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S Schenk

Publications and source records attributed to S Schenk.

At least 55 records · Page 3Linked to original sources
PubMed1996

Diversity of human T cell receptor sequences of T cell clones with specificity for Bet v 1 peptide/MHC II complexes.

T cell clones (TCC) were raised from the peripheral blood of patients suffering from tree pollen allergy. All TCC were restricted by HLA-DR molecules. In order to investigate possible intervention targets in Type I allergic diseases, we have examined T cell receptor (TCR) alpha- and beta-chain nucleotide sequences of several allergen-reactive human CD4+ TCC specific for four frequently found epitopes of Bet v 1, the major birch pollen allergen. In general, TCC specific for the 4 epitopes investigated, used diverse TCRAV and TCRBV gene segments. Moreover, the junctional regions encoding the third complementarity determining regions (CDR3) of the TCR showed striking heterogeneities in length and amino acid composition. A more restricted use of two J gene segments (TCRBJ1S4 and 2S7) was only observed in the beta-chain of TCR used by TCC specific for epitope 1. In addition, all TCC specific for epitope 4 showed an arginine residue in the N-terminal region of their TCRBV CDR3 loops despite their sequence diversities. In view of the striking heterogeneities found, therapeutical strategies aimed at the clonal deletion of allergen-specific T cell clones, providing help for IgE synthesis, may not be feasible. Moreover, our results cast a doubt on the theory, that the CDR3 exclusively provides the primary contact with the peptide bound in the major histocompatibility (MHC) groove, and suggest additional interaction with MHC class II.

Allergens↗
PubMed1996

Acute and repeated exposure to caffeine: effects on reinstatement of extinguished cocaine-taking behavior in rats.

Previously, we demonstrated that caffeine dose-dependently reinstated extinguished cocaine-taking behavior in rats. In the present study, we determined whether this effect of caffeine would extinguish with repeated exposures. Rats were first trained to self-administered cocaine intravenously. Once reliable self-administration was obtained, the pumps that delivered cocaine were turned off and the lever-pressing behavior was extinguished. Every 4 days the rats were given an injection of caffeine (20.0 mg/kg) and its ability to reinstate responding was measured. Some rats received each of four exposures to caffeine in the previously cocaine-associated environment. Other rats received the first three exposures to caffeine in the home cage and the last exposure to caffeine in the previously cocaine-associated environment. The results indicated that although caffeine was an effective cue for reinstatement of extinguished cocaine taking, the effect was reduced when repeated exposures occurred in the test environment. In addition, when 4 drug-free days were interspersed between self-administration and reinstatement testing, the caffeine effect was greater than when testing was conducted 1 day following the last self-administration session. Thus, extended withdrawal increases the priming effects of caffeine. The results are discussed in terms of the effectiveness of cue exposure as an adjunct to current therapies for cocaine abuse.

Analysis of Variance↗
PubMed1996

Sequence comparisons of the CDR3 hyper-variable loops of human T cell receptors specific for three major T cell epitopes of the birch pollen allergen Bet v 1.

We have analysed the T cell receptor (TCR) alpha and beta chain sequences of 16 human CD4+ T cell clones (TCCs) specific for three important epitopes of the major birch pollen allergen Bet v 1. The TCCs were raised from the peripheral blood of eight patients with birch pollen allergy, showing allergic rhino-conjunctivitis and allergic asthma. The TCCs from these individuals were specific for Bet v 1-derived peptides: amino acids (aa)77-92 (epitope 1), aa93-108 (epitope 2) and aa113-126 (epitope 3). The DNA sequence analysis of the TCRAV and BV regions revealed heterogeneous repertoires for recognition of the peptides. Multiple combinations of AV/AJ and BV/BJ were used. However, some inter-individual restriction was evident. A limited selection of AVS and the normally infrequently used BV1S4 was obvious in TCCs specific for epitope 1. The TCRBV13 was more frequent in TCCs recognizing epitope 3. A very narrow distribution in length could be seen in the CDR3 sequences of the beta chain of TCRs with specificity for epitopes 1 and 2. Inter-individual positional micro-restriction was observed for the aa motif LR in the tCDR3 (epitope 1), for the aa residue M in the alphaCDR3 and for the aa residue G in the betaCDR3 (epitope 3). Our results illustrate clearly that each antigenic peptide derived from a single allergen, is capable of selecting different characteristics in the responding repertoire of TCRs, thus increasing the complexity of allergen-recognition by T lymphocytes. Therefore, our findings limit the potential use of TCR targeted therapeutical strategies in Type I allergy.

