The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma

Current knowledge about molecular mechanisms underlying disease progression and drug resistance in multiple myeloma (MM) is still limited. Here, we analyzed the potential pathogenetic role of the Y-box binding protein YB-1 in MM. YB-1 is a member of the cold-shock domain protein superfamily and involved in various cellular functions such as proliferation. Immunohistochemical analyses revealed that neither normal bone marrow (BM) plasma cells (PCs), premalignant PCs of patients with monoclonal gammopathy of unknown significance (MGUS), nor MM cells with a mature morphology showed expression of YB-1 in situ. In contrast, YB-1 was strongly expressed in situ in normal PC precursor blasts as well as in a MM subset and in vitro in all of the evaluated MM cell lines. The YB-1-expressing MM cells were characterized by an immature morphology and a highly proliferative phenotype as defined by Ki 67 expression. We observed that siRNA-mediated knockdown of YB-1 decreased proliferation and induced apoptosis in MM cells even in the presence of BM stromal cells. Furthermore, we found that overexpression of YB-1 mediated resistance toward doxorubicin-induced apoptosis in MM cells. Thus, YB-1 contributes to disease progression, survival, and drug resistance in MM and might therefore provide an attractive therapeutic target.     

The optimization of technological processes,stability and microbiological evaluation of innovative natural ingredients-based multiple emulsion

Abstract

For the last couple of decades, multiple emulsions were prepared either by the re-emulsification of primary emulsion or they were produced by an emulsion inversion and their technological peculiarities were widely investigated. The aim of our study was to investigate and determine the optimal technological parameters of innovative multiple emulsion, prepared directly—by addition of ethanolic rosemary extract in the presence of polymeric emulsifier—and evaluate its stability by experimental surface response design approach. The results revealed that simplified W/O/W emulsification process is stirring time and stirring speed sensitive: the change of stirring time from 5 to 15?min at 600?rpm resulted in increased viscosity (from 1705.6?±?62.2 to 3364.1?±?112.5?mPA/s) and smaller oil droplet size (from 33.09?±?1.51 to 17.81?±?0.78?μm), though the conductivity increased from 800?±?2 to 882?±?2 μS/cm (p?<?.05). The second mixing stage (1000?rpm) had a negative effect on the conductivity of W/O/W emulsion because of the inner aqueous phase encapsulation efficiency. Ethanolic rosemary extract was used as multifunctional agent: not only to form multiple emulsion but also to preserve it; microbiological assay confirmed its effectiveness. A stable W/O/W type drug delivery system was successfully created without additional technological stages, phase inversion or surfactants.     

The temporary effect of short-term endotracheal intubation on vocal function

The objective of the study was to assess and perceive the vocal and pharyngeal symptoms and acoustic changes of voice after short-term endotracheal intubation and to evaluate the relation between these changes and the endotracheal tube parameters, number of intubation attempts, duration of anaesthesia, experience of anaesthesiologist. A total of 108 patients were evaluated preoperatively, 1–2 and 24 h after extubation. The vocal and pharyngeal symptoms, voice acoustic characteristics and maximum phonation time (MPT) were evaluated to find the relationship with endotracheal tube parameters, number of intubation attempts, duration of anaesthesia, experience of anaesthesiologist. All vocal and pharyngeal symptoms increased significantly at 24 h and remained significantly increased at 24 h after general anaesthesia. The vocal acoustic parameters changed significantly at 1–2 h: decrease of MPT and increase relative average perturbation were recorded. The day after the short-term intubation: only noise to harmony ratio and habitual pitch remains significantly changed. The most important endotracheal tube parameters that affect significantly (P value <0.05) the vocal function were the size of tube, cuff volume and number of intubation attempts. In relation to the anaesthesia, the changes of the acoustic parameters did not associate significantly with the anaesthesia-related parameters. No statistically significant relationship between experience of an anaesthesiologist and changes of the voice after anaesthesia was detected. Though being short-term, endotracheal anaesthesia is an invasive procedure, and its temporary influence on vocal function is important.     

