Haakon Breien Benestad

• Aas, Sigve Nyvik; Seynnes, Olivier R.; Benestad, Haakon Breien & Raastad, Truls (2019). Strength training and protein supplementation improve muscle mass, strength, and function in mobility-limited older adults: a randomized controlled trial. Aging Clinical and Experimental Research.  ISSN 1594-0667. . doi: 10.1007/s40520-019-01234-2
• Benestad, Haakon Breien (2019). Kan trening redusere risiko for Alzheimers sykdom?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(7), s 1- 2 . doi: 10.4045/tidsskr.19.0086
• Hamarsland, Håvard; Handegard, Vilde; Kåshagen, Mauritz; Benestad, Haakon Breien & Raastad, Truls (2019). No Difference Between Spray Dried Milk and Native Whey Supplementation with Strength Training. Medicine & Science in Sports & Exercise.  ISSN 0195-9131.  51(1), s 75- 83 . doi: 10.1249/MSS.0000000000001758 Fulltekst i vitenarkiv. Vis sammendrag

  Background: A rapid digestibility and high leucine content are considered important for maximal stimulation of muscle protein synthesis. Consequently, with these properties, native whey may hold greater anabolic potential than milk, when supplemented in combination with strength training. Our aim was to compare the effects of supplementation with milk or native whey, during a 12-week strength training period, on gains in muscle mass and strength in young adults. Methods: In this double-blinded, randomized, controlled study a total of 40 untrained young men and women received two daily servings of either milk or native whey containing 20 g of protein, during a 12-week strength training intervention. Muscle strength, lean mass, thigh muscle cross sectional area, m. vastus lateralis thickness and muscle fiber cross sectional area were assessed before and after the training period. In addition, the acute phosphorylation of the anabolic kinases p70S6K, 4E-BP1 and eEF-2 in response to a standardized workout and supplementation was investigated before and after the 12-week training period. Results: Muscle mass and strength increased, by all measures applied (5-16%, P < 0.001), with no differences between groups (P > 0.25). p70S6K phosphorylation increased (~1000%, P < 0.02) 2 hours after exercise in the untrained and trained state, but no differences in anabolic signaling were observed between supplements (P > 0.40). No correlation between these acute measures and changes in muscle mass or strength were observed. Conclusion: Supplementation with milk or native whey during a 12-week strength training period did not differentially affect muscle mass and strength in young untrained individuals.

• Hamarsland, Håvard; Aas, Sigve Nyvik; Nordengen, Anne Lene; Holte, Kari; Garthe, Ina; Paulsen, Gøran; Cotter, Matthew; Børsheim, Elisabet; Benestad, Haakon Breien & Raastad, Truls (2018). Native whey induces similar post exercise muscle anabolic responses as regular whey, despite greater leucinemia, in elderly individuals. The Journal of Nutrition, Health & Aging.  ISSN 1279-7707. . doi: 10.1007/s12603-018-1105-6 Fulltekst i vitenarkiv. Vis sammendrag

  Objective: Elderly muscle seems less sensitive to the anabolic stimulus of a meal. Changes in blood concentrations of leucine are suggested as one important trigger of the anabolic response in muscle. The aim of this study was to investigate whether native whey protein, containing high amounts of leucine, may be a more potent stimulator of muscle protein synthesis (MPS) in elderly than regular whey protein (WPC-80) or milk. Design: Randomized controlled partial crossover. Setting: Norwegian School of Sport Sciences. Participants: 21 healthy elderly men and women (≥70 years). Intervention: Participants received either 20 g of WPC-80 and native whey (n = 11) on separate days in a crossover design, or milk (n = 10). Supplements were ingested immediately and two hours after a bout of lower body heavy-load resistance exercise. Measurements: Blood samples and muscle biopsies were collected to measure blood concentrations of amino acids by gas-chromatography mass spectrometry (GCMS), phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting and mixed muscle fractional synthetic rate (FSR) by use of [2H5]phenylalanine-infusion, GCMS and isotope-ratio mass spectrometry. Results: Native whey increased blood leucine concentrations more than WPC-80 (P < 0.05), but not p70S6K phosphorylation or mixed muscle FSR. Both whey supplements increased blood leucine concentrations (P < 0.01) and P70S6K phosphorylation more than milk (P = 0.014). Native whey reached higher mixed muscle FSR values than milk (P = 0.026) 1-3h after exercise. Conclusions: Despite greater increases in blood leucine concentrations than WPC-80 and milk, native whey was only superior to milk concerning increases in MPS and phosphorylation of P70S6K during a 5-hour post-exercise period in elderly individuals.

• Benestad, Haakon Breien (2017). Genmodifiserte T-celler mot kreft. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  137(10), s 709 . doi: 10.4045/tidsskr.17.0321
• Hamarsland, Håvard; Nordengen, Anne Lene; Aas, Sigve Nyvik; Holte, Kristin Tosterud; Garthe, Ina; Paulsen, Gøran; Cotter, Matthew; Børsheim, Elisabet; Benestad, Haakon Breien & Raastad, Truls (2017). Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial. Journal of the International Society of Sports Nutrition.  ISSN 1550-2783.  14:43, s 1- 12 . doi: 10.1186/s12970-017-0202-y Vis sammendrag

  Background: Protein intake is essential to maximally stimulate muscle protein synthesis, and the amino acid leucine seems to possess a superior effect on muscle protein synthesis compared to other amino acids. Native whey has higher leucine content and thus a potentially greater anabolic effect on muscle than regular whey (WPC-80). This study compared the acute anabolic effects of ingesting 2 × 20 g of native whey protein, WPC-80 or milk protein after a resistance exercise session. Methods: A total of 24 young resistance trained men and women took part in this double blind, randomized, partial crossover, controlled study. Participants received either WPC-80 and native whey (n = 10), in a crossover design, or milk (n = 12). Supplements were ingested immediately (20 g) and two hours after (20 g) a bout of heavy-load lower body resistance exercise. Blood samples and muscle biopsies were collected to measure plasma concentrations of amino acids by gas-chromatography mass spectrometry, muscle phosphorylation of p70S6K, 4E–BP1 and eEF-2 by immunoblotting, and mixed muscle protein synthesis by use of [2H5]phenylalanine-infusion, gas-chromatography mass spectrometry and isotope-ratio mass spectrometry. Being the main comparison, differences between native whey and WPC-80 were analysed by a one-way ANOVA and comparisons between the whey supplements and milk were analysed by a two-way ANOVA. Results: Native whey increased blood leucine concentrations more than WPC-80 and milk (P < 0.05). Native whey ingestion induced a greater phosphorylation of p70S6K than milk 180 min after exercise (P = 0.03). Muscle protein synthesis rates increased 1–3 h hours after exercise with WPC-80 (0.119%), and 1–5 h after exercise with native whey (0.112%). Muscle protein synthesis rates were higher 1–5 h after exercise with native whey than with milk (0.112% vs. 0.064, P = 0.023). Conclusions: Despite higher-magnitude increases in blood leucine concentrations with native whey, it was not superior to WPC-80 concerning effect on muscle protein synthesis and phosphorylation of p70S6K during a 5-h post-exercise period. Native whey increased phosphorylation of p70S6K and muscle protein synthesis rates to a greater extent than milk during the 5-h post exercise period.

