Osteogenic differentiation of bone marrow stromal cells is hindered by the presence of intervertebral disc cells.

BACKGROUND Clinical observations indicate that the presence of nucleus pulposus (NP) tissue during spinal fusion hinders the rate of disc ossification. While the underlying mechanism remains unknown, this observation could be due to incomplete removal of NP cells (NPCs) that secrete factors preventing disc calcification, such as bone morphogenetic protein (BMP) antagonists including noggin and members of the DAN (differential screening selected gene aberrative in neuroblastoma) family. METHODS Monolayer human bone marrow-derived mesenchymal stem cells (MSCs) were cocultured withNPCs and annulus fibrosus cells (AFCs) embedded in alginate for 21 days. At the end of coculture, MSCs were stained for mineral deposition by alizarin red, and relative expression of bone-related genes [Runt-related transcription factor 2, (RUNX2), Osteopontin (OPN), and Alkaline phosphatase (ALP)] and ALP activity were analyzed. Relative expression of three BMP antagonists, chordin (CHRD), gremlin (GREM1), and noggin (NOG), was determined in primary human NPCs and AFCs. These cells were also stained for Gremlin and Noggin by immunocytochemistry. RESULTS Alizarin red staining showed that MSC osteogenesis in monolayer cultures was inhibited by coculture with NPCs or AFCs. ALP activity and RT-PCR analyses confirmed these results and demonstrated inhibition of osteogenesis of MSC in the presence of disc cells. NOG was significantly up-regulated in MSCs after coculture. Relative gene expression of intervertebral disc (IVD) cells showed higher expression of GREM1 in NPCs than in AFCs. CONCLUSIONS We show that primary IVD cells inhibit osteogenesis of MSCs. BMP inhibitors NOG, GREM1 and CHRD were expressed in IVD cells. GREM1 appears to be differentially expressed in NPCs and AFCs. Our results have implications for the design and development of treatments for non-union in spinal fusion.

Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine

An isoform of the mammalian renal type II Na/Pi-cotransporter is described. Homology of this isoform to described mammalian and nonmammalian type II cotransporters is between 57 and 75%. Based on major diversities at the C terminus, the new isoform is designed as type IIb Na/Pi-cotransporter. Na/Pi-cotransport mediated by the type IIb cotransporter was studied in oocytes of Xenopus laevis. The results indicate that type IIb Na/Pi-cotransport is electrogenic and in contrast to the renal type II isoform of opposite pH dependence. Expression of type IIb mRNA was detected in various tissues, including small intestine. The type IIb protein was detected as a 108-kDa protein by Western blots using isolated small intestinal brush border membranes and by immunohistochemistry was localized at the luminal membrane of mouse enterocytes. Expression of the type IIb protein in the brush borders of enterocytes and transport characteristics suggest that the described type IIb Na/Pi-cotransporter represents a candidate for small intestinal apical Na/Pi-cotransport.

Increased fibrinogen levels at diagnosis are associated with adverse outcome in patients with acute myeloid leukemia

Increased plasma fibrinogen levels are associated with shortened overall survival (OS) in some solid tumor types. In contrast, the prognostic significance of varying fibrinogen levels in acute myeloid leukemia (AML) at diagnosis is unknown. In this study, we assessed the prognostic significance of fibrinogen levels in AML patients. In a comprehensive retrospective single-center study, we determined the survival rates of 375 consecutive AML patients undergoing at least one cycle of intensive chemotherapy induction treatment. Patients were dichotomized between low (<4.1 g/L) and high fibrinogen levels (≥4.1 g/L) at diagnosis of AML before initiation of treatment. Subsequently, quartile ranges were applied to analyze the association of varying fibrinogen levels on survival. We observed that the rates of complete remission, early death, and admission to intensive care unit were equal in the low versus high fibrinogen group. However, OS was significantly better in the low fibrinogen group (27.3 vs 13.5 months; p = 0.0009) as well as progression-free survival (12.3 vs 7.8 months; p = 0.0076). This survival difference remained significant in the multivariate analysis (p = 0.003). Assessing quartiles of fibrinogen values, we further confirmed this observation. Our data suggest that high fibrinogen levels at diagnosis of AML are associated with unfavorable OS and progression-free survival but not with increased mortality during induction treatment.

