| 1. |
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| 2. |
- Abazov, V. M., et al.
(författare)
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Measurement of the production fraction times branching fraction f(b -> Lambda(b)) . B(Lambda(b) -> J/psi Lambda)
- 2011
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 84:3, s. 031102-
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Tidskriftsartikel (refereegranskat)abstract
- The Lambda(b)(udb) baryon is observed in the decay Lambda(b) -> J/psi Lambda using 6.1fb(-1) of p (p) over bar collisions collected with the D0 detector at root s = 1/96 TeV. The production fraction multiplied by the branching fraction for this decay relative to that for the decay B(0) -> J/psi K(s)(0) is measured to be 0.345 +/- 0.034(stat) +/- 0.033(syst) +/- 0.003(PDG). Using the world average value of f(b -> B(0)) . B(B(0) -> J/psi K(s)(0) = (1.74 +/- 0.08) x 10(-5), we obtain f(b -> Lambda(b)) . B(Lambda(b) -> J/psi Lambda) = (6.01 +/- 0.60(stat) +/- 0.58(syst) +/- 0.28(PDG)) x 10(-5). This measurement represents an improvement in precision by about a factor of 3 with respect to the current world average.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 5. |
- Holmes, Michael V., et al.
(författare)
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Mendelian randomization of blood lipids for coronary heart disease
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36:9, s. 539-539
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a priormeta-analysis (threshold P < 2 x 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P <= 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestrictedallele score (48SNPs) was associated with CHD(OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
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| 6. |
- Vermeulen, Bram D., et al.
(författare)
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Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation : an individual patient data meta-analysis
- 2021
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 35:7, s. 3492-3505
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Tidskriftsartikel (refereegranskat)abstract
- Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1–3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1–3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. Conclusions: This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.
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| 7. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 8. |
- Analatos, Apostolos, et al.
(författare)
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Evaluation of resection of the gastroesophageal junction and jejunal interposition (Merendino procedure) as a rescue procedure in patients with a failed redo antireflux procedure. A single-center experience
- 2018
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Ingår i: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary antireflux surgery has high success rates but 5 to 20% of patients undergoing antireflux operations can experience recurrent reflux and dysphagia, requiring reoperation. Different surgical approaches after failed fundoplication have been described in the literature. The aim of this study was to evaluate resection of the gastroesophageal junction with jejunal interposition (Merendino procedure) as a rescue procedure after failed fundoplication.Methods: All patients who underwent a Merendino procedure at the Karolinska University Hospital between 2004 and 2012 after a failed antireflux fundoplication were identified. Data regarding previous surgical history, preoperative workup, postoperative complications, subsequent investigations and re-interventions were collected retrospectively. The follow-up also included questionnaires regarding quality of life, gastrointestinal function and the dumping syndrome.Results: Twelve patients had a Merendino reconstruction. Ten patients had undergone at least two previous fundoplications, of which one patient had four such procedures. The main indication for surgery was epigastric and radiating back pain, with or without dysphagia. Postoperative complications occurred in 8/12 patients (67%). During a median follow-up of 35 months (range 20-61), four (25%) patients had an additional redo procedure with conversion to a Roux-en-Y esophagojejunostomy within 12 months, mainly due to obstructive symptoms that could not be managed conservatively or with endoscopic techniques. Questionnaires scores were generally poor in all dimensions.Conclusions: In our experience, the Merendino procedure seems to be an unsuitable surgical option for patients who require an alternative surgical reconstruction due to a failed fundoplication. However, the small number of patients included in this study as well as the small number of participants who completed the postoperative workout limits this study.
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| 9. |
- Delcoigne, Bénédicte, et al.
(författare)
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Blood neurofilament light levels segregate treatment effects in multiple sclerosis
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. OBJECTIVE: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS). METHODS: Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide). RESULTS: The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations. CONCLUSION: Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.
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| 10. |
- Hestvik, Anne Lise K., et al.
(författare)
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Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes
- 2022
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Background: Teriflunomide 14 mg (Aubagio (R)) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting. Methods: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals. Results: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naive and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations. Conclusion: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies.
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| 11. |
- Kung, Chih Han, et al.
