Assessment of the prognostic impact of the Epstein–Barr virus-encoded latent membrane protein-1 expression in Hodgkin's disease

We have examined expression of the Epstein–Barr virus (EBV) latent membrane protein-1 (LMP1) in the malignant Hodgkin and Reed–Sternberg (HRS) cells of Hodgkin's disease (HD) and its impact on response to treatment and on survival. Paraffin tissue from 100 adult immunocompetent patients with HD were analysed using immunohistochemistry to identify LMP1 expression. According to the Rye classification, 8% of patients had lymphocyte predominance (LP) subtype, 48% had nodular sclerosis (NS) disease, 37% were of the mixed cellularity (MC) subtype and 7% were of the lymphocyte depletion (LD) subtype. During the five year follow-up period 27 patients died and 74 patients achieved a complete remission. Patients with LD subtype were older (P = 0.03), less frequently achieved complete remission (P = 0.01), had shorter disease-free survival (P = 0.01) and overall survival (P = 0.002) compared with the other subtypes of HD. LMP1 expression was found in the tumour cells of 26% of cases of HD. LMP1 expression was less common in NS disease than in the other subtypes (P = 0.05), whereas an association between MC subtype and LMP1 expression was not found (P = 0.22). Using the log-rank test there were no differences in overall survival or disease-free survival based on EBV status either when all patients were analysed or when LD and LP subtypes were excluded. However, the presence of EBV was associated with significantly longer disease-free survival in the subgroup of patients ≤ 30 years old (P = 0.02) and in those patients ≤ 34 years old (P = 0.05). In contrast, there was a trend for shorter disease-free survival for EBV-positive patients in the subgroup > 35 years old, but this difference was not statistically significant (P = 0.11). A similar trend was observed in patients > 50 years old. Analysis of the impact of LMP1 expression in patients who had different stage and B symptoms status showed that expression of EBV was associated with longer disease-free survival (P = 0.019) in early stage (1 + 2) patients without B symptoms. Significant differences in the other subgroups based on EBV status was not found. Factors adversely affecting the likelihood to achieve a complete remission were: absence of LMP1 expression (OR 6.4, 95% Cl 1.07–38.5, P = 0.04), age (OR 1.68, 95%Cl 1.15–2.5, P = 0.007) and subtype of HD (OR 3.32, 95%Cl 1.11–9.94, P = 0.03). Age and subtype of HD had an independent impact on overall survival (P = 0.01). We conclude that expression of LMP1 in HRS cells has a favourable impact on prognosis for HD patients, but that this effect may be restricted to young adult patients and those with early stage disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

Enrichment of Echinacea angustifolia with Bauer Alkylamide 11 and Bauer Ketone 23 Increased Anti-inflammatory Potential through Interference with COX-2 Enzyme Activity

Bauer alkylamide 11 and Bauer ketone 23 were previously found to be partially responsible forEchinacea angustifolia anti-inflammatory properties. This study further tested their importance using the inhibition of prostaglandin E2 (PGE2) and nitric oxide (NO) production by RAW264.7 mouse macrophages in the absence and presence of lipopolysaccharide (LPS) and E. angustifolia extracts, phytochemical enriched fractions, or pure synthesized standards. Molecular targets were probed using microarray, qRT-PCR, Western blot, and enzyme assays. Fractions with these phytochemicals were more potent inhibitors of LPS-induced PGE2 production than E. angustifolia extracts. Microarray did not detect changes in transcripts with phytochemical treatments; however, qRT-PCR showed a decrease in TNF-α and an increase of iNOS transcripts. LPS-induced COX-2 protein was increased by an E. angustifolia fraction containing Bauer ketone 23 and by pure phytochemical. COX-2 activity was decreased with all treatments. The phytochemical inhibition of PGE2 production byEchinacea may be due to the direct targeting of COX-2 enzyme

Cochlea-Versorgung bei einseitig und asymmetrisch ertaubten Patienten - wie hoch ist der Hörgewinn?

