| 1. |
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| 2. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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Neuromyelitis optica spectrum disorder with increased aquaporin-4 microparticles prior to autoantibodies in cerebrospinal fluid : a case report
- 2019
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Ingår i: Journal of Medical Case Reports. - : BioMed Central (BMC). - 1752-1947. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuromyelitis optica spectrum disorders are severe autoimmune inflammatory diseases of the central nervous system associated with the presence of immunoglobulin G antibodies against the water channel protein aquaporin-4. During exacerbation, specific aquaporin-4 immunoglobulin G may be produced intrathecally. We measured extracellular aquaporin-4 microparticles in the cerebrospinal fluid of a patient who later developed the typical symptoms and signs of a neuromyelitis optica spectrum disorder.CASE PRESENTATION: A 17-year-old South American girl developed acute severe motor and vocal tics and difficulties in walking, peripheral numbness, muscle pain, and bilateral headache. At age 22, she had a multitude of motor and psychiatric symptoms. Over the years, she fulfilled the diagnostic criteria for anorexia nervosa, depression, sleep disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, agoraphobia, social anxiety disorder, development coordination disorder, attention-deficit/hyperactivity disorder, hypomania, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, conversion disorder, psychosis, and schizotypal personality syndrome. At age 24, she was found to have elevated titers of aquaporin-4 antibodies in serum, suggestive of probable neuromyelitis optica. She subsequently developed visual impairment, and swollen optic nerves were verified by magnetic resonance imaging. She was thus treated with a chimeric monoclonal antibody targeted against the pan-B-cell marker CD20 (rituximab), and almost all symptoms, including the psychiatric symptoms, rapidly decreased. We found a significant increase of extracellular microparticles of aquaporin-4 in cerebrospinal fluid sampled from our patient when she was 22 years old, 2 years before the full clinical development of neuromyelitis optica.CONCLUSIONS: Microparticles of aquaporin-4 represent subcellular arrangements that may influence the pathogenesis of neuromyelitis optica spectrum disorders and may serve as biomarkers for the underlying cellular disturbances. The increase of aquaporin-4 microparticles in cerebrospinal fluid may be used for early diagnostic purposes; for prevention; and for evaluation of effective treatment, long-term follow-up studies, and elucidating the pathophysiology in neuromyelitis optica spectrum disorders. Further studies of aquaporin-4 microparticles in cerebrospinal fluid of patients with neuromyelitis optica and similar neuropsychiatric disorders are thus called for.
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| 3. |
- Beleza-Meireles, Ana, et al.
(författare)
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Complex aetiology of an apparently Mendelian form of mental retardation
- 2008
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 9, s. 6-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mental Retardation is a common heterogeneous neurodevelopment condition, which causes are still largely elusive. It has been suggested that half of the phenotypic variation of intelligence is explained by genetic variation. And genetic or inherited factors indeed account for most of the cases of mental retardation with an identifiable cause. However, only a few autosomal genes have been mapped and identified to date. In this report, the genetic causes for an apparently recessive form of mental retardation, in a large nordern swedish pedigree, are investigated. METHODS: After extensive evaluation of the patients, which ruled out recognizable patterns of malformation and excluded known causes of MR, a comprehensive genome-wide linkage analysis, with 500 microsatellite markers, was performed in 24 members of this family. Additionally, a genome-wide copy number analysis, using an affimetrix 250 K SNP chip, was performed in this pedigree. RESULTS: No significant LOD score was found with either parametric and non-parametric linkage analysis. The highest scores are located at chromosomes 13, 15 and 17. Genome-wide copy number analysis identified no clear cause for the disorder; but rather, several variants were present in the family members, irrespective of their affected status. CONCLUSION: These results suggest that mental retardation in this family, unlikely what was expected, has a heterogeneous aetiology; and that several lower effect genes variants might be involved. To demonstrate such effects, our family may be too small. This study also indicates that the ascertainment of the cause of MR may be challenging, and that a complex aetiology may be present even within a pedigree, constituting an additional obstacle for genetic counselling. Variants in genes involved in molecular mechanisms of cellular plasticity, in genes involved in the development of underlying neural architectures, and in genes involved in neurodevelopment and in the ongoing function of terminally differentiated neurons may underlie the phenotypic variation of intelligence and explain instances of intellectual impairment.
