| 1. |
- Hjern, Anders, et al.
(författare)
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Outcome and prognostic factors for adolescent female in-patients with anorexia nervosa : 9- to 14-year follow-up
- 2006
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 189:Nov, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier studies have indicated poor long-term outcomes for patients with anorexia nervosa. Aims: To study health and social outcomes of adolescent in-patients with anorexia nervosa in relation to prognostic factors. Method: A register study based on socio-economic and health data was conducted for a national cohort of female residents in Sweden born between 1968 and 1977, including 748 in-patients with anorexia nervosa. Results: At follow-up 9-14 years after hospital admission, 8.7% of patients with anorexia nervosa had persistent psychiatric health problems demanding hospital care and 21.4% were dependent on society for their main income; the stratified relative risks were 5.8 (95% CI 4.7-7.6) and 2.6 (2.3-3.0) respectively, compared with the general female population. The mortality rate for patients with anorexia nervosa was 1.2% and the stratified risk ratio for maternity was 0.6 (95% CI 0.5-0.7). Long duration of hospital care and psychiatric comorbidity were predictors of persistent psychiatric problems and financial dependency on society. Conclusions: The outcome in this cohort of adolescent in-patients with anorexia nervosa was considerably better than that reported in previous studies.
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| 2. |
- Jablonska, Beata, et al.
(författare)
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School performance and hospital admissions due to self-inflicted injury : a Swedish national cohort study.
- 2009
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 38:5, s. 1334-1341
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Self-inflicted injury in youth has increased in many Western countries during recent decades. Education is the most influential societal determinant of living conditions in young people after early childhood. This study tested the hypothesis that school performance predicts self-inflicted injury. METHODS: A national cohort of 447 929 children born during 1973-77 was followed prospectively in the National Patient Discharge Register from the end of their ninth and last year of compulsory school until 2001. Multivariate Cox analyses of proportional hazards were used to test hypotheses regarding grades in ninth grade as predictors of hospital admission due to self-inflicted injury. RESULTS: The risk of hospital admission because of self-inflicted injury increased steeply in a step-wise manner with decreasing grade point average. Hazard ratios were 6.2 (95% confidence interval 5.5-7.0) in those with the lowest level of grade point average compared with the highest. The risks were similar for women and men. Adjustment for potential socio-economic confounders in a multivariate proportional hazards regression analysis attenuated this strong gradient only marginally. CONCLUSION: School performance is a strong factor for predicting future mental ill-health as expressed by self-inflicted injury.
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| 3. |
- Kärrlander, Maria, et al.
(författare)
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Histidine-rich glycoprotein can prevent development of mouse experimental glioblastoma
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:12, s. e8536-
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Tidskriftsartikel (refereegranskat)abstract
- Extensive angiogenesis, formation of new capillaries from pre-existing blood vessels, is an important feature of malignant glioma. Several antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors are currently in clinical trials as therapy for high-grade glioma and bevacizumab was recently approved by the FDA for treatment of recurrent glioblastoma. However, the modest efficacy of these drugs and emerging problems with anti-VEGF treatment resistance welcome the development of alternative antiangiogenic therapies. One potential candidate is histidine-rich glycoprotein (HRG), a plasma protein with antiangiogenic properties that can inhibit endothelial cell adhesion and migration. We have used the RCAS/TV-A mouse model for gliomas to investigate the effect of HRG on brain tumor development. Tumors were induced with platelet-derived growth factor-B (PDGF-B), in the presence or absence of HRG. We found that HRG had little effect on tumor incidence but could significantly inhibit the development of malignant glioma and completely prevent the occurrence of grade IV tumors (glioblastoma).
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| 4. |
- Lindberg, Nanna, 1982-
(författare)
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Cellular Origin and Development of Glioma
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gliomas are the most common primary tumors of the central nervous system believed to arise from glial cells. Invasive growth and inherent propensity for malignant progression make gliomas incurable despite extensive treatment. I have developed a life-like orthotopic glioma model and used this and other in vivo models to study basic mechanisms of glioma development and treatment. Previous studies had indicated that experimental gliomas could arise from glial stem cells and astrocytes. The present thesis describes the making and characterization of a novel mouse model, Ctv-a, where gliomas are induced from oligodendrocyte progenitor cells (OPCs). Our study shows that OPCs have the capacity to give rise to gliomas and suggests in light of previous data that the differentiation state of the cell of origin affects tumor malignancy. CDKN2A encodes p16INK4a and p14ARF (p19Arf in mouse) commonly inactivated in malignant glioma. Their roles in experimental glioma have been extensively studied and both proteins have tumor suppressor functions in glial stem cells and astrocytes. Here, we demonstrate that p19Arf only could suppress gliomagenesis in OPCs while p16Ink4a had no tumor suppressive effect. Functional DNA repair is pivotal for maintaining genome integrity, eliminating unsalvageable cells and inhibiting tumorigenesis. We have studied how RAD51, a central protein of homology-directed repair, affected experimental glioma development and have found that expression of RAD51 may protect against genomic instability and tumor development. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a central feature of malignant progression in glioma. Antiangiogenic treatment by inhibition of vascular endothelial growth factor receptor signaling is used in the clinic for treatment of some cancers. We have investigated the effect of an alternative antiangiogenic protein, histidine-rich glycoprotein (HRG), on glioma development and found that HRG could inhibit the formation of malignant gliomas and completely prevent the formation of glioblastoma.
