Verarbeitung schlafbezogener Stimuli

Previous work suggests that people with poor sleep quality, especially patients with primary insomnia, show an attentional preference for sleep-related stimuli (sleep-related attentional bias). Studies investigating this effect have generally used standardised reaction time experiments, in which the effects of a large number of sleep-related stimuli were averaged. Here, we analysed the data of two studies in order to investigate the contribution of single sleep-related stimuli (words) to sleep-related attentional bias. Results showed that effect sizes of the stimuli were relatively stable between the two studies. Knowing effect sizes of individual stimuli is important for the construction of future attentional paradigms, as well as providing a better understanding of the magnitude and content of sleep-related attentional bias.     

Immunological system status and the appearance of respiratory system disturbances in thymectomized patients

INTRODUCTION: Adult-onset thymoma may be responsible for several diseases, such as pure red cell aplasia, myasthenia gravis, and immunodeficiency (Good's syndrome). Thymectomy does not always improve the patient's condition, and may even produce additional symptoms. Its pathogenesis is still not entirely understood, but autoimmunological processes and bone marrow defect are the most frequently suggested. MATERIALS AND METHODS: Eleven patients (mean age: 56.2+/-15.5 years) were analyzed 6 months to 10 years after thymectomy due to thymoma as were 25 healthy persons serving as controls. Enzyme-linked immunosorbent assay (ELISA) and flow cytometry techniques were used to evaluate the immunological status of the subjects. RESULTS: Good's syndrome was diagnosed in one patient, 4 subjects suffered from myasthenia gravis, and recurrent infections of upper and lower respiratory tract appeared in 9 patients. The immunological analyses (ELISA and flow cytometry) revealed a significantly lower IgG level (p<0.05), percentage of peripheral blood B lymphocytes (p<0.0005), and CD4:CD8 ratio (p<0.05) in thymectomized patients compared with the healthy controls. The percentages of CD4+ and CD8+ T lymphocytes expressing CD28 antigen were significantly lower in thymectomized patients than in healthy subjects (p<0.005 and p<0.01, respectively). The percentage of naive T helper lymphocytes was significantly lower in the patients than in the control group (p<0.05). CONCLUSIONS: Immunodeficiency and recurrent infections may be the first symptoms of immunological disturbances after thymectomy in adults. It is suggested that regular medical monitoring of these patients is important in preventing further complications, which may result in irreversible lung tissue destruction.     

Host immune response in B-cell lymphomas: friend or foe?

The interaction of B-cell malignancies with the host immune system is a dynamic and bilateral process. Certain lymphomas more commonly arise within a background of autoimmunity or chronic infection. Initiation of these tumors is commonly reliant on antigenic stimulation and/or T-cell help. Apart from its tumor-fueling role, the host immune response plays a critical role in cancer immunosurveillance and immunoediting. The concept of immunoediting holds that the immune system sculpts the tumor's immunogenicity in a dynamic process that involves three essential phases: elimination, equilibrium, and escape. Data obtained by studying gene-targeted animals and human lymphomas that support the critical role of the immune response in the initiation, progression, and immunoediting of lymphoid malignancies are summarized here. A thorough understanding of this interaction will lead to the identification of more rational treatment targets and improved immunotherapies in B-cell lymphomas.     

In-situ-PCR und PCR-in-situ-Hybridisierung am Paraffingewebe Neue diagnostische Möglichkeiten in der Pathologie

