Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA -238A, IL1B -31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1beta, respectively. Alleles CD14 -159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. METHODS: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. RESULTS: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN 2/ 2; IL1B -31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. CONCLUSIONS: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.

BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma

The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose deregulation by genomic lesions is implicated in the pathogenesis of GC-derived diffuse large B cell lymphoma (DLBCL) and, less frequently, follicular lymphoma (FL). The biological function of BCL6 is only partially understood because no more than a few genes have been functionally characterized as direct targets of BCL6 transrepression activity. Here we report that the anti-apoptotic proto-oncogene BCL2 is a direct target of BCL6 in GC B cells. BCL6 binds to the BCL2 promoter region by interacting with the transcriptional activator Miz1 and suppresses Miz1-induced activation of BCL2 expression. BCL6-mediated suppression of BCL2 is lost in FL and DLBCL, where the 2 proteins are pathologically coexpressed, because of BCL2 chromosomal translocations and other mechanisms, including Miz1 deregulation and somatic mutations in the BCL2 promoter region. These results identify an important function for BCL6 in facilitating apoptosis of GC B cells via suppression of BCL2, and suggest that blocking this pathway is critical for lymphomagenesis.

Psychoedukative und bewältigungsorientierte Gruppentherapie für SchizophreniepatientInnen

Anliegen: Es sollte evaluiert werden, in wieweit Patienten mit Schizophrenie oder einer schizoaffektiven Erkrankung von einem psychoedukativen, bewältigungsorientierten Therapieprogramm profitieren können. Methode: Für die Evaluation wurde ein kontrolliertes prospektives Studiendesign herangezogen. Zum Einsatz kam in der Experimentalgruppe das “Therapiemanual zur Psychoedukation und Krankheitsbewältigung” (PKB), das neben gezielter Information über die Erkrankung und die Pharmakotherapie Strategien vermittelt, wie Frühwarnsignale erkannt und der Umgang mit ihnen erlernt werden können. Darüber hinaus werden auch Aspekte zu „gesundem“ Verhalten behandelt. Als Kontrollgruppe diente eine Patientengruppe mit supportiven Gesprächen bzw. eine Gruppe mit dem Schwerpunkt der Arbeitsrehabilitation. Um die Effekte der PKB zu evaluieren, wurden der psychopathologische Status, wissensbezogene sowie soziale Variablen zu verschiedenen Messzeitpunkten (vor der Therapie, nach Therapieende, 12 Monate nach Therapieende) erhoben. Als abhängige Variablen dienten der Wissensstand über die Erkrankung, Rehospitalisierungen, soziale Integration und Bewältigungsstrategien. Ergebnisse: 82 Patienten nahmen an der Studie teil. Sowohl in der Experimentalgruppe als auch in der Kontrollgruppe wurde eine signifikante Verbesserung des Allgemeinzustandes und der Psychopathologie beobachtet. Die Ergebnisse der Gruppen unterschieden sich insofern, dass in der Experimentalgruppe weniger Rehospitalisierungen im ersten Jahr nach Studienende vermerkt wurden und die Teilnehmer sich anderer Copingstrategien bedienten (signifikant weniger depressive Krankheitsverarbeitung und Bagatellisierung). Schlussfolgerungen: In der Behandlung von Schizophrenie können unterschiedliche Interventionen wirksam sein. Fragestellungen, welche Patienten von welcher Art der therapeutischen bzw. rehabilitativen Intervention profitieren können, sollten weiterhin Gegenstand intensiver Forschung sein.

Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

OBJECTIVE: To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD) with deficient haptic perception. METHODS: Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices. RESULTS: We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients. CONCLUSION: PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

Preserving middle lobe to improve lung function in non-small-cell lung cancer

When a lung tumor arises in segment 6, the close anatomical relationship to the middle lobe bronchus may make a lower bilobectomy necessary. Sleeve lobectomy may be an alternative. These procedures were compared retrospectively in 36 patients operated on between January 2005 and December 2006 with non-small-cell lung cancer (stage I-IIIB) of the right lower lobe. Sleeve lobectomy was performed in 21 patients and bilobectomy in 15 (41%). Preoperative lung function was comparable in both groups. Radical resection was achieved in 34/36 patients. Operation time was 121 min for sleeve lobectomy and 144 min for bilobectomy. Chest tubes were removed after 5 days in both groups. Postoperative lung function was better after sleeve lobectomy than bilobectomy (forced expiratory volume in 1st sec: 78% vs. 69%). Preservation of the middle lobe by sleeve lobectomy is feasible. There was no evidence that this resection was less radical, and complication rates were similar in both groups.

Cross-Border Banking

Der aktuelle Band der Reihe «Schweizerische Bankrechtstagung», befasst sich vertieft mit dem Thema des «Cross-Border Banking». Im Zentrum der Tagung vom Februar 2009 in Bern standen dabei weniger die Politik als vielmehr das Recht und praktische Fragen, die sich im Zusammenhang mit dem grenzüberschreitenden Bankverkehr stellen. Die Themen: Amtshilfe und Rechtshilfe – Neue Entwicklungen, Euro-Zahlungen gemäss den SEPA-Rulebooks (insbesondere die Haftung der Banken), Rechtliche Risiken im grenzüberschreitenden Verkehr, Aufsicht über international tätige Finanzgruppen – Konsequenzen für die Bank, Praktische Fragen der Vorort-Kontrolle, Die Standards zur Aufhebung des Bankgeheimnisses, Die Verletzung des Bankgeheimnisses – Individual- und Unternehmensstrafrecht.