Immunohistochemical analysis of 1844 human epithelial and haematopoietic tumours and sarcomas for IDH1R132H mutation

Sahm F, Capper D, Meyer J, Hartmann C, Herpel E, Andrulis M, Mechtersheimer G, Petersen I, Paulus W & von Deimling A
(2011) Histopathology  58, 1167–1172
Immunohistochemical analysis of 1844 human epithelial and haematopoietic tumours and sarcomas for IDH1R132H mutation Aims: Mutations in the isocitrate dehydrogenase 1 gene have been identified recently to play a key role in diffuse astrocytoma and oligodendroglioma as well as in acute myeloid leukaemia. In glioma, IDH1R132H is the most common mutation type, which is associated with younger patient age and longer patient survival compared to wild‐type status. Sequencing analyses of carcinomas and lymphomas have detected IDH1 mutations in only a small fraction of cases. In those studies, IDH1R132H was also the most frequent mutation. The aim of the present study was to analyse a comprehensive series of human tumours for IDH1R132H mutation. Methods and results: A total of 1844 formalin‐fixed paraffin‐embedded tumours, including carcinomas, sarcomas and haematopoietic tumours were investigated immunohistochemically using a mutation‐specific antibody for IDH1^R132H. Our positive control series consisted of a collection of diffuse astrocytomas and oligodendrogliomas. No IDH1R132H mutation was found in this series. Conclusions: IDH1R132H mutations occur almost exclusively in glioma and acute myeloid leukaemia.     

Simultaneous nephrectomy and coronary artery bypass grafting through extended sternotomy

A 37-year-old man with end-stage idiopathic dilated cardiomyopathy underwent an orthotopic heart transplant followed by a reoperation with mitral annuloplasty for severe mitral regurgitation. Shortly thereafter, he developed severe tricuspid regurgitation and severe recurrent mitral regurgitation due to annuloplasty ring dehiscence. The dehisced annuloplasty ring was refixated, followed by tricuspid annuloplasty through a right anterolateral thoracotomy. After four years of follow-up, there are no signs of recurrent mitral or tricupid regurgitation and the patient remains in NYHA class II. Pushing the envelope on conventional surgical procedures in marginal donor hearts (both before and after transplantation) may not only improve the patient??s functional status and reduce the need for retransplantation, but it may ultimately alleviate the chronic shortage of donor hearts.     

Antigenic characterisation of yeast-expressed lyssavirus nucleoproteins

In Europe, three genotypes of the genus Lyssavirus, family Rhabdoviridae, are present, classical rabies virus (RABV, genotype 1), European bat lyssavirus type 1 (EBLV-1, genotype 5) and European bat lyssavirus type 2 (EBLV-2, genotype 6). The entire authentic nucleoprotein (N protein) encoding sequences of RABV (challenge virus standard, CVS, strain), EBLV-1 and EBLV-2 were expressed in yeast Saccharomyces cerevisiae at high level. Purification of recombinant N proteins by caesium chloride gradient centrifugation resulted in yields between 14-17, 25-29 and 18-20 mg/l of induced yeast culture for RABV-CVS, EBLV-1 and EBLV-2, respectively. The purified N proteins were evaluated by negative staining electron microscopy, which revealed the formation of nucleocapsid-like structures. The antigenic conformation of the N proteins was investigated for their reactivity with monoclonal antibodies (mAbs) directed against different lyssaviruses. The reactivity pattern of each mAb was virtually identical between immunofluorescence assay with virus-infected cells, and ELISA and dot blot assay using the corresponding recombinant N proteins. These observations lead us to conclude that yeast-expressed lyssavirus N proteins share antigenic properties with naturally expressed virus protein. These recombinant proteins have the potential for use as components of serological assays for lyssaviruses.