• Nilsen, Tormod Skogstad; Thorsen, Lene; Fosså, Sophie Dorothea; Wiig, Martin; Kirkegaard, Camilla; Skovlund, Eva; Benestad, Haakon Breien & Raastad, Truls (2016). Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy. Scandinavian Journal of Medicine & Science in Sports.  ISSN 0905-7188.  26(9), s 1026- 1035 . doi: 10.1111/sms.12543 Vis sammendrag

  Androgen deprivation therapy (ADT) improves lifeexpectancy in prostate cancer (PCa) patients, but is asso-ciated with adverse effects on muscle mass. Here, weinvestigated the effects of strength training during ADTon muscle fiber cross-sectional area (CSA) and regulatorsof muscle mass. PCa patients on ADT were randomizedto 16 weeks of strength training (STG) (n = 12) or acontrol group (CG; n = 11). Muscle biopsies wereobtained from m. vastus lateralis and analyzed by immu-nohistochemistry and western blot. Muscle fiber CSAincreased with strength training (898 μm2, P = 0.04), withthe only significant increase observed in type II fibers(1076 μm2, P = 0.03). There was a trend toward a differ-ence in mean change between groups myonuclei number(0.33 nuclei/fiber, P = 0.06), with the only significantincrease observed in type I fibers, which decreased themyonuclear domain size of type I fibers (P = 0.05). Satel-lite cell numbers and the content of androgen receptorand myostatin remained unchanged. Sixteen weeks ofstrength training during ADT increased type II fiber CSAand reduced myonuclear domain in type I fibers in PCapatients. The increased number of satellite cells normallyseen following strength training was not observed.

• Bøyum, Arne; Forstrøm, Rune Johansen; Sefland, Iren; Sand, Kristin Larsen & Benestad, Haakon Breien (2014). Intricacies of redoxome function demonstrated with a simple in vitro chemiluminescence method, with special reference to vitamin B12 as antioxidant.. Scandinavian Journal of Immunology.  ISSN 0300-9475.  80(6), s 390- 397 . doi: 10.1111/sji.12220
• Knudsen, Eirunn; Carlsen, Harald; Bøyum, Arne; Benestad, Haakon Breien & Iversen, Per Ole (2014). No major role for the transcription factor NF-κB in bone marrow function during peritonitis in the mouse. International journal of hematology.  ISSN 0925-5710.  100(2), s 111- 118 . doi: 10.1007/s12185-014-1598-7
• Paulsen, Gøran; Cumming, Kristoffer T.; Holden, Geir; Hallén, Jostein; Rønnestad, Bent; Sveen, Ole; Skaug, Arne; Paur, Ingvild; Bastani, Nasser Ezzatkhah; Østgaard, Hege Nymo; Buer, Charlotte; Midttun, Magnus; Freuchen, Fredrik; Wiig, Håvard; Ulseth, Elisabeth Tallaksen; Garthe, Ina; Blomhoff, Rune; Benestad, Haakon Breien & Raastad, Truls (2014). Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized controlled trial. Journal of Physiology.  ISSN 0022-3751.  592(8), s 1887- 1901 . doi: 10.1113/jphysiol.2013.267419 Vis sammendrag

  In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2 max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: -13 ± 54%; PGC-1α: -13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

• Aas, Vigdis; Sand, Kristin Larsen; Åsheim, Hans-Christian; Benestad, Haakon Breien & Iversen, Jens Gustav Heber (2013). C-Reactive Protein Triggers Calcium Signalling in Human Neutrophilic Granulocytes via FcγRIIa in an Allele-Specific Way. Scandinavian Journal of Immunology.  ISSN 0300-9475.  77(6), s 442- 451 . doi: 10.1111/sji.12049
• Knudsen, Eirunn; Iversen, Per Ole; Bøyum, Arne; Seierstad, Therese; Nicolaysen, Gunnar & Benestad, Haakon Breien (2011). G-CSF enhances proliferation and mobilization, but not the maturation rate, of murine myeloid cells. European Journal of Haematology.  ISSN 0902-4441.  87(4), s 302- 311 . doi: 10.1111/j.1600-0609.2011.01658.x
• Bøyum, Arne; Skrede, Knut Kristian; Myhre, Oddvar; Tennfjord, Vivi-Ann; Neurauter, Christine Gran; Tolleshaug, Helge; Knudsen, Eirunn; Opstad, Per Kristian; Bjørås, Magnar & Benestad, Haakon Breien (2010). Calprotectin (S100A8/S100A9) and myeloperoxidase: Co-regulators of formation of reactive oxygen species. Toxins.  ISSN 2072-6651.  (2), s 95- 115 . doi: 10.3390/toxins2010095 Fulltekst i vitenarkiv.
• Paulsen, Gøran; Crameri, R; Benestad, Haakon Breien; Fjeld, Jan Gunnar; Mørkrid, Lars; Hallén, Jostein & Raastad, Truls (2010). Time Course of Leukocyte Accumulation in Human Muscle after Eccentric Exercise. Medicine & Science in Sports & Exercise.  ISSN 0195-9131.  42(1), s 75- 85 . doi: 10.1249/MSS.0b013e3181ac7adb Vis sammendrag

  PAULSEN. G., R. CRAMERI, H. B. BENESTAD, J. G. HELD. L. MORKRID, J. HALLEN, and T. RAASTAD. Time course of Leukocyte Accumulation in Human Muscle after Eccentric Exercise. Med. Sci. Sports Exerc., Vol. 42, No. 1, pp. 75-85, 2010. Put-pose: To investigate the little course of leukocyte accumulation in eccentric exercised human muscles and its relation to recovery of muscle function and soreness. Methods: Eleven young males performed 300 unilateral. maximal voluntary, eccentric actions with the musculus quadriceps femoris (30 degrees.s(-1)). Before and at regular intervals for 7 d after exercise, force-generating capacity was measured with maximal concentric knee extensions (60 degrees.s(-1)). Accumulation of radiolabeled (autologous) leukocytes was measured with scintigraphy. Biopsies from musculus vastus lateralis were obtained 0.5, 4, 8, 24, 96, and 168 It after exercise from both the exercised leg and the control leg. Muscle cross-sections were stained with antibodies against leukocytes (CD16 and CD68). Muscle soreness was rated oil a visual analog scale. Results: Immediately after exercise, the Subjects' ability to generate force was reduced by 47 +/- 5%. Muscle function recovered slowly and was not fully restored after 1 wk. Radiolabeled leukocytes accumulated ill file Muscles during the first hour (3-24 h) after exercise, and leukocytes were at the same time observed histologically. primarily in the endomysium and perimysium. A pail of the accumulated radiolabeled leukocytes appeared to be located within local blood vessels. The highest numbers of CD16(+) and CD68(+) cells were found 4 and 7 (1 after exercise. There was a positive correlation between accumulation of radiolabeled leukocytes and muscle weakness measured 1-3 d after exercise (r = 0.8. P < 0.05) and, surprisingly. a negative correlation between radiolabeled leukocyte accumulation and Muscle soreness (r = -0.96, P < 0.01). Conclusion: Exercise-induced Muscle damage initiated a rapid local inflammatory response that gradually increased over the next days, Halted recovery Of muscle function Was associated with local accumulation of leukocytes, whereas muscle soreness could not be explained by the presence of leukocytes.

