-
Abrahamsen, Tore G
(2019).
Helping on call paediatricians to identify acute primary immunodeficiency diseases.
Acta Paediatrica.
ISSN 0803-5253.
108(12),
s. 2127–2128.
doi:
10.1111/apa.15000.
-
Stray-Pedersen, Asbjørg; Sorte, Hanne Sørmo; Rødningen, Olaug Kristin; Lyle, Robert; Gonzaga-Jauregui, C G & Hanson, C I
[Vis alle 16 forfattere av denne artikkelen]
(2012).
THE UTILITY OF EXOME SEQUENCING IN PRIMARY IMMUNODEFICIENCY DISEASES AND IMMUNODYSREGULATIVE DISORDERS.
Journal of Clinical Immunology.
ISSN 0271-9142.
32(Supp. 1),
s. 184–185.
-
Andersen, C; Pettersen, Renate Regine; Aresvik, D; Wright, Marianne & Abrahamsen, Tore G
(2008).
Gliotoxin mediated apoptotic cell death in Jurkat cells.
International Journal of Infectious Diseases.
ISSN 1201-9712.
12,
s. S47–S47.
-
Aresvik, Dina; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne
(2008).
5-Fluorouracil Induces Cell Death in Jurkat E6 T cells.
-
Aresvik, Dina; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne
(2008).
5-Fluorouracil Induced Cell Death in leukemic T-cell line Jurkat E6.
Vis sammendrag
Background:
Cytostatics are widely used to treat paediatric cancer with the intension to eliminate cancer cells by apoptosis. 5-Fluorouracil (5-FU) is frequently used in the treatment of malignancies. Previous studies with 5-FU and different cell lines indicate that the pro-apoptotic protein Bax and the tumor suppressor protein p53 are central actors in this process.
The acute leukemic T-cell line Jurkat E 6 has mutations in both genes and 5-FU therefore needs to activate alternative death pathways. Previously, we have shown that incubation with 5-FU apparently triggers apoptosis in Jurkat cells in a dose-dependent manner, with a maximal response within 72 hours; death response was attenuated in presence of general caspase inhibitor.
Methods:
Jurkat T cells were treated with 5-FU for different time periods. Caspase-3 activity and changes in the mitochondrial membrane potential were measured by flow cytometry. Expression PARP and Mcl-1, was examined by Western blot.
Results:
Flow cytometric analysis showed activation of caspase-3 in a time- and dose-dependent manner. Using Western blot we observed decreasing levels of anti-apoptotic and increasing levels of pro-apoptotic proteins. Treatment with 5-FU induced a breakdown of the mitochondrial membrane potential.
Conclusion:
We proved that Jurkat T cells, previously thought of being resistant, can indeed be induced to undergo cell death, using adequate doses of 5-FU and over time. The apoptotic pathway induced by 5-FU in this cell line may provide a rational basis for the design of chemotherapy. Those findings may indicate new insight in cancer therapy.
-
Lappegård, KT; Christiansen, D; Abrahamsen, Tore G; Salvesen, Bodil; Lambris, JD & Mollnes, TE
(2007).
Complement is essential for phenotypic shift of leukocytes to a pro-inflammatory and pro-thrombotic state in a whole blood model of sepsis: Evidence from genetically complement-deficient patients.
Molecular Immunology.
ISSN 0161-5890.
44,
s. 3919–3919.
-
Abrahamsen, Tore G
(2007).
Livet med Marthe.
[Avis].
Kvinner og Klær (KK).
Vis sammendrag
Marthe (8) har immunsvikt. Jeg har brukt mye tid på Marthe, sier professor Tore Abrahamsen på Rikshospitalet. Han lover foreldrene at det finnes et svar. Et sted. En gang. Målet er å kunne stille en så nøyaktig diagnose som mulig, aller helst helt ned til det syke genet.
-
Lappegård, KT; Christiansen, D; Fadnes, D; Abrahamsen, Tore G; Salvesen, Bodil & Lambris, JD
[Vis alle 7 forfattere av denne artikkelen]
(2007).
Complement is essential for phenotypic shift of leukocytes to a pro-inflammatory and pro-thrombotic state in a whole blood model of inflammation: Evidence from genetically complement-deficient patients.
-
Aresvik, Dina; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne
(2007).
5-Fluorouracil induces Death in Jurkat E6 cells.
