| 1. |
- Treusch, Sebastian, et al.
(författare)
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Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast
- 2011
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Ingår i: Science. - Washington : American association of advancement in science. - 0036-8075 .- 1095-9203. ; 334:6060, s. 1241-1245
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Tidskriftsartikel (refereegranskat)abstract
- Aβ (beta amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained using yeast as a model system.
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| 2. |
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| 3. |
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| 4. |
- Bergqvist, D, et al.
(författare)
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Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis
- 1988
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 75:9, s. 888-891
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Tidskriftsartikel (refereegranskat)abstract
- A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a low molecular weight heparin fragment for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the heparin fragment was given the evening before surgery, and further doses were given thereafter every evening. There were 1002 analysable patients, 826 having received correct prophylaxis. Of these 1002 patients, 64 per cent were operated on for malignant disease. A total of 20 patients died, 10 in each group. The frequency of deep vein thrombosis was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2-5.0 per cent, P = 0.02) [corrected]. The frequency of bleeding was 6.7 per cent among the heparin fragment patients and 2.7 per cent among the patients given conventional heparin (P = 0.01), but all bleeds were of minor degree and there was no difference in the reoperation rate for bleeding, or in the transfusion requirements. Local pain at the injection site was reported significantly less often among patients given the heparin fragment.
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| 5. |
- Bergqvist, D, et al.
(författare)
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Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin
- 1990
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Ingår i: Seminars in Thrombosis and Hemostasis. - 1098-9064. ; 16:Suppl., s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There were 1002 analyzable patients, 826 having received correct prophylaxis. Sixty three percent of the patients were operated on for malignant diseases. The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2 to 5.0%, p = 0.02). In patients with malignancies the reduction was from 11.2 to 6.4% (p = 0.06). The frequency of bleeding was 6.7% among the heparin fragment patients and 2.7% among the patients given conventional heparin (p = 0.01). The corresponding frequencies for patients with malignancies were 3.2 and 2.8%, respectively (p = 0.28). All bleedings were minor and of no clinical significance. Local pain at the injection site was reported significantly less often among patients with the fragment. Twenty patients died, 13 with malignant disease, mortality being the same in the two groups. It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery, also when the histology shows malignancy. Thus, the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines, better thromboprophylactic effect, and less local pain at injection sites. A disadvantage is the slight increase in hemorrhagic side effects, all of minor clinical importance and not seen in patients undergoing surgery for malignancy.
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| 6. |
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| 7. |
- Eriksson, Anna, et al.
(författare)
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The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia
- 2012
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 2, s. e81-
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Tidskriftsartikel (refereegranskat)abstract
- Aberrantly expressed tyrosine kinases have emerged as promising targets for drug development in acute myeloid leukemia (AML). We report that AKN-028, a novel tyrosine kinase inhibitor (TKI), is a potent FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor (IC50=6 nM), causing dose-dependent inhibition of FLT3 autophosphorylation. Inhibition of KIT autophosphorylation was shown in a human megakaryoblastic leukemia cell line overexpressing KIT. In a panel of 17 cell lines, AKN-028 showed cytotoxic activity in all five AML cell lines included. AKN-028 triggered apoptosis in MV4-11 by activation of caspase 3. In primary AML samples (n=15), AKN-028 induced a clear dose-dependent cytotoxic response (mean IC50 1 μM). However, no correlation between antileukemic activity and FLT3 mutation status, or to the quantitative expression of FLT3, was observed. Combination studies showed synergistic activity when cytarabine or daunorubicin was added simultaneously or 24 h before AKN-028. In mice, AKN-028 demonstrated high oral bioavailability and antileukemic effect in primary AML and MV4-11 cells, with no major toxicity observed in the experiment. In conclusion, AKN-028 is a novel TKI with significant preclinical antileukemic activity in AML. Possible sequence-dependent synergy with standard AML drugs and good oral bioavailability has made it a candidate drug for clinical trials (ongoing).
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| 8. |
- Jivegård, Lennart, 1950, et al.
(författare)
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Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.
- 2005
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Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 29:2, s. 190-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.
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| 9. |
- Kald, A, et al.
(författare)
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Reoperation as surrogate endpoint in hernia surgery. A three year follow-up of 1565 herniorrhaphies.