(författare)
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Extent of lymphadenectomy has no impact on postoperative complications after gastric cancer surgery in Sweden
- 2017
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Ingår i: Chinese Journal of Cancer Research. - : Chinese Journal of Cancer Research. - 1000-9604. ; 29:4, s. 313-322
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Curative gastric cancer surgery entails removal of the primary tumor with adequate margins including regional lymph nodes. European randomized controlled trials with recruitment in the 1990’s reported increased morbidity and mortality for D2 compared to D1. Here, we examined the extent of lymphadenectomy during gastric cancer surgery and the associated risk for postoperative complications and mortality using the strengths of a population-based study. Methods: A prospective nationwide study conducted within the National Register of Esophageal and Gastric Cancer. All patients in Sweden from 2006 to 2013 who underwent gastric cancer resections with curative intent were included. Patients were categorized into D0, D1, or D1+/D2, and analyzed regarding postoperative morbidity and mortality using multivariable logistic regression. Results: In total, 349 (31.7%) patients had a D0, 494 (44.9%) D1, and 258 (23.4%) D1+/D2 lymphadenectomy. The 30-d postoperative complication rates were 25.5%, 25.1% and 32.2% (D0, D1 and D1+/D2, respectively), and 90-d mortality rates were 8.3%, 4.3% and 5.8%. After adjustment for confounders, in multivariable analysis, there were no significant differences in risk for postoperative complications between the lymphadenectomy groups. For 90-d mortality, there was a lower risk for D1 vs. D0. Conclusions: The majority of gastric cancer resections in Sweden have included only a limited lymphadenectomy (D0 and D1). More extensive lymphadenectomy (D1+/D2) seemed to have no impact on postoperative morbidity or mortality.
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| 12. |
- Lund, Mikael, et al.
(författare)
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Effects of neoadjuvant chemo or chemoradiotherapy for oesophageal cancer on perioperative haemodynamics A prospective cohort study within a randomised clinical trial
- 2016
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Ingår i: European Journal of Anaesthesiology. - : Lippincott Williams & Wilkins. - 0265-0215 .- 1365-2346. ; 33:9, s. 653-661
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Neoadjuvant chemoradiotherapy might improve oncological outcome compared with chemotherapy after surgery for oesophagus or gastrooesophageal junction cancer. However, radiotherapy may induce cardiovascular side-effects that could increase the risk of perioperative adverse effects and postoperative morbidity. OBJECTIVES The aim of this study was to compare the perioperative haemodynamics in patients undergoing oesophagectomy following neoadjuvant chemotherapy or chemoradiotherapy for cancer. DESIGN A prospective single-centre cohort study within a randomised multi-centre trial. SETTING A Swedish University Hospital from January 2009 to March 2013. PATIENTS A total of 31 patients (chemotherapy 17, chemoradiotherapy 14) included in a multi-centre trial randomising chemotherapy vs. chemoradiotherapy and operated at Karolinska University Hospital, Huddinge. INTERVENTIONS Cisplatin and 5-fluorouracil, either with or without concurrent radiotherapy (40 Gy), were given prior to surgery. Cardiac function was assessed with LiDCOplus (LiDCO Ltd, London, United Kingdom), echocardiography, troponin T and N-terminal pro-B-type natriuretic peptide, before, during and after surgery. MAIN OUTCOME MEASURES The primary outcome was the interaction effect of the neoadjuvant treatment on stroke volume index during the perioperative period. Secondary outcomes were the interaction effects of oxygen delivery index, cardiac index, echocardiography and biochemical markers. RESULTS The groups were matched regarding comorbidities, but patients in the chemoradiotherapy group were older (66 vs. 60 years P = 0.03). Haemodynamic values changed in a similar way in both groups during the study period. The chemoradiotherapy group had a lower cardiac index before surgery (2.9 vs. 3.4 l min(-1) m(-2), P = 0.03). On the third postoperative day, both groups displayed a hyperdynamic state compared with baseline, with no increase in troponin T, and a similar increase in N-terminal pro-B-type natriuretic peptide. CONCLUSION Neoadjuvant chemoradiotherapy for oesophageal or gastrooesophageal junction cancer seems to induce only a marginal negative effect on cardiac function compared with neoadjuvant chemotherapy. This difference did not remain when patients' haemodynamics were challenged by surgery.
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| 13. |
- Lund, Mikael, et al.