Vis sammendrag
Chemotherapeutic drugs are widely administrated to treat cancer and may eliminate responsive cells by inducing apoptosis. The thymidylate synthase inhibitor 5-Fluorouracil (5-FU) is frequently used in the treatment of malignancies. Previous studies with different cell lines indicate that the pro-apoptotic protein Bax and the tumor suppressor protein p53 are central actors in this process.
The leukemic T-cell line Jurkat E 6 does express transcripts for p53 and Bax but lacks the functional proteins due to mutations. 5-FU may activate alternative death pathways in Jurkat cells. We therefore have initiated studies on the impact of 5-FU on Jurkat cells.
Jurkat T cells were treated with increasing doses of 5-FU for different time periods. Staurosporine was included as a positive control. In some experiments, cells were pretreated with a general caspase inhibitor, Z-VAD-FMK.
Cell death was analyzed by flow cytometry, after Annexin V-Fluos and propidium iodide staining. Hydroethidine staining was used to determine mitochondrial ROS generation.Gene expression of pro- and anti-apoptotic proteins was examined by real-time PCR.
Flow cytometry analysis shows that incubation with 5-FU triggers apoptosis in Jurkat cells. The cells die in a dose-dependent manner and a maximal response was observed within 72 hours. Using a pan-caspase inhibitor Z-VAD-FMK we observed that the death response was attenuated. We also observed increased mitochondrial ROS generation after 48 hours of incubation with 5-FU. Results from real-time PCR suggest that expression of anti-apoptotic proteins is increased.
5-FU induces apoptosis in Jurkat cells in a time- and dose-dependent manner.
5-FU signaling is mediated through caspase dependent and independent pathways. ROS production suggest mitochondrial involvement.
-
Klingenberg, Claus; Rønnestad, Arild Erlend; Anderson, Annaliesa; Abrahamsen, Tore G; Flægstad, Trond & Sollid, J.E.
(2006).
Persistent strains of coagulase negative staphylococci in a neonatal intensive care unit are characterized by high levels of biofilm production and antibiotic resistance.
European Society for Pediatric Infectious Diseases, Meeting Abstract Book.
Vis sammendrag
Background and aims
Coagulase-negative staphylococci (CoNS) are the major cause of nosocomial sepsis in the neonatal intensive care unit (NICU). We wanted to investigate whether persistent CoNS strains possess specific bacterial characteristics compared with sporadic strains.
Methods
During a 12-year period we obtained 180 CoNS blood culture isolates from 150 neonates at one single NICU. All isolates were typed with pulsed field gel electrophoresis (PFGE). We also performed multi locus sequence typing (MLST) on 90 S. epidermidis isolates. Phenotypic antibiotic susceptibility to a broad range of antibiotics was analyzed with Etest. Virulence genes encoding methicillin and aminoglycoside resistance were detected with PCR. In addition, we analyzed phenotypic biofilm production and genetic determinants for biofilm formation.
Results
There was a high degree of concurrence between PFGE- and MLST- typing. Four S. epidermidis clusters contained 66 (6 - 9 - 15 - 36) isolates, one S. haemolyticus cluster 14 isolates, and one S. hominis cluster 7 isolates. The other 93 isolates were divided among 62 PFGE-types. S. epidermidis cluster strains were isolated from children with lower birth weight compared with non-clusters strains (1420 g versus 2034 g, p = 0.001). Cluster strains were evenly distributed among isolates causing sepsis and isolates considered as contaminants. Antibiotic resistance rates (methicillin, gentamicin, erythromycin, clindamycin and fusidic acid) and biofilm production were significantly higher among cluster strains compared with non-cluster strains.
Conclusions
CoNS cluster isolates were characterized by high levels of biofilm production and antibiotic resistance, enabling them to survive and persist in the NICU environment. Persistent strains colonized and invaded the smallest infants who were exposed to more invasive procedures and had longer hospital stay.
-
Løvoll, Ø.; Wisløff, TF; Abrahamsen, Tore G; Pedersen, M.; Bergsaker, M.A.R. & Møller, P
[Vis alle 7 forfattere av denne artikkelen]
(2006).
Cost-Effectiveness of Adding 7-Valent Pneumococcal Conjugate (PCV-7) Vaccine to the Norwegian Childhood Vaccination - Impact of Herd Immunity.
