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Biomedical subjects

S Schenk

Publications and source records attributed to S Schenk.

At least 19 recordsLinked to original sources
PubMed2006

Chronic benzylpiperazine (BZP) exposure produces behavioral sensitization and cross-sensitization to methamphetamine (MA).

BACKGROUND: Like other psychostimulant drugs, acute exposure to benzylpiperazine (BZP) increases dopaminergic neurotransmission, producing hyperactivity and stereotypy. The consequences of repeated BZP exposure have not however been investigated. The effects of acute and repeated BZP and methamphetamine (MA) exposure on locomotor activity and stereotypy were measured in order to determine whether there was sensitization and cross-sensitization between these two psychostimulant drugs. METHODS: The effects of acute treatment with MA (0.0, 0.5, 1.0 and 2.0 mg/kg, intraperitoneal (IP)) or BZP (0.0, 5.0, 10.0, 20.0 and 40.0 mg/kg, IP) on locomotor activity and stereotypy were determined. Effects of repeated exposure were determined in other groups that received five daily injections of 2.0 mg/kg MA, 20.0 mg/kg BZP or vehicle. Following a 2-day withdrawal period, rats from each treatment group received either a low dose MA (0.5 mg/kg) or BZP (10.0 mg/kg). RESULTS: MA and BZP produced dose-dependent hyperactivity and stereotypy. Repeated MA and BZP resulted in a potentiated locomotor but not stereotypy response. Following the withdrawal period, MA pretreated rats exhibited a sensitized locomotor and stereotypy response to the low dose MA and a conditioned response to saline. BZP pretreated rats also demonstrated a sensitized locomotor response to the low dose of BZP and MA. CONCLUSIONS: The present findings indicate that repeated exposure to BZP results in sensitization and cross-sensitization to MA.

Animals↗
PubMed2006

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.

Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

Assisted Circulation↗
PubMed2005

Initial deficit and recovery of function after MDMA preexposure in rats.

RATIONALE: 3,4-methylenedioxymethamphetamine (MDMA) exposure was reported to result in deficits in serotonergic neurotransmission with concomitant behavioral suppression and tolerance to MDMA. Some data have also suggested that the neurochemical deficits recover over time, raising the question as to whether behavioral suppression would show a similar recovery. OBJECTIVES: The possibility of recovery of behavioral deficits was examined in the present study. Rats were administered an MDMA pretreatment regimen that was shown to produce numerous serotonergic deficits and behavioral suppression 2 weeks thereafter. The full expression of MDMA-produced hyperactivity was dependent upon serotonergic integrity, therefore, the present study aimed to determine whether MDMA pretreated rats were tolerant to MDMA 2 weeks after exposure. Further, because serotonergic deficits have shown recovery over time, similar behavioral tests were conducted at a later time point to determine whether functional recovery was evident. METHODS: MDMA-produced hyperactivity was measured at different withdrawal periods (2 and 12 weeks) to determine initial effects and the possibility of recovery of function. RESULTS: In saline-pretreated control rats, +/-MDMA (0.0-10.0 mg/kg) produced a dose-dependent increase in locomotor activity. Rats that had received prior exposure to MDMA (4 x 10 mg/kg MDMA injections administered at 2 h intervals) demonstrated tolerance when the activity was measured 2 weeks after pretreatment. For these rats, there was a downward shift in the dose-effect curve for MDMA-produced hyperactivity. MDMA-produced hyperactivity in rats that were tested 12 weeks after pretreatment was, however, comparable to controls, suggesting recovery of function. CONCLUSION: These data are consistent with the idea that high dose MDMA exposure produces neuroadaptations that exhibit recovery with extended abstinence from the drug.

Animals↗
PubMed2005

[Neurofeedback-based EEG alpha and EEG beta training. Effectiveness in patients with chronically decompensated tinnitus].

BACKGROUND: Persisting tinnitus is an often devastating disease condition with restricted and rarely successful therapeutic options. PATIENTS AND METHODS: The present study investigates the therapeutic effect of short term neurofeedback-based EEG-Alpha- and EEG-Beta-training in 40 patients suffering from "chronic decompensated tinnitus". Patients were assigned to the Alpha or Beta group according to results of an initial EEG monitored stress-test. Four patients were excluded because they showed abnormal reactions in both EEG patterns. RESULTS: During 12 sessions, 23 patients succeeded to increase EEG Alpha activity by 16% (p< or =0.042) while 13 patients achieved no decrease of EEG Beta activity. However, both groups showed a significant reduction of subjective tinnitus annoyance by the end of the therapy (p< or =0.001) CONCLUSIONS: The results indicate that neurofeedback may represent a new promising technique in the therapy of chronic decompensated tinnitus. However, it remains to be established whether the reduction of tinnitus annoyance results from the altered brain activity patterns supported by the neurofeedback learning process.