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| 4. |
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| 5. |
- Erikson, Catarina, et al.
(författare)
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Non-visual effects of lighting
- 1983
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Ingår i: Neuroendocrinology Letters. - 0172-780X. ; 5:6, s. 412-412
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Etemadikhah, Mitra, et al.
(författare)
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Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia.
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| 7. |
- Johansson, Viktoria, et al.
(författare)
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Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders.
- 2017
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer. - 0940-1334 .- 1433-8491. ; 267:5, s. 391-402
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling. Two pairs were concordant for schizophrenia, and 11 pairs discordant for schizophrenia, schizoaffective disorder or bipolar disorder, and four pairs were not affected by psychotic disorders. Markers of microglia activation [monocyte chemoattractant protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble cluster of differentiation 14 (sCD14)], markers of β-amyloid metabolism (AβX-38, AβX-40, AβX-42 and Aβ1-42), soluble amyloid precursor proteins (sAPP-α and sAPP-β), total tau (T-tau), phosphorylated tau (P-tau), and CSF/serum albumin ratio were measured in CSF using immunoassays. Heritability of the CSF markers was estimated, and associations to psychiatric and cognitive measurements were analyzed. Heritability estimates of the microglia markers were moderate, whereas several neurodegenerative markers showed high heritability. In contrast, AβX-42, Aβ1-42, P-tau and CSF/serum albumin ratio were influenced by dominant genetic variation. Higher sCD14 levels were found in twins with schizophrenia or bipolar disorder compared to their not affected co-twins, and higher sCD14-levels were associated with psychotic symptoms. The study provides support for a significant role of sCD14 in psychotic disorders and a possible role of microglia activation in psychosis.
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| 8. |
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| 9. |
- Kegel, Magdalena E., et al.
(författare)
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Kynurenic acid and psychotic symptoms and personality traits in twins with psychiatric morbidity
- 2017
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 247, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of psychotic symptoms and personality traits were made using the Scales for Assessment of Negative and Positive symptoms, the Structured Clinical Interview for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire - Brief. A total score for psychotic symptoms and personality traits was constructed for analysis. CSF KYNA was associated with the score for psychotic symptom and personality traits. TNF-α and IL-8 were associated, and the intra-pair differences scores of TNF-α and IL-8 were highly correlated. Intraclass correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-α. The association between KYNA and psychotic symptoms further supports a role of KYNA in psychotic disorders.
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| 10. |
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| 11. |
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| 12. |
- Lindholm Carlström, Eva, et al.
(författare)
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Linkage and exome analysis implicate multiple genes in non-syndromic intellectual disability in a large Swedish family
- 2019
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNon-syndromic intellectual disability is genetically heterogeneous with dominant, recessive and complex forms of inheritance. We have performed detailed genetic studies in a large multi-generational Swedish family, including several members diagnosed with non-syndromic intellectual disability. Linkage analysis was performed on 22 family members, nine affected with mild to moderate intellectual disability and 13 unaffected family members.Methods Family members were analyzed with Affymetrix Genome-Wide Human SNP Array 6.0 and the genetic data was used to detect copy number variation and to perform genome wide linkage analysis with the SNP High Throughput Linkage analysis system and the Merlin software. For the exome sequencing, the samples were prepared using the Sure Select Human All Exon Kit (Agilent Technologies, Santa Clara, CA, USA) and sequenced using the Ion Proton (TM) System. Validation of identified variants was performed with Sanger sequencing.ResultsThe linkage analysis results indicate that intellectual disability in this family is genetically heterogeneous, with suggestive linkage found on chromosomes 1q31-q41, 4q32-q35, 6p25 and 14q24-q31 (LOD scores of 2.4, simulated p-value of 0.000003 and a simulated genome-wide p-value of 0.06). Exome sequencing was then performed in 14 family members and 7 unrelated individuals from the same region. The analysis of coding variation revealed a pathogenic and candidate variants in different branches of the family. In three patients we find a known homozygous pathogenic mutation in the Homo sapiens solute carrier family 17 member 5 (SLC17A5), causing Salla disease. We also identify a deletion overlapping KDM3B and a duplication overlapping MAP3K4 and AGPAT4, both overlapping variants previously reported in developmental disorders.Conclusions DNA samples from the large family analyzed in this study were initially collected based on a hypothesis that affected members shared a major genetic risk factor. Our results show that a complex phenotype such as mild intellectual disability in large families from genetically isolated populations may show considerable genetic heterogeneity.