The International Conference on Emerging Infectious Diseases: Abstracts Book.
s. 177–177.
-
Abrahamsen, Tore G
(2006).
Diagnostikk av sepsis hos nyfødte.
Tidsskrift for Den norske legeforening.
ISSN 0029-2001.
126(14).
Vis sammendrag
Ved nyfødtsepsis kan diagnostikken være vanskelig, og behandling med bredspektret antibiotika blir ofte startet før en infeksjon er verifisert når det foreligger klinisk mistanke. Symptomene er uspesifikke - det kan like gjerne være hypotermi som feber eller pustestopp (apné) som rask pust (takypné) - «Det er noe galt med denne ungen». I ettertid kan det vise seg at det i stedet for infeksjon foreligger for eksempel hjerneblødning. Påvisning av bakteremi hos disse barna begrenses av mengde blod og antall kulturer som det er mulig og forsvarlig å ta. Konvensjonell infeksjonsdiagnostikk, som leukocytter med differensialtelling og CRP i blod, er mål på en akuttfasereaksjon og kan også være forhøyet ved andre tilstander enn infeksjon. Den infeksjonsutløste leukocyttreaksjonen er heller ikke nødvendigvis som forventet. En umoden beinmarg kan hos noen nyfødte vise en ineffektiv granulopoese som gir leukopeni i stedet for leukocytose, muligens fordi beinmargen er «uttømt». Det er derfor ikke vanskelig å forstå at sepsis hos nyfødte gir legene «hodebry».
-
Aresvik, Dina; Atneosen-Åsegg, Monika; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne
(2006).
The effect of 5-FU om Jurkat E6 cells with respect to bcl-2 family proteins.
Vis sammendrag
Programmed cell death or apoptosis is a mechanism that is involved in all aspects of life; including tissue homeostasis, the clearance of damaged cells and the immune defense. The use of chemotherapeutic agents in cancer patients is intended to induce stress and DNA damage in the cancer cells, hopefully leading to cell death. Apoptosis can occur in two ways: either by the extrinsic pathway and direct signaling of membrane death receptors or by the intrinsic path through regulation of bcl-2 family proteins, causing a loss of mitochondria membrane potential, thereby leading to apoptosis. Both paths involve a cascade of activated caspases which lead to DNA fragmentation and apoptosis. DNA damage is often followed by a cell cycle arrest and DNA repair mechanisms, but a substantial dose of chemotherapeutic agents will lead eventually to apoptosis. In addition, cancer cells often become resistant to anticancer drugs.
The purpose of this study is to delineate the signal transduction pathway for 5-Fluorouracil (5-FU) in Jurkat E6 cells, a T cell line. 5-FU attacks directly nucleic acids and affects the cell cycle. First we have examined whether Jurkat T cells can be used to establish a model system in which to analyze these effects. We have treated them with 5-FU with increasing doses and time. By using flow-cytometry we have established death curves. We have further analyzed the expression of all possible pro- and anti-apoptotic proteins and verified the most relevant ones by Western blot. So far we observed that bak is present as a multimer after stimulation with Staurosporine and 5-FU.
-
Abrahamsen, Tore G
(2005).
Foreldre har feberfobi.
[Avis].
Aftenposten.
Vis sammendrag
Barn trenger noen runder med feber i året. Feberen har en jobb å gjøre. Reduser pillebruken, råder barnelege Tore G. Abrahamsen. Mange foreldre lider av feberhysteri. Litt varme kinn og blanke barneøyne - og de iler til esken med febersenkende medisin. Jo høyere feber, jo sykere er barnet, tenker det bekymrede opphav. Som selvfølgelig vil barnets beste...
-
Abrahamsen, Tore G
(2005).
Immunsvikt ved gastrointestinale symptomer.
-
Abrahamsen, Tore G
(2005).
Alvorlig immunsvikt. Behandlingsresultater i historisk perspektiv.
-
Abrahamsen, Tore G
(2005).
Primær immunsvikt.
-
Klingenberg, Claus; Aarag, E.; Rønnestad, Arild Erlend; Sollid, J.E.; Abrahamsen, Tore G & Flægstad, Trond
(2005).
Biofilm forming coagulase-negative Staphylococci are associated with decreased neonatal inflammatory response in late onset sepsis.
