Geschlechtskrankheiten

Ohne Zusammenfassung     

Maturation of obligatory auditory responses and their neural sources: evidence from EEG and MEG

Neural auditory responses are known to change from childhood to adulthood. The most prominent components of the event-related potentials (ERPs) found in children are the P1 and N2, while the P1 and N1 are strongest in adults. Previous dipole localizations showed regions of the auditory cortex (AC) underlying these responses. An N1 in children, however, has only been observed in older age or under certain experimental conditions different than commonly applied in adults. The current study aimed to further elucidate on auditory processing and related components in school-aged children. To do this, MEG and EEG was recorded in adults and 9 to 10year old children, while presenting pure tones either repetitively or randomly among tones of different pitch. Furthermore, the current paradigm was explicitly designed to not only investigate the P1 and N2 in children, but moreover to examine N1 modulations based on different refractory states caused by the two conditions. Our results are clear cut. In adults, P1(m) and N1(m) components were localized in AC regions, with the N1(m) largely attenuated for repetitive tones. The P1(m) and N2(m) components observed in children were also localized in AC regions. Most importantly, ERP modulations in the N1 time window (i.e., larger responses for random than repetitive tones) were remarkably similar for adults and children, both in amplitude and latency. This effect indicates that the N1 sub-component reflecting frequency-specific refractoriness is fully developed in 9 to 10year old children. Thus, previous interpretations on the function and maturation of the N1 need reconsideration.     

The role of Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and CARD15/NOD2 mutations in the susceptibility and phenotype of Crohn's disease

BACKGROUND: We investigated the influence of 2 common Toll-like receptor 4 (TLR4) polymorphisms on susceptibility and disease characteristics of Crohn's disease (CD). METHODS: Genomic DNA from 204 patients with CD and 199 unrelated controls was analyzed for the presence of 2 single nucleotide polymorphisms in the TLR4 gene, resulting in the amino acid substitutions Asp299Gly and Thr399Ile. In addition, the carrier status for the 3 common CD-associated CARD15/NOD2 gene mutations, Arg702Trp, Gly908Arg, and 1007fs, was determined. The frequency of the different genotypes was compared, and a detailed genotype-phenotype correlation was performed. RESULTS: An almost 2-fold increase in the frequency of the TLR4 Asp299Gly phenotype was observed in patients with CD (14.2%) compared with healthy controls (7.5%, P = 0.038, odds ratio = 2.03). The prevalence of a stricturing phenotype was increased in patients heterozygous for 1 of the TLR4 polymorphisms studied (Asp299Gly, 34.5%; Thr399Ile, 36.7%) compared with patients with wild-type TLR4 (17.1% and 16.7%; P = 0.04 and 0.02, respectively). The presence of the Asp299Gly polymorphism in the absence of CARD15/NOD2 mutations was a particularly strong predictor of the stricturing disease phenotype that was present in 47.4% of the patients with Asp299Gly+/NOD2- compared with 10.1% of the patients with the Asp299Gly-/NOD2+ status (P = 0.0009; P = 0.0004 for Thr399Ile+/NOD2- versus Thr399Ile-/NOD2+). In contrast, there was a trend toward a higher prevalence of the penetrating phenotype in the TLR4-/NOD2+ group (71.6%) compared with the TLR4+/NOD2- group (47.4%, P = 0.059). CONCLUSIONS: The TLR4 Asp299Gly polymorphism is a risk factor for CD. TLR4 and CARD15/NOD2 mutations may contribute to distinct disease phenotypes.     

Detection and quantification of functionally defined hematopoietic progenitor cells and tissue specific mRNA within the peripheral blood of myeloma patients after administration of granulocyte colony-stimulating factor and erythropoietin

