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Biomedical subjects

B Opitz

Publications and source records attributed to B Opitz.

At least 19 recordsLinked to original sources
PubMed2006

Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells.

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently lowered IL-8 expression. Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.

Cell Culture Techniques↗
PubMed2005

Sensory and cognitive mechanisms for preattentive change detection in auditory cortex.

In order to react adequately to potentially relevant information outside the focus of attention, our brain preattentively scans the acoustic environment for irregularities. Two different mechanisms are currently discussed: (i) a sensory one based on differential states of refractoriness of neurons sensitive to the features of a regular event and of neurons sensitive to features of an irregular event; (ii) a cognitive one based on a comparison of short-lived memory representations encoding current stimulation and the invariance inherent in recent recurrent stimulation. Here, we identified regions that mediate either of the two mechanisms by combining functional magnetic resonance imaging with an experimental protocol controlling for refractoriness. The sensory mechanism was associated with activity in the primary auditory cortex, whereas the cognitive one revealed activity in nonprimary auditory areas in the anterior part of Heschl's Gyrus. Moreover, it turned out that in the traditional oddball paradigm both mechanisms contribute to irregularity detection.

Acoustic Stimulation↗
PubMed2003

Distributed cortical networks for syntax processing: Broca's area as the common denominator.

Different types of syntactic information (word category, grammatical gender) are processed at different times during word recognition. However, it is an open issue which brain systems support these processes. In the present event-related fMRI study, subjects performed either a syntactic gender decision task on German nouns (GEN), a word category decision task (WC, nouns vs. prepositions), or a physical baseline task (BASE). Reaction times in WC were faster than in GEN, supporting earlier electrophysiological results. Relative to BASE, both syntactic tasks activated the inferior tip of BA 44. In addition, BA 45 showed activation in GEN, whereas BA 47 was activated in WC. The imaging data indicate that the inferior portion of BA 44 together with type-specific prefrontal areas supports both initial word category related and later syntactic processes.

Adult↗
PubMed2003

Phonological processing during language production: fMRI evidence for a shared production-comprehension network.

Studies of phonological processes during language comprehension consistently report activation of the superior portion of Broca's area. In the domain of language production, however, there is no unequivocal evidence for the contribution of Broca's area to phonological processing. The present event-related fMRI study investigated the existence of a common neural network for phonological decisions in comprehension and production by using production tasks most comparable to those previously used in comprehension. Subjects performed two decision tasks on the initial phoneme of German picture names (/b/ or not? Vowel or not?). A semantic decision task served as a baseline for both phonological tasks. The contrasts between each phonological task and the semantic task were calculated, and a conjunction analysis was performed. There was significant activation in the superior portion of Broca's area (Brodmann's area (BA) 44) in the conjunction analysis, also present in each single contrast. In addition, further left frontal (BA 45/46) and temporal (posterior superior temporal gyrus) areas known to support phonological processing in both production and comprehension were activated. The results suggest the existence of a shared fronto-temporal neural network engaged in the processing of phonological information in both perception and production.

Adult↗
PubMed2003

Serum beta-carotene and alpha-tocopherol in horses fed beta-carotene via grass-meal or a synthetic beadlet preparation with and without added dietary fat.

The serum response of beta-carotene as an indicator of bioavailability was compared after feeding beta-carotene (0.8 mg/kg body weight) either from grass meal or a synthetic beadlet preparation (Lucarotin). Both were each given without or with added dietary vegetable fat (2-2.5% vs. 6.6% fat in dry matter) in a Latin square design with four horses. The nutritionally complete diet was supplemented with alpha-tocopherol (4 mg/kg body weight). Each treatment period (4 weeks, two serum samples) was followed by a washout period of 4 weeks with low intakes of beta-carotene (traces) and alpha-tocopherol (0.5 mg/kg body weight). Within 4 weeks of supplementation, serum beta-carotene increased about 10-fold, from a mean initial concentration of 0.05-0.53 micromol/l. There was no effect of beta-carotene source and of fat addition, respectively. Faecal excretion of beta-carotene ranged from 55 to 81% of intake. No beta-carotene was detected in any urine sample. Serum alpha-tocopherol (across all time points and animals, n=64) was 14.5 micromol/l. During supplementation, the values were significantly higher than during washout-periods. Additional dietary fat did not affect the serum response. Faecal excretion of alpha-tocopherol ranged from 69 to 121% of intake. Fat addition resulted in a significant decrease of serum cholesterol. In conclusion, the natural and the synthetic source of beta-carotene showed significant and identical bioavailability independent of additional fat.