Vis sammendrag
Background: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late onset sepsis in neonates. They are often multi-resistant to antibiotics and the ability to form biofilm is considered their main virulence determinant. The relationship between antibiotic resistance, biofilm formation and clinical outcome of CoNS infections is largely unknown.
Methods: During a 12-year period we identified 150 neonates having 164 suspected septic episodes with growth of CoNS in blood culture. We examined the relationship between antibiotic resistance, phenotypic biofilm production and genetic determinants for biofilm formation in different CoNS species, and their correlation with neonatal inflammatory response.
Results: Eighty-five episodes were defined as true sepsis, and 79 episodes of CoNS growth in blood culture were considered contaminations. Significantly higher prevalences of both phenotypic and genotypic β-lactam and aminoglycoside resistance were seen in invasive isolates compared with contaminants. Sixty-one percent of S. epidermidis isolates produced biofilm compared with 26 % of CoNS non-epidermidis (P < 0.001). As expected there was a strong correlation between the presence of icaD and biofilm production. We observed no difference in phenotypic biofilm production or genetic determinants for biofilm formation between invasive isolates and contaminants. C-reactive protein (CRP) levels as a marker of inflammatory response were higher in CoNS sepsis caused by methicillin and aminoglycoside resistant versus susceptible isolates (P = 0.031). In contrast, there was a significant association between a lower CRP response and biofilm positive isolates (P = 0.018). Antibiotic resistance was significantly correlated with biofilm production in S. epidermidis, but not in other CoNS species.
Conclusions: Evasion of the host immune system by biofilm formation seems to be a clinically relevant mechanism in CoNS causing neonatal sepsis. The close contact of bacteria within a biofilm may facilitate horizontal exchange of genetic information. This might explain the high level of multidrug-resistance in biofilm positive S. epidermidis. The impact of antibiotic resistance and virulence determinants on clinical outcome of neonatal CoNS sepsis warrants additional clinical studies.
-
Abrahamsen, Tore G
(2004).
Feber hos barn - venn eller fiende?
Tidsskrift for Den norske legeforening.
ISSN 0029-2001.
124(12).
Vis sammendrag
Førskolebarn er hyppig utsatt for sykdom, og om lag halvparten av disse sykdomsepisodene fører til kontakt med lege.
Når et barn får feber, er det for foreldrene et konkret tegn på at barnet er sykt. For den moderne familie betyr det at dagsrytmen forandres: Barnet kan ikke gå i barnehagen, og en av foreldrene må være hjemme i stedet for å gå på arbeid. Det er dessuten mye angst knyttet til feber, og mange foreldre og helsepersonell synes å tro at jo høyere feberen er, desto alvorligere er infeksjonen. Hvorfor ikke da gi det syke barnet et febernedsettende legemiddel?
-
Berild, Dag; Abrahamsen, Tore G; Andresen, S.; Bjørløw, E. & Ivanova, S.
(2004).
The effect of a controlled intervention to improve antibiotic use in a Russian Paediatric hospital.
-
Sigstad, Hanne Marie Høybråten; Bjerkely, B.; Stray-Pedersen, Asbjørg; Sandersen, Heidi & Abrahamsen, Tore G
(2004).
Description of daily life for children and adolescents with primary immunodeficiencies (PID) in Norway.
-
Stray-Pedersen, Asbjørg; Aaberge, IS & Abrahamsen, Tore G
(2004).
Ataxia-teleangiectasia and antibody responses to pneumococcal conjugate vaccine plus pneumococcal polysaccharide vaccine.
-
-
-
Ørstavik, Karen Helene; Kristiansen, Marianne; Knudsen, Gun Peggy Strømstad; Storhaug, K; Vege, Åshild & Eiklid, Kristin
[Vis alle 9 forfattere av denne artikkelen]
(2004).
Novel splicing mutation in the NEMO (IKK-gamma) gene with impaired IkBa degradation in a family with severe immunodeficiency and both skewed and random X inactivation in female carriers.
-
Warris, A.; Netea, M.G.; Gaustad, Peter; Kullberg, B.J.; Verweij, P. E. & Abrahamsen, Tore G
(2003).
Aspergillus fumigatus induces Amphotericin A (AmB) tolerance and inhibits AmB induced cytokine release.
-
Stray-Pedersen, Asbjørg; Garred, P; Heggelund, Lars; Holmskow, U; Vermeesch, J. & Abrahamsen, Tore G
(2003).