Allergens↗
PubMed1995

Tenascin-C in serum: a questionable tumor marker.

In normal adult tissue tenascin-C (TN-C) is usually expressed at low levels. However, it is strongly induced in many tumors as well as in other pathological conditions often associated with inflammation. To evaluate the diagnostic significance of TN-C, we established a sensitive sandwich ELISA to determine TN-C levels in serum. Furthermore, we investigated the distribution of TN-C variants in serum and found the large TN-C isoforms to be predominant. We measured TN-C in sera from 15 healthy persons, 75 tumor patients and 84 patients selected due to their elevated levels of the acute-phase protein C-reactive protein (CRP), which is a very specific marker for infection and inflammation. It was found that sera from cancer patients can have elevated TN-C levels; however, the increase was more pronounced in persons with high levels of CRP. There appeared to be a correlation of TN-C levels with the levels of CRP. In view of these facts, the diagnostic value of TN-C levels in serum as a potential tumor marker seems to be questionable, since our data show that TN-C levels can be elevated as a consequence of infection and inflammation.

Acute-Phase Reaction↗
PubMed1995

Nonallergic individuals recognize the same T cell epitopes of Bet v 1, the major birch pollen allergen, as atopic patients.

The immune response toward allergens in nonallergic healthy individuals was investigated. To boost immune responses, two injections of birch pollen extract were administered to five nonallergic volunteers. T cell lines (TCL) with specificity for Bet v 1, the major birch pollen allergen, were established and analyzed for epitope specificity using overlapping peptides. Forty-nine T cell clones (TCC) specific for Bet v 1 were isolated from TCLs. Comparison with TCL and TCC established from birch pollen-allergic patients was performed. All TCC revealed the Th phenotype. Epitope specificities of TCL and TCC from nonatopics were identical to those found in allergic individuals. No association between MHC class II molecules and particular epitopes could be observed. In nonallergic as well as in allergic individuals, cytokine production in response to specific stimulation revealed a majority of Th-clones producing IL-4 and IFN-gamma. However, TCC derived from atopic individuals revealed a higher IL-4/IFN-gamma ratio. Immunoblot and ELISA revealed Bet v 1-specific IgG in nonallergic individuals before and after booster injections, but no IgE could be detected. High levels of Bet v 1-specific IgG and IgE could be detected in birch pollen-allergic patients. It can be concluded, that nonatopic and allergic individuals display the same repertoire of T cell specificities. In allergic individuals, the activation of allergen-specific TCC leads to a higher ratio of produced IL-4 vs IFN-gamma, which is responsible for enhanced IgE production.

Allergens↗
PubMed1995

The complexity in regulating the expression of tenascins.

The tenascins are a growing family of extracellular matrix proteins of typical multidomain structure. The prototype to be discovered was tenascin-C. It shows a highly regulated expression pattern during embryonic development and is often transiently associated with morphogenetic tissue interactions during organogenesis. In the adult organism reexpression of tenascin-C occurs in tumors and many other pathological conditions. Tenascin-C expression can be regulated by many different growth factors and hormones. Furthermore, mechanical strain exerted by fibroblasts seems to induce the expression of tenascin-C. This could represent a mechanism of translating mechanical forces into protein patterns, a step of potential relevance in the organization of embryogenesis. Tenascin-C as well as tenascin-R are believed to counteract the cell adhesion and spreading activity of fibronectin, thereby facilitating cell movement.