Animal Feed↗
PubMed2002

Broca's area in the human brain is involved in the selection of grammatical gender for language production: evidence from event-related functional magnetic resonance imaging.

The neural correlates of the selection of grammatical gender during overt picture naming were investigated by event-related functional magnetic resonance imaging in the left hemisphere. Relative to simply naming a picture, the production of the definite determiner of the picture name (requiring gender selection) resulted exclusively in pronounced activation of a single region in the superior portion of Broca's area. This activation was not present in contrasts reflecting lexical access (naming a picture vs. saying "jaja" to a smiley) or articulation (saying "jaja" vs. rest). Rather, lexical access activated other inferior frontal regions, insula, fusiform and inferior temporal gyrus. Articulation involved insula, Rolandic operculum, motor and premotor cortex and superior temporal gyrus. The results are discussed with respect to data from studies investigating gender processing during language comprehension.

Adult↗
PubMed2001

Toll-like receptor-2 mediates Treponema glycolipid and lipoteichoic acid-induced NF-kappaB translocation.

Recently Toll-like receptors (TLRs) have been found to be involved in cellular activation by microbial products, including lipopolysaccharide, lipoproteins, and peptidoglycan. Although for these ligands the specific transmembrane signal transducers TLR-4, TLR-2, or TLR-2 and -6 have now been identified, the molecular basis of recognition of lipoteichoic acids (LTAs) and related glycolipids has not been completely understood. In order to determine the role of TLRs in immune cell activation by these stimuli, experiments involving TLR-2-negative cell lines, TLR-expression plasmids, macrophages from TLR-4-deficient C3H/HeJ-mice, and inhibitory TLR-4/MD-2 antibodies were performed. Glycolipids from Treponema maltophilum and Treponema brennaborense, as well as highly purified LTAs from Staphylococcus aureus and Bacillus subtilis exhibited TLR-2 dependence in nuclear factor kappaB activation and cytokine induction; however, T. brennaborense additionally appeared to signal via TLR-4. Fractionation of the T. brennaborense glycolipids by hydrophobic interaction chromatography and subsequent cell stimulation experiments revealed two peaks of activity, one exhibiting TLR-2-, and a second TLR-4-dependence. Furthermore, we show involvement of the signaling molecules MyD88 and NIK in cell stimulation by LTAs and glycolipids by dominant negative overexpression experiments. In summary, the results presented here indicate that TLR-2 is the main receptor for Treponema glycolipid and LTA-mediated inflammatory response.

Animals↗
PubMed2001

Conscious recollection and illusory recognition: an event-related fMRI study.

In this event-related functional magnetic resonance imaging (fMRI) study we examined the neuronal correlates of the subprocesses underlying recognition memory. In an explicit memory task, participants had to discriminate studied ('old') words from semantically related and unrelated 'new' (unstudied) words. We examined whether the correct rejection of semantically related words which were similar to old words, which had elicited correct responses, was based on conscious recollection of study phase information. In this task, false-positive responses to semantically related new words can be assumed to result from the assessment of the semantic similarity between test words and studied words with minimal recollection. For correct identification of old words and correct rejection of new related words we found common activation in a variety of brain areas that have been shown to be involved in conscious recollection, among them the left middle frontal gyrus, the precuneus, the retrosplenial cortex, the left parahippocampal gyrus and the thalamus. For correct responses to old words, the frontomedian wall, the posterior cingulate cortex and the nucleus accumbens were additionally activated, suggesting an emotional contribution to these judgements. Correct rejections of related new words were associated with additional activation of the right middle frontal gyrus, suggesting higher monitoring demands for these more difficult recognition judgements. False-positive responses to semantically related new words were associated with enhanced activation in the frontomedian wall. The results point to an important role of the prefrontal cortex as well as medial temporal and medial parietal regions of the brain in successful memory retrieval and conscious recollection.

