- Retinoids in leukemia and cellular processes
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- Monoclonal and Polyclonal Antibodies Research
- Autophagy in Disease and Therapy
- PARP inhibition in cancer therapy
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
- Biochemical and Molecular Research
- Reproductive System and Pregnancy
- Peptidase Inhibition and Analysis
- Antioxidant Activity and Oxidative Stress
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Glycosylation and Glycoproteins Research
- Estrogen and related hormone effects
- Phosphodiesterase function and regulation
University of Oslo
2013-2023
Institute of Physiology and Basic Medicine
2015
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
2015
Norwegian Cancer Society
1989-1999
Institutt for Eksperimentell Medisinsk Forskning
1998
Hipple Cancer Research Center
1997
Cancer Research Center
1997
Sanford Burnham Prebys Medical Discovery Institute
1997
Kohler (New Zealand)
1993
Kaiser Foundation Hospital
1993
Abstract TGF-beta and agents that elevate intracellular cAMP levels are potent inhibitors of B cell activation in vitro have been shown to arrest stimulated cells the G1 phase cycle. We tested effects 1 cAMP-inducing agent, forskolin, on viability resting from human peripheral blood, found both caused a significant, dose-dependent increase death relative spontaneous medium alone, as measured by vital dye staining with propidium iodide. Apoptosis was be overall mode demonstrating DNA...
In the present paper we demonstrate that retinol-retinol-binding protein and chylomicron remnant retinyl esters in concentrations normally found human plasma inhibit growth of normal B lymphocytes. Physiological retinoic acid (about 30 nM) were less active than physiological retinol 3 microM). Pharmacological more plasma. Retinol (3 microM) inhibited anti-IgM-mediated DNA synthesis as measured by [3H]thymidine uptake at 72 h 78%. Furthermore, cells blocked mid-G1 phase cell cycle. Thus,...
B cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common paediatric cancer. BCP-ALL blasts typically retain wild type p53, and are therefore assumed to rely on indirect measures suppress transformation-induced p53 activity. We have recently demonstrated that second messenger cyclic adenosine monophosphate (cAMP) through activation of protein kinase A (PKA) has ability inhibit DNA damage-induced accumulation thereby promote survival leukaemic blasts. Development in bone...
W e report that a human neoplastic B cell line (Reh) contains CAMP-dependent protein kinase (cAK) type I (cAKI), but is practically devoid of cAK I1 (cAKII).However, these cells contain novel cAKI isozyme consisting an RIa-RIP heterodimer in association with phosphotransferase activity (RIaRIPC,) eluting from DW-cellulose columns at salt concentration characteristic cAKII. Immunoprecipitation 8-a~ido-[~~P]cAMP-labeled extracts and DEAE fractions employing specific antibodies directed against...
Abstract Here we report that human B lymphocytes can be positively selected directly from buffy coats applying the anti‐CD19 antibody AB1 coupled to magnetic beads. This isolation protocol is highly efficient and isolated cell population of very high purity viability. As judged by cycle analysis various parameters for activation, cells are still in a resting state after isolation. Furthermore, different functional assays have shown procedure does not interfere with either activation or...
Autophagy plays an important role in cellular remodelling during differentiation and development, however little is known about its regulation stem cells. Here we show that cAMP, a well-known factor for mesenchymal cells (MSCs), also potent inducer of autophagy these We have previously shown activation the cAMP-signaling pathway inhibits proliferation MSCs despite induction cell cycle component cyclin E. Here, demonstrate critical E autophagy. Our data suggest model which via ERK-mediated...
Abstract The mechanisms whereby vitamin A stimulates the immune system are poorly understood. In current study, we attempted to elucidate potential of action all-trans retinoic acid (atRA) on proliferation human T lymphocytes. We found that physiological levels atRA potently augmented cell when added in combination with common cell-stimulating agents. This was reflected a time- and concentration-dependent stimulation cycle machinery. presence led elevated cyclin D3, -E, -A, decreased...
We have studied the expression of two different tumor necrosis factor receptors (TNFR; 55 kDa and 75 kDa) on resting activated human peripheral blood B lymphocytes using specific monoclonal antibodies (mAb). Flow cytometric analysis revealed that most cells expressed small amounts 75-kDa TNFR, TNFR was markedly up-regulated upon stimulation with anti-mu or Staphylococcus aureus Cowan strain I (SAC). In contrast, 55-kDa low as well cells. cell activation accompanied by an increased binding...
Retinol is transported in plasma bound to a specific transport protein, retinol-binding protein. We prepared 125I-tyramine cellobiose-labeled rat protein and studied its tissue uptake 1, 5, 24 h after intravenous injection into rats. The liver was the organ containing most radioactivity at all time points studied. After 5 h, 30 22% of injected dose were recovered liver, respectively. separating parenchymal nonparenchymal cells 5-h group, we found that both cell fractions contained...
We describe two monoclonal antibodies, HH1 and HH2. Both reacted selectively with surface immunoglobulin (slg)‐positive human B cells. antibodies stained on average 7–8% of peripheral blood mono nuclear They have not been found to react cells or cell lines other haematopoietic lineages, except that HH2 was positive a small percentage the erythroid line K562. The molecular weight antigen 95 kD, as established by Western blotting. Neither these Ig determinants, Fc receptors, complement known...
Abstract Cyclic AMP functions as a negative regulator of cell proliferation in variety systems. We show here that the normal and neoplastic B cells can be inhibited by high intracellular levels cAMP. Thus forskolin treatment precursor line Reh induced rapid increase cAMP level, which was followed an accumulation GO/G1 phase cycle over period 2–3 days. Similar inhibition after 3 days observed whether present continuously or only during first 5 hr. Both c‐myc c‐Ha‐ras protein were transiently...
In humans, two cDNAs have been isolated encoding beta-galactoside alpha 2,6-sialyltransferase, differing only in part of the 5' untranslated region. Primer extension data show that are near full-length clones. RNase protection analysis different cell types showed transcript corresponding to 2,6-sialyltransferase cDNA from a B-cell library resided mature B cells. contrast, placenta was found all cells tested. Our results also indicate existence third hepatoma line HepG2. Mature were express...
During B- and T-cell ontogeny, extensive apoptosis occurs at distinct stages of development. Agents that increase intracellular levels cAMP induce in thymocytes mature B cells, prompting us to investigate the role signaling human CD10+ B-precursor cells. We show for first time forskolin (which increases cAMP) CD10- cells a dose-dependent manner (19%-94% with 0-1,000 microM after 48 hours incubation, IC50 = 150 microM). High were also obtained by exposing analogue 8-chlorophenylthio-cAMP...
In this work we have isolated a cDNA clone encoding the B cell antigen CD75. The amino acid sequence of CD75 is shown to be identical that human alpha 2,6 sialyltransferase, believed primarily associated with Golgi complex. This first demonstration surface expression sialytransferase which, in cells, may play an important role intercellular adhesion and presentation events.
Our study aimed to investigate, in vivo, the relationship between vitamin A status and NF-kappaB activity, a transcription factor central regulating inflammatory immune responses. We used novel transgenic murine NF-kappaB-luciferase reporter model that enabled molecular imaging of activity live mice via an intensified image-capture apparatus. Whole-body luminescence, which reflects overall was elevated 2.2-fold A-deficient (VAD) compared with control mice. Specifically, VAD increased...