Infections and neutrophils in the pathogenesis of bronchiolitis obliterans syndrome in children after allogeneic stem cell transplantation

It is plausible that infections post‐hematopoietic SCT play a role in the pathogenesis of BOS. A prospective study for children with history, questionnaire, examination, PFTs, and blood counts at one, three, six, nine, 12, 18, and 24 months post‐SCT was conducted. Between September 2009 and September 2011 (n = 39), six developed BOS at 200 days (range 94–282), three patients had probable clinical respiratory infection, and all six had higher neutrophil count compared to non‐BOS patients (4.7 vs. 2.4 at three months and 6.3 vs. 2.9 at six months ×10⁹/L, p = 0.03). Contribution of clinical and subclinical infection needs to be considered in the pathogenesis of BOS.     

Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase

BACKGROUND AND AIMS: Chronic lymphocytic leukaemia (CLL) is a frequent non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Assessment of cell cycle phase kinetics might be important for prediction of clinical behaviour and prognosis. METHODS: Distribution of neoplastic cells in CLL within the cell cycle was evaluated by determining the labelling indices (LI, i.e. percentage of positive cells) of markers specific for late G1-phase (cyclin E), S-phase (cyclin A), and G2/M-phase (cyclin B1), and Mcm2, a novel marker of proliferative potential, in a large cohort of patients (n = 79) using tissue microarray (TMA) technology. Utilising a combination of these markers, an algorithm was developed--subtracting the combined LIs of cyclin E, cyclin A and cyclin B1 from the LI of Mcm2--to determine the percentage of tumour cells residing in early G1-phase, which is probably a critical state for the malignant potential of CLL. RESULTS: 27.11% of cells had acquired proliferative potential as indicated by expression of Mcm2. Only a small number of cells were found to be in late G1-phase (7.16%), S-phase (3.31%) or G2/M-phase (0.98%), while 15.66% of cells were considered to be in early G1-phase. CONCLUSION: Cell cycle phase distribution can easily be assessed by immunohistochemistry in routinely processed paraffin-embedded specimens. A large number of neoplastic cells in CLL have proliferative potential, with a significant sub-population residing in early G1-phase. Estimates of these cells may identify cases likely to exhibit a more aggressive biological behaviour and adverse clinical course.     

Diabetes mellitus und Fettlebererkrankungen

Die Gastroenterologie - Die nichtalkoholische Fettlebererkrankung (NAFLD) stellt eine häufige, aber oft unterschätze Komorbidität des Diabetes mellitus dar. Sie kann nicht nur Folge...     

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

Alkaloids are a group of natural products with interesting pharmacological properties and a long history of medicinal application. Their complex molecular structures have fascinated chemists for decades, and their total synthesis still poses a considerable challenge. In a previous review, we have illustrated how biocatalysis can make valuable contributions to the asymmetric synthesis of alkaloids. The chemo-enzymatic strategies discussed therein have been further explored and improved in recent years, and advances in amine biocatalysis have vastly expanded the opportunities for incorporating enzymes into synthetic routes towards these important natural products. The present review summarises modern developments in chemo-enzymatic alkaloid synthesis since 2013, in which the biocatalytic transformations continue to take an increasingly ‘central’ role.

This review article discusses developments in the chemo-enzymatic synthesis of alkaloids since 2013, showcasing how modern methods of organic synthesis and biocatalysis are combined to establish novel routes towards these important natural products.