Maan mahtavimmat hybridisankarit. Supersankarit ja sankaruus The Avengers –sarjakuvissa 1970-luvun Yhdysvalloissa.

Tutkielma tarkastelee The Avengers –sarjakuvien supersankareita ja sankaruutta osana amerikkalaisten sankaritarinoiden sekä –myyttien jatkumoa, kiinnittäen erityistä huomiota myös siihen, miten yhteiskunnassa tapahtuvat sosiaaliset ja kulttuuriset murrokset näkyvät aikansa sarjakuvissa. Supersankarit ovat vain yksi, varsin nuori sankaruuden muoto amerikkalaisen populaarikulttuurin historiassa, ja tutkimuksen tarkoitus onkin selvittää, mistä moderni supersankari on saanut inspiraationsa. Supersankari ei kuitenkaan ole yksiselitteinen, staattinen sankaruuden ilmentymä, vaan se elää ja muuttuu aikansa mukana siinä missä muukin kulttuuri. Tutkimuksen lähdeaineistona ovat kaikki Marvel Comicsin 1970-luvulla julkaisemat The Avengers –sarjakuvat, joita vuosikymmenen aikana ehdittiin julkaista 118 kappaletta. Huomion keskiössä ovat nimenomaan Marvelin supersankarit, joiden uniikki inhimillisyys ja samaistuttava epätäydellisyys aikanaan mullistivat käsityksiä supersankareista ja sankaruudesta ylipäänsä. Tutkielma sijoittuu Yhdysvaltoihin, jossa sarjakuvat alun perin julkaistiin, ja kiinnostuksen kohteena ovat nimenomaan amerikkalaista yhteiskuntaa ravistelleet mullistukset kyseisenä vuosikymmenenä. Pääpainotus tutkielmassa on sarjakuvien kytkeminen amerikkalaisen sankaruuden ja kylmän sodan konteksteihin. Mikään populaarikulttuurin ilmiö ei synny tyhjiössä, eivätkä näin ollen syntyneet Marvelin supersankaritkaan, vaan heidän juurensa voidaan nähdä klassisissa amerikkalaisissa sankaritarinoissa, uuden ajan menestystarinoissa sekä sosiaalisiin ja kulttuurisiin muutoksiin perustuvissa mahdollisuuksien tarinoissa. Myös kylmä sota sekä sen luoma epävarmuuden ja pelon ilmapiiri vaikuttivat siihen, millainen supersankari 1970-luvun sarjakuvissa seikkaili, ja millaiseksi hän vuosikymmenen kuluessa muuttui. The Avengers –sarjakuvien supersankarit voidaan nähdä niin kulttuurisen historiansa kuin aikansakin muovaamina hybrideinä. Ei ole vain yhtä sankarimyyttiä, josta Marvelin supersankarit ovat saaneet inspiraationsa, vaan heissä yhdistyy niin klassisten kuin modernienkin sankaritarinoiden piirteitä. Supersankarit heijastelevat myös vahvasti yhteiskunnan poliittisia, sosiaalisia ja kulttuurisia muutoksia, ottaen niistä oppia ja kasvaen niiden mukana.

Increasing value add in white collar work using lean methods

The efficient indirect office work brings competitive advantage for companies in a rapidly changing business environment. The direct work methods in factory floors have been developed already for decades, but the office work is an area where the potential to improve the value add has not been studied and utilized systematically so far. The first objective of the thesis work is to find useful method for identifying and managing value add using literature. The usefulness of the method is validated in the case company`s environment. The second objective of the work is to understand what kind of effort is required to create more efficient target setting for the white collar employees. The operative level targets should be linked more tightly to the company strategy. Lean methods are selected as a tool for the improvement, since they are widely used in all kinds of industries and they are already familiar in other functions in the case company. Based on the literature review, suitable improvement methods are selected. The core of the lean is to identify the value add of a customer and eliminate the waste. Also visual control, cross functional work team, flow office and continuous improvement are used. The methods are tested in one production line and the results and feedback indicate that methods are useful in the studied environment.