Jenny Odeberg - Academia.edu (original) (raw)

Papers by Jenny Odeberg

Cell Transplantation, 2011

Cell transplantation therapies for central nervous system (CNS) deficits such as spinal cord inju... more Cell transplantation therapies for central nervous system (CNS) deficits such as spinal cord injury (SCI) have been shown to be effective in several animal models. One cell type that has been transplanted is neural precursor cells (NPCs), for which there are several possible sources. We have studied NPCs derived from human embryonic stem cells (hESCs) and human fetal CNS tissue (hfNPCs), cultured as neurospheres, and the expression of pluripotency and neural genes during neural induction and in vitro differentiation. mRNA for the pluripotency markers Nanog, Oct-4, Gdf3, and DNMT3b were downregulated during neural differentiation of hESCs. mRNA for these markers was found in nonpluripotent hfNPC at higher levels compared to hESC-NPCs. However, Oct-4 protein was found in hESC-NPCs after 8 weeks of culture, but not in hfNPCs. Similarly, SSEA-4 and CD326 were only found in hESC-NPCs. NPCs from both sources differentiated as expected to cells with typical features of neurons and astrocyt...

Monographs in Virology, 2003

... 5370 Human Cytomegalovirus Escapes Cell-Mediated Immune Responses Jenny Odeberg,Cecilia Söde... more ... 5370 Human Cytomegalovirus Escapes Cell-Mediated Immune Responses Jenny Odeberg,Cecilia Söderberg Nauclér ... 41 Fahnestock ML, Johnson JL, Feldman RM, Neveu JM, Lane WS, Bjorkman JP ... Martinozzi S, Grzeschik M, Hengel H, Ellwart JW, Pla M, Weiss EH: Cutting ...

This article cites 41 articles, 23 of which can be accessed free

Addiction Research & Theory, 2020

Introduction: Besides supply reduction, preventive interventions to reduce harm from gambling inc... more Introduction: Besides supply reduction, preventive interventions to reduce harm from gambling include interventions for the reduction of demand and to limit negative consequences. Several interventions are available for gamblers, e.g. limit-setting. Reviews have been published examining the evidence for specific measures as well as evaluating the effect of different measures at an overall level. Only a few of these have used a systematic approach for their literature review. The aim of this systematic review and meta-analysis is twofold. First, to assess the certainty of evidence of different preventive measures in the field of educational programs and consumer protection measures, including both land-based and online gambling. The second is to present shortcomings in eligible studies to highlight what type of information is needed in future studies. Method: This systematic review included measures administered in both real-life settings and online. Twenty-eight studies fulfilled our inclusion criteria and had low or moderate risk of bias. Results: The results showed that only two measures (long term educational programs and personalized feedback) had an impact on gambling behavior. Follow-up period was short, and measures did not include gambling as a problem. The certainty in most outcomes, according to GRADE, was very low. Several shortcomings were found in the studies. Discussion: We concluded that the support for preventive measures is low and that a consensus statement regarding execution and methods to collect and analyze data for preventive gambling research is needed. Our review can serve as a starting point for future responsible gambling reviews since it evaluated certainty of evidence.

PeerJ, 2018

Objective To systematically review the efficacy of psychological, pharmacological, and combined t... more Objective To systematically review the efficacy of psychological, pharmacological, and combined treatments for binge eating disorder (BED). Method Systematic search and meta-analysis. Results We found 45 unique studies with low/medium risk of bias, and moderate support for the efficacy of cognitive behavior therapy (CBT) and CBT guided self-help (with moderate quality of evidence), and modest support for interpersonal psychotherapy (IPT), selective serotonin reuptake inhibitors (SSRI), and lisdexamfetamine (with low quality of evidence) in the treatment of adults with BED in terms of cessation of or reduction in the frequency of binge eating. The results on weight loss were disappointing. Only lisdexamfetamine showed a very modest effect on weight loss (low quality of evidence). While there is limited support for the long-term effect of psychological treatments, we have currently no data to ascertain the long-term effect of drug treatments. Some undesired side effects are more commo...