• Paulsen, Gøran; Egner, Ingrid; Drange, Mads; Langberg, Henning; Benestad, Haakon Breien; Fjeld, Jan Gunnar; Hallén, Jostein & Raastad, Truls (2010). A COX-2 inhibitor reduces muscle soreness, but does not influence recovery and adaptation after eccentric exercise. Scandinavian Journal of Medicine & Science in Sports.  ISSN 0905-7188.  20(1, online), s 195 Vis sammendrag

  The aim of this study was to investigate the effect of a cyclooxygenase (COX)-2 inhibitor on the recovery of muscle function, inflammation, regeneration after, and adaptation to, unaccustomed eccentric exercise. Thirty-three young males and females participated in a double-blind, placebo-controlled experiment. Seventy unilateral, voluntary, maximal eccentric actions with the elbow flexors were performed twice (bouts 1 and 2) with the same arm, separated by 3 weeks. The test group participants were administered 400 mg/day of celecoxib for 9 days after bout 1. After both bouts 1 and 2, concentric and isometric force-generating capacity was immediately reduced ( approximately 40-50%), followed by the later appearance of muscle soreness and increased serum creatine kinase levels. Radiolabelled autologous leukocytes (detected by scintigraphy) and monocytes/macrophages (histology) accumulated in the exercised muscles, simultaneously with increased satellite cell activity. These responses were reduced and recovery was faster after bout 2 than 1, demonstrating a repeated-bout effect. No differences between the celecoxib and placebo groups were detected, except for muscle soreness, which was attenuated by celecoxib. In summary, celecoxib, a COX-2 inhibitor, did not detectably affect recovery of muscle function or markers of inflammation and regeneration after unaccustomed eccentric exercise, nor did the drug influence the repeated-bout effect. However, it alleviated muscle soreness.

• Paulsen, Gøran; Egner, I.M.; Drange, M.; Langberg, H.; Benestad, Haakon Breien; Fjeld, Jan Gunnar; Hallén, J. & Raastad, T. (2009). A COX-2 inhibitor reduces muscle soreness, but does not influence recovery and adaptation after eccentric exercise. Scandinavian Journal of Medicine & Science in Sports.  ISSN 0905-7188. . doi: 10.1111/j.1600-0838.2009.00947.x
• Benestad, Haakon Breien & Laake, Petter (2008). Forskning: metode og planlegging, I: Petter Laake; Haakon Breien Benestad & Bjørn Reino Olsen (red.),  Forskning i medisin og biofag. 2. utgave.  Gyldendal Akademisk.  ISBN 978-82-05-38487-3.  Kapittel 4.
• Nestvold, Janne M.; Omdal, Bente Kahrs; Dai, K-Z; Martens, A; Benestad, Haakon Breien; Vaage, John Torgils & Rolstad, Bent (2008). A second prophylactic MHC-mismatched bone marrow transplantation protects against rat acute myeloid leukemia (BNML) without lethal graft-versus-host disease. Transplantation.  ISSN 0041-1337.  85(1), s 102- 111 . doi: 10.1097/01.tp.0000296856.53493.1f
• Benestad, Haakon Breien & Laake, Petter (2007). Reseach methodology: Strategies, planning and analysis, In Petter Laake; Haakon Breien Benestad & Bjørn Reino Olsen (ed.),  Research Methodology in the Medical and Biological Sciences.  Academic Press.  ISBN 978-0-12-373874-5.  4.  s 93 - 124
• Paulsen, Gøran; Benestad, Haakon Breien; Strøm-Gundersen, Inger; Mørkrid, Lars; Lappegård, Knut Tore & Raastad, Truls (2005). Delayed Leukocytosis and Cytokine Response to High-Force Eccentric Exercise. Medicine & Science in Sports & Exercise.  ISSN 0195-9131.  37(11), s 1877- 1883
• Benestad, Haakon Breien (2004). Basalmedisinsk forskning: Strategier og metoder, I: Haakon Breien Benestad & Petter Laake (red.),  Forskningsmetode i medisin og biofag.  Gyldendal Akademisk.  Kapittel 6.  s 199 - 214
• Benestad, Haakon Breien (2004). Vitenskapelig kommunikasjon, I: Haakon Breien Benestad & Petter Laake (red.),  Forskningsmetode i medisin og biofag.  Gyldendal Akademisk.  Kapittel 13.  s 413 - 443
• Benestad, Haakon Breien & Laake, Petter (2004). Forord, I: Haakon Breien Benestad & Petter Laake (red.),  Forskningsmetode i medisin og biofag.  Gyldendal Akademisk.  forord.  s 5 - 7
• Benestad, Haakon Breien & Laake, Petter (2004). Forskning: Metode og planlegging, I: Haakon Breien Benestad & Petter Laake (red.),  Forskningsmetode i medisin og biofag.  Gyldendal Akademisk.  Kapittel 3.  s 83 - 113
• Bøyum, Arne; Fjerdingstad, HB; Tennfjord, VA; Benestad, Haakon Breien & Lovhaug, D (2004). Specific antibodies to mouse Sca-1- (Ly-6A/E) or Thy-1-positive haematopoietic progenitor cells induce formation of nitric oxide which inhibits subsequent colony formation. European Journal of Haematology.  ISSN 0902-4441.  73, s 427- 430
• Iversen, Per Ole; Nicolaysen, Anne; Hjeltnes, Nils; Njå, Arild & Benestad, Haakon Breien (2004). Preserved granulocyte formation and function, as well as bone marrow innervation, in subjects with complete spinal cord injury. British Journal of Haematology.  ISSN 0007-1048.  126, s 870- 877
• Olsen, Bjørn Reino & Benestad, Haakon Breien (2004). Basalmedisinsk forskning: strategier og metoder, I: Haakon Breien Benestad & Petter Laake (red.),  Forskningsmetode i medisin og biofag.  Gyldendal Akademisk.  Kapittel 6.  s 199 - 214
• Knudsen, Eirunn; Benestad, Haakon Breien; Seierstad, Therese & Iversen, Per Ole (2004). Macrophages in spleen and liver direct the migration pattern of rat neutrophils during inflammation. European Journal of Haematology.  ISSN 0902-4441.  73, s 109- 122
• Raastad, Truls; Risøy, Bjørn Audun; Benestad, Haakon Breien; Fjeld, Jan Gunnar & Hallén, Jostein (2003). Temporal relation between leukocyte accumulation in muscles and halted recovery 10-20h after strength exercise. Journal of applied physiology.  ISSN 8750-7587.  95
• Risøy, Bjørn Audun; Raastad, Truls; Hallén, Jostein; Lappegård, K.T.; Bæverfjord, Kjersti; Kravdal, Astrid; Siebke, Else-Marie & Benestad, Haakon Breien (2003). Delayed leukocytosis after a hard strength and endurance exercise: Aspects of regulatory mechanisms. BMC Physiology.  ISSN 1472-6793.  3, s 14
• Østby, Ivar; Benestad, Haakon Breien & Grøttum, Per (2003). Mathematical modeling of human granulopoiesis: the possible importance of regulated apoptosis. Mathematical Biosciences.  ISSN 0025-5564.  186, s 1- 27
• Knudsen, Eirunn; Iversen, Per Ole; Rooijen, Nico Van & Benestad, Haakon Breien (2002). Macrophage-dependent regulation of neutrophil mobilization and chemotaxis during development of sterile peritonitis in the rat. European Journal of Haematology.  ISSN 0902-4441.  69, s 284- 296 Vis sammendrag