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| 5. |
- Lindberg, Nanna, 1982-, et al.
(författare)
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Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma
- 2009
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 28:23, s. 2266-2275
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas are primary brain tumors mainly affecting adults. The cellular origin is unknown. The recent identification of tumor-initiating cells in glioma, which share many similarities with normal neural stem cells, has suggested the cell of origin to be a transformed neural stem cell. In previous studies, using the RCAS/tv-a mouse model, platelet-derived growth factor B (PDGF-B)-induced gliomas have been generated from nestin or glial fibrillary acidic protein-expressing cells, markers of neural stem cells. To investigate if committed glial progenitor cells could be the cell of origin for glioma, we generated the Ctv-a mouse where tumor induction would be restricted to myelinating oligodendrocyte progenitor cells (OPCs) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase. We showed that PDGF-B transfer to OPCs could induce gliomas with an incidence of 33%. The majority of tumors resembled human WHO grade II oligodendroglioma based on close similarities in histopathology and expression of cellular markers. Thus, with the Ctv-a mouse we have showed that the cell of origin for glioma may be a committed glial progenitor cell.
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| 6. |
- Lindblad, Frank, et al.
(författare)
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Anorexia nervosa in young men : A cohort study
- 2006
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Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 39:8, s. 662-666
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The current study investigates the background and outcome of anorexia nervosa (AN) in young men. Method: All (N = 61) men, born in 1968-1977 with hospital care in Sweden between 1987 and 1992 due to AN, were compared with the general population. Information about socioeconomic background, health-related outcome (hospital care for AN, other psychiatric diagnoses, abuse of alcohol/drugs and/or suicide attempt), and social outcome (major income from sick leave/sick pension or >= 6 months social welfare, living with birth parents, and living with child and partner; education level) was taken from national registers.Results: On a group level, the findings suggest some differences between male patients with AN and the male population without AN concerning social background, capacity to support oneself, and living with partner and child. Mental ill-health outcome was almost the same for men with AN as for the general population.Conclusion: Male gender in AN - on a group level - suggests a good psychiatric prognosis.
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| 7. |
- Lindblad, Frank, et al.
(författare)
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Improved survival in adolescent patients with anorexia nervosa : a comparison of two Swedish national cohorts of female inpatients
- 2006
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Ingår i: American Journal of Psychiatry. - 0002-953X .- 1535-7228. ; 163:8, s. 1433-1435
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The authors examined two cohorts of female inpatients with anorexia nervosa a decade apart to determine whether there had been any changes in terms of survival. Method: The Swedish National Registers, which contain information about hospital discharges and deaths for the entire population, were used to investigate differences in mortality. Subjects born between 1958 and 1967 and hospitalized due to anorexia nervosa between 1977 and 1981 (N=564) were compared with subjects born between 1968 and 1977 and hospitalized due to anorexia nervosa between 1987 and 1991 (N=554). The cohorts were followed from first hospital admission until 1992 and 2002, respectively. Results: Twenty-five deaths (4.4%) were recorded within the cohort hospitalized between 1977 and 1981, and seven deaths (1.3%) occurred in the cohort hospitalized between 1987 and 1991. The hazard ratio of death for the 1977—1981 cohort relative to the 1987—1991 cohort was 3.7. Conclusions: Mortality among female patients with anorexia nervosa in hospital care in Sweden has decreased dramatically, which is probably related to the introduction of specialized care units.
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| 8. |
- Tchougounova, Elena, et al.
(författare)
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Sox5 can suppress platelet-derived growth factor B-induced glioma development in Ink4a-deficient mice through induction of acute cellular senescence
- 2009
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 28:12, s. 1537-1548
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Tidskriftsartikel (refereegranskat)abstract
- SOX5 is a member of the high-mobility group superfamily of architectural non-histone proteins involved in gene regulation and maintenance of chromatin structure in a wide variety of developmental processes. Sox5 was identified as a brain tumor locus in a retroviral insertional mutagenesis screen of platelet-derived growth factor B (PDGFB)-induced mouse gliomas. Here we have investigated the role of Sox5 in PDGFB-induced gliomagenesis in mice. We show that Sox5 can suppress PDGFB-induced glioma development predominantly upon Ink4a-loss. In human glioma cell lines and tissues, we found very low levels of SOX5 compared with normal brain. Overexpression of Sox5 in human glioma cells led to a reduction in clone formation and inhibition of proliferation. Combined expression of Sox5 and PDGFB in primary brain cell cultures caused decreased proliferation and an increased number of senescent cells in the Ink4a-/- cells only. Protein analyses showed a reduction in the amount and activation of Akt and increased levels of p27(Kip1) upon Sox5 expression that was dominant to PDGFB signaling and specific to Ink4a-/- cells. Upon inhibition of p27(Kip1), the effects of Sox5 on proliferation and senescence could be reversed. Our data suggest a novel pathway, where Sox5 may suppress the oncogenic effects of PDGFB signaling during glioma development by regulating p27(Kip1) in a p19(Arf)-dependent manner, leading to acute cellular senescence.
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