Omhandertagande av aldre som inkommer akut till sjukhus - med fokus pa skora aldre : En systemati... more Omhandertagande av aldre som inkommer akut till sjukhus - med fokus pa skora aldre : En systematisk litteraturoversikt

Human cytomegalovirus (HCMV) is a member of the herpes virus family. HCMV is a ubiquitous pathoge... more Human cytomegalovirus (HCMV) is a member of the herpes virus family. HCMV is a ubiquitous pathogen, causing severe morbidity and mortality in immunocompromised patients, and is a major factor in congenital birth defects. Most adult individuals become carriers of latent HCMV after an asymptomatic infection, and have antibodies against HCMV proteins (are seropositive). Experimental studies of HCMV infection has revealed many interesting features and effects of virally encoded genes to enable infected cells to escape immune recognition as well as to be protected from immune effector mechanisms. T cells recognize virus-encoded peptides presented in the context of HLA class 1 and class 11 surface molecules. CD4+ T lymphocytes primarily react against HLA class ll-viral peptide complexes, whereas CD8+ T lymphocytes react against HLA class I-peptide complexes. NK cells, on the other hand, are usually thought to be more cytotoxic against cells that express lower concentrations of HLA class 1 molecules. HCMV has developed multiple immune evasion mechanisms to be able to co-exist with its host. Here, we have investigated the mechanisms of HCMV immune evasion strategies. Several new strategies to avoid specific T cell activation and to resist NK cytotoxicity have been described. Resistance to NK killing is independent on the expression of the virally encoded class 1 homologue UL18, which has been suggested to be a major candidate for delivering inhibitory signals to NK cells. We have defined a new inhibitory pathway that leads to increased resistance of HCMV infected cells to cytolytic proteins released by activated NK cells. This insensitivity to cytolytic proteins is mediated by the viral protein UL16 and is presumably caused by a redistribution of calreticulin, a protein that has been shown to protect cells from perforin destruction through a membrane stabilization effect. In addition, we have found that HCMV infected macrophages have a reduced capacity to activate a specific T cell proliferative response, compared to uninfected cells. This, in part, is caused by an abundant viral protein pp65, which mediates an accumulation of HLA-DR to lysosomes and degradation of the HLA-DR a-chain. Interestingly, UL18 interacts directly with immunoreactive T lymphocytes, to limit T cell activation. T cells exposed to HCMV express activation markers, produce lower levels of cytokines, but lack proliferative capacity. These cells do not enter apoptosis and can therefore be described as "anergic". These findings increase the current knowledge of how HCMV can avoid detection and elimination by the host immune system

Cell Death & Differentiation, 2015

Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemo... more Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor.

Age and ageing, Jan 25, 2015

urinary incontinence (UI) is a common symptom among older people, with a higher prevalence among ... more urinary incontinence (UI) is a common symptom among older people, with a higher prevalence among frail older persons living in nursing homes. Despite consequences such as reduced health and quality of life, many older people do not seek help for their symptoms, resulting in missed opportunity for treatment. the aim of this study was to investigate the evidence and the effect of conservative treatment of UI and the quality of life among older and frail older persons. a systematic review of randomised controlled studies and prospective, non-randomised studies was conducted, evaluating interventions of conservative treatment of UI in an older population (65 years or older). A total of 23 studies fulfilled the inclusion criteria and 9 were of high or moderate quality. Fourteen studies were of low quality and were therefore excluded from the analysis. documented and effective conservative treatments are available even for older persons with UI. Pelvic muscle exercise, physical training i...