  Pro-inflammatory cytokines attract leukocytes to inflamed tissues and activate them. Few attempts have been made to identify the sources of cytokines in vivo. We examined the importance of peritoneal macrophages in the mobilization and homing of neutrophils to a sterile peritonitis in the rat, with emphasis on their cytokine production. Macrophages, present in virtually all tissues, are known to be easily activated and to serve as an important source of cytokines. Flow cytometric analysis of cells stained intracellularly with tagged antibodies against various cytokines revealed that the peritoneal macrophages were stimulated to produce the following cytokines: interleukin (IL)-1beta, macrophage inflammatory protein-2 (MIP-2), and keratinocyte-derived cytokine (KC). High numbers of neutrophils, activated on arrival into the peritoneal cavity, also produced IL-1beta, whereas lower numbers contained interleukin-6, tumor necrosis factor-alpha, MIP-2, KC, and MIP-1alpha. This marked activation of peritoneal neutrophils was also reflected by increased surface expression of CD11b. On the other hand, peritoneal macrophages expressed high basal levels of CD11b, which were reduced 24 h after the onset of inflammation. In rats selectively depleted of macrophages by i.p. injection of liposome-containing clodronate, the massive influx of neutrophils to the peritoneal cavity was markedly reduced, as was the rapid mobilization of mature bone marrow neutrophils. Local macrophages are important both for the accumulation of neutrophils in the inflamed peritoneal cavity and for the early mobilization of neutrophils from the bone marrow. Macrophage-derived IL-1beta, MIP-2, and KC are possible mediators of neutrophil homing to inflamed tissues.

• Galtung, Hilde Kanli; Sørlundsengen, Vibeke; Sakariassen, Kjell S. & Benestad, Haakon Breien (2002). Effect of radiologic contrast media on cell volume regulatory mechanisms in human red blood cells. Academic Radiology.  ISSN 1076-6332.  9, s 878- 885 Vis sammendrag

  RATIONALE AND OBJECTIVES: The authors peris studyto evaluate cell volume regulation in human red blood cells (RBCs) after incubation in solutions of three contrast mediaformed th: iohexol (830 mOsm), ioxaglate (520 mOsm), and iodixanol (300 mOsm). MATERIALS AND METHODS: Whole blood sampled from six healthy subjects was exposed to Ringer solutions containing 25% or 5% vol/vol iohexol (final osmolality, 440 or 340 mOsm, respectively), ioxaglate (final osmolality, 395 or 335 mOsm, respectively), iodixanol (final osmolality, 330 or 315 mOsm, respectively), or NaCl (control solutions with the same osmolality as that of the contrast media). In some experiments, control RBCs were subjected to a hyposmotic solution (100 mOsm). RBC volumes were obtained with a Coulter counter. RESULTS: The RBCs showed normal regulatory cell shrinkage after hyposmotically induced swelling. All 25% vol/vol contrast material solutions and their control solutions induced RBC shrinkage (range, 6% +/- 1 [standard error] to 22% +/- 3). The same was true for cells exposed to 5% vol/vol contrast material (range, 4% +/- 1 to 7% +/- 1). The shrinkage phase was followed by cell swelling (10% +/- 2 to 20% +/- 2 for 25% contrast material and their control solutions and 8% +/- 1 to 15% +/- 2 for 5% contrast material and their control solutions). No contrast material-exposed RBCs increased their volumes to the level reached with their control solutions. CONCLUSION: RBCs exposed to hyperosmotic iohexol, ioxaglate, or iodixanol solutions shrank and then swelled. The degree of shrinkage and subsequent swelling could not be explained simply with the osmolality of the test solutions. Physicochemical properties of the contrast media must be involved, putatively affecting electrolyte fluxes over the RBC membrane. Possible targets of these effects are the K+/Cl- symporter, K+ channels, and the Na+/K+/Cl- symporter.

• Iversen, Per Ole; Sorensen, D.R. & Benestad, Haakon Breien (2002). Inhibitors of angiogenesis selectively reduce the malignant cell load in rodent models of human myeloid leukemias. Leukemia.  ISSN 0887-6924.  16(3), s 376- 381
• Sorensen, D.R.; Read, T.A.; Porwol, T.; Olsen, Bennedichte C. Rappana; Timpl, R.; Sasaki, T.; Iversen, Per Ole; Benestad, Haakon Breien; Sim, K.L. & Bjerkvig, R. (2002). Endostatin reduces vascularization, blood flow, and growth in a rat gliosarcoma. Neuro-Oncology.  ISSN 1522-8517.  4, s 1- 8
• Engh, Espen; Strøm-Gundersen, Inger; Benestad, Haakon Breien & Rolstad, Bent (2001). Long-term donor chimerism after MHC (RT1) mismatched bone marrow transplantation in the rat: the role of host alloreactive NK cells. Scandinavian Journal of Immunology.  ISSN 0300-9475.  54, s 198- 203
• Iversen, Per Ole; Hjeltnes, Nils; Holm, Bjørn; Flatebo, Torun; Strøm-Gundersen, Inger; Rønning, Wenche; Stanghelle, Johan K & Benestad, Haakon Breien (2000). Depressed immunity and impaired proliferation of hematopoietic progenitor cells in patients with complete spinal cord injury. Blood.  ISSN 0006-4971.  96(6), s 2081- 2083 Vis sammendrag

  The bone marrow is supplied with both sensory and autonomic neurons, but their roles in regulating hematopoietic and immunocompetent cells are unknown. Leukocyte growth and activity in patients with stable and complete spinal cord injuries were studied. The innervation of the bone marrow below the injury level lacked normal supraspinal activity, that is, a decentralized bone marrow. Lymphocyte functions were markedly decreased in injured patients. Long-term colony formation of all hematopoietic cell lineages, including dendritic cells, by decentralized bone marrow cells was substantially reduced. It was concluded that nonspecific and adaptive lymphocyte-mediated immunity and growth of early hematopoietic progenitor cells are impaired in patients with spinal cord injuries. Possibly, this reflects cellular defects caused by the malfunctioning neuronal regulation of immune and bone marrow function.