Animals↗
PubMed1995

T-cell epitopes of Phl p 1, major pollen allergen of timothy grass (Phleum pratense): evidence for crossreacting and non-crossreacting T-cell epitopes within grass group I allergens.

BACKGROUND: The use of peptides representing T-cell epitopes of allergens is a modern concept for improvement of specific immunotherapy. A prerequisite for this approach is the identification of T-cell epitopes of atopic allergens. METHODS: T-cell lines and 40 T-cell clones (TCC) specific for Phl p 1, the group I allergen of timothy grass (Phleum pratense), were established from the peripheral blood of nine patients allergic to grass pollen and mapped for epitope specificity by using overlapping dodecapeptides. Phenotype and cytokine production profile of TCC were investigated. Representative TCC were analyzed for HLA-restriction, T-cell receptor V beta gene usage, and crossreactivity with grass pollen extracts from Dactylis glomerata, Poa pratensis, Lolium perenne, Secale cereale, and selected amino acid sequence-derived peptides. RESULTS: Patients displayed IgE binding to all grass species investigated. Forty TCC were established. Fifteen T-cell epitopes could be identified on Phl p 1. Of 40 TCC, 39 displayed the helper cell (Th) phenotype; one clone was CD8+. Specific stimulation induced a Th2-like type of cytokine production in 20 of 39 TCC. Crossreactivity studies revealed crossreacting and non-crossreacting T-cell epitopes. CONCLUSION: Phl p 1, a major grass pollen allergen, harbors multiple T-cell epitopes. Species-specific and crossreacting T-cell epitopes exist among group I allergens of grasses. Epitope recognition patterns could not be correlated with particular HLA haplotypes. A restricted T-cell receptor V beta gene usage was not observed.

Allergens↗
PubMed1995

Dermo-epidermal separation is associated with induced tenascin expression in human skin.

Tenascin, a large glycoprotein of the extracellular matrix, shows a site-restricted distribution during embryogenesis, and can be found in adults in a variety of pathological conditions. In normal skin, tenascin is expressed at low levels, but it is upregulated in skin tumours, in a number of skin diseases with epidermal hyperproliferation and during wound healing. Several tenascin variants have been described, and these arise by alternative splicing. Using a monoclonal antibody recognizing all tenascin variants, and polyclonal antibodies specific for the large tenascin variants, we have investigated tenascin expression in bullous diseases such as epidermolysis bullosa, pemphigus, bullous pemphigoid and pemphigoid gestationis. By immunohistochemistry, we have found increased tenascin staining in all patient skin samples, with a more pronounced tenascin expression in samples of autoimmune bullous diseases. The large tenascin variants seem to be major forms of tenascin occurring in healthy skin. In patients with blistering diseases, however, these large variants appear to represent a subpopulation of the induced tenascin accumulation. These findings suggest different functions for the tenascin variants in normal and diseased skin.

Animals↗
PubMed1994

Sensitization to cocaine's motor activating properties produced by electrical kindling of the medial prefrontal cortex but not of the hippocampus.

A substantial body of evidence has accumulated that implicates NMDA systems in the neural changes that are associated with the development of both electrical kindling of limbic sites and sensitization to the behavioral effects of repeated stimulant exposure. This study sought to establish whether electrical kindling of the brain was a sufficient condition for inducing sensitization to cocaine's motor activating effects and, if so, whether the cross sensitization was a result of kindling of a specific locus. Rats received daily electrical stimulation of either the medial prefrontal cortex or the hippocampus. Other rats received the electrode implants and were handled daily but received no electrical stimulation. Stage 5 seizures developed in response to the stimulation in 32-35 days. Once this criterion of kindling was established and following a 14 day waiting period the effectiveness of cocaine (0.0, 5.0 or 10.0 mg/kg) in elevating horizontal motor activity was determined. For all 3 groups (sham controls, prefrontal cortical and hippocampal stimulated rats) cocaine produced a dose-dependent increase in horizontal activity. The sham controls and hippocampal rats did not differ in the magnitude of the cocaine-produced effect. However, rats that had received stimulation of the prefrontal cortex showed heightened levels of cocaine-induced activity that were particularly apparent in response to 10.0 mg/kg cocaine. These data suggest that kindling of the prefrontal cortex had sensitized rats to the behavioral effects of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Four recombinant isoforms of Cor a 1, the major allergen of hazel pollen, show different reactivities with allergen-specific T-lymphocyte clones.

