Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

Abstract Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodeling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in plateletinduced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling

Spatial and temporal assessment of rural-urban land-use gradient effects on water quality and periphyton communities in tributaries of Durham Region, Ontario

This study examines the effects of longitudinal and local land-use gradients on water quality and periphyton within four watersheds representing varying rural-urban land-use types and intensities. Although numerous studies have identified how specific land-use gradients (e.g., urban or agricultural land-use) affect water quality and periphyton, it is not fully understood how varying intensities and types of rural-urban land-use gradients affect water quality and algae both within and across watersheds sharing similar physiography and climate. Therefore, this study aimed to determine how variation in rural-urban land-use gradients affect water quality and periphyton along the cumulative flow path of tributaries (i.e., longitudinal), as well as across tributaries where sites were approximately matched for distance from headwaters. To assess spatial variation without the confounding effects of seasonality, I analysed water quality, algal biomass, and community composition from a set of algal growth substrates that were deployed in all study creeks (Lynde, Oshawa, Bowmanville and Soper) during May, 2015. Additionally, I examined the spatial and temporal variation of water quality and algal community structure in all tributaries from May ??? August, 2015

Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression

SummarySignaling proteins driving the proliferation of stem and progenitor cells are often encoded by proto-oncogenes. EphB receptors represent a rare exception; they promote cell proliferation in the intestinal epithelium and function as tumor suppressors by controlling cell migration and inhibiting invasive growth. We show that cell migration and proliferation are controlled independently by the receptor EphB2. EphB2 regulated cell positioning is kinase-independent and mediated via phosphatidylinositol 3-kinase, whereas EphB2 tyrosine kinase activity regulates cell proliferation through an Abl-cyclin D1 pathway. Cyclin D1 regulation becomes uncoupled from EphB signaling during the progression from adenoma to colon carcinoma in humans, allowing continued proliferation with invasive growth. The dissociation of EphB2 signaling pathways enables the selective inhibition of the mitogenic effect without affecting the tumor suppressor function and identifies a pharmacological strategy to suppress adenoma growth

Rectal cancer : Aspects on preoperative radiation, surgery and local recurrence

Rectal cancer is one of the most common malignant diseases in Sweden and is diagnosed in about 1.900 patients annually. Potentially curative surgery can be performed in 60-70% of these patients. Local recurrence is a major problem af ter surgery for rectal cancer. In Sweden, the local recurrence rate af ter potentially curative surgery has been 25-40% in different reports. Adjuvant radiation has been tried to improve local contro!. The Stockholm Rectal Cancer Study Group have performed two randomised trials on high dose, short term, preoperative radiotherapy in operable rectal adenocarcinoma. In the first trial a twofield radiation technique to a relatively large target volume was used. The second trial used a four-field technique to the pelvis only. The trials inc1uded 1.406 patients during 1980-1993. Preoperative radiation significantly reduced the local recurrence rate in both trials. In the second trial the overall survival was improved in curatively operated patients. There was an increased postoperative mortali.ty in irradiated patients. This increased mortality was statistically significant in the first but not in the second trial. This thesis was based on the patients inc1uded in the Stockholm Trials and had the following aims: To assess if patient outcome is related to the operative method, hospital or surgeon. To review the causes of postoperative death and to analyse factors putatively associated with an increased risk for postoperative mortality. To assess possible late radiation complications. To analyse if preoperative radiotherapy alters the c1inical course in patients with local recurrence. It is conc1uded that the operative method, i.e. abdominoperineal resection or anterior resection, has no significant influence on patient outcome. The effects of preoperative radiotherapy are similar with both types of operations. Patient outcome af ter surgery is related to the individual surgeon. The proportional reduction in local recurrence rate af ter preoperative radiotqerapy may be similar for most institutions and surgeons, but the absolute reduction is probably small when the local failure rate af ter surgery alone is low. Symptomatic cardiovascular disease, old age and distant metastases are independent risk factors for postoperative death. In patients with such risk factors, the addition of radiation may further increase that risk. There are also late adverse effects, such as venous thromboembolism, fractures and fistulas after high dose, short term, preoperative radiation in rectal cancer. The c1inical course in patients with local recurrence is similar irrespective of whether the patient has received radiotherapy before the primary operation. In summary, the risk of local recurrence and the risk of early and late adverse effects of the radiation should be considered in all rectal cancer patients on an individual basis, before a decision is taken to recommend preoperative radiotherapy

Effekter vid känd, okänd och oväntad arbetstid. : Mentala färdigheters inflytande på fysiologiska och upplevelsebaserade variabler vid uthållighetsarbete.