A boy with severe pulmonal infectious problems due to NKX2.1 haploinsufficiency and mannan-binding lectin deficiency.
-
Wright, Marianne; Clausen, H; Mollnes, Tom Eirik & Abrahamsen, Tore G
(2003).
Aspergillus fumigatus elicits a complement response in a liver cell line (HepG2 cells).
-
Abrahamsen, Tore G
(2002).
Indikasjon for anleggelse av blodkultur hos barn.
-
Steen-Johnsen, Jon; Abrahamsen, Tore G & Ørstavik, Karen Helene
(2002).
Genetisk drama med løsning etter 30 år.
-
Etokebe, Godfrey Essien; Bogen, Bjarne; Abrahamsen, Tore G & Spurkland, Anne
(2002).
TNFR6 gene mutation detection by denaturing high performance liquid chromatogarphy (DHPLC).
-
Stray-Pedersen, Asbjørg; Lindman, C.; Stoltenberg, Lauritz; Heiberg, Arvid; Vermeesch, J. & Mellbye, Ove J.
[Vis alle 7 forfattere av denne artikkelen]
(2002).
Respiratory distress, neurologic abnormalities, subclinical hypothyroidism and immuodeficiency due to microdelition of chromosome 14q12 and NKX1-2 haploinsufficiency.
-
Stray-Pedersen, Asbjørg; Refsum, D.; Aaberge, Ingeborg S.; Mellbye, Ove J. & Abrahamsen, Tore G
(2002).
Three siblings with disseminated molluscum contagiosum, transient neutropenia and variable antibody deficency.
-
-
-
Abrahamsen, Tore G & Erichsen, Hans Christian
(2007).
Single Nucleotide Polymorphisms in Genes Encoding Vitamin C Transport Proteins and Inflammatory Cytokines: Risk of Colon Adenoma and Preterm Birth.
Unipub forlag.
ISSN 9788280726834.
Vis sammendrag
Forsker og lege på barneavdelingen på Sykehuset Buskerud HF, Hans Christian Erichsen, har påvist en sammenheng mellom C vitamin og for tidlig fødsel. Prosjektet som ble utført ved National Institutes of Health i USA, er viktig av flere årsaker. For tidlig fødsel, dvs. mer enn tre uker før termin, er en av hovedårsakene til sykehusinnleggelse av spedbarn. Videre er for tidlig fødte barn mer utsatt for mange sykdommer enn barn født til termin. Sykehusinnleggelse og sykdom hos nyfødte medfører en stor belastning for foreldre og barn og er i tillegg også svært ressurskrevende for samfunnet. Det er tidligere påvist en sammenheng mellom lavt inntak av frukt og grønnsaker og for tidlig fødsel. En har antatt at C vitamin spiller en viktig rolle uten at en har kunnet fastslå dette sikkert. I doktoravhandlingen ”Single Nucleotide Polymorphisms in Genes Encoding Vitamin C Transport Proteins and Inflammatory Cytokines: Risk of Colon Adenoma and Preterm Birth” har Erichsen og hans kollegaer kartlagt og analysert to gener som er viktige for C vitamin transport i kroppen. Ved å analysere DNA hos ca. 250 kvinner som fødte for tidlig, og hos ca. 500 kvinner som fødte til termin, kunne en påvise at kvinner med en vanlig variant (hos 30%) av det ene genet, har tre ganger høyere risiko enn andre for å føde for tidlig. Resultatene fra dette forskningsarbeidet knytter for tidlig fødsel direkte til et av genene for C vitamin transport og støtter tidligere forskning som viser at lavt inntak av C vitamin kan øke risikoen for å føde for tidlig. I doktorgradsarbeidet undersøkte en også betydningen av C vitamin transport genene i forhold til risiko for tykktarmskreft. Resultatene kan tyde på at en genvariant er forbundet med redusert risiko for kreftutvikling.
-
Rønnestad, Arild Erlend & Abrahamsen, Tore G
(2006).
Neonatal septicaemia: Epidemiology, diagnostic and therapeutic aspects.
Unipub forlag.
ISSN 82-8072-833-3.
-
Etokebe, Godfrey Essien & Abrahamsen, Tore G
(2004).
Physical separation of alleles at polymorphic loci.
Universitetet i Oslo.