• Wang, Xiu Li; Brekken, Kristin B.; Siebke, Else-Marie; Stokke, Gro & Benestad, Haakon Breien (2000). Granulocytopoiesis versus cytokine activities in peritoneal diffusion chamber cultures in the mouse. European Journal of Haematology.  ISSN 0902-4441.  64, s 93- 103 Vis sammendrag

  Regulation of granulocyte formation was studied by correlating granulocytopoiesis in diffusion chambers with activities of putative regulatory cytokines in such chambers. The implantation procedure increased the levels in 1- and 2-d chambers of interleukin 6 (IL-6), G-CSF, TNF-alpha,and non-specific granulocyte/macrophage (G/M) colony-stimulating activities (CSA), assessed with bioassays and immunoassays. The activities subsided rapidly thereafter. They could be increased by vinblastine, cyclophosphamide, and a sterile inflammatory reaction (s.c. implanted copper rods;Cu-r). Anti-inflammatory indomethacin curtailed the IL-6, but raised the TNF-alpha, G-CSF, and CSA levels in Cu-r mice. Interferon inducer poly-I:C augmented G-CSF, but decreased TNF-alph levels. Mouse blood cells cultured in chambers expanded their granulocyte/macrophage progenitor population rapidly during the first week of culture; this population being significantly larger on day 3 in perturbed than in unperturbed mice. A marked decline followed in the second week, significantly larger in mice given cytotoxic treatment than in controls. Peritoneal G-CSF and TNF-alpha may explain progenitor and granulocyte growth and development in diffusion chambers during the first week of culture. GM-CSF and IL-3 were apparently without any influence. None of the peritoneal cytokines assayed could explain the population decline during the second week, which was possibly caused by exhaustion of earlier progenitor cells, rather than by intra-chamber feedback mechanisms.

• Iversen, Per Ole; Nicolaysen, Anne; Kvernebo, Knut; Benestad, Haakon Breien & Nicolaysen, Gunnar (1999). Human Cytokines modulate arterial vascular tone via endothelial reseptors. Pflügers Archiv: European Journal of Physiology.  ISSN 0031-6768.  439, s 93- 100
• Iversen, Per Ole; Nicolaysen, Anne; Kvernebo, Knut; Benestad, Haakon Breien & Nicolaysen, Gunnar (1999). Human cytokines modulate arterial vascular tone via endothelial receptors. Pflügers Archiv: European Journal of Physiology.  ISSN 0031-6768.  439(1-2), s 93- 100
• Wang, Xiu Li; Fjerdingstad, Hege; Strøm-Gundersen, Inger & Benestad, Haakon Breien (1999). Maturation Rate of Mouse Neutrophilic Granulocytes: Acceleration by Retardation of Proliferation, but No Detectable Influence from G-CSF or Stromal Cells. Stem Cells.  ISSN 1066-5099.  17(5), s 253- 264 Vis sammendrag

  Our purpose was to examine the possible influence of stromal and humoral mediators on granulocytic maturation rates. Sorted immature murine progenitor (Lin-Sca-1+) cells were cultured in peritoneal diffusion chambers (DCs) with or without a confluent layer of irradiated bone marrow stromal cells on one of the micropore membrane walls. In other experiments, 10 microg/kg/d recombinant G-CSF (rhG-CSF) was administered continuously into DC host mice through s.c. implanted osmotic minipumps. Operationally, maturation rate was assessed as the ratio between the number of polymorphonuclear cells (PMN) and proliferative granulocytes (PG) in short-term cultures, based on the differential cell counts, and supported by flow cytometric measurement of a granulocytic differentiation marker; and by the emergence time of PMN in the DCs, obtained by extrapolation. Also, increased maturation is associated with increased cell density, as reflected by the positioning of the granulocytes during centrifugation in a discontinuous Percoll gradient. This method, as well as the conversion rate of 3H-thymidine labeled PG into the heavier non-PG maturational stages, were also used as indicators of maturation rate. After five, six, and seven days of culture in the peritoneal cavity, DC cells were harvested. Their proliferative status, based on measurement of incorporated bromodeoxyuridine, was determined, and their maturation rates were evaluated. Proliferation of immature granulocytic progenitor cells was apparently inhibited by direct contact with bone marrow stromal cells, and stimulated by G-CSF during the early stage of culturing. However, the subsequent maturation rate, which could be accelerated by increasing culture cellularity, thus decreasing PG proliferation rate, was not detectably influenced by either stromal cells or G-CSF.

• Wang, Xiu Li; Strøm-Gundersen, Inger; Fjerdingstad, Hege & Benestad, Haakon Breien (1999). Ectopic haematopoiesis in the mouse: roles of stroma and cytokines in granulocytopoiesis in in vivo diffusion chamber cultures. European Journal of Haematology.  ISSN 0902-4441.  63, s 313- 324 Vis sammendrag

  We have examined a possible role of two different types of irradiated stromal cells, i.e. murine bone marrow (BM) stromal cells and stromal cell line MS-5R, when cocultured with murine blood-borne progenitors or sorted Lin- Sca-1+ bone marrow cells in vivo in peritoneal diffusion chambers (DC). Retrieval and quantification of the cultured cells were performed after 4, 7, and 14 d. Granulocyte and/or macrophage colony-forming cells (G/M-CFC) were enumerated in subcultures from the DC. G/M-CFC production was not enhanced in the stroma-contact cultures, in comparison with the standard stroma-non-contact cultures, but early granulocytopoiesis was stimulated. Perturbation of the humoral environment of DC was investigated in a number of ways, for example with continuous infusion of rhG-CSF from a subcutaneous implanted minipump to DC host mice, with DC host mice carrying a transplantable leukaemia, secreting interleukin 3 (IL-3), and with injections of various cytokines. None of these interventions sustained the expansion of the G/M-CFC population. In conclusion, for ectopic haematopoiesis to take place, several requirements must be met. Relevant stromal cells apparently affect haematopoiesis both via direct cell-cell interactions and via humoral mediators (viz. cytokines) which they secrete.

• Engh, Espen; Benestad, Haakon Breien; Strøm-Gundersen, Inger; Vaage, John Torgils; Bell, Eric B. & Rolstad, Bent (1998). Role of classical (RT1.A) and nonclassical (RT1.c) MHC class I regions in natural killer cell-mediated bone marrow allograft rejection in rats. Transplantation.  ISSN 0041-1337.  65(3), s 319- 324 Vis sammendrag

  Background: We have studied the role of the different MHC (RT1) subregions in acute NK cell mediated bone marrow allograft rejection in lethally irradiated, bone marrow cell (BMC) reconstituted rats. Methods: We employed a series of MHC congenic and intra-MHC recombinant rat strains, so that effects of mismatches in defined RT1 subregions could be studied systematically. BMC allograft survival was measured as 125IUdR uptake in the spleen between day 5 and 7 after irradiation and BMC reconstitution. Results: We found that in some RT1 haplotype combinations nonclassical RT1.C disparities by themselves determined graft rejection, while in another combination mismatch for an isolated classical RT1.A region was decisive for engraftment. Also, RT1 homozygous rats were fully capable of rejecting semiallogeneic F1 hybrid BM cells. The acute rejection of BM cells was most likely mediated by NK cells, as athymic nude rats, lacking alloreactive T cells but with normal alloreactive NK cells, showed the same patterns of rejection as did normal rats. Nude rats also rejected allogeneic lymphocytes, a previously documented NK mediated phenomenon, with identical requirements of MHC disparity. Conclusion: This investigation shows that rat effector NK cells are radioresistant, independent of the thymus, and capable of recognizing both classical and nonclassical class I region products in vivo. The studies furthermore illustrate the underlying importance of NK cells in determining BM transplant survival.