Zusammenfassung In-situ-PCR und PCR-in-situ-Hybridisierung sind neue molekularbiologische Methoden für Forschung und Diagnostik, die die Empfindlichkeit einer Polymerasekettenreaktion mit dem Vorteil der In-situ-Hybridisierung verbinden, gesuchte DNS-Abschnitte spezifisch einzelnen Zellen zuzuordnen. Zus?tzlich kann durch optische Kontrolle des Reaktionsproduktes die Gefahr falsch-positiver Resultate durch Kontamination mit Fremd-DNS minimiert werden. In den letzten Jahren wurde eine Vielzahl von Anwendungsprotokollen beschrieben, die es erlauben, spezifische DNA- und RNA-Sequenzen mit Hilfe dieser Methode in einfacher Weise darzustellen. Grunds?tzlich werden 2 verschiedene Methoden des DNS-Nachweises verwendet, die indirekte PCR-in-situ-Hybridisierung (PCRisHyb) und die direkte In-situ-PCR (isPCR). Anhand eines Fallbeispiels wird eine schnelle und reproduzierbare Methode für die PCRisHyb bzw. die isPCR an formalinfixiertem Paraffinmaterial vorgestellt und beide Techniken verglichen. Bei beiden durchgeführten Methoden (isPCR und PCRisHyb) zeigt sich eine gut sichtbare Darstellung des Amplifikationsproduktes bei optimal erhaltener Gewebsmorphologie. Der Vorteil der indirekten PCRisHyb liegt in der h?heren Spezifit?t, w?hrend die direkte isPCR schneller, einfacher und kostengünstiger durchzuführen ist.      

Synopse unbalancierter chromosomaler Aberrationen beim Neuroblastom durch komparative genomische Hybridisierung (CGH)

Zusammenfassung Das Neuroblastom ist der h?ufigste solide Tumor des frühen Kindesalters. Diese ph?notypisch und genotypisch heterogene Tumorentit?t weist auch klinisch unterschiedliche Krankheitsverl?ufe auf. Von den zahlreichen chromosomalen Aberrationen, die bisher beim Neuroblastom beschrieben worden sind, haben sich eine Deletion auf Chromosom 1p sowie eine N-myc-Amplifikation als wichtige Prognosefaktoren herauskristallisiert. über die Bedeutung weiterer chromosomaler Aberrationen des Neuroblastoms besteht noch Unklarheit. Mittels Einsatz der CGH konnten wir jetzt aufzeigen, da? diese noch junge cytogenetische Methode die prognostisch relevanten Aberrationen des Neuroblastoms sicher detektiert. Da durch die CGH Aussagen über das gesamte Tumorgenom in nur einem Versuchsansatz erstellt werden, gelang es uns, neue Erkenntnisse zur Bedeutung auch anderer, bisher wenig beschriebener DNA Imbalanzen zu gewinnen. Mit dieser Untersuchung wird erstmals gezeigt, da? sich die CGH als Routineverfahren bei der Prim?rdiagnostik von Neuroblastomen anbietet und somit nicht nur als Screeningmethode für die Grundlagenforschung dient.      

Graduierung von malignen Weichgewebstumoren Historische Entwicklung und aktueller Stand

Zusammenfassung Die Arbeit gibt einen überblick der historischen Entwicklung der Graduierung von malignen Weichgewebstumoren. Die M?glichkeiten der Malignit?tsgraduierung dieser Tumoren kann man bis in die Mitte des 19. Jahrhunderts zurückverfolgen. Seit den 70er Jahren ist eine auff?llige Entwicklung auf diesem Gebiet zu beobachten, die ihren H?hepunkt in den 80er Jahren erreichte. Die Graduierung der malignen Weichgewebstumoren kann in 5 Phasen eingeteilt werden. Aus der Vielzahl der M?glichkeiten der Malignit?tsgraduierung wurden 5 praxisrelevanteGrading-Systeme ausgew?hlt, auf Vergleichbarkeit und Handhabbarkeit anhand von 339 Patienten mit malignen Weichteiltumoren überprüft und einem simplen und einem komplexen multifaktoriellen System der Vorzug gegeben.      