Adult↗
PubMed2005

Female patient with proximal myotonic myopathy and ventricular tachycardia.

A 68-year-old woman with known proximal myotonic myopathy was transferred to our hospital for further diagnostic and therapeutic evaluation after successful termination of an episode of sustained ventricular tachycardia. In 2001, the myopathy was diagnosed after symptomatic weakness of the hip flexors. A cardiomyopathy with slight reduction of systolic left ventricular function was found in 2002. Coronary angiography excluded relevant coronary artery disease. The electrophysiologic examination could provoke atrial flutter, but neither a ventricular tachycardia nor a delay in the AV conduction was found. ECG and Holter ECG did not reveal any abnormalities. A reduction of the left ventricular systolic function (EF 45%) with normal size of cardiac chambers was demonstrated by echocardiography. It is known that in the patient group with myotonic dystrophies cardiac involvement manifests itself as cardiomyopathy, conduction disturbance or arrhythmia. However, only a small percentage of all patients with myotonic myopathy actually suffer from cardiac involvement. Among the different types of cardiac involvement, conduction disturbances requiring pacemaker implantation are most frequent. Only some patients develop ventricular tachycardias, and even cases of sudden cardiac death have been described. As a result of the case reports in the literature and the findings in our patient an ICD system was implanted on March 4, 2004.

Aged↗
PubMed2002

[Delayed discovery of vertebral sarcoidosis].

Vertebral bone sarcoidosis is rare and may be difficult to diagnose. Clinical manifestations are often poor and the discovery can be fortuitous. We report a case of a 64 year old woman whose vertebral sarcoidosis diagnosis was established 20 years after the primary discovery of a cured thoracic sarcoidosis.

Biopsy↗
PubMed2001

The LG3 module of laminin-5 harbors a binding site for integrin alpha3beta1 that promotes cell adhesion, spreading, and migration.

Laminins are a family of extracellular matrix glycoproteins involved in cell adhesion and migration. A major obstacle to understanding their structure-function relationships is the lack of small laminin domains capable of replicating integrin-binding, cell-adhesive, and migratory functions of the intact molecule. Here, we show that the recombinant LG3 (rLG3) module (26 kDa) of laminin-5 (Ln-5) alpha(3) chain replicated key Ln-5 activities. rLG3 but not rLG1 or rLG2 supported cell adhesion and migration of at least two distinct cell lines, in an integrin alpha(3)beta(1)-dependent manner. Cell adhesion to rLG3 was regulated by divalent cations and accompanied by cell spreading and tyrosine phosphorylation of FAK focal adhesion kinase. The integrin binding activity of rLG3 was confirmed by rLG3 affinity chromatography of detergent cell lysates, which resulted in specific purification of integrin alpha(3)beta(1). To our knowledge, this is the first report directly demonstrating that a recombinant laminin LG module is an active domain capable of supporting integrin-dependent cell adhesion and migration.

Amino Acid Sequence↗
PubMed2001

A novel approach of direct ex vivo epitope mapping identifies dominant and subdominant CD4 and CD8 T cell epitopes from Listeria monocytogenes.

We used a novel approach for the direct ex vivo identification and characterization of T cell epitopes based on the screening of peptide spot libraries with freshly isolated splenocytes in a sensitive enzyme-linked immunospot (ELISPOT) assay. This technique was applied for the analysis of splenocytes from Listeria monocytogenes-infected BALB/c and C57BL/6 mice. The screening of peptide spot libraries covering the whole listeriolysin O and p60 of L. monocytogenes confirmed all known CD4 and CD8 T cell epitopes of these proteins and additionally revealed six new H-2(d) and six new H-2(b)-restricted T cell epitopes. New epitopes were categorized into CD4 and CD8 T cell epitopes by ex vivo ELISPOT analysis with separated T cell populations. The quantitative analysis of cells reactive with these CD4 and CD8 T cell epitopes revealed the existence of dominant and subdominant CD4 and CD8 T cell populations during L. monocytogenes infection. As a consequence of these data we suggest that ELISPOT-based screening of peptide spot libraries could be a general approach for the rapid identification and characterization of pathogen-specific T cell populations during various infectious diseases.

Animals↗
PubMed2001

Influence of a conditioned light stimulus on cocaine self-administration in rats.