Adult↗
PubMed2001

Calculation of gross energy in pet foods: new data on heat combustion and fibre analysis in a selection of foods for dogs and cats.

Seven pectin samples, six galactomannan sources, five carrageen samples, four alginate samples, one sample of gum traganth, agar agar and gum arabicum, two xanthan samples, two inulin samples and a galacto oligosaccharide, 22 cellulose samples, six lignin samples, four starch samples, nine protein samples, six isolated fats, three meat samples, two lung samples, two samples of skimmed milk powder, 12 prepared complete dry dog foods, 21 moist dog foods, nine dry and 25 moist cat foods and 10 faecal samples were analysed for heat combustion (adiabatic bomb calorimetry), crude nutrients, acid detergent fibre (ADF), and acid detergent lignin (ADL). Some of the non-starch polysaccharides which gave low levels of crude fibre and ADF were also analysed for total, insoluble and soluble fibre. The heat combustion of cellulose ranged between 17.0 and 17.5 kJ/g organic matter (OM). The variation was somewhat larger for other non-starch polysaccharides (pectin, galactomannan sources, carageen, alginate, gums, xanthan, inulin) where heat combustion ranged between 14.0 and 18.2 kJ/g OM. The heat combustion of lignin averaged 25.5 kJ/g OM with considerable variation (17.0-29.2 kJ/g OM). Starch had a narrow range (17.2-17.3 kJ/g OM). Heat combustion of protein samples varied between 22.0 and 24.6 kJ/g, and of fat samples varied between 38.0 and 39.6 kJ/g OM. When cellulose was analysed for crude fibre only between 62 and 85% OM was detected. ADF analyses of cellulose ranged between 75 and 93% OM. The crude fibre content of all other non-starch polysaccharides did not exceed 13% OM, with the exception of pectins (ADF 0.7-37% OM) and alginates (ADF 39-66% OM), the ADF content was also below 13% in these samples. In contrast the total fibre content was above 80% OM in all non-starch noncellulose polysaccharides and the percentage of soluble fibre was high (25-93% OM). Unprocessed lignin gave high readings for crude fibre (39-61% OM) and ADF (96-99% OM), while processed lignin had low crude fibre content (< 1% OM) and low ADF content (< 32%). ADL determined unprocessed lignin (78-91% OM), but again processed lignin was analysed incompletely (< 29%). Pectin and alginate gave false positive ADL readings of up to 31% OM, while all other non-starch polysaccharides were not determined by ADL. When gross energy was calculated with the factors (kJ/g) 24 for protein, 38 for fat and 17 for all carbohydrate, including fibre, there was a good correlation between calculated gross energy and heat combustion in 67 pet foods as well as in meat, lung and skimmed milk powder. In contrast to this the same factors underestimated heat combustion of faeces by around 8%.

Animal Feed↗
PubMed2000

Activation of mitogen-activated protein kinases p42/44, p38, and stress-activated protein kinases in myelo-monocytic cells by Treponema lipoteichoic acid.