Suramin inhibits macrophage activation by human group IIA phospholipase A2, but does not affect bactericidal activity of the enzyme

Objective:  Suramin is a polysulphonated napthylurea antiprotozoal and anthelminitic drug, which also presents inhibitory activity against a broad range of enzymes. Here we evaluate the effect of suramin on the hydrolytic and biological activities of secreted human group IIA phospholipase A₂ (hsPLA₂GIIA). Materials and Methods:  The hsPLA₂GIIA was expressed in E. coli, and refolded from inclusion bodies. The hydrolytic activity of the recombinant enzyme was measured using mixed dioleoylphosphatidylcholine/dioleoylphosphatidylglycerol (DOPC/DOPG) liposomes. The activation of macrophage cell line RAW 264.7 by hsPLA₂ GIIA was monitored by NO release, and bactericidal activity against Micrococcus luteus was evaluated by colony counting and by flow cytometry using the fluorescent probe Sytox Green. Results:  The hydrolytic activity of the hsPLA₂ GIIA was inhibited by a concentration of 100 nM suramin and the activation of macrophages by hsPLA₂ GIIA was abolished at protein/suramin molar ratios where the hydrolytic activity of the enzyme was inhibited. In contrast, both the bactericidal activity of hsPLA₂ GIIA against Micrococcus luteus and permeabilization of the bacterial inner membrane were unaffected by suramin concentrations up to 50 μM. Conclusions:  These results demonstrate that suramin selectively inhibits the activity of the hsPLA₂ GIIA against macrophages, whilst leaving the anti-bacterial function unchanged. Received 26 June 2008; returned for revision 8 August 2008; received from final revision 11 September 2008; accepted by J.Skotnicki 8 October 2008     

Leukocyte depletion during cardiac surgery with extracorporeal circulation in high risk patients

Background:  Cardiopulmonary bypass is associated with systemic inflammation that may contribute to increased perioperative mortality. Depletion of circulating leukocytes may reduce the inflammatory response. We studied the effect of a leukocyte depleting filter on leukocyte activation during cardiopulmonary bypass in high risk patients. Methods:  Fifty patients undergoing coronary artery bypass grafting with a preoperative high risk were randomly placed in an arterial line leukocyte filter group (n = 25) with a leukocyte depleting filter. Blood sampling took place from the arterial line to analyze polymorphnuclear elastase and myeloperoxidase at six time points, including: A) before the induction of anesthesia, B) before the induction of the cardiopulmonary bypass C) 1 min after the release of the aorta clamp, D) the end of the operation, E) 1 h postoperative, and F) 24 h postoperative. Results:  Levels of polymorphonuclear elastase, (PMNE), and myeloperoxidase (MPO) were found to be higher after the release of the aortic cross clamp in the leukocyte filter group; these levels remained elevated until 24 hours after surgery and were high in comparison to preoperative baseline levels. The differences in PMNE between both groups at time points C and D (p < 0.005) and E (p < 0.05) were statistically significant. The serum levels of the S-100B and neuron specific enolase (NSE) were found to be elevated between time points C and E in both groups without statistical significance. The in-hospital mortality was 16% (4 patients) in leukocyte filter group and 4% in control group (1 patient). Conclusions:  Interestingly, the activation of neutrophils was more pronounced in the LF group. The use of a leucocyte depleting filter was not advantageous for this patient cohort for clinical or biomedical endpoints. Received 17 February 2008; returned for revision 21 May 2008; received from final revision 6 August 2008; accepted by M. Katori 8 August 2008     