Objective:  Hematopoietic progenitor cells (HPC) as well as tissue committed stem cells expressing mRNA specific to various somatic tissues are thought to be part of the CD34⁺ bone marrow compartment. In this study, we explore and quantify their mobilization in patients with multiple myeloma undergoing chemotherapy upon administration of granulocyte colony-stimulating factor (G-CSF) plus/minus erythropoietin (EPO).
Patients and methods:  HPC were quantified by flow cytometry and functional assays within the blood of healthy donors and myeloma patients before and after chemotherapy followed by G-CSF or G-CSF + EPO given subcutaneously. The mRNA expression was studied by quantitative polymerase chain reaction (PCR). Cytokines and peripheral blood protease levels were measured by an enzyme-linked immunosorbent assay.
Results:  EPO did not significantly alter the number of HPC mobilized by G-CSF alone, and mRNA specific for liver, brain, muscle and kidney was detected in both treatment groups. Quantitative PCR analysis revealed a 2.7-fold increased expression of glial fibrillary acidic protein after G-CSF + EPO administration compared to G-CSF alone ( P  = 0.003). The concentration of G-CSF rose from 62 ± 22 pg/mL and 48 ± 10 pg/mL to 28 ± 9 ng/mL and 85 ± 10 ng/mL after 10 d of treatment with G-CSF and G-CSF + EPO, respectively. The concentration of neutrophil elastase (NE) rose only in the G-CSF group by a factor 1.5.
Conclusion:  The alteration of G-CSF and NE levels as well as the expression of tissue committed RNA after the administration of EPO in addition to G-CSF indicate that different growth factors mobilize different stem cells that might potentially be used for the support of tissue repair in future treatment protocols.     

Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis

The myeloperoxidase enzyme (MPO) is expressed specifically in myeloid cells and catalyzes the formation of hypochlorous acid and other cytotoxic oxidants. We previously reported that two alleles of MPO exist which differ in promoter strength due to a base difference in an Alu-encoded hormone response element. The present study shows that the higher expressing MPO genotype is overrepresented in early onset multiple sclerosis in females, implicating MPO in this demyelinating disease. Contrary to the general conception that macrophages lack MPO, immunohistochemical analysis shows that MPO is present in microglia/macrophages in and around MS lesions as shown by colocalization with major histocompatibility antigens HLA-DR and phagocytized myelin. Also, MPO mRNA sequences are detected in cDNA derived from isolated human adult microglia. This is the first evidence that MPO is present in microglia/macrophages at MS lesions, that MPO gene expression occurs in microglia and that MPO plays a role in MS pathogenesis as shown by the allelic disequilibrium in early onset disease.     

Complete genome sequence and analysis of Wolinella succinogenes

To understand the origin and emergence of pathogenic bacteria, knowledge of the genetic inventory from their nonpathogenic relatives is a prerequisite. Therefore, the 2.11-megabase genome sequence of Wolinella succinogenes, which is closely related to the pathogenic bacteria Helicobacter pylori and Campylobacter jejuni, was determined. Despite being considered nonpathogenic to its bovine host, W. succinogenes holds an extensive repertoire of genes homologous to known bacterial virulence factors. Many of these genes have been acquired by lateral gene transfer, because part of the virulence plasmid pVir and an N-linked glycosylation gene cluster were found to be syntenic between C. jejuni and genomic islands of W. succinogenes. In contrast to other host-adapted bacteria, W. succinogenes does harbor the highest density of bacterial sensor kinases found in any bacterial genome to date, together with an elaborate signaling circuitry of the GGDEF family of proteins. Because the analysis of the W. succinogenes genome also revealed genes related to soil- and plant-associated bacteria such as the nif genes, W. succinogenes may represent a member of the epsilon proteobacteria with a life cycle outside its host.     

Is auditory evoked potential augmenting/reducing affected by acute tryptophan depletion?

Several lines of evidence suggest that the auditory evoked potential (AEP) augmenting/reducing slope may serve as a biological marker of central serotonergic activity. According to Hegerl and Juckel (Biol. Psychiatry, 33, 1993, 173), reduced serotonergic activity is hypothesized to increase the slope of the AEP amplitude stimulus intensity function (ASF-slope). Hints for this hypothesis were investigated by employing the acute tryptophan depletion paradigm in 18 healthy females. A within-subject, placebo controlled double-blind cross over design was used for that purpose. Subjects ingested both a 50 g amino-acid drink with (placebo condition) and without tryptophan (depletion condition). With respect to the N1/P2-slope, test-retest reliability of a 1 week interval ranged between r=0.56 and 0.58 for the pre-ingestion baseline recording sessions. Affect was not altered by tryptophan depletion and not related to the ASF-slope. The comparison between placebo and depletion conditions did not reveal significant alterations of the ASF-slope, neither after 5 nor 6 h post-ingestion. Thus, the results do not support the assumption of the ASF-slope reflecting central serotonergic function.