Purified preparations of allergenic proteins from plants, and in particular from pollens, consist of multiple closely related isoforms. These isoforms are highly similar in their amino acid sequences, yet they display different properties with respect to antibody binding. In this study we report of differential potencies of cross-reacting tree pollen allergens and cloned isoforms of these allergens to activate allergen-specific T-lymphocyte clones (T-cell clones; TCC). Six TCC with specificity for Bet v 1, a representative tree pollen major allergen, were established from peripheral blood of five birch-pollen-allergic donors. All TCC displayed the helper-cell phenotype. Five TCC reacted with distinct epitopes present on natural (n) and on recombinant (r) Bet v 1. One TCC could not be stimulated with r Bet v 1, in spite of strong reactivity with purified natural Bet v 1. The TCC were tested in proliferation assays using purified n Bet v 1, n Cor a 1 (the homologous major allergen of hazel pollen), r Bet v 1, four recombinant isoforms of Cor a 1 and peptides representing corresponding T-cell stimulating regions (isoepitopes) on these proteins. The clones showed different patterns of reactivity in response to stimulation with the five recombinant molecules and the corresponding peptides. Certain exchanges of amino acids within stimulating peptides correlated with a lack of proliferation of the TCC tested. These findings are important with respect to the use of broadly cross-reactive recombinant allergens or allergen-derived peptides for immunotherapy of type I allergy.

Allergens↗
PubMed1994

Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans.

BACKGROUND/AIMS: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. METHODS: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol.kg-1.h-1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol.kg-1.h-1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. RESULTS: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol.kg-1.h-1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. CONCLUSIONS: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antral and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.

Adult↗
PubMed1994

Augmentation of the neurochemical effects of cocaine in the ventral striatum and medial prefrontal cortex following preexposure to amphetamine, but not nicotine: an in vivo microdialysis study.

This study assessed the ability of cocaine to increase synaptic levels of dopamine (DA) in the ventral striatum (VS) and medial prefrontal cortex (mPFC) following repeated daily exposure to amphetamine or nicotine. In vivo microdialysis was used to assay DA levels in the awake freely moving male Sprague-Dawley rats. Three days following guide cannula implantation, subjects received 9 daily preexposure injections of amphetamine (1.0 mg/kg salt weight, IP), nicotine (0.6 mg/kg base weight, SC), or vehicle. Probes were then inserted and perfused with Ringer's solution overnight. Once stable baseline levels of DA were established, the subjects received a cocaine (15 mg/kg, IP) challenge injection and dialysate samples were collected every 20 minutes. Subjects preexposed to vehicle exhibited a 200% increase in DA levels in the VS and a 170% increase in the mPFC following the cocaine injection. DA recovery was significantly augmented in both regions in amphetamine-preexposed subjects with 450% and 285% increases above baseline levels observed in the VS and mPFC, respectively. In contrast, cocaine-induced DA levels in nicotine-preexposed subjects did not differ significantly from vehicle-preexposed controls in either brain region. Data are discussed in terms of alterations in the locomotor activating and reinforcing effects of cocaine following similar preexposure procedures.

Amphetamine↗
PubMed1994

Tenascins.

Explore the source record for details and available documents.

Alternative Splicing↗
PubMed1994

Persistence of the ability of amphetamine preexposure to facilitate acquisition of cocaine self-administration.

