| 1. |
- Aklillu, Eleni, et al.
(författare)
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Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression.
- 2009
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Ingår i: Pharmacogenetics and genomics. - 1744-6872. ; 19:4, s. 267-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin. Individuals with atypical depression (AD) are particularly responsive to treatment with MAO inhibitors (MAOIs). Biomarker tests are essential for prompt diagnosis of AD, and to identify those with an altered brain neurotransmitter metabolism who may selectively respond to MAOI therapy. METHODS: In a sample of 118 Scandinavian patients with treatment-resistant depression who are naive to MAOI therapy, we investigated the associations between a common MAOA functional promoter polymorphism (MAOA-uVNTR), cerebrospinal fluid (CSF) neurotransmitter metabolites, and AD susceptibility. The metabolites for dopamine (homovanillic acid, HVA), serotonin (5-hydroxyindoleacetic acid) and noradrenaline (3-methoxy-4-hydroxyphenylglycol) were measured in the CSF. RESULTS: AD was associated with the female sex and a higher HVA in CSF (P=0.008). The carriers of the MAOA-uVNTR short allele were significantly overrepresented among women with AD (P=0.005; odds ratio=4.76; 95% confidence interval=1.5-13.1; statistical power=80.0%). Moreover, the MAOA-uVNTR genotype significantly influenced the HVA concentration (P=0.01) and showed a strong trend in relation to 5-hydroxyindoleacetic acid concentration (P=0.057) in women. The mediational statistical analyses showed the CSF-HVA concentration as a key driver of the relationship between MAOA-uVNTR genotype and AD. CONCLUSION: The association of the MAOA-uVNTR with both susceptibility to AD and dopamine metabolite (HVA) concentration lends further biological plausibility for high MAO-A enzyme activity as a mechanistic factor for genetic predisposition to AD through altered dopamine turnover. Our observations provide new evidence on the in-vivo functional significance of the MAOA-uVNTR short allele as a high activity variant.
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| 2. |
- Arnäs, Per-Olof, 1969, et al.
(författare)
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Empty container management in depots before and after outsourcing of container inspection - A flow and cost related comparison
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study is to assess the effects on outsourcing parts of the process of returning empty containers to depots. The work is based on a case study that includes review of relevant literature, semi-structured interviews and a time studies. The depot operator normally performs inspection of empty containers and administration at the gate to the depot. This in-house inspection means longer turnaround times and also a lower quality of the inspection. The depot operator then introduces a new arrangement where containers are inspected at a different location and by a third-party actor outside the depot. As a result personnel with special training carry out the inspection that leads to both a somewhat decreased inspection time and also a higher quality of the inspection. The results demonstrate that an outsourced inspection could lead to shorter turnaround times and that more efficient flows can be obtained. Additionally, an increased efficiency is achieved in the gate of the depot and for the inspection activity.
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| 3. |
- Barregård, Lars, 1948, et al.
(författare)
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Toxicokinetics of mercury after long-term repeated exposure to thimerosal-containing vaccine.
- 2011
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Ingår i: Toxicological sciences : an official journal of the Society of Toxicology. - : Oxford University Press (OUP). - 1096-0929. ; 120:2, s. 499-506
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Tidskriftsartikel (refereegranskat)abstract
- The preservative thimerosal contains ethyl mercury (EtHg). Concerns over possible toxicity have re-emerged recently due to its presence in (swine and other) flu vaccines. We examined the potential accumulation of mercury in adults given repeated injections of a thimerosal-preserved vaccine for many years. Fifteen female patients were recruited from an outpatient clinic running a clinical trial with repeated injections (1 ml every 3-4 weeks) of a staphylococcus toxoid vaccine containing 0.01% thimerosal to treat chronic fatigue syndrome. Fifteen untreated female patients with the same diagnoses served as controls. Blood samples were taken before injecting the vaccine, 1 day later, about 2 weeks later, and just before the next injection. In the 15 controls, samples were taken twice. Blood was analyzed for total mercury and EtHg. The toxicokinetics were assessed for each patient separately as well as with a population-based pharmacokinetic model. Total mercury in blood increased on Day 1 in all treated patients (median: 0.33, range: 0.17-1.3 μg/l), as did EtHg (median: 0.14 μg/l, range: 0.06-0.43 μg/l). After a few weeks, levels were back to normal and similar to those in controls. Levels of methyl mercury (MeHg; from fish consumption) were much higher than those of EtHg. After exclusion of an outlier, the mean half-life in a population-based model was 5.6 (95% CI: 4.8-6.3) days. The results indicate that mercury from thimerosal is not accumulated in blood in adults. This is in accordance with short half-lives and rapid metabolism of EtHg to inorganic mercury.
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| 4. |
- Berggren, Ulf, et al.