- 1998
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Ingår i: European Journal of Surgery. - : Oxford University Press (OUP). - 1102-4151 .- 1741-9271. ; 164:1, s. 45-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Analysis of reoperation and recurrence rates three years after repair of groin hernias.DESIGN: Prospective audit by questionnaire and selective follow-up.SETTING: Eight Swedish hospitals.SUBJECTS: All groin hernia operations done during 1992 on patients between the ages of 15 and 80 years.MAIN OUTCOME MEASURES: Postoperative complications, reoperation for recurrence, and recurrence.RESULTS: During 1992, 1565 hernia operations were done. The postoperative complication rate was 8% (125/1565). At 36 months postoperatively 108 recurrences had already been reoperated on, six patients with recurrences were on the waiting list for reoperation and a further 36 recurrences had been detected at follow-up. The interhospital variation in recurrence rate ranged from 3% to 20%. Postoperative complications, recurrent hernia, direct hernia and hospital catchment area over 100000 inhabitants were all factors associated with an increased relative risk of recurrence.CONCLUSIONS: The recurrence rate exceeded the reoperation rate for recurrence by almost 40% which should be taken into account if the reoperation rate is used as the endpoint after repairs of groin hernia. An audit scheme, based on prospective recording, reoperation rate, and (periodic) calculation of the recurrence rate may be used to identify risk factors for recurrence and areas in need of improvement.
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| 10. |
- Arnbjörnsson, E., et al.
(författare)
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Laparoscopy for nonpalpable testis in childhood : Is inguinal exploration necessary when vas and vessels are not seen?
- 1996
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Ingår i: European Journal of Pediatric Surgery. - : Georg Thieme Verlag KG. - 0939-7248 .- 1439-359X. ; 6:1, s. 7-9
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Tidskriftsartikel (refereegranskat)abstract
- A case of bilateral nonpalpable testes is described. Ultrasonography showed no testis. Laparoscopy revealed no intraabdominal testis, vas or vessels. Human chorionic gonadotrophine test suggested the presence of testicular tissue Computed tomography showed a testis present in each inguinal canal. Inguinal exploration confirmed the finding. This case stresses the importance of careful interpretation of the laparoscopic findings together with other diagnostic methods in localizing testicular tissue in patients with nonpalpable testes.
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| 11. |
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| 12. |
- Bergqvist, D, et al.
(författare)
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Abdominal trauma in persons older than 60 years
- 1982
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Ingår i: Acta Chirurgica Scandinavica. - 0001-5482. ; 148:7, s. 569-573
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal trauma occurring in persons older than 60 years over a 30-year period (1950-79) in a well defined region of Sweden was reviewed. The 177 patients comprised 12.5% of the total with abdominal trauma during that period. Road traffic accidents were the main cause of trauma (48% of cases). The incidence of motor-car accidents rose sharply during the first two decades of the study. Injuries to the liver and bile ducts and multiple intra-abdominal injuries were more common in the elderly than in younger patients, but injury to the abdominal wall was less common. A tendency towards more severe injuries and multiple trauma with extra-abdominal involvement emerged during the study period. The mortality rate was 27.6% in the patients older than 60, but 9.1% in the overall patient series with abdominal trauma. One-third of all the deaths among the older patients were directly due to the abdominal trauma. One consequence of the increasing numbers of old people in the general population is probably that more and more cases of abdominal trauma will be seen in the higher age groups.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Lindhagen, Johan E., et al.
(författare)
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Application of bridging-law concepts to short-fibre composites : 1. DCB test procedures for bridging law and fracture energy
- 2000
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Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:6, s. 871-883
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Tidskriftsartikel (refereegranskat)abstract
- This is the first paper in a series of four where notch sensitivities, fracture energies and bridging laws of short-fibre polymer composites are investigated. In the context of crack-bridging, the bridging law is an important material parameter. The bridging law can be used in combination with a stress analysis to address failure problems, for instance large-scale bridging, where linear elastic fracture mechanics is not valid. The bridging law of the material is sensitive to material composition and fibre architecture. Owing to the lack of established procedures, it is of interest to develop experimental and analytical methods for determination of the bridging law and fracture energy of short-fibre polymer composites. A method based on a large DCB specimen loaded by pure bending moments is used. Commercial GMT and SMC materials are investigated in addition to chopped-strand-mat laminates based on glass fibres of two different lengths and two thermoset matrices of different ductility. Fracture energies and bridging law data are successfully determined. All materials demonstrate softening bridging laws and this is discussed on the basis of observed mechanisms of failure and existing micromechanical models.
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| 17. |
- Lindhagen, J. E., et al.