Syfte och frågeställningar: Syftet i den här studien har varit att undersöka hur fysiologiska och upplevelsebaserade variabler skiljer sig vid känd, okänd och oväntad arbetstid samt i förhållande till mentala färdigheter. För att uppnå syftet undersöktes följande frågor. Hur påverkas fysiologiska och upplevelsebaserade variabler vid känd, okänd och oväntad arbetstid? Vilket samband finns det mellan mentala färdigheter och de fysiologiska respektive upplevelsebaserade variablerna? Metod: Avsikten är att upprepa tidigare studier men med nya parametrar. Testpersonerna var uthållighetstränade (57,1 ml/kg/min ±3,7SD) män med en medelålder på 37 år (±3,8SD). Vid tre olika testtillfällen utförde testpersonerna (n=7) tre olika test. Vid alla testtillfällen sprang testpersonerna på löpband i 20 minuter med en hastighet som motsvarade 80 % av maximalt syreupptag. Vid test A fick testpersonerna veta att de skulle springa i 20 minuter. Vid test B fick testpersonerna veta att de skulle springa i 10 minuter, men i den tionde minuten fick testpersonerna veta att de skulle springa ytterligare10 minuter. Vid test C fick testpersonerna ingen information om hur lång tid de skulle springa, men i den tjugonde minuten fick testpersonerna veta att testet avslutades efter totalt 20 minuter. Resultat: Inga signifikanta skillnader i de fysiologiska variablerna mellan test A, B och C har kunnat fastställdes. Det finns dock en tendens att syreupptaget var lägre i test B än test A och C (p<0,10). Testresultaten visar att syreupptaget sjönk mellan minut 19 och 20 i test C. De upplevelsebaserade variablerna visade inte heller på signifikanta skillnader mellan olika tester, men uppskattad ansträngning verkade vara lägre i intervallet minut 14-19 i test B jämfört med test A och C, samt att syreupptaget också här sjönk för test C mellan minut 19 och 20. Sambanden mellan de fysiologiska samt upplevelsebaserade variablerna och de mentala färdigheterna resulterade i ett signifikant lägre syreupptag (p<0,05) i test B i förhållande till test C. Vid hög self-efficacy och högt mental toughness poäng, samt ett mer stabilt känslomässigt förlopp vid hög poäng på cognitive reappraisal. Testpersonernas användning av self-talk verkade vara test specifik då mängden positivt self-talk ökade från test A till B till C oavsett viken ordning testerna utfördes. Slutsats: Studien visar motstridiga resultat jämfört med tidigare refererade studier. Det finns ett samband mellan de fysiologiska och upplevelsebaserade variablerna, typ av test och mentala färdigheter. Sambandet är dock otydligt och bör undersökas noggrannare

Radionuclide fluxes at a plant manufacturing dicalcium phosphate for domestic animals

We have studied a phosphate rock plant which produces dicalcium phosphate (DCP), used as a source of calcium and phosphorus for domestic animals. A by-product in the manufacturing process is calcium chloride which is used in the oil industry, the food industry and as road-salt. The objectives of our study were to describe the fluxes of radionuclides from the U-238 decay series and to estimate the radiation doses to workers at the plant. The radionuclides in the phosphate rock were found to be in secular radioactive equilibrium with U-238, With an average activity concentration of 837 Bq kg(-1). Separation and concentration processes were observed at different stages in the plant. Most of the Ra-226 was found in the calcium chloride, while the major part of the U-238, about 950 Bq kg(-1), was found in the dicalcium phosphate. The annual occupational effective dose to the workers was found to be below the 1 mSv limit recommended by ICRP (1991a) for the public. This study has shown a good example of an important non-nuclear industry with a high input of natural radionuclides with several conceivable pathways to man

Ett smörgåsbord av möjligheter : en värderande analys av Passus avhopparstöd för personer som lämnar gäng och kriminalitet

