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  • Andersson, Christin, et al. (författare)
  • Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
  • 2008
  • Ingår i: Neurobiology of Aging. - 0197-4580. ; 29:10, s. 1466-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression.OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline.METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM).RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up.CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
  • Axelsson, Markus, et al. (författare)
  • Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
  • 2014
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - 1477-0970. ; 20:1, s. 43-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
  • Jansson, Nina, et al. (författare)
  • Maternal hormones linking maternal body mass index and dietary intake to birth weight
  • 2008
  • Ingår i: American Journal of Clinical Nutrition. - 0002-9165. ; 87:6, s. 1743-1749
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Obese women often give birth to large-for-gestational age infants (typically defined as a birth weight greater than the 90th percentile), who are at risk of birth injuries and of developing metabolic syndrome later in life. The mechanisms underlying increased fetal growth remain to be established. OBJECTIVE: We aimed to identify maternal hormones that can explain the link between dietary intake, body mass index (BMI), and birth weight. DESIGN: Pregnant women with BMIs (in kg/m(2)) ranging from 17 to 44 (n = 49) were recruited in gestational weeks 8-12. Serum hormone concentrations were measured and dietary history interviews were performed in the first and third trimesters. Multiple regression models were produced to identify hormones that correlate with birth weight and are influenced by BMI or dietary factors. RESULTS: We found a strong positive correlation between BMI and first- and third-trimester insulin and leptin concentrations and a negative correlation between BMI and first-trimester adiponectin and first- and third-trimester insulin-like growth factor binding protein-1 (IGFBP-1). Maternal total fat intake in the first trimester was positively correlated with maternal leptin and inversely correlated with adiponectin. In addition, third-trimester total fat intake was positively correlated with circulating resistin concentrations. First-trimester maternal serum resistin was positively correlated with birth weight, whereas third-trimester maternal IGFBP-1 was negatively correlated with birth weight. CONCLUSIONS: High first-trimester maternal serum resistin and low third-trimester IGFBP-1 were correlated with increased birth weight. We propose that low serum concentrations of IGFBP-1 represent a link between high BMI and increased fetal growth by increasing the bioavailability of insulin-like growth factor-I, which up-regulates placental nutrient transport.
  • Lännerström, Linda, et al. (författare)
  • Losing independence
  • 2013
  • Ingår i: BMC Public Health. - 1471-2458. ; 13, s. 745
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Sickness absence is a multifaceted problem. Much is known about risk factors for being long-term sick-listed, but there is still little known about the various aftermaths and experiences of it. The aim of this qualitative study was to describe, analyze and understand long-term sickness-absent people's experiences of being sick-listed.METHODS: The design was descriptive and had a phenomenological approach. Sixteen long-term sickness-absent individuals were purposively sampled from three municipalities in Sweden in 2011, and data were collected through semi-structured, individual interviews. The interview questions addressed how the participants experienced being sick-listed and how the sick-listing affected their lives. Transcribed interviews were analysed using Giorgi's phenomenological method.RESULTS: The interviews revealed that the participants' experiences of being sick-listed was that they lost their independence in the process of stepping out of working society, attending the mandatory steps in the rehabilitation chain and having numerous encounters with professionals. The participants described that their life-worlds were radically changed when they became sick-listed. Their experiences of their changing life-worlds were mostly highly negative, but there were also a few positive experiences. The most conspicuous findings were the fact that stopping working brought with it so many changes, the participants' feelings of powerlessness in the process, and their experiences of offensive treatment by and/or encounters with professionals.CONCLUSIONS: Sick-listed persons experienced the process of being on long-term sickness absent as very negative. The negative experiences are linked to consequences of stopping to work, consequences of social insurance rules and to negative encounters with professionals handling the sickness absence. The positive experiences of being sick-listed were few in the present study. There is a need to further examine the extent of these negative experiences are and how they affect sick-listed people's recovery and return to work. Long-term sickness absence; sick leave; experiences; interviews; phenomenology; Sweden.
  • Edberg, Andreas, 1974-, et al. (författare)
  • A comparative study of three different PCR assays for detection of Mycoplasma genitalium in urogenital specimens from men and women
  • 2008
  • Ingår i: Journal of Medical Microbiology. - 0022-2615. ; 57:Pt 3, s. 304-309
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare conventional 16S rRNA gene PCR, real-time 16S rRNA gene PCR and real-time Mycoplasma genitalium adhesin protein (MgPa) gene PCR as detection methods for M. genitalium infection. The study also determined the prevalence of M. genitalium in male and female patients attending a sexually transmitted infections clinic in a rural area in the west of Sweden. First void urine (FVU) and/or urethral swabs were collected from 381 men, and FVU and/or cervical swabs and/or urethral swabs were collected from 298 women. A total of 213 specimens were used in the PCR comparative study: 98 consecutively sampled specimens from patients enrolled in the prevalence study, 36 consecutively sampled specimens from patients with symptoms of urethritis and 79 specimens from patients positive for M. genitalium by real-time MgPa gene PCR in the prevalence study. A true-positive M. genitalium DNA specimen was defined as either a specimen positive in any two PCR assays or a specimen whose PCR product was verified by DNA sequencing. The prevalence of M. genitalium infection in men and women was 27/381 (7.1 %) and 23/298 (7.7 %), respectively. In the PCR comparative study, M. genitalium DNA was detected in 61/76 (80.3 %) of true-positive specimens by conventional 16S rRNA gene PCR, in 52/76 (68.4 %) by real-time 16S rRNA gene PCR and in 74/76 (97.4 %) by real-time MgPa gene PCR. Real-time MgPa gene PCR thus had higher sensitivity compared with conventional 16S rRNA gene PCR and had considerably increased sensitivity compared with real-time 16S rRNA gene PCR for detection of M. genitalium DNA. Real-time MgPa gene PCR is well suited for the clinical diagnosis of M. genitalium.