Einleitung: Für Patienten mit einseitiger Taubheit und Patienten mit einer asymmetrischen Schwerhörigkeit stellt die Cochlea Implantation eine Therapieoption dar. Ziel der Arbeit war es aufzuzeigen, in welchem Maße diese Patientengruppen von einem Cochlea Implantat profitieren. Material und Methoden: 14 Patienten mit einseitiger Ertaubung und 44 Patienten mit asymmetrischem Hörverlust wurden nach jeweils einseitiger Cochlea Implantation untersucht. Anhand von Standard-Testverfahren wurden das Hör-Sprachverständnis (Ruhe und Störgeräusch) sowie bei den einseitig Ertaubten das Lokalisationsvermögen ermittelt. Die Patienten erhielten Fragebögen (HHIE, Oldenburger Inventar, APHAB) zur Erfassung des Hör-Handicaps und des subjektiven Hörgewinnes. Ergebnisse: Die Patienten mit einseitiger Ertaubung wiesen einen Zeitraum von progredienter Hypakusis bis Ertaubung von 3,8 Jahren auf, die asymmetrisch Ertaubten von 10,15 Jahren (Mittelwerte). Die Nachbeobachtungsdauer betrug durchschnittlich 24 Monate. Bis auf wenige Ausnahmen profitierten die Patienten in Bezug auf ihr Hör-Sprachverständnis und das räumliche Hörverständnis. Subjektiv profitierten auch bimodal versorgte Patienten. Die Entwicklung des Hör-Sprachverstehens sowie der subjektiv empfundene Hörgewinn fallen jedoch individuell unterschiedlich aus. Schlussfolgerung: Patienten mit einseitiger oder asymmetrischer Ertaubung profitieren von einem Cochlea Implantat. Jedoch sind eine gezielte Patientenselektion, eine realistische Erwartungshaltung sowie eine hohe Trainingsbereitschaft seitens des Betroffenen entscheidend für den Therapieerfolg.Der Erstautor gibt keinen Interessenkonflikt an

The Effects of Endurance Exercise and Diet on Atherosclerosis in Young and Aged ApoE -/- and Wild-Type Mice

Background: Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice. Objective: This study aimed at comparing multiple age-dependent factors that may influence atherosclerosis in a transgenic mouse model. Methods: Young (14 weeks) and aged (49-52 weeks) C57BL/6 wild-type (WT) and atherosclerosis-prone ApoE -/- mice were subjected to physical endurance exercise on a treadmill, with or without a high-fat diet. Five weeks later, the frequencies of regulatory T cells (T REGs ) in lymph nodes were assessed by flow cytometry, plasmatic cytokines (interleukin [IL]-1\u3b2, IL-6, IL-10, IL-17, interferon-\u3b3, tumor necrosis factor-\u3b1, and transforming growth factor [TGF]-\u3b2 1 ) levels were determined by Luminex assay. Lipids (cholesterol and triglycerides) and anti-heat shock protein 60 (HSP60) autoantibodies were measured by ELISA. Aortic lesion sizes were assessed by en face imaging. Microarray analysis and qPCR of skeletal muscle gene expression were also performed. Results: Exercise leads to a reduction of aortic lesions in young ApoE -/- and aged WT mice independent of diet. In most groups, this reduction was followed by an increased proportion of T REGs and TGF-\u3b2 1 levels. Moreover, gene expression analysis showed that exercise seems to affect the AMPK signaling pathway. In particular, PGC-1\u3b1 1 mRNA was induced in aged WT mice, whereas it was reduced in young ApoE -/- mice. In addition, GSEA analysis showed a marked reduction in the insulin signaling pathway in aged ApoE -/- mice. Conclusion: Practicing endurance exercise seems to be enough for reducing early aortic lesion formation, independent of diet. However, this was only true in mice with smaller aortic lesions, since mice with large, advanced, complicated atherosclerotic plaques did not show any reduction in lesion size with exercise training