We have shown previously that phenol/water extracts derived from two novel Treponema species, Treponema maltophilum, and Treponema brennaborense, resembling lipoteichoic acid (LTA), induce cytokines in mononuclear cells. This response was lipopolysaccharide binding-protein (LBP)-dependent and involved Toll-like receptors (TLRs). Here we show that secretion of tumor necrosis factor-alpha induced by Treponema culture supernatants and extracted LTA was paralleled by an LBP-dependent phosphorylation of mitogen-activated protein kinases (MAPKs) p42 and p44, and p38, as well as the stress-activated protein kinases c-Jun N-terminal kinases 1 and 2. Phosphorylation of p42/44 correlated with an increase of activity, and tumor necrosis factor-alpha levels were significantly reduced by addition of inhibitors of p42/44 and p38, PD 98059 and SB 203580, respectively. Treponeme LTA differed from bacterial lipopolysaccharide regarding time course of p42/44 phosphorylation, exhibiting a prolonged activation of MAPKs. Furthermore, MAPK activation and cytokine induction failed to be strictly correlated. Involvement of TLR-4 for phosphorylation of p42/44 was shown employing the neutralizing anti-murine TLR-4 antibody MTS 510. In TLR-2-negative U373 cells, the compounds studied differed regarding MAPK activation with T. maltophilum leading to a stronger activation. In summary, the data presented here show that treponeme LTA are able to activate the MAPK and stress-activated protein kinase pathway involving LBP and TLR-4.

Animals↗
PubMed2000

Involvement of lipopolysaccharide binding protein, CD14, and Toll-like receptors in the initiation of innate immune responses by Treponema glycolipids.

Culture supernatants from Treponema maltophilum associated with periodontitis in humans and Treponema brennaborense found in a bovine cattle disease accompanied with cachexia caused a dose-dependent TNF-alpha synthesis in human monocytes increasing with culture time. This activity could be reduced significantly by blocking the CD14-part of the LPS receptor using the My 4 mAb and by polymyxin B. In the murine macrophage cell line RAW 264.7, Treponema culture supernatants induced TNF-alpha secretion in a LPS binding protein (LBP)-dependent fashion. To enrich for active compounds, supernatants were extracted with butanol, while whole cells were extracted using a phenol/water method resulting in recovery of material exhibiting a similar activity profile. An LPS-LBP binding competition assay revealed an interaction of the treponeme phenol/water extracts with LBP, while precipitation studies implied an affinity to polymyxin B and endotoxin neutralizing protein. Macrophages obtained from C3H/HeJ mice carrying a Toll-like receptor (TLR)-4 mutation were stimulated with treponeme extracts for NO release to assess the role of TLRs in cell activation. Furthermore, NF-kappaB translocation in TLR-2-negative Chinese hamster ovary (CHO) cells was studied. We found that phenol/water-extracts of the two strains use TLRs differently with T. brennaborense-stimulating cells in a TLR-4-dependent fashion, while T. maltophilum-mediated activation apparently involved TLR-2. These results indicate the presence of a novel class of glycolipids in Treponema initiating inflammatory responses involving LBP, CD14, and TLRs.

Acute-Phase Proteins↗
PubMed2000

Segregating semantic and syntactic aspects of processing in the human brain: an fMRI investigation of different word types.

The processing of single words that varied in their semantic (concrete/abstract word) and syntactic (content/function word) status was investigated under different task demands (semantic/ syntactic task) in an event-related functional magnetic resonance imaging experiment. Task demands to a large degree determined which subparts of the neuronal network supporting word processing were activated. Semantic task demands selectively activated the left pars triangularis of the inferior frontal gyrus (BA 45) and the posterior part of the left middle/superior temporal gyrus (BA 21/22/37). In contrast, syntactic processing requirements led to an increased activation in the inferior tip of the left frontal operculum (BA 44) and the cortex lining the junction of the inferior frontal and inferior precentral sulcus (BA 44/6). Moreover, for these latter areas a word class by concreteness interaction was observed when a syntactic judgement was required. This interaction can be interpreted as a prototypicality effect: non-prototypical members of a word class, i.e. concrete function words and abstract content words, showed a larger activation than prototypical members, i.e. abstract function words and concrete content words. The combined data suggest that the activation pattern underlying word processing is predicted neither by syntactic class nor semantic concreteness but, rather, by task demands focusing either on semantic or syntactic aspects. Thus, our findings that semantic and syntactic aspects of processing are both functionally distinct and involve different subparts of the neuronal network underlying word processing support a domain-specific organization of the language system.

Adult↗
PubMed1999

Combining electrophysiological and hemodynamic measures of the auditory oddball.