  • Fritsch Fredin, Maria, et al. (författare)
  • Predicting and monitoring colitis development in mice by micro-computed tomography
  • 2008
  • Ingår i: Inflammatory Bowel Diseases. - 1078-0998. ; 14:4, s. 491-499
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT. METHODS: Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development. RESULTS: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders. CONCLUSIONS: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.
  • Oreland, Sadia, et al. (författare)
  • Short- and long-term consequences of different early environmental conditions on central immunoreactive oxytocin and arginine vasopressin levels in male rats
  • 2010
  • Ingår i: Neuropeptides. - 0143-4179. ; 44:5, s. 391-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous studies have provided evidence for an important role for the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in establishment of social behaviour early in life, such as mother-pup interactions. However, there are few reports examining the consequences of early-life experiences on OT and AVP in male offspring. We have used the maternal separation (MS) model to study the effect of different early environmental conditions in rats. The purpose was to study OT and AVP in rats subjected to prolonged daily MS (360 min, MS360), short daily MS (15 min, MS15) and conventional animal facility rearing (AFR) during postnatal days 1-21. In addition, the influence of the presence or absence of littermates during MS, i.e. litter-wise (l) or individual (i) MS, was assessed. The immunoreactive (ir) peptide levels were measured in the hypothalamus, amygdala and pituitary gland of 3 and 10 weeks old male rats. Assessment in 3-week-old rats revealed that MS15 was associated with low ir OT levels in the hypothalamus and amygdala and high levels in the pituitary gland compared with the MS360 and AFR condition. In the amygdala, differences between groups were also detected in adulthood. MS studies commonly use either MS15 or AFR as a control for prolonged MS. The present results show differences in MS360 rats as compared to MS15 but not AFR rats. Consequently, comparisons between prolonged MS with either short periods of MS or AFR will generate divergent results, hence, making the outcome of MS difficult to compare between studies. Moreover, the different early environments had no effect on ir AVP levels. In conclusion, OT in the amygdala was most sensitive to MS. Besides both short- and long-term consequences, distinct effects were seen after litter and individual separation, respectively. We propose that environmentally induced alterations in OT transmission due to disrupted mother-pup interactions early in life may cause altered susceptibility to challenges later in life.
  • Wallén-Mackenzie, Åsa, et al. (författare)
  • Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function.
  • 2009
  • Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 29:7, s. 2238-51
  • Tidskriftsartikel (refereegranskat)abstract
    • A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glutamatergic neurons within the forebrain, the Vglut2-expressing neurons, in neuronal circuitry of higher brain function. Vglut2 expression was selectively deleted in the cortex, hippocampus, and amygdala of preadolescent mice, which resulted in increased locomotor activity, altered social dominance and risk assessment, decreased sensorimotor gating, and impaired long-term spatial memory. Presynaptic VGLUT2-positive terminals were lost in the cortex, striatum, nucleus accumbens, and hippocampus, and a downstream effect on dopamine binding site availability in the striatum was evident. A connection between the induced late-onset, chronic reduction of glutamatergic neurotransmission and dopamine signaling within the circuitry was further substantiated by a partial attenuation of the deficits in sensorimotor gating by the dopamine-stabilizing antipsychotic drug aripiprazole and an increased sensitivity to amphetamine. Somewhat surprisingly, given the restricted expression of Vglut2 in regions responsible for higher brain function, our analyses show that VGLUT2-mediated neurotransmission is required for certain aspects of cognitive, emotional, and social behavior. The present study provides support for the existence of a neurocircuitry that connects changes in VGLUT2-mediated neurotransmission to alterations in the dopaminergic system with schizophrenia-like behavioral deficits as a major outcome.
  • Newson, RB, et al. (författare)
  • The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin
  • 2014
  • Ingår i: Clinical and Experimental Allergy. - Wiley-Blackwell. - 0954-7894. ; 44:2, s. 250-260
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system.OBJECTIVE: We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma.METHODS: The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures.RESULTS: One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons.CONCLUSIONS AND CLINICAL RELEVANCE: Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.
  • Blomgren, Klas, 1963-, et al. (författare)
  • Pathological apoptosis in the developing brain
  • 2007
  • Ingår i: Apoptosis. - 1360-8185. ; 12:5, s. 993
  • Forskningsöversikt (refereegranskat)abstract
    • More than half of the initially-formed neurons are deleted in certain brain regions during normal development. This process, whereby cells are discretely removed without interfering with the further development of remaining cells, is called programmed cell death (PCD). The term apoptosis is used to describe certain morphological manifestations of PCD. Many of the effectors of this developmental cell death program are highly expressed in the developing brain, making it more susceptible to accidental activation of the death machinery, e.g. following hypoxia-ischemia or irradiation. Recent evidence suggests, however, that activation and regulation of cell death mechanisms under pathological conditions do not exactly mirror physiological, developmentally regulated PCD. It may be argued that the conditions after e.g. ischemia are not even compatible with the execution of PCD as we know it. Under pathological conditions cells are exposed to various stressors, including energy failure, oxidative stress and unbalanced ion fluxes. This results in parallel triggering and potential overshooting of several different cell death pathways, which then interact with one another and result in complex patterns of biochemical manifestations and cellular morphological features. These types of cell death are here called "pathological apoptosis," where classical hallmarks of PCD, like pyknosis, nuclear condensation and caspase-3 activation, are combined with non-PCD features of cell death. Here we review our current knowledge of the mechanisms involved, with special focus on the potential for therapeutic intervention tailored to the needs of the developing brain.
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