Immunophenotyping without antibodies: New perspectives for lymphoma characterization

Aims: Accurate classification of haematological malignancies is a prerequisite for their correct diagnosis, prognosis and therapy. Clear classification of lymphomas is often hindered by the limited number of available cell surface protein markers that are suitable for immunophenotyping. A systematic and quantitative analysis of cell surface proteins is thus required to identify new protein markers on lymphoma subtypes in an unbiased and discovery-driven approach. Methods: Nine Hodgkin and non-Hodgkin B cell lines of diffuse large cell type and mediastinal type were investigated by cell surface capture (CSC) technology, a mass spectrometry-based method to identify cell surface glycoproteins. Selected proteins are verified by antibody-based methods, including flow cytometry and immunohistochemistry on cell line arrays. Results: A total of 747 predicted transmembrane proteins were identified from all cell lines, including 142 CD (cluster of differentiation) annotated proteins. A group of differentially expressed cell surface glycoproteins between Hodgkin and non-Hodgkin B cell lines was revealed via quantitative CSC technology. In addition to classical and expected CD molecules such as CD20 and CD30, less frequently expressed molecules such as CD2 on Hodgkin lymphoma (HL) cell lines were identified by CSC and verified by immunohistochemistry in cell lines and primary lymphoma tissue. A panel of CSC-identified differentiation glycoprotein candidates is currently under investigation on tissue microarrays (TMAs) from patient sample

Identifizierung VHL-assoziierter Veränderungen im klarzelligen Nierenzellkarzinom: Anwendung von kombinierten Genom- und Expressionsanalysen

Zusammenfassung: Das sporadische Nierenzellkarzinom (NZK) ist ein heterogener solider Tumor, der traditionell basierend auf morphologischen Kriterien in weitere Subtypen unterteilt wird. In den letzten Jahren konnten unter Anwendung molekularer Hochdurchsatzanalysen genetische, transkriptionelle und translationale Alterationen identifiziert werden. Diese Marker eignen sich zum einen für die molekulare Klassifizierung des NZK und haben zum anderen prognostische Wertigkeit. Die isolierte Betrachtung genetischer, transkriptioneller und translationaler Veränderungen verhindert jedoch ein tieferes Verständnis für die komplexen Vorgänge der Karzinogenese. Wir fassen hier aktuelle Forschungsergebnisse zur molekularen Charakterisierung des NZK zusammen und stellen ein systembiologisches Konzept zur Identifizierung neuer Tumormarker vor. Diese könnten zukünftig Einsatz in der Diagnostik und Therapie des sporadischen NZK finde

Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care

Background: poorly controlled hypertension is independently associated with mortality, cardiovascular risk and disease progression in chronic kidney disease (CKD). In the UK, CKD stage 3 is principally managed in primary care, including blood pressure (BP) management. Controlling BP is key to improving outcomes in CKD. This study aimed to investigate associations of BP control in people with CKD stage 3.Methods: 1,741 patients with CKD 3 recruited from 32 general practices for the Renal Risk in Derby Study underwent medical history, clinical assessment and biochemistry testing. BP control was assessed by three standards: National Institute for Health and Clinical Excellence (NICE), National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Descriptive statistics were used to compare characteristics of people achieving and not achieving BP control. Univariate and multivariate logistic regression was used to identify factors associated with BP control.Results: the prevalence of hypertension was 88%. Among people with hypertension, 829/1426 (58.1%) achieved NICE BP targets, 512/1426 (35.9%) KDOQI targets and 859/1426 (60.2%) KDIGO targets. Smaller proportions of people with diabetes and/or albuminuria achieved hypertension targets. 615/1426 (43.1%) were only taking one antihypertensive agent. On multivariable analysis, BP control (NICE and KDIGO) was negatively associated with age (NICE odds ratio (OR) 0.27; 95% confidence interval (95% CI) 0.17-0.43) 70–79 compared to &lt;60), diabetes (OR 0.32; 95% CI 0.25-0.43)), and albuminuria (OR 0.56; 95% CI 0.42-0.74)). For the KDOQI target, there was also association with males (OR 0.76; 95% CI 0.60-0.96)) but not diabetes (target not diabetes specific). Older people were less likely to achieve systolic targets (NICE target OR 0.17 (95% CI 0.09,0.32) p?&lt;?0.001) and more likely to achieve diastolic targets (OR 2.35 (95% CI 1.11,4.96) p?&lt;?0.001) for people &gt;80 compared to?&lt;?60).Conclusions: suboptimal BP control was common in CKD patients with hypertension in this study, particularly those at highest risk of adverse outcomes due to diabetes and or albuminuria. This study suggests there is scope for improving BP control in people with CKD by using more antihypertensive agents in combination while considering issues of adherence and potential side effects.<br/

Evaluation of Adjunctive Mycophenolate for Large Vessel Giant Cell Arteritis

Funding: We are grateful to Versus Arthritis (grant 22088) and PMR/GCA Scotland for supporting our workPeer reviewedPublisher PD