OncoImmunology, 2015

Patients with glioblastoma multiforme (GBM) are immunosuppressed and have a broad range of immuno... more Patients with glioblastoma multiforme (GBM) are immunosuppressed and have a broad range of immunological defects in both innate and adaptive immune responses. GBMs are frequently infected with human cytomegalovirus (HCMV), a virus capable of causing immunosuppression. In 42 HCMV-positive GBM patients in a clinical trial (VIGAS), we investigated T-cell phenotypes in the blood and assessed their relation to survival. Blood was collected before and 3, 12, and 24 weeks after surgery, and the frequency of T-cell subsets was compared with that in 26 age-matched healthy controls. GBM patients had lower levels of CD3 cells than the controls, but had significantly higher levels of CD4 C CD28 ¡ T cells before and 3 and 12 weeks after surgery and increased levels of CD4 C CD57 C and CD4 C CD57 C CD28 C T cells at all-time points. These T-cell subsets were associated with both immunosenescence and HCMV infection. GBM patients also had higher levels of gd T cells at all-times after surgery and lower levels of CD4 C CD25 C cells before and 3 weeks after surgery than healthy controls. Overall survival was significantly shorter in patients with higher levels of CD4 C CD28 ¡ T cells (p D 0.025), CD4 C CD57 C T (p D 0.025) cells, and CD4 C CD28 ¡ CD57 C CD28 ¡ T cells (p < 0.0004) at 3 weeks after surgery. Our findings indicate that signs of immunosenescence in the CD4 C compartment are associated with poor prognosis in patients with HCMV-positive GBMs and may reflect the HCMV activity in their tumors.

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Geriatrics & Gerontology International, 2015

The prevalence and severity of urinary incontinence (UI) increase with age and comorbidity. The b... more The prevalence and severity of urinary incontinence (UI) increase with age and comorbidity. The benefits of pharmacotherapy for UI in the elderly are questionable. The aim of the present study was to systematically review the efficacy of pharmacological treatment for UI in the elderly and frail elderly. Methods: We searched PubMed, EMBASE, Cochrane library and Cinahl databases through October 2013 to identify prospective controlled trials that evaluated pharmacological treatment for UI in persons aged ≥65 years. Elderly persons living in nursing homes were regarded as frail elderly. Outcomes were urinary leakage, quality of life and adverse events. Results: We screened 1038 abstracts and assessed 309 full-text articles. We identified 13 trials of high or moderate quality; 11 evaluated anticholinergic drugs and two evaluated duloxetine. Oxybutynin, the only drug studied in the frail elderly population, had no effect on urinary leakage or quality of life in elderly with urgency UI (UUI). Seven trials evaluated the effects of darifenacin, fesoterodine, solifenacin, tolterodine or trospium. Urinary leakage decreased (standard mean difference: −0.24, 95% confidence interval −0.32-0.15), corresponding to a reduction of half a leakage per 24 h. Common side-effects of treatment were dry mouth and constipation. Data were insufficient for evaluation of the effect on quality of life or cognition. The evidence was insufficient to evaluate the effects of duloxetine. No eligible studies on mirabegron and estrogen were found. Conclusions: Anticholinergics have a small, but significant, effect on urinary leakage in older adults with UUI.

International Urogynecology Journal, 2014

Urinary incontinence (UI) is common among the elderly, but the literature is sparse on the surgic... more Urinary incontinence (UI) is common among the elderly, but the literature is sparse on the surgical treatment of UI among the elderly. This systematic review aims to assess the effectiveness of surgical interventions as treatment for urinary incontinence in the elderly population ≥65 years of age. Randomized controlled trials (RCT) and prospective nonrandomized studies (NRS) were included. The databases PubMed (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), and Cinahl (EBSCO) were searched for the period 1966 up to October 2013. The population had to be ≥65 years of age and had to have undergone urethral sling procedures, periurethral injection of bulking agents, artificial urinary sphincter surgery, bladder injection treatment with onabotulinumtoxin A or sacral neuromodulation treatment. Eligible outcomes were episodes of incontinence/urine leakage, adverse events, and quality of life. The studies included had to be at a moderate or low risk of bias. Mean difference (MD) or standard mean difference (SMD)as well as risk difference (RD) and the 95 % CI were calculated. Five studies-all on the suburethral sling procedure in women- that fulfilled the inclusion criteria were identified. The proportion of patients reporting persistent SUI after surgery ranged from 5.2 to 17.6 %. One study evaluating quality of life (QoL) showed a significant improvement after surgery. The complication rates varied between 1 and 26 %, mainly bladder perforation, bladder emptying disturbances, and de novo urge. The suburethral sling procedure improves continence as well as QoL among elderly women with SUI; however, evidence is limited.