(författare)
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Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction : a prospective cohort pilot study within a randomized clinical trial
- 2015
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Methods: Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. Results: 40 patients participated (chemoradiotherapy, n = 17; chemotherapy, n = 23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p = 0.02, p = 0.01, and p = 0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p = 0.09 and p = 0.09). NT-proBNP increased following chemoradiotherapy (p = 0.05) but not after chemotherapy (p > 0.99), and there was a trend towards an interaction effect (p = 0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p = 0.03) and was more pronounced after chemoradiotherapy with a trend towards an interaction effect (p = 0.10). Conclusions: Neoadjuvant chemoradiotherapy but not chemotherapy before surgery for cancer of the esophagus or GE-junction seems to induce an acute negative effect on both systolic and diastolic left ventricular function. Future studies on neoadjuvant treatment for esophageal cancer are suggested to add measurements of cardiac function.
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| 14. |
- Tsai, Jon A., et al.
(författare)
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Albumin-bound lipids induce free cytoplasmic calcium oscillations in human osteoblast-like cells
- 2007
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Ingår i: Cell Biochemistry and Function. - : Wiley. - 0263-6484 .- 1099-0844. ; 25:3, s. 245-249
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Tidskriftsartikel (refereegranskat)abstract
- [Ca2+](i) oscillations were found in human osteoblast-like cells (hOB cells) exposed to high-lipid bovine serum albumin (BSA), but not when exposed to low-lipid BSA. These [Ca2+](i) oscillations were inhibited by heptanol and suramin, which implies that gap junctions and purinergic signalling may be important for these [Ca2+](i) oscillations. The high-lipid BSA preparation that was used contains arachidonic acid. [Ca2+](i) oscillations could be induced by low lipid albumin with arachidonic acid added. The albumin-bound lipids were also important for osteoblast growth since DNA synthesis and the total cell protein content was higher in hOB cells exposed to high-lipid BSA. The effect of arachidonic acid on hOB cell proliferation was bone-donor dependent; both stimulatory and inhibitory effects were observed. The physiological importance of albumin-bound lipids is unclear; given that albumin has only minimal contact with osteoblasts under normal conditions. Only when bone capillaries are disrupted, e.g. during a fracture, would significant amounts of albumin reach osteoblasts. Albumin-bound lipids could therefore contribute to stimulation of osteoblast proliferation during fracture healing.
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| 15. |
- Tsai, Jon A., et al.
(författare)
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Effects of synovial fluid from aseptic prosthesis loosening on collagen production in osteoblasts
- 2009
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Ingår i: International Orthopaedics. - : Springer Science and Business Media LLC. - 0341-2695 .- 1432-5195. ; 33:3, s. 873-877
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Tidskriftsartikel (refereegranskat)abstract
- Synovial fluid from a loose prosthesis may act as a vehicle for factors that regulate bone turnover. The effect of such synovial fluid on osteoblasts has been studied. Synovial fluid obtained from patients who underwent revision hip arthroplasty because of aseptic prosthesis loosening was studied regarding the effect on protein synthesis, procollagen I mRNA expression, the secretion of procollagen I carboxyterminal propeptide (PICP) and osteocalcin in MG63 osteoblasts. Protein synthesis was increased and procollagen I mRNA expression was decreased by synovial fluid from patients with prosthesis loosening. Synovial fluid stimulated the total PICP in cell medium, but there was no change after correction for cell protein content in the cells. Synovial fluid in patients with prosthesis loosening has a general stimulatory effect on collagen formation and osteoblast proliferation because of a stimulatory effect on cell growth. Aseptic prosthesis loosening may be associated with an increase in bone formation.
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| 16. |
- Tsai, Jon A., et al.
(författare)
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One-lung ventilation during thoracoabdominal esophagectomy elicits complement activation
- 2009
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 152:2, s. 331-337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) during thoracoabdominal esophagectomy may induce an inflammatory response that can contribute to the induction and propagation of frequently occurring postoperative respiratory distress. Markers of such a response might be detected in the pulmonary as well as in the systemic circulation. Inflammation and tissue damage may be key pathogenetic pathways and we hypothesized that 1-lung ventilation may induce an inflammatory cascade reflected by markers for such a response. MATERIALS AND METHODS: Thirty patients with esophageal cancer were randomized to OLV (n = 16) or 2-lung ventilation (TLV; n = 14) during the thoracic part of the operation. Compounds involved in inflammation and coagulation were measured perioperatively and during the 1st, 2nd, 3rd, and 10th postoperative d. RESULTS: During the perioperative phase, the proinflammatory cytokine interleukin-6 and thrombin, measured as thrombin-antithrombin complexes, started to increase. Thrombin, which can induce complement activation, peaked at the end of surgery and interleukin-6 at the 1st to 2nd postoperative d, but there were no differences between the OLV and TLV groups. C3a and terminal complement complex (TCC) started to increase on the 2nd postoperative d and continued to do so for the rest of the study period. The increase of TCC was significantly higher in the OLV group compared to the TLV group, whereas C3a attained similar levels in the 2 groups. CONCLUSIONS: OLV is associated with an augmented inflammatory response as reflected by the activation of the TCC. This may induce pulmonary tissue damage and recruitment of inflammatory cells.