(författare)
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Application of bridging-law concepts to short-fibre composites 4. FEM analysis of notched tensile specimens
- 2000
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Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:16, s. 2895-2901
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Tidskriftsartikel (refereegranskat)abstract
- This is the fourth paper in a series of four where notch sensitivities, fracture energies and bridging laws in short-fibre polymer composites are investigated. In this paper finite-element modelling (FEM) of centre-hole-notched tensile specimens is performed, with different bridging laws governing crack growth. Crack lengths, crack profiles and stress distributions are predicted. The results are compared with experimentally determined crack shapes from an earlier investigation. Only with softening bridging laws can the experimental results be matched. The predicted crack lengths are sensitive to bridging-law parameters. When bridging laws determined by the double cantilever beam (DCB) method are applied, the predicted crack lengths and profiles show good correlation with the experimental results. The results support the validity of the DCB method to determine bridging laws in short-fibre composites.
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| 18. |
- Lindhagen, J. E., et al.
(författare)
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Application of bridging-law concepts to short-fibre composites - Part 1 : DCB test procedures for bridging law and fracture energy
- 2000
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Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:6, s. 871-883
-
Tidskriftsartikel (refereegranskat)abstract
- This is the first paper in a series of four where notch sensitivities, fracture energies and bridging laws of short-fibre polymer composites are investigated. In the context of crack-bridging, the bridging law is an important material parameter. The bridging law can be used in combination with a stress analysis to address failure problems, for instance large-scale bridging, where linear elastic fracture mechanics is not valid. The bridging law of the material is sensitive to material composition and fibre architecture. Owing to the lack of established procedures, it is of interest to develop experimental and analytical methods for determination of the bridging law and fracture energy of short-fibre polymer composites. A method based on a large DCB specimen loaded by pure bending moments is used. Commercial GMT and SMC materials are investigated in addition to chopped-strand-mat laminates based on glass fibres of two different lengths and two thermoset matrices of different ductility. Fracture energies and bridging law data are successfully determined. All materials demonstrate softening bridging laws and this is discussed on the basis of observed mechanisms of failure and existing micromechanical models.
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| 19. |
- Lindhagen, J. E., et al.
(författare)
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Application of bridging-law concepts to short-fibre composites - Part 2. Notch sensitivity
- 2000
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Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:6, s. 885-893
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Tidskriftsartikel (refereegranskat)abstract
- This is the second paper in a series of four where notch sensitivities, fracture energies and bridging laws are studied in short-fibre polymer composites. Estimates based on an order-of-magnitude criterion indicate that previous notch sensitivity studies on short-fibre composites are limited to small notch sizes in the ductile region. For this reason, centre-hole notch sensitivity is studied experimentally as a function of relatively large notch diameters in the range 15-60 mm. The materials have different matrices, glass-fibre content and fibre lengths. The onset of notch sensitivity is observed for all materials (glass-mat thermoplastics, sheet-moulding compounds and chopped-strand-mat laminates), although large notch sizes are required. The reasons for this are discussed as well as the influence of different material parameters. On the basis of the material bridging law and laminate Young's modulus, it was possible to rank different short-fibre composites with respect to notch sensitivity.
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| 20. |
- Lindhagen, J. E., et al.
(författare)
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Application of bridging-law concepts to short-fibre composites Part 3 : Bridging law derivation from experimental crack profiles
- 2000
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Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:16, s. 2883-2894
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Tidskriftsartikel (refereegranskat)abstract
- This is the third paper in a series of four where notch sensitivity, fracture energy and bridging laws are studied in short-fibre polymer composites. Here, bridging laws are derived from experimental crack-opening profiles in centre-hole notched tensile specimens. The materials studied are three types of commercial glass-mat composites with different reinforcement structures and matrices. The materials have softening bridging laws and the calculated fracture energies from bridging laws are in good agreement with values determined directly by experiment. The calculated maximum local bridging stress is found to be higher than the uniaxial tensile strength. An outline of a failure criterion for notched specimens based on the crack-bridging approach is presented.
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| 21. |
- Lindhagen, J.E., et al.