Stem Cell Research, 2009

Transplantation of human neural stem cells (NSCs) and their derivatives is a promising future tre... more Transplantation of human neural stem cells (NSCs) and their derivatives is a promising future treatment for neurodegenerative disease and traumatic nervous system lesions. An important issue is what kind of immunological reaction the cellular transplant and host interaction will result in. Previously, we reported that human NSCs, despite expressing MHC class I and class II molecules, do not trigger an allogeneic T cell response. Here, the immunocompetence of human NSCs, as well as differentiated neural cells, was further studied. Astrocytes expressed both MHC class I and class II molecules to a degree equivalent to that of the NSCs, whereas neurons expressed only MHC class I molecules. Neither the NSCs nor the differentiated cells triggered an allogeneic lymphocyte response. Instead, these potential donor NSCs and astrocytes, but not the neurons, exhibited a suppressive effect on an allogeneic immune response. The suppressive effect mediated by NSCs most likely involves cell-cell interaction. When the immunogenicity of human NSCs was tested in an acute spinal cord injury model in rodent, a xenogeneic rejection response was triggered. Thus, human NSCs and their derived astrocytes do not initiate, but instead suppress, an allogeneic response, while they cannot block a graft rejection in a xenogeneic setting.

Scandinavian Journal of Immunology, 2002

A number of reports have suggested that human cytomegalovirus (HCMV)-infected fibroblasts are res... more A number of reports have suggested that human cytomegalovirus (HCMV)-infected fibroblasts are resistant to natural killer (NK) lysis, and that the HCMV-encoded human leucocyte antigen (HLA) class I homologue UL18 may be responsible for this effect. While fibroblasts are easy to infect in vitro, their role in HCMV pathogenesis in vivo is unclear. Here, we have established systems to address NK recognition of infected endothelial cells and macrophages, two important HCMV cellular reservoirs in vivo. The HCMV-infected endothelial cells exhibited increased resistance to NK killing, and, in most experiments, infected macrophages demonstrated a decreased susceptibility to NK lysis. Infection with the mutant HCMV strain RV670, lacking the genes US1-9 and US11 that are responsible for downregulation of HLA class I molecules, also led to decreased NK susceptibility. Furthermore, reduced NK susceptibility was independent of the expression of the HLA class I homologue UL18, since cells infected with the UL18Delta HCMV strain were also less susceptible to NK killing. These results suggest that HCMV-induced resistance to NK cytotoxicity in endothelial cells and macrophages is independent of known pathways that interfere with the expression of cellular HLA class I A, B and C surface antigens and the HCMV encoded class I homologue UL18.

Journal of Virology, 2001

After a primary infection, human cytomegalovirus (HCMV) establishes lifelong latency in myeloid l... more After a primary infection, human cytomegalovirus (HCMV) establishes lifelong latency in myeloid lineage cells, and the virus has developed several mechanisms to avoid immune recognition and destruction of infected cells. In this study, we show that HCMV utilizes two different strategies to reduce the constitutive expression of HLA-DR, -DP, and -DQ on infected macrophages and that infected macrophages are unable to stimulate a specific CD4 + T-cell response. Downregulation of the HLA class II molecules was observed in 90% of the donor samples and occurred in two phases: at an early (1 day postinfection [dpi]) time point postinfection and at a late (4 dpi) time point postinfection. The early inhibition of HLA class II expression and antigen presentation was not dependent on active virus replication, since UV-inactivated virus induced downregulation of HLA-DR and inhibition of T-cell proliferation at 1 dpi. In contrast, the late effect required virus replication and was dependent on th...