• Benestad, Haakon Breien; Iversen, Per Ole & Njå, Arild (1998). Response: Nerves to Murine Bone Marrow: Roles in the Cell Production or Cell Release?. Blood.  ISSN 0006-4971.  92(8), s 2971- 2998
• Benestad, Haakon Breien; Strøm-Gundersen, Inger; Iversen, Per Ole; Haug, Egil & Njå, Arild (1998). No Neuronal Regulation of Murine Bone Marrow Function. Blood.  ISSN 0006-4971.  91(4), s 1280- 1287 Vis sammendrag

  Bone marrow is innervated by efferent (sympathetic) and afferent nerves, but it is not clear whether these nerves affect cell formation or release in any significant way. To elucidate this problem, we studied mice neonatally sympathectomized with 6-hydroxydopamine and adult mice in which one hind limb was surgically denervated. Progenitor and transit cell numbers and proliferative activity were estimated in bone marrow, blood, and spleen. In addition, we performed unilateral electrical stimulation of nerve fibers to tibial marrow, and applied a cell mobilizing stimulus (bleeding, granulocyte colony-stimulating factor injection, or intraperitoneal injection of a chemotactic substance) to investigate cell egress from the marrow. Blood flow to hindleg bone marrow was assessed with the radioactive microsphere technique. Except for a smaller bone marrow cell population and lower body weight in neonatally sympathectomized mice, we found no clear indications that bone marrow innervation influenced cell production. Nor did the innervation detectably affect cell release from the marrow. Electrical stimulation of hind limb nerves did not change the blood flow to the marrow, while it markedly decreased blood flow to the overlying muscle. We therefore conclude that no obvious function can be ascribed to tibial marrow innervation in the mouse.

• Benestad, Haakon Breien; Sørensen, Trond; Iranpour, Kamran Mobarekeh; Liestøl, Knut; Yogesan, Kanagasingam; Strøm-Gundersen, Inger; Wang, Xiu Li & Løvhaug, Dagfinn (1998). Digital image analysis of hematopoietic colonies in vitro. Experimental Hematology.  ISSN 0301-472X.  26, s 936- 941 Vis sammendrag

  A system for automatic analysis of in vitro haematopoietic colonies is described and evaluated. With the standard resolution of video cameras, the improvement obtained by utilising features other than size and darkness when classifying potential colonies, appears to be limited. This was confirmed by comparing results obtained with the test system and a commercial one. However, for some applications it may be useful to add specific methods, e.g. to separate merged colonies. Digital image analyses provide new possibilities, for instance to measure the total cellularity of the dish or to analyse colonies according to size and cell densities of each colony. Examples provided are time course studies of colony development, cellularity feedback effects on colony sizes, and the bell-shaped dose-response curves for the growth stimulation obtained by certain conditioned media on a subpopulation of progenitor cells that gives rise to large colonies.

• Knudsen, Eirunn; Seierstad, Therese; Vaage, John Torgils; Naper, Christian; Benestad, Haakon Breien; Rolstad, Bent & Maghazachi, Azzam A. (1997). Cloning, functional activities and in vivo tissue distribution of rat NKR-P1+ TCR alpha beta + cells. International Immunology.  ISSN 0953-8178.  9(7), s 1043- 1051
• Aas, Vigdis; Lappegård, J. T.; Siebke, Else-Marie & Benestad, Haakon Breien (1996). Modulation by interferons of hyman neutrophilic granulocyte migration. Journal of Interferon and Cytokine Research.  ISSN 1079-9907.  16, s 929- 935 Vis sammendrag

  The effect of various interferons (HN) on neutrophilic granulocyte (PMN) random and directed migration is incompletely understood, We, therefore, investigated PMN migration with a novel micropore membrane technique, No chemotactic effect of either 10-10000 U/ml IFN-alpha or IFN-beta, or 1-1000 U/ml IFN- gamma was observed on PMN isolated from normal human venous blood, However, when present on both sides of the micropore membrane, all the IFN (1000 U/ml IFN-alpha and IFN-beta, 100 U/ml IFN- gamma) inhibited both random and directed migration toward zymosan-activated serum (ZAS), IFN-gamma was the most potent inhibitory agent and produced an inhibition of about 30%, When the bacterial peptide fMLP was used as a chemoattractant, IFN- gamma also depressed chemotaxis, Taking the reduced random migration of IFN-gamma treated cells into account, however, chemotaxis per se-toward both ZAS and fMLP-was not significantly affected, Random migration and directed migration assessed simultaneously with PMN from the same donor were clearly correlated for both control and IFN-gamma treated cells, suggesting that a general antimotility effect of IFN-gamma might explain both reduced random migration and chemotaxis, The antimotility effect of IFN-gamma was not dependent on protein synthesis or on tyrosine kinase activity, In fact, inhibition of tyrosine kinase with herbimycin A increased the ZAS-stimulated motility of both control and IFN-gamma-inhibited PMN, In conclusion, our data indicate that IFN depress both random and directed PMN migration by mechanisms that do not involve protein synthesis or protein tyrosine kinase activity

• Benestad, Haakon Breien (1996). The diffusion chamber technique: An in vivo culture method applicable to various scientific problems, In V P Nefedov (ed.),  Homeostasis: New facts and hypotheses. Part II. (AMSE Transactions, Scientific Siberian. Series A. Exact & Natural Sciences).  AMSE (Advancement of Modelling and Simulation Techniques in Enterprises) Press, Krasnoyarsk (Russia) - Tassin (France).  s 4 - 26
• Engh, Espen; Benestad, Haakon Breien & Rolstad, Bent (1996). Role of Natural Killer Cells and Classical (RT1.A) vs Nonclassical (RT1.C) Class I Molecules in Acute Bone Marrow Allograft Rejection in Lethally Irradiated Rats. Transplantation Proceedings.  ISSN 0041-1345.  28(6), s 3265- 3266
• Løvås, K; Knudsen, Eirunn; Iversen, Per Ole & Benestad, Haakon Breien (1996). Sequestration patterns of transfused rat neutrophilic granulocytes under normal and inflammatory conditions. European Journal of Haematology.  ISSN 0902-4441.  56, s 221- 229

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• Benestad, Haakon Breien (2016). Et eventyrlig liv. Hans Landstad (1880-1957): sort får, seilskipsmannskap og sjefskonstruktør. Michael - Det norske medisinske selskaps tidsskrift.  ISBN 978-82-92871-88-1.  194 s.
• Laake, Petter; Benestad, Haakon Breien & Olsen, Bjørn Reino (ed.) (2015). Research in Medical and Biological Sciences: From Planning and Preparation ot Grant Application and Publication.. Academic Press.  ISBN 978-0-12-799943-2.  566 s.
• Laake, Petter; Benestad, Haakon Breien & Olsen, Bjørn Reino (red.) (2008). Forskning i medisin og biofag. 2. utgave. Gyldendal Akademisk.  ISBN 978-82-05-38487-3.  550 s.
• Laake, Petter; Benestad, Haakon Breien & Olsen, Bjørn Reino (ed.) (2007). Research Methodology in the Medical and Biological Sciences. Academic Press.  ISBN 978-0-12-373874-5.  512 s.
• Benestad, Haakon Breien & Laake, Petter (red.) (2004). Forskningsmetode i medisin og biofag. Gyldendal Akademisk.  476 s.
• Benestad, Haakon Breien; Poleszynski, Dag Viljen & Veiberg, Randi (1995). Idealisme - nytter det?. Grøndahl Dreyer.  ISBN 82-504-2298-8.  244 s.