(författare)
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Bridging law determination in short fibre composites by a DCB-test
- 2000
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Ingår i: E S I S Publication. - 1566-1369. ; 27, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- For short fibre polymer composites such as chopped strand mat laminates (CSM), glass mat thermoplastics (GMT) and sheet moulding compounds (SMC), conventional methods to measure fracture energy are often not valid since linear elastic fracture mechanics (LEFM) criteria are not fulfilled. For the case of a long bridged crack with a small damage zone perpendicular to the crack, a crack bridging approach may instead be used. In this context, the bridging law is an important material parameter. The bridging law in combination with stress analysis can be used to address problems where LEFM is invalid. The bridging law of the material is related to material composition and fibre architecture. It is therefore of interest to develop an experimental method for determination of bridging law and fracture energy in short-fibre polymer composites. A method based on a large double cantilever beam (DCB) specimen loaded by pure bending moments is used. Commercial GMT and SMC materials are investigated as well as CSM laminates. Fracture energy and bridging law data are determined. All materials demonstrate softening bridging laws and this is discussed based on observed mechanisms of failure.
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| 22. |
- Lindhagen, Johan.E., et al.
(författare)
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Temperature changes in polymer composites during tensile loading
- 1997
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Ingår i: Journal of Materials Science. - 0022-2461 .- 1573-4803. ; 32:15, s. 4071-4076
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Tidskriftsartikel (refereegranskat)abstract
- Temperature changes in polymeric composite laminates subjected to uniaxial monotonic tensile loading were studied. The laminates were transverse and longitudinal unidirectional glass fibre-epoxy and carbon fibre-epoxy laminates, and hybrid crossply laminates with longitudinal glass fibre-epoxy and transverse carbon fibre-epoxy layers. The temperature decreased linearly with increased tensile stress in the elastic region, except for longitudinal carbon fibre specimens (where the fibres have a small but negative coefficient of thermal expansion), which exhibited a small temperature increase. The occurrence of non-linear stress-strain behaviour in transverse carbon fibre specimens altered the rate of temperature change. When cracks appeared in laminates, the temperature immediately started to rise. The temperature changes in crossply laminates were interpreted from measurements on unidirectional specimens and knowledge of the damage mechanisms.
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| 23. |
- Lindhagen, Johan, et al.
(författare)
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Low Temperature Strength and Notch Sensitivity of Glass Mat Polypropylene
- 1997
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Ingår i: Journal of cold regions engineering. - 0887-381X .- 1943-5495. ; 11:3, s. 180-197
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Tidskriftsartikel (refereegranskat)abstract
- Literature on the effects of lowered temperature on the toughness of random short fiber composites have neither offered a clear trend nor explained the mechanisms of failure. In this work, unnotched and notched strengths at room temperature and -30°C of two glass mat polypropylenes with different fiber architectures are investigated. Observations are explained based on models for Young's modulus and notch sensitivity. Increases in strength and stiffness with lowered temperature are caused by increased matrix modulus and yield stress. Fiber bridging operating in a damage zone of substantial length was the major toughening mechanism and forms the basis for the modeling approach for notch sensitivity. Increased notch toughness at low temperature is caused by increased work of fracture in the damage zone. The increased matrix modulus and yield stress lead to an increased toughening efficiency of short fibers.
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| 24. |
- Lindhagen, Johan, et al.
(författare)
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Microscopical damage mechanisms in glass fiber reinforced polypropylene
- 1998
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Ingår i: Journal of Applied Polymer Science. - 0021-8995 .- 1097-4628. ; 69:7, s. 1319-1327
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Tidskriftsartikel (refereegranskat)abstract
- The damage mechanisms in two structurally different glass mat reinforced polypropylene materials were studied. In situ microscopy was applied during the tensile testing of thin notched sheets. Micrographs of the damage processes in the two materials are presented. The major points of damage initiation were transversely oriented fibers and fiber bundles. In the swirled mat material, cracks grew along the fiber bundles; crack formation and growth was relatively unaffected by macroscopical stress concentration. In the short fiber material, crack growth occurred at the notch. In both materials the maximum load was determined by the fibers oriented in the longitudinal direction. The different damage mechanisms were interpreted in terms of damage zone size
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| 25. |
- Lindhagen, Johan, et al.
(författare)
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Notch sensitivity and damage mechanisms of glass mat reinforced polypropylene
- 1997
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Ingår i: Polymer Composites. - : Wiley. - 0272-8397 .- 1548-0569. ; 18:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- Notch Sensitivities of two structurally different glass-mat reinforced polypropylene materials (GMT) were investigated. Center hole notches in tensile specimens were used in the tests. The results show that the short fiber material has higher unnotched strength, but also higher notch sensitivity compared to a swirled mat material. Reasons for this are discussed, focusing on microstructural differences. Predictions from four different failure criteria were compared with the experimental notched strength data. The point stress and damage zone criteria were found to give the best descriptions.
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