RATIONALE: A number of studies have suggested that the continued presentation of stimuli associated with cocaine may contribute to drug-seeking and drug-taking. The influence of conditioned stimuli on the maintenance of self-administration has not, however, been systematically investigated. OBJECTIVES: This study was designed to determine whether omission of a stimulus that had been paired with self-administered cocaine would influence the maintenance of cocaine self-administration and whether the effect was dependent on cocaine dose or session length. METHODS: During self-administration training, self-administered cocaine infusions were always paired with the illumination of a light. On test days, self-administered cocaine was delivered either with or without the cocaine-associated cue. For one group of rats, responding maintained by cocaine (0.50 mg/kg per infusion) was measured during daily 18-h sessions. For other groups, responding maintained by additional doses of cocaine (0.125, 0.25, or 1.0 mg/kg per infusion) was measured during daily 8-h sessions. For a final group, daily test sessions (4-5 h) produced the dose-effect curve (0.015-1.0 mg/kg per infusion) by repeatedly reducing the cocaine dose from a starting dose of 1.0 mg/kg per infusion. RESULTS: Removal of the light cue decreased cocaine self-administration. The magnitude of this effect was dependent on the dose of self-administered cocaine and on the test session duration. Greater decrements in responding were produced as session length increased or when low doses of cocaine were self-administered. CONCLUSIONS: These findings demonstrate that in the absence of a cocaine-associated stimulus, cocaine self-administration is attenuated and that maintenance of cocaine self-administration is maximally affected by the presence or absence of the conditioned stimulus when the self-administered dose is low and/or when session duration is long.

Animals↗
PubMed2001

[Safety and efficacy of LK565--a new polymer ultrasound contrast medium].

We tested a newly developed ultrasound contrast agent (LK565) from poly-aspartic acid (PAA; particle size 3 microns; particle content: air) in 15 healthy male probands (20-38 years) in doses of 10, 30 and 100 mg intravenously. One day and immediately before the study a routine laboratory test, an ECG and an EEG were performed. The EEG was continued through the complete time period that the ultrasound contrast lasted, i.e., up to one hour after the injection. All probands were followed clinically for 24 hours when the routine laboratory and the ECG were repeated. All subjects tolerated the contrast agent well. There were no changes in either the EEG or in the ECGs performed throughout the study. There were no significant laboratory changes except for a small and transient increase in the neutrophil count in five probands receiving the highest dose. All injections with 10 mg led to a significant improvement in the color Doppler signal. All injections with 30 and 100 mg led to a very strong echo contrast lasting for 5 to 12 minutes in the harmonic B-mode. Using the latter, fragments of intramyocardial coronaries could be visualized. The tested ultrasound polymer contrast agent was safe, well tolerated and efficient in this acute study.

Adult↗
PubMed2001

Effect of the kappa-opioid receptor agonist, U69593, on reinstatement of extinguished amphetamine self-administration behavior.

Previous research has indicated that pretreatment with the kappa-opioid receptor agonist, U69593, decreased the ability of experimenter-administered cocaine to reinstate extinguished cocaine self-administration behavior. This effect was specific to cocaine-produced drug seeking since U69593 failed to attenuate the ability of experimenter-administered amphetamine to reinstate extinguished cocaine self-administration behavior. One possibility is that U69593 selectively attenuates the behavioral effects of the drug that was originally self-administered. In order to test this hypothesis, the present study examined the effect of U69593 (0.0 or 0.32 mg/kg) on the reinstatement of extinguished amphetamine self-administration behavior produced by experimenter-administered injections of cocaine and amphetamine. Following extinction of amphetamine self-administration (0.04 mg/kg/infusion) the ability of cocaine (0.0, 5.0, 10.0 or 20.0 mg/kg) or amphetamine (0.0, 0.3, 1.0 or 3.0 mg/kg) to reinstate extinguished self-administration behavior was measured. Both drugs reinstated extinguished responding and the reinstatement was attenuated by pretreatment with U69593. The data indicate that the ability of U69593 to decrease drug seeking is not restricted to subjects experienced with cocaine self-administration. Self-administration history does, however, determine the effect of U69593 on amphetamine-produced drug seeking.

Amphetamine↗
PubMed2001

A novel polymorphism in the promoter of the RAGE gene is associated with non-small cell lung cancer.