Protective effect of retinoid against endotoxin-induced mastitis in rats

Objective:  A lipopolysaccharide (LPS) induced mastitis model in rats was used to study the protective effect of retinoid. Materials and methods:  Commencing at gestation day 10, retinoid (dissolved in olive oil) or an equal volume of olive oil was administered to rats daily by gavage until parturition. LPS or pyrogen-free physiological saline was inoculated into the mammary gland 72h after parturition and the rats were euthanized at 12h post-infection. Results:  Myeloperoxidase (MPO), N-acetyl -β-D- glucosaminidase (NAGase), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8) in mammary tissues and CD4⁺/CD8⁺ in peripheral blood were increased and serum MPO and IL-2 in mammary tissues were decreased 12h after LPS infusion. Retinoid decreased MPO, NAGase, and TNF-α in mammary tissue and increased IL-2 in serum. Four thousand and 8000 I.U/kg•d of retinoid significantly decreased the infiltration of PMNs in mammary alveoli and ameliorated the imbalance of CD4+/CD8+ in peripheral blood. Conclusion:  These results suggest that retinoid protected against LPS-induced mastitis in a rat model. Received 18 March 2008; returned for revision 21 April 2008; received from final revision 22 June 2008; accepted by I. Ahnfeld-R?nne 10 July 2008     

Regulation of innate and adaptive immune responses by the related cytokines IL-12, IL-23, and IL-27

The functional characterization and subsequent purification of T cell growth factor/interleukin (IL)-2 in the early 1980s established this secreted protein as a key mediator of immune cell activation and provided the prototype that enabled the discovery of numerous cytokines over the ensuing two decades. While soluble immunoregulatory factors were initially identified functionally as biological activities present in the culture supernatants of activated lymphocytes/monocytes, this methodology shifted radically following the completion of the human genome sequence. Computer-generated structural modeling algorithms have replaced functional assays and biochemical purification as the initial means of discovering new cytokines. To date, a total of 31 interleukins, as well as over a dozen other related hematopoietic factors, have been identified. These cytokines and their receptors may be grouped on the basis of structural homologies as well as by shared ligand and receptor subunits. The challenge now at hand is to define the biological functions of the newly identified cytokines and to elucidate the common and divergent roles of related family members. This point is well illustrated by the IL-12/IL-23/IL-27 family, whose members share ligand and receptor subunits and play somewhat overlapping roles in innate and adaptive immune responses. These three cytokines are not entirely redundant, as they may preferentially activate na?ve or memory T cells, induce discrete T cell cytokine profiles, contribute to distinct stages of host immune responses to infectious agents, and differentially promote autoimmunity. Further elucidation of the unique functions of the IL-12 family members may lead to improved immunodiagnostics and therapies.     

ApoE phenotype is associated with inflammatory markers in middle-aged subjects

Objectives:  Apolipoprotein (apo) E phenotype has been associated with inflammation markers. The determinants of these associations and the relationship between novel inflammation marker, resistin, and apoE phenotype are studied here. Methods and Results:  Middle-aged subjects of the population- based cohort (n = 526) of the OPERA– study were studied. Intima-media thickness (IMT) was measured with carotid ultrasound. The results suggest that, apoE phenotype was a significant independent predictive factor for resistin (p < 0.01) and hsCRP (p < 0.01) levels. The association of ApoE phenotype with hsCRP was seen among the subjects with the normal renal function (p = 0.005). ApoE4 was associated (p < 0.01) with the lowest hsCRP in the lowest IMT quartile while it's relation with the highest resistin levels was evident in the highest IMT quartile. Conclusions:  ApoE phenotype is an independent determinant of plasma resistin and hsCRP levels. The extent of atherosclerosis and renal function seem to modify the effects of apoE phenotype on inflammatory parameters. Received 6 April 2008; returned for revision 6 August 2008; received from final revision 27 October 2008; accepted by M. Katori 28 October 2008     

Influence of mouse genetic background on wear particle-induced in vivo inflammatory osteolysis