Gäng framställs inte sällan som ett hot mot samhällets ordning. Våldsamma uppgörelser mellan olika konstellationer har sedan åtminstone 20-hundratalets inledning återkommit i upphettade politiska diskussioner såväl som i medierna. Krav på mer kraftfulla åtgärder har varit gängse, ofta med starka repressiva inslag där polis och kriminalvård varit de centrala aktörerna. Denna rapport belyser gängtillvaron, och framförallt vägen ut från sådana från ett annat håll. Här får vi möta personer som fått nog av gänget och vill starta om med ett annat slags liv. Vi möter personer med låg tillit till samhällets förmåga att stödja dem i vägen ut, och undersöker vad det är i Passus avhopparverksamhet som skänker hopp om att ett annat liv är möjligt. Den väg de har att vandra är i många fall lång och det finns mycket som utmanar under resan, och som skulle kunna få dem att vända tillbaka. Genom att erbjuda ett flexibelt stöd som kopplar an till den enskilde när, på det sätt och i de avseenden som behövs exemplifierar Passus hur ett stödarbete skulle kunna se ut. Nämligen att erbjuda ett smörgåsbord fullt av möjligheter. Rapporten vänder sig till alla som professionellt, i sin utbildning eller på annat sätt har intresserade av arbete med gäng och att skapa alternativ till gängtillvaron. Den är skriven av Kristina Alstam, lektor i socialt arbete vid Göteborgs universitet, Torbjörn Forkby, professor i socialt arbete och Daniel Holm, adjunkt i socialt arbete, de två senare vid Linnéuniversitetet

Removal of radionuclides at a waterworks.

A waterworks with an average production rate of 1.3 m3 s(-1), providing several large cities in the province of Scania with drinking water has been studied regarding its capacity to remove several natural and anthropogenic radionuclides. The raw water is surface water from lake Bolmen which is transported through an 80 km long tunnel in the bedrock before it enters the waterworks. The method used for purification is a combination of coagulation-flocculation and filtration in sand filters. Two different purification lines are currently in use, one using Al2(SO4)3 as a coagulant and one using FeCl3. After coagulation and flocculation the precipitate is removed and the water is passed through two different sand filters (rapid filtration and slow filtration). Water samples were collected at the lake, the inlet to the waterworks, after each of the flocculation basins (Al2(SO4)3 and FeCl3), after rapid filtration and from the municipal distribution network. The samples were analysed with respect to their content of uranium, thorium, polonium, radium, plutonium and caesium. The results show a high removal capacity for uranium (about 85%), thorium (>90%), plutonium (>95%) and polonium (>90% in the coagulation-flocculation process) while caesium, strontium and radium pass through the purification process with almost unchanged activity concentrations. During transportation of the water in the tunnel it was also observed that infiltration of groundwater leads to a change in isotopic ratios and/or activity concentrations for the naturally occurring radionuclides and plutonium

Impact of Using Linear Optimization Models in Dose Planning for HDR Brachytherapy

Purpose: Dose plans generated with optimization models hitherto used in HDR brachytherapy have shown a tendency to yield longer dwell times than manually optimized plans. Concern has been raised for the corresponding undesired hot spots and various methods to mitigate these have been developed. The hypotheses of this work are a) that one cause for the long dwell times is the use of objective functions comprising simple linear penalties and b) that alternative penalties, being piecewise linear, would lead to reduced length of individual dwell times. Methods: The characteristics of the linear penalties and the piecewise linear penalties are analysed mathematically. Experimental comparisons between the two types of penalties are carried out retrospectively for a set of prostate cancer patients. Results: While most dose-volume parameters do not differ significantly between the two types of penalties significant changes can be seen in the dwell times. On the average, total dwell times were reduced by 4.2%, with a reduction of maximum dwell times by 30%, using the alternative penalties. Conclusion: The use of linear penalties in optimization models for HDR brachytherapy is one cause for undesired longer dwell times appearing in mathematically optimized plans. By introducing alternative penalties significant reduction in dwell times can be achieved for HDR brachytherapy dose plans. Although various constraints as to reduce the long dwell times have been developed our finding is of fundamental interest in showing the shape of the objective function to be one reason for their appearance