(författare)
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Subnormal alpha-2-adrenoceptor-mediated sedation during 6 months of sobriety in male type 1 alcohol-dependent subjects
- 2003
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 38, s. 321-326
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In the present study, α2-adrenoceptor function was investigated over 6 months of sobriety in eight male alcohol-dependent subjects. Methods: Subjects were investigated with repeated clonidine (CLON, 2 μg/kg body weight intravenously) challenge tests at days 1 and 7, and months 2 and 6 after the end of a period of heavy alcohol intake. CLON-induced sedation was rated at challenge tests. Mental well-being was self-reported before all challenge tests. Three challenge tests were performed at 1-week intervals in six male healthy controls. Results: Sedation was significantly lower after CLON at all time-points for the challenge tests in alcohol-dependent subjects compared with mean values for three challenge tests in controls. Three dimensions of mental well-being were negatively correlated with scores of CLON-induced sedation at month 6. Conclusions: α2-Adrenoceptor function is subnormal, as assessed by CLON-induced sedation, for at least 6 months after termination of alcohol intake. Whether this subnormal receptor function is pre-existing and possibly genetically determined or is a consequence of long-term alcohol intake must be further investigated, as should this receptor status in alcohol-dependent subjects with longer time-periods of sobriety.
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| 5. |
- Bjärstig, Therese, 1978-, et al.
(författare)
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Between protocol and reality : Swedish municipal comprehensive planning
- 2018
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Ingår i: European Planning Studies. - : Informa UK Limited. - 0965-4313 .- 1469-5944. ; 26:1, s. 35-54
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Tidskriftsartikel (refereegranskat)abstract
- Spatial planning using a landscape approach has been recognized as being essential for reconciling ecological, cultural and socioeconomic dimensions in sustainable development (SuD). Although embraced as a concept, there is a lack of planning tools capable of incorporating multi-level, multifunctional and multi-sectoral perspectives, especially in a rural context. The departure point in this paper is the legal requirements for municipal comprehensive planning (MCP) in Sweden and an e-mail survey about incentives, stakeholder involvement, policy integration and implementation in MCP in all 15 Swedish mountain municipalities. The purpose of this explorative study is to examine whether MCP could be a tool in planning for SuD. Results indicate a general lack of resources and a low status of MCP that affect, and even limit, stakeholder involvement, policy integration and implementation. However, legal requirements for MCP are targeted at SuD, and municipal personnel responsible for planning appreciate the potential of MCP. Therefore, there is potential to develop the MCP into an effective landscape planning tool. To accomplish this, the status of an active planning process has to be raised, the mandate of the local planning agency has to be secured, and residents and land users have to be involved throughout the planning process.
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| 6. |
- Blomberg, Jonas, et al.
(författare)
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Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by myalgia and a sometimes severe limitation of physical activity and cognition. It is exacerbated by physical and mental activity. Its cause is unknown, but frequently starts with an infection. The eliciting infection (commonly infectious mononucleosis or an upper respiratory infection) can be more or less well diagnosed. Among the human herpesviruses (HHV-1 -8), HHV-4 (Epstein-Barr virus; EBV), HHV-6 (including HHV-6A and HHV-6B), and HHV-7, have been implicated in the pathogenesis of ME/CFS. It was therefore logical to search for serological evidence of past herpesvirus infection/reactivation in several cohorts of ME/CFS patients (all diagnosed using the Canada criteria). Control samples were from Swedish blood donors. We used whole purified virus, recombinant proteins, and synthetic peptides as antigens in a suspension multiplex immunoassay (SMIA) for immunoglobulin G (IgG). The study on herpesviral peptides based on antigenicity with human sera yielded novel epitope information. Overall, IgG anti-herpes-viral reactivities of ME/CFS patients and controls did not show significant differences. However, the high precision and internally controlled format allowed us to observe minor relative differences between antibody reactivities of some herpesviral antigens in ME/CFS versus controls. ME/CFS samples reacted somewhat differently from controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens. We conclude that ME/CFS samples had similar levels of IgG reactivity as blood donor samples with HHV-1-7 antigens. The subtle serological differences should not be over-interpreted, but they may indicate that the immune system of some ME/CFS patients interact with the ubiquitous herpesviruses in a way different from that of healthy controls.
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| 7. |
- Blomberg, Jonas, et al.
(författare)
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No evidence for xenotropic murine leukemia-related virus infection in Sweden using internally controlled multiepitope suspension array serology
- 2012
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Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 19:9, s. 1399-1410
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Tidskriftsartikel (refereegranskat)abstract
- Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gamma-retroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive-and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.
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| 8. |
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| 9. |
- Elfaitouri, Amal, et al.
(författare)
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Epitopes of Microbial and Human Heat Shock Protein 60 and Their Recognition in Myalgic Encephalomyelitis
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. 55-
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Tidskriftsartikel (refereegranskat)abstract
- Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.
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| 10. |
- Elfaitouri, A, et al.
(författare)
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Murine Gammaretrovirus Group G3 Was Not Found in Swedish Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans. Results: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria. Conclusions: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors.
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