OBJECTIVE AND DESIGN: Genetics may influence wear particle-induced inflammatory osteolysis after joint replacement. In the present work, mice with three different genetic backgrounds were used to test this hypothesis. TREATMENT: C57BL/6J, Balb/c and Kunming mouse were used. Each kind of mouse was divided into those receiving 30 mg UHMWPE particle implantation onto the calvariae and those receiving a sham operation. METHODS: Mice of each group were sacrificed one week after surgery. Calvariae were harvested for immunological assay of TNF-alpha and IL-1 beta secretion in supernatants of calvariae organ culture and histological analysis of calvarial sagittal suture osteolysis and osteoclastogenesis. RESULTS: Although UHMWPE particles induced obvious calvarial sagittal suture osteolysis and osteoclastogenesis in all strains as compared with their corresponding control mice, the most significant change was found in C57BL/6J mice, less severe in Balb/c mice and much less severe in Kunming mice. In agreement with pathological findings, UHMWPE particles induced the highest IL-1 beta secretion in C57BL/6J mice, compared with Balb/c and Kunming mice. However, no difference was observed concerning TNF-alpha secretion among these mice. CONCLUSION: Our data suggests that genetics had a significant influence on wear particle-induced inflammation, osteoclastogenesis and osteolysis. The influence of genetic background on implant life in patients with joint replacement warrants further investigation.     

Fibroepithelialer Polyp des Nierenbeckens

Zusammenfassung Benigne fibroepitheliale Polypen des Nierenbeckens sind ?u?erst selten. Wegen des Malignit?tsverdachtes in den bildgebenden Verfahren wurde im vorliegenden Fall eine Ureternephrektomie durchgeführt. Die histologische Untersuchung ergab jedoch keinen Anhalt für Malignit?t. Bei den hier vorliegenden Befunden eines benignen fibroepithelialen Polypen des Nierenbeckens ergibt sich die Frage, ob eine Hamartie vorliegt oder ein reaktives postentzündliches Geschehen mit primitivem myxoidem Stroma im polyp?sen Bereich und zunehmender submuk?ser Fibrose der Polypenbasis im Ureter.      

Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats

Objective and design:  Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. Materials:  Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. Treatment:  n-STZ diabetic rats were treated with chlorpropamide (200mg/kg, 15d, by gavage) 8 weeks after STZ injection. Methods:  Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. Results:  Chlorpropamide treatment improved glucose tolerance, β-cell function (assessed by HOMA-β), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. Conclusion:  Chlorpropamide treatment by restoring β-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats. Received 16 February 2007; returned for revision 19 August 2007; received from final revision 15 January 2008; accepted by S. Stimpson 17 March 2008     

Epithelial cells as immune effector cells: The role of CD40

Through the expression of inflammatory mediators and immune-related molecules, epithelial cells function as immune effector cells in a wide variety of tissues; the expression of the CD40 receptor on these cells contributes this role. Engagement of CD40 activates epithelial cells and results in their release of pro- and anti-inflammatory mediators as well as pro-fibrotic molecules. As such, epithelial CD40 has been implicated in the pathogenesis of inflammatory disorders, generation of self-tolerance, and rejection of allografts.     

Toll like receptor-2 modulates both innate and adaptive immune responses during chronic fungal asthma in mice

OBJECTIVE AND DESIGN: We investigated the effect of TLR2 gene deletion in a murine model of chronic fungal asthma. METHODS: TLR2 wildtype (TLR2(+/+)) and TLR2 deficient (TLR2(-/-)) mice were sensitized to soluble A. fumigatus antigens and challenged with live A. fumigatus conidia, and the extent of allergic airways disease was analyzed in both groups of mice at 3, 7, 14, and 30 days after conidia. RESULTS: At day 7 post-conidia, TLR2(-/-) mice exhibited significantly lower airway hyperresponsiveness, airway inflammation, and whole lung Th2 cytokine levels compared with the TLR2(+ / +) group. TLR2 deletion also significantly reduced mucus cell metaplasia and peribronchial fibrosis at day 30 after conidia. However, fungal material persisted in the TLR2(-/-) group, and at day 30 after conidia TLR2(-/-) mice exhibited enhanced airway neutrophil recruitment and airway hyperresponsiveness. CONCLUSION: Thus, during chronic fungal asthma in mice, TLR2 is a major contributor to the maintenance of the adaptive Th2-cytokine driven and anti-fungal innate responses.