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| 13. |
- Nielsen, T. Rune, et al.
(författare)
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Validation of a brief Multicultural Cognitive Examination (MCE) for evaluation of dementia
- 2019
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 34:7, s. 982-989
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study were to present the psychometric properties of a newly designed cognitive screening instrument, the Multicultural Cognitive Examination (MCE), and to compare it with the Rowland Universal Dementia Assessment Scale (RUDAS) in a multicultural population. Methods: The study was a Western European cross-sectional multicenter study. The MCE consists of four components evaluating separate cognitive functions and was constructed by adding measures of memory, verbal fluency, and visuospatial function to the RUDAS to create a scale with 0 to 100 points. Results: A total of 66 patients with dementia and 123 cognitively intact participants were included across six memory clinics; 96 had minority ethnic background, and 93 had majority ethnic background. Moderate to large differences were present between patients with dementia and control participants on all MCE components. The MCE significantly improved diagnostic accuracy compared with using the RUDAS alone, with area under the curves of.918,.984, and.991 for the RUDAS, MCE composite, and demographically corrected composite scores, respectively. Diagnostic accuracy of the MCE did not significantly differ between minority and majority ethnic groups. Across MCE subcomponents, patients with Alzheimer's disease (AD) dementia performed significantly poorer on the memory component compared with those with non-AD dementia. Conclusions: The MCE is a brief cross-cultural cognitive screening instrument that expands evaluation of the cognitive functions covered by the RUDAS, does not require any specialized training, and may be useful for classification of mild dementia or dementia subtypes.
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| 14. |
- Nielsen, T. Rune, et al.
(författare)
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Validation of a European Cross-Cultural Neuropsychological Test Battery (CNTB) for evaluation of dementia
- 2019
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 34:1, s. 144-152
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study were to establish the diagnostic accuracy of the European Cross-Cultural Neuropsychological Test Battery (CNTB) for dementia in different ethnic populations in Western Europe, to examine its ability to differentiate cognitive impairment profiles for dementia subtypes, and to assess the impact of demographic variables on diagnostic properties. Methods: The study was a Western European cross-sectional multi-center study. A total of 66 patients with dementia and 118 cognitively intact participants were included across six memory clinics; 93 had ethnic minority background and 91 had ethnic majority background. Tests in the CNTB cover global cognitive function, memory, language, executive functions, and visuospatial functions. Results: Significant differences with moderate to large effect sizes were present between patients with dementia and control participants on all CNTB measures. Area under the curves (AUC) ranged from.62 to.99 with a mean AUC across all measures of.83. Comparison of ethnic minority and majority groups generally revealed higher sensitivity in the minority group but no significant difference in the mean AUC's across all measures (.84 vs78, P =.42). Comparison of impairment profiles for patients with Alzheimer's disease (AD) and non-AD dementia revealed that AD patients were significantly more impaired on the memory domain, whereas patients with non-AD dementia were more impaired on the executive functions domain. Conclusions: The CNTB was found to have promising cross-cultural diagnostic properties for evaluation of dementia in the targeted minority and majority populations and could represent a valid cross-cultural alternative to other well-established neuropsychological test batteries when assessing patients from these populations.
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| 15. |
- Nielsen, T. Rune, et al.
(författare)
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Validation of the Rowland Universal Dementia Assessment Scale (RUDAS) in a multicultural sample across five Western European countries : diagnostic accuracy and normative data
- 2019
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Ingår i: International Psychogeriatrics. - 1041-6102. ; 31:2, s. 287-296
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Tidskriftsartikel (refereegranskat)abstract
- Background:: With increasing cultural diversity and growing elderly immigrant populations in Western European countries, the availability of brief cognitive