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| 17. |
- Tsai, Jon A
(författare)
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Parathyroid hormone-related protein (PTHrP), calcium and human osteoblast-like cells
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parathyroid hormone-related protein (PTHrP) may cause humoral hypercalcernia of malignancy (HHM) when overproduced by malignant tumors, but is also produced in lower amounts under normophysiological conditions in practically all cell types, including osteoblasts. One of the aims of the present study was to investigate interactions between PTHrP and osteoblasts, to elucidate bone-regulating functions of PTHrP. The well-characterized primary cultures of normal human osteoblast-like cells (hOB cells) that were used, reflect human bone physiology better than osteoblastic cell lines. The N-terminal fragment of PTHrP increased intracellular cyclic adenosine monophospate (cAMP) in hOB cells, whereas there was no effect on free cytoplasmic calcium ([Ca2+]i), The content of insulin-like growth factor (IGF) I and II, IGF binding protein (IGFBP) 4 and 5 in conditioned medium from hOB cells was also stimulated by N-terminal PTHrP. IGF-I, IGF-II and IGFBP-5 are anabolic factors, whereas IGFBP-4 has catabolic effects. Therefore, the present findings give insight into the mechanisms behind the ambiguous effects of PTHrP, which may have both anabolic and catabolic effects on bone. There was also a negative correlation between IGFBP-4 and IGFBP-5, as well as a negative correlation between IGFBP-4 in conditioned medium and the age of the hOB cell donors. This implies that the catabolic effect of IGFBP-4 from osteoblasts may be amplified by a relatively low production of IGFBP-5, and vice versa, and that an intrinsic age-related increase in locally produced IGFBP-4 in osteoblasts may play a role in the development of age-related osteoporosis. IL- 10 increased messenger RNA expression and secretion of PTHrP in hOB cells, whereas the production of TGF-ß was decreased. Thus, IL-1beta], which has well documented bone-resorbing effects, may exert indirect effects on osteoblasts by regulating the production of PTHrP, which increases bone resorption, and TGF-ß, which is an important anabolic factor for bone. TGF-ß is also considered to be a coupling factor that controls the interaction between osteoclasts and osteoblasts in the bone remodeling process. Patients with HHM may display increased levels of IL-1, in addition to elevated PTHrP. The fact that IL-1ß decreased TGF-ß in hOB cells therefore indicates a possible mechanism behind the uncoupled bone remodeling process in patients with HEM. Oscillations in the [Ca2+]i level were found in hOB cells, but only in the presence of albumin with a high lipid content, and not when exposed to low lipid albumin. The oscillations were dependent on extracellular calcium ([Ca2+]O), as well as intracellular calcium stores, and intercellular gap junction communication. High lipid albumin also had a stimulatory effect on DNA synthesis compared to low lipid albumin. However, the precise relationship between [Ca2+]i oscillations and DNA synthesis has not been fully clarified. A relative decrease in pericellular osmolality induced [Ca2+]i transients in hOB cells. This indicates a potential signaling pathway for the anabolic effects of mechanical stimuli on bone, since a decrease in osmolality causes cellular swelling and stretching of the plasma membrane, and therefore mimics mechanical stimulation. A high concentration of [Ca2+]O increased [Ca2+]i in hOB cells and stimulated DNA synthesis through a protein kinase C-dependent mechanism. Since osteoblasts can be exposed to high concentrations of [Ca2+]O released during osteoclastic bone resorption, this indicates that [Ca2+], may be a coupling factor in the bone remodeling process, which recruits and stimulates osteoblasts through these signaling pathways.
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