The neural mechanisms of deviancy and target detection were investigated by combining high density event-related potential (ERP) recordings with functional magnetic resonance imaging (fMRI). ERP and fMRI responses were recorded using the same paradigm and the same subjects. Unattended deviants elicited a mismatch negativity (MMN) in the ERP. In the fMRI data, activations of transverse/superior temporal gyri bilateral were found. Attended deviants generated an MMN followed by an N2/P3b complex. For this condition, fMRI activations in both superior temporal gyri and the neostriatum were found. These activations were taken as neuroanatomical constraints for the localization of equivalent current dipoles. Inverse solutions for dipole orientation provide evidence for significant activation close to Heschl's gyri during deviancy processing in the 110-160-ms time interval (MMN), whereas target detection could be modeled by two dipoles in the superior temporal gyrus between 320 and 380 ms.

Acoustic Stimulation↗
PubMed1999

The functional neuroanatomy of novelty processing: integrating ERP and fMRI results.

Recent research indicates that non-tonal novel events, deviating from an ongoing auditory environment, elicit a positive event-related potential (ERP), the novel P3. Although a variety of studies examined the neural network engaged in novelty detection, there is no complete picture of the underlying brain mechanisms. This experiment investigated these neural mechanisms by combining ERP and functional magnetic resonance imaging (fMRI). Hemodynamic and electrophysiological responses were measured in the same subjects using the same experimental design. The ERP analysis revealed a novel P3, while the fMRI responses showed bilateral foci in the middle part of the superior temporal gyrus. When subjects attended to the novel stimuli only identifiable novel sounds evoked a N4-like negativity. Subjects showing a strong N4-effect had additional fMRI activation in right prefrontal cortex (rPFC) as compared to subjects with a weak N4-effect. This pattern of results suggests that novelty processing not only includes the registration of deviancy but may also lead to a fast access and retrieval of related semantic concepts. The fMRI activation pattern suggests that the superior temporal gyrus is involved in novelty detection, whereas accessing and retrieving semantic concepts related to novel sounds additionally engages the rPFC.

Acoustic Stimulation↗
PubMed1999

[Medical confidentiality in the former DDR].

In accordance with the communist ideology of the GDR, interventions in the private domain of citizens were made without any compunction. Notwithstanding, Section 136 of the Penal Code of the GDR made it a punishable offence to divulge in professional secrets. However, this regulation only simulated the right and obligation to respect professional secrets. Organs of the state continually disregarded medical confidentiality. Besides this, there were numerous statutory medical notifications which were also a severe burden to the relationship of trust between the physician and patient. The State Security Service of the GDR also constantly infringed medical confidentiality. In "research work" carried out at the "Juridical University" of the State Security Service, a thorough strategy of procuring information actually protected by medical confidentiality was ceveloped. The physician has sole responsibility in maintaining medical confidentiality. This also applies to the period of the GDR. There are examples of physicians resisting the State Security Service.

Confidentiality↗
PubMed1998

A MEG analysis of the P300 in visual discrimination tasks.

Based on recent research that indicated that P300 scalp topography varies as a function of task and/or information to be processed, this study examined scalp-recorded magnetic fields correlated with the P300 by means of whole-head magnetoencephalography. Subjects performed two discrimination tasks, in which targets, defined on either object or spatial characteristics of the same visual stimuli, had to be discriminated. Based on the across-subject root mean square (RMS) functions a sequence of 4 components could be identified in both tasks, N1m, P3m, and two later components, which, based on their estimated neuronal sources, were classified as representing motor processes during and following the manual responses to target stimuli. Reliable between-task differences in source localization were obtained for the P3m component, but not for the other components. Inferior-medial sources were found for the P3m evoked by both spatial and object targets, with these sources being located about 3.5 cm more anterior for object targets. These results suggest that different neuronal sources, possibly located in subcortical regions in the vicinity of the thalamus, contribute to the P3m evoked by target stimuli defined by either object or spatial stimulus characteristics.

Adult↗