Enzyme‐cleavable tandem peptides for quantitative studies in MS‐based proteomics

A novel type of peptide standard is introduced that consists of two peptides combined in one synthetic molecule and separated by a proteolytic cleavage site. Upon enzymatic digestion, the two peptides are released in a molar one‐to‐one ratio. This method enables the generation of exact equimolar mixtures of two peptides of any nature and origin, thereby providing a valuable tool for the investigation of fundamental phenomena in MS. The applicability of the method is exemplified by the analysis of the effect of peptide sequence variations on the relative ionization efficiency in ESI‐ and MALDI‐MS.     

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: comments from the Dutch ACS working group

On behalf of the Dutch ACS working group, we discuss multiple recommendations which have been implemented in the 2015 ESC guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation.     

Predicting the outcomes of pulmonary hypertension is a breathtaking task

Netherlands Heart Journal -     

Effects of oral and inhaled salbutamol and oral pirbuterol on right and left ventricular function in chronic bronchitis.

In many patients with chronic bronchitis and emphysema right and left ventricular ejection fractions (RVEF and LVEF) are reduced. A study was conducted using multiple gated equilibrium radionuclide ventriculography to compare the effects of oral salbutamol 4 mg and pirbuterol 15 mg on cardiac function in 12 patients with chronic bronchitis (forced expiratory volume in one second 0.86 (SEM 0.12) 1; arterial oxygen pressure 8.2 (SEM 0.5) kPa (61.7 (SEM 3.8) mm Hg)). Different doses of nebulised salbutamol (500 microgram and 5 mg) were also compared in nine of the patients. Both oral salbutamol and oral pirbuterol produced significant increases in RVEF and LVEF at 60 and 90 minutes after drug ingestion (p less than 0.01 in each case). There were no significant differences between salbutamol and pirbuterol in their effects on RVEF and LVEF. Inhaled salbutamol at doses commonly prescribed had no significant effect on RVEF and LVEF after 20 and 60 minutes. Salbutamol and pirbuterol given by mouth have similar actions on RVEF and LVEF. Further studies are necessary to assess the effects of long term B2 agonists in this group of patients.     

The keratin polypeptide patterns in heterotypically recombined epithelia of skin and mucosa of adult mouse

Epithelial-mesenchymal interactions were investigated considering both morphologic criteria and keratin polypeptide expression in homotypic and heterotypic recombinants of adult mouse skin and oral mucosa. Two series of cross-recombinants of epithelia with different morphology and keratin patterns were chosen: (a) footpad epidermis/ear dermis and ear epidermis/footpad dermis; (b) palate epithelium/cheek connective tissue and cheek epithelium/palate connective tissue. Homotypic and heterotypic recombinants were prepared after EDTA-separation of the original tissues and then grown on syngeneic mice in subcutaneously prepared protected graft chambers. EDTA-separation is especially suited to completely separate the epidermal-dermal union, and the transplantation procedure used strictly prevents contamination with host epithelium. Five weeks after implantation keratins were analyzed by one and two-dimensional gel electrophoresis and peptide mapping. In both series, homotypic recombination of the tissues did not alter the original morphology and keratin polypeptide composition of the individual epithelial components. Ear epidermis displayed no significant changes in structure or keratin pattern in heterotypic recombinants. Recombined with ear dermis, footpad epidermis showed acquisition of some morphologic features typical for ear epidermis and slight changes in keratin composition which were, however, difficult to interpret due to the normal similarities of footpad keratin with that of ear. In contrast, the heterorecombinants of the palate/cheek series exhibited considerable alterations in their keratin patterns. Either epithelium showed suppression of distinct keratin subunits and de novo expression of subunits characteristic of the epithelium normally associated with the connective tissue component. The keratin patterns of both matches closely resembled each other and represented patterns intermediate between the normal patterns. This partial, however, significant modulation in the expression of differentiation markers was paralleled by similarly directed changes in the architecture of the heterotransplanted tissues, thus indicating that both morphogenesis and cytodifferentiation of certain adult epithelia can be influenced by extrinsic mesenchymal factors.