The receptor for advanced glycosylation endproducts (RAGE) is abundant at both the transcriptional and translational level in normal lung but is not expressed in non-small cell lung cancer (NSCLC). In order to determine whether sequence variations might be responsible for the inactivation of RAGE in NSCLC, we investigated the RAGE gene in primary NSCLCs and in the corresponding normal tissues of nine patients. Although sequence analysis revealed no somatic, tumor-associated mutations, six novel sequence variants were identified: T-->A in the promoter region 388 bp upstream of the start codon: T-->A in exon 1 (Ala2Ala), C-->G in exon 3 (Val89Val), C-->T in intron 6, G-->C and C-->G in exon 10 (Arg365Ser and Arg369Gly). In addition, we detected a 63 bp deletion in the promoter region (358-421 bp upstream of the start codon) in one NSCLC patient. The T-->A transversion in the promoter region was detected in three of nine patients. Further analysis of this polymorphic locus in 54 NSCLC patients and 59 non-cancer controls revealed a significant difference in the genotype distribution between NSCLC patients and controls. Interestingly, the AA genotype was more common in NSCLC patients (20.8%) than in controls (3.5%). The cumulative occurrence of the AA variant in NSCLC suggests that this genotype is a putative risk factor for NSCLC development.

Aged↗
PubMed2001

Effects of the kappa-opioid receptor agonist, U69593, on the development of sensitization and on the maintenance of cocaine self-administration.

Previous studies showed that prior administration of kappa-opioid agonists decreased the development of sensitization to some of the behavioral effects of cocaine. The present study sought to determine whether the development of sensitization to cocaine's reinforcing effects was also sensitive to antagonism by kappa-opioid agonists. During a pretreatment phase, the kappa-opioid agonist, U69593 (0.0 or 0.32 mg/kg) was administered prior to (1) 2 daily injections of cocaine (0.0 or 20.0 mg/kg), or (2) cocaine or saline administered via a yoking procedure. Cocaine pretreatment decreased the latency to acquisition of cocaine self-administration. However, prior administration of U69593 during the pretreatment phase failed to attenuate the development of this sensitized response to cocaine's reinforcing effect. In other groups, the effect of acute U69593 pretreatment on the maintenance of cocaine self-administration was examined during a 10 hr session. During training and testing, a stimulus was associated with each self-administered cocaine infusion for one group whereas responding of another group was reinforced by a cocaine infusion alone. On the test day, pretreatment with U69593 (0.32 mg/kg) decreased responding during each hour of the 10 hr session for the group that was reinforced with cocaine plus the cocaine-associated stimulus. U69593 failed to produce a long-lasting disruption of cocaine self-administration for rats that were trained and tested without the cocaine-associated stimulus. These data suggest that the acquisition and maintenance of cocaine self-administration are differentially sensitive to manipulations of kappa-opioid systems. Further, the disruption of cocaine self-administration by U69593 may be due to interactions with mechanisms that underlie facilitative effects of stimuli that have been associated with self-administered cocaine infusions.

Animals↗
PubMed2001

Genomic organization and chromosomal mapping of SPARC-like 1, a gene down regulated in cancers.

Human SPARC-like 1 (SPARCL1), also known as MAST9 or hevin, is a member of the SPARC protein family. Originally we identified SPARCL1 as one of the genes down regulated in human non-small cell lung cancer (NSCLC). Recent reports indicate that the down regulation of SPARCL1 also occurs in prostate and colon carcinomas, suggesting that SPARCL1 inactivation is a common event not only in NSCLCs but also in other tumors of epithelial origin. In the present work we report the cloning and mapping of the genomic locus of human SPARCL1. Using fluorescence in situ hybridization analysis, SPARCL1 was localized to chromosome 4q22-25, a region often deleted in human cancers. Furthermore, we show that the intron/exon organization of the human SPARCL1 gene is similar to its murine homologue SC1. SPARCL1 contains 11 exons and 10 introns which span approximately 47 kb of the genome. We also sequenced the 5'-flanking region of the human SPARCL1 gene containing 2.4 kb of the putative promoter region. The data presented herein are a prerequisite for deletion/mutation analysis of the SPARCL1 gene in tumors. In addition, knowledge of the SPARCL1 promoter sequence allows to investigate the regulation of SPARCL1 expression on the transcriptional level. Taken together our results will help to clarify the function of SPARCL1 in tumor formation.

Base Sequence↗
PubMed2000

Ignition of combustible/air mixtures by small radiatively heated surfaces.

Optical radiation as an ignition source in potentially explosive atmospheres was investigated for a number of explosive mixtures with respect to the most important case occurring in practice, i.e., absorption of the radiation by a solid target. Iron oxide was used as the target material. The combustibles were selected in compliance with the well-known temperature classes and apparatus groups to allow a useful graduation of the power limits to be applied.

Absorption↗