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• Benestad, Haakon Breien (2019). Anti-IL-23-antistoffer mot prostatakreft?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(2), s 1- 2 . doi: 10.4045/tidsskr.18.0873
• Benestad, Haakon Breien (2019). Humane pancreasceller kan endres til insulinproduserende celler i mus. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(8) . doi: 10.4045/tidsskr.19.0236
• Benestad, Haakon Breien (2019). Kulde gir epigenetiske endringer i spermier. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(1) . doi: 10.4045/tidsskr.18.0866
• Benestad, Haakon Breien (2019). S?vnmangel fremmer arteriosklerose. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(9) . doi: 10.4045/tidsskr.19.0293
• Benestad, Haakon Breien (2019). Tolkning av EKG med kunstig intelligens. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(6) . doi: 10.4045/tidsskr.19.0119
• Benestad, Haakon Breien (2018). Hurtigtesting for individualisert kreftbehandling. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(13) . doi: 10.4045/tidsskr.18.0407
• Benestad, Haakon Breien (2018). Hvordan oppst?r immunologisk hukommelse?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(10) . doi: 10.4045/tidsskr.18.0206
• Benestad, Haakon Breien (2018). Hvorfor er så mange eldre plaget med kløe?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(14) . doi: 10.4045/tidsskr.18.0504
• Benestad, Haakon Breien (2018). Kan aldersbetinget muskeltap hemmes med legemidler?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(17) . doi: 10.4045/tidsskr.18.0725
• Benestad, Haakon Breien (2018). Ny behandling mot tørre øyne?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(17) . doi: 10.4045/tidsskr.18.0706
• Benestad, Haakon Breien (2018). Tyroksin kan også virke raskt. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(7) . doi: 10.4045/tidsskr.18.0116
• Benestad, Haakon Breien; Sand, Kristin Larsen & Bruusgaard, Jo C. (2018). Less than recommended training of aerobic fitness and muscle strength: What to expect?. Acta Physiologica.  ISSN 1748-1708.  224(4) . doi: 10.1111/apha.13104
• Benestad, Haakon Breien & Valeur, Jørgen (2018). Har tarmfloraen betydning for utvikling av multippel sklerose?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(3), s 235- 235
• Benestad, Haakon Breien & Laake, Petter (2015). Research Strategies, Planning and Analysis, In Petter Laake; Haakon Breien Benestad & Bjørn Reino Olsen (ed.),  Research in Medical and Biological Sciences: From Planning and Preparation ot Grant Application and Publication..  Academic Press.  ISBN 978-0-12-799943-2.  Kapittel 4.  s 89 - 104
• Benestad, Haakon Breien (2014). Re: En mann i 80-årene med muskelstivhet og hudblødninger :. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  134(14), s 1344 . doi: 10.4045/tidsskr.14.0819
• Benestad, Haakon Breien & Laake, Petter (2014). Dårlig tittel - dårlig manus?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  134(4), s 382- 382 . doi: 10.4045/tidsskr.14.0143
• Benestad, Haakon Breien (2012). Fysiologiens forandring gjennom 40 år. Michael Quarterly.  ISSN 1504-0658.  9(4), s 389- 399
• Olsen, Ingar & Benestad, Haakon Breien (2011, 09. august). Økt arteriosklerose av kolin?.  Tidsskrift for Den norske legeforening, 2011;131 (15):1408.
• Benestad, Haakon Breien (2010). Vitenskapelig uredelighet - alvorlig, forsettlig eller grovt uaktsomt?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  130(5), s 515- 516
• Bøyum, A.; Skrede, Knut Kristian; Myhre, Oddvar; Tennfjord, VA; Neurauter, Christine Gran; Tolleshaug, Helge; Knudsen, E.; Opstad, Per Kristian; Bjørås, Magnar & Benestad, Haakon Breien (2010). Calprotectin (S100A8/S100A9) og myeloperoksidase : ko-regulatorer av dannelsen av reaktive oksygen-metabolitter (ROS). Vis sammendrag

  Problemstilling Inflammatoriske mediatorer stimulerer produksjon av reaktive oksygen metabolitter (ROS: O2־, H2O2, OH´) i polymorfonukleære neutrofile granulocytter (PMN). HOCl er viktig i mikrobeforsvar og dannes av myeloperoksidase i PMN, og kan detekteres i et chemiluminescence-assay. Metode Luminol-chemiluminescence ble målt som relative lysverdier i et luminometer (Luminoskan, Termo Labsystems, Helsinki, Finland), med 96-brønner (White Cliniplate, Thermo Fisher Scientific, Vantaa-Finland). Resultater og konklusjoner Vi har vist at calprotectin (S100A8/A9), som det finnes rikelig av i PMN-cytosol, også stimulerer dannelse av chemiluminescence som respons på H2O2 i et cellefritt system, noe som ikke er vist tidligere. Myeloperoksidase og calprotectin virket synergistisk. Calprotectin-indusert chemiluminescence økte, mens myeloperoksidase-stimulert chemiluminescence gikk ned ved pH > 7.5. For myeloperoksidase var NaCl nødvendig for chemiluminescence, men ikke for calprotectin. 4-hydroksy-benzosyre, som binder OH´, fjernet nesten calprotectin-stimulert chemiluminescence, men økte myeloperoksidase-aktiviteten moderat. Kombinasjonen av nativt calprotectin, eller rekombinante S100A8/A9 proteiner, med NaOCl medførte en markant økning i chemiluminescence. NaOCl kan være den synergistiske lenken mellom myeloperoksidase og calprotectin. Ved høyere konsentrasjoner av S100A9 forsvant denne stimuleringen, noe som kan forklares ved en switch fra pro-oksidant til anti-oksidant funksjon. Vi foreslår at OH´ er den dominerende ROS produsert av calprotectin, en funksjon som ikke er beskrevet tidligere. Virksomhetsområde: Annet

• Benestad, Haakon Breien & Wisløff, Finn Georg B (2008). Forskningsetikk og Universitetet i Oslo. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  128(15), s 1683- 1684
• Lycke, Kirsten Hofgaard; Benestad, Haakon Breien & Sandberg, Torill Marlene (2007). Development of teaching and learning at the University of Oslo.
• Nestvold, Janne M.; Omdal, Bente Kahrs; Dai, KZ; Benestad, Haakon Breien & Rolstad, Bent (2006). The role of repeated MHC mismatched bone marrow transplantation in the resistance against a rat acute myelogenous leukaemia (BNML). Tissue Antigens.  ISSN 0001-2815.  67, s 476- 477
• Benestad, Haakon Breien (2003). Basalforskning nyttig for klinikken?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  123(12), s 1644
• Bøyum, Arne; Fjerdingstad, Hege; Tennfjord, V-A.; Benestad, Haakon Breien & Løvhaug, Dagfinn (2003). Specific antibodies to mouse SCA-1 (LY-6A/E) and THY-1 (human and mouse) positive hemopoietic progenitor cells induce formation of nitric oxide which inhibits subsequent colony formation.
• Paulsen, Gøran; Gylterud, Simen; Fjeld, Jan Gunnar; Benestad, Haakon Breien; Hallén, Jostein & Raastad, Truls (2003). Force deficit after eccentric exercise is related to muscle leukocyte infiltration.
• Risøy, Bjørn Audun; Raastad, Truls; Lappegård, K.T. & Benestad, Haakon Breien (2003). Delayed leukocytosis after vigorous exercise:can it reveal the granulocyte mobilizers in inflammatory disorders?.
• Knudsen, Eirunn; Iversen, Per Ole; Seierstad, Therese; Rooijen, Nicovan van & Benestad, Haakon Breien (2002). Macrophages determine neutrophil granulocyte kinetics and ecotaxis ("homing") in rats with a sterile perotonitis. Vis sammendrag

