those RGCs that are capable of regenerating an axon. After optic nerve section (ONS) and simulta neous application of FG to the nerve stump (group 1 experiments), GAP-43 immunoreactive RGCs (between 2 and 21 days after ONS) always represented a subfrac tion ofboth FG-Iabeled (Le., surviving) RGCs and RGCs exhibiting c-JUN. GAP-43 immunoreactive RCCs repre sented 22% of RGCs normally present in rat retinae and 25% of surviving RGCs at 5 days after ONS but were reduced to 2% and 1%, wh ich is 6% and 5% ofsurvivors at 14 and 21 days, respectively. In animals that received a peripheral nerve (PN) graft after ONS (group 2 experi ments), RGCs with regenerating axons were identified by FG application to the graft at 14 and 21 days. When
TL;DR: In this paper, the authors compared the sedimentological, palaeoecological, architectural, stratigraphic and sequential aspects of German Jurassic reefs in terms of their sedimentological (including diagenetic), palaeoencology, architectural and structural aspects.
Abstract: In order to elucidate the control of local, regional and global factors on occurrence, distribution and character of Jurassic reefs, reefal settings of Mid and Late Jurassic age from southwestern Germany, Iberia and Romania were compared in terms of their sedimentological (including diagenetic), palaeoecological, architectural, stratigraphic and sequential aspects. Upper Jurassic reefs of southern Germany are dominated by siliceous sponge—microbial crust automicritic to allomicritic mounds. During the Oxfordian these form small to large buildups, whereas during the Kimmeridgian they more frequently are but marginal parts of large grain-dominated massive buildups. Diagenesis of sponge facies is largely governed by the original composition and fabric of sediments. The latest Kimmeridgian and Tithonian spongiolite development is locally accompanied by coral facies, forming large reefs on spongiolitic topographic elevations or, more frequently, small meadows and patch reefs within bioclastic to oolitic shoal and apron sediments. New biostratigraphic results indicate a narrower time gap between Swabian and Franconian coral development than previously thought. Palynostratigraphy and mineralostratigraphy partly allow good stratigraphic resolution also in spongiolitic buildups, and even in dolomitised massive limestones.
TL;DR: The results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour.
Abstract: Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 x 1 microliter per side) of vehicle, a low (3.0 microgram/microliter) or a high (6.0 microgram/microliter) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.
TL;DR: This article intends to inform a broader audience on a fascinating class of protein toxins (bacteriocins) which usually kill only cells of the same species.
Abstract: This article intends to inform a broader audience on a fascinating class of protein toxins (bacteriocins) which usually kill only cells of the same species. Those who gained a deeper interest in bacteriocins can find a comprehensive description of the field in a recent book based on a conference (James et al. 1992), and in more specialized review articles dealing with certain aspects (Pugsley 1984a, b), or certain colicins (De Graaf and Oudega 1986; Harkness and Olschlager 1991; Lazdunski et al. 1988). The older literature has been reviewed by Brandis and Smarda (1971), Reeves (1972), Hardy (1975) and Konisky (1982).