This study assessed the enduring effects of amphetamine preexposure on the subsequent reinforcing effects of cocaine. Rats received nine daily injections of either d-amphetamine SO4 (2.0 mg/kg, IP) or vehicle 45 days prior to testing of the acquisition of cocaine (0.25 mg/kg/infusion) self-administration. The latency to acquire reliable cocaine self-administration was shorter (day 3) in the amphetamine-preexposed rats than in the vehicle-preexposed rats (day 6). These data are comparable to those observed when testing was carried out 1 day following the treatment. In previous studies, shorter latencies to acquisition also occurred when the training dose of cocaine was increased, suggesting that the treatment had sensitized rats to cocaine's reinforcing properties. These effects of amphetamine exposure persist for 45 days following treatment, which suggest a long-lasting phenomenon.

Animals↗
PubMed1994

Reinstatement of extinguished cocaine-taking behavior by cocaine and caffeine.

Interactions between caffeine and cocaine have been demonstrated in a number of behavioral paradigms. The present study was undertaken in an attempt to determine whether caffeine could reinstate extinguished cocaine-taking behavior in rats. Experienced self-administering rats were first put through extinction training. The rats were then given an injection of either saline, cocaine (5.0, 10.0, or 20.0 mg/kg), or caffeine (5.0, 10.0, 20.0, 40.0 mg/kg). Both cocaine and caffeine induced a dose-dependent increase in the number of responses made on the previously cocaine-associated lever. These results confirm findings that the originally self-administered drug can serve as a prime to reinstate drug-taking behavior, and that nondopaminergic agonists can also provide an effective prime to reinstate responding. Potential mechanisms for these effects are discussed.

Animals↗
PubMed1994

Failure of ritanserin to block the discriminative or reinforcing stimulus effects of cocaine.

Ritanserin, a 5-HT2/1C antagonist, has been suggested to reduce the preference for cocaine in rats. In the present experiment, the action of ritanserin was investigated in locomotor activity, cocaine drug discrimination, and cocaine self-administration paradigms in rats. A low dose of ritanserin (1.0 mg/kg) was without effect on locomotor activity, while a higher dose (10.0 mg/kg) reduced both horizontal and vertical locomotor activity counts during the first 30 min of the test session. Ritanserin (0.32-32 mg/kg) did not significantly affect the discrimination of 10 mg/kg of cocaine, nor did a dose of 10.0 mg/kg significantly modify the dose-effect curve for cocaine discrimination. Ritanserin (1.0 and 10.0 mg/kg) had no significant effect on the dose-response curve for cocaine self-administration. Thus, ritanserin was without effect against either the discriminative or reinforcing stimulus effects of cocaine, suggesting that ritanserin has limited efficacy as a potential treatment for cocaine abuse.

Animals↗
PubMed1994

Molecular and functional characterization of allergens: basic and practical aspects.

Well-defined allergen preparations are, in the first line, a prerequisite for exact diagnosis, but will be supposedly useful tools in immunotherapy of Type I (IgE-mediated) allergic diseases. The allergens have to be available in standardized and highly purified form in sufficient quantities. By applying recombinant DNA techniques this goal can be achieved with respect to both, characterization and reproducibility of allergen preparations. As an example, purified recombinant non-fusion Betv1 revealed identical immunological properties with respect to interaction with both, anti-Betv1 antibodies and Betv1-specific T cell clones when compared with natural Betv1 purified from birch pollen. Moreover, cloning of allergens yielded a number of deduced primary structures of allergens, which allows computer-aided comparisons with already known amino acid sequences. Significant sequence similarities with well-described proteins may point at a biological and biochemical function of the cloned allergen, which might be of interest for considerations why a certain protein within an extract represents an allergen. Furthermore, the interaction of small peptides synthesized according to amino acid sequences of cloned allergens with allergen-specific T and B cells can be investigated. Respective results will yield information about the regulation of IgE synthesis and, thus, might point at new concepts of immunotherapy.

Allergens↗