  We hypothesize that neutrophils (PMN) normally ¿ and even in inflammation ¿ end their lives in macrophages exposed to the blood stream, subsequent to adherence to these cells, apoptosis and engulfment. Therefore, we examined the role of liver and spleen macrophages in rats with a sterile (casein-provoked) peritonitis. Blood PMN were collected from donor rats, transfused into congenic or syngeneic rats, and tracked with flow cytometric or radiometric methods. Phagocytosable particles (e.g. polystyrene beads) had been injected i.v. in prospective PMN recipients, to possibly perturb the kinetics, function, and fate of transfused PMN. Similarly, other recipient rats had been depleted of liver macrophages (Kupffer cells) by injection of liposome-encapsulated clodronate. Higher doses depleted spleen macrophages as well. The sequestration patterns of transfused PMN remained unchanged upon injection of the polystyrene beads. In marked contrast, homing to macrophage-depleted liver and spleen was substantially reduced. On the other hand, the bone marrow uptake of PMN was augmented in the depleted rats, and donor cells circulated longer (18 hours) than normal after transfusion. In rats depleted of liver macrophages only, sequestration was lowered in the liver, but not in marrow and spleen. Under all experimental conditions, only a small portion of transfused PMN migrated to the inflamed peritoneal cavity. In conclusion, liver and spleen macrophages clear PMN from circulation, and this capacity is robust and not easily decreased by exposure to inert phagocytosable particles.

• Raastad, Truls; Risøy, Bjørn Audun; Benestad, Haakon Breien & Fjeld, Jan Gunnar (2001). Leukocyte infiltration in muscles after strength exercise.
• Iversen, Per Ole; Sørensen, Dag R. & Benestad, Haakon Breien (2001). Anti-angiogenic drugs retard progression of two experimental leukemias. Vis sammendrag

  Angiogenesis is essential for growth, invasion and metastasis of solid tumors. Angiogenesis inhibitors, like endostatin (ES) and phosphomannopentaose sulphate (PI-88), have retarded and in some cases stopped growth in various models of cancer. A role for angiogenesis in the pathophysiology of hematological malignancies has also been suggested. We have tested this suggestion in two leukemia models, i. e. juvenile myelomonocytic leukemia (JMML) developing in severe combined immunodeficient, nonobese diabetic (SCID/NOD) mice, and a promyelocytic leukemia transplantable to the Brown Norwegian rat (BNML). Flow cytometry was used to monitor the growth of transplanted cells in the bone marrow of the mouse and rat recipients. Human-specific fluorescent antibodies to CD45 were employed to mark JMML and normal human bone marrow cells; the RM-124 antibody to tag the BNML cells. Immunohistochemistry with anti-von Willebrand factor was used to assess the density of microvessels in bone marrow sections. Eight weeks after leukemic cell transplantation, with daily injections of the drugs for the last four weeks, the leukemic cell burden had been reduced from almost 90 % of all mouse marrow cells retrieved to about 15 % with ES, to about 35 % with PI-88, and to about 10 % with ES + PI-88. Normal human bone marrow cells transplanted as a control constituted 55-60 % of the mouse marrow cells. This ratio was not detectably changed by drug treatments. In SCID/NOD mice, microvessel density after JMML transplantation was high, almost ten times higher than in the other groups. However, PI-88 only reduced the vessel density to twice control value. JMML colony numbers in semi-solid cultures were not significantly altered by ES or PI-88. Very similar findings were made with the BNML model, confirming the synergism between ES and PI-88 concerning both leukemic cell growth and reduction of microvascularity. Again, neither leukemic nor normal cell growth in cell suspension cultures (3H-thymidine incorporation) was significantly affected by ES or PI-88. In conclusion, anti-angiogenic therapy may be a valuable adjunct to cytotoxic or other modes of leukemia therapy.

• Knudsen, Eirunn; Iversen, Per Ole; Rooijen, Nicovan van & Benestad, Haakon Breien (2001). Macrophage-dependent regulation of neutrophil chemotaxis during the development of sterile peritonitis in the rat.
• Raastad, Truls; Risøy, Bjørn Audun; Benestad, Haakon Breien; Fjeld, Jan Gunnar & Hallén, Jostein (2000). The biphasic recovery course of maximal force-generating capacity is associated with increased appearance of leukocytes in exercised muscle.
• Benestad, Haakon Breien (2000). Bloddannende stamcellers formering i cellekultur. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  120(24), s 2948
• Benestad, Haakon Breien (2000). Communicative skills - A matter of negligence?. Experimental Hematology.  ISSN 0301-472X.  28, s 1- 2
• Benestad, Haakon Breien (2000). Endotelceller spiller viktige regulatoriske roller. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  120(23), s 2830- 2830
• Benestad, Haakon Breien (2000). Nevroimmunologi - et spennende, nytt forskningsfelt. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  120(20), s 2710- 2710
• Benestad, Haakon Breien (2000). Patofysiologi i farger. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  120(21), s 2541- 2541
• Iversen, Per Ole; Hjeltnes, Nils; Holm, Bjørn; Gundersen, I.S.; Flatebo, Torun; Rønning, Wenche; Stanghelle, Johan K; Oftebro, H.; Bjørklund, U.H.; Nicolaysen, A.; Njå, Arild & Benestad, Haakon Breien (1999). Decreased colony formation by bone marrow cells and compromised cellular immunity in tetraplegia.
• Wang, Xiu Li; Brekken, Kristin B.; Siebke, Else-Marie; Stokke, Gro; Sørlid, Hanne Kristin & Benestad, Haakon Breien (1999). GRANULOCYTOPOIESIS VERSUS CYTOKINE ACTIVITIES IN PERITONEAL DUFFUSION CHAMBER CULTURES IN THE MOUSE.
• Wang, Xiu Li; Fjerdingstad, Hege; Strøm-Gundersen, Inger & Benestad, Haakon Breien (1999). MATURATION RATE OF MOUSE NEUTROPHILIC GRANULOCYTES; ACCELERATION BY RETARDATION OF PROLIFERATION, BUT NO DETECTABLE INFLUENCE FROM G-CSF OR STROMAL CELLS.
• Wang, Xiu Li; Fjerdingstad, Hege; Strøm-Gundersen, Inger & Benestad, Haakon Breien (1999). Maturation rate of neutrophilic granulocytes; constant or variable?.
• Benestad, Haakon Breien (1996). The diffusion chamber technique: An in vivo culture method applicable to studies on haematopoietic homeostasis.
• Benestad, Haakon Breien & Iversen, Jens Gustav (1996). An introduction to: Biomedical Laboratory Research.

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