Journal of Virology, 2003

Several reports have shown that human cytomegalovirus (HCMV)-infected cells are resistant to NK l... more Several reports have shown that human cytomegalovirus (HCMV)-infected cells are resistant to NK lysis. These studies have focused on receptor-ligand interactions, and different HCMV proteins have been indicated to mediate inhibitory NK signals. Here, we report that the HCMV protein UL16 is of major importance for the ability of HCMV-infected cells to resist NK cell-mediated cytotoxicity. Fibroblasts infected with the UL16 deletion mutant HCMV strain exhibited a 70% increased sensitivity to NK killing at 7 days postinfection compared to AD169-infected cells. Interestingly, HCMV-infected cells did not appear to engage inhibitory molecules on NK cells, since the levels of granzyme B were not reduced in supernatants obtained from NK cell cocultures with infected target cells compared to uninfected target cells. Furthermore, HCMV-infected cells, but not cells infected with the UL16 deletion mutant HCMV strain, exhibited a significantly increased resistance to the action of cytolytic prot...

Journal of Neuroscience Research, 2006

In vitro expanded neural precursor cells (NPCs) may provide a stable source for cell therapy. In ... more In vitro expanded neural precursor cells (NPCs) may provide a stable source for cell therapy. In search of the optimal cell source for spinal cord repair, we investigated influences of gestational age, regional heterogeneity, and long-term in vitro propagation. The cellular content of neurosphere cultures prior to and after in vitro differentiation was studied by immunocytochemistry and flow cytometry. Human forebrain and spinal cord NPCs deriving from first-trimester tissue were cultured as neurospheres in the presence of epidermal growth factor, basic fibroblast growth factor, and ciliary neurotrophic factor. Proteins characteristic for embryonic stem cells, i.e., Tra-1-60, Tra-1-81, and SSEA-4, were present in approximately 0.5% of the cells in donor tissues and neurospheres. The proportions of nestin- and proliferating cell nuclear antigen-immunoreactive (IR) cells were also maintained, whereas the CD133-IR population increased in vitro. Glial fibrillary acidic protein-IR cells increased in number, and in contrast the fraction of beta-tubulin III-IR cells decreased, at and beyond passage 5 in spinal cord but not forebrain cultures. However, dissociated and in vitro-differentiated forebrain- and spinal cord-derived neurospheres generated similar proportions of neurons, astrocytes, and oligodendrocytes. Gestational age of the donor tissue, which ranged from 4.5 to 12 weeks for forebrain and from 4.5 to 9.5 weeks for spinal cord, did not affect the proportion of cells with different phenotypes in culture. Thus, cellular composition of human neurosphere cultures differs as a result of long-term in vitro propagation and regional heterogeneity of source tissue, despite expansion under equal culture conditions. This could in turn imply that human spinal cord and forebrain NPCs present different repair potentials in in vivo settings.

Journal of Neuroimmunology, 2005

The ability to expand human neural precursor cells in vitro offers new possibilities for future c... more The ability to expand human neural precursor cells in vitro offers new possibilities for future cell therapies. However, concern over immunologically based rejection of in vitro-expanded human neural cells confounds their use as donor cells. Here, we demonstrate that the expression of human leukocyte antigen (HLA) class I and II molecules, but not the co-stimulatory proteins CD40, CD80 and CD86, substantially increase during expansion of neurospheres. Furthermore, peripheral lymphocytes were unresponsive when co-cultured with in vitro-expanded neural cells. Taken together, these results suggest a low immunogenicity of these cultured human neural cells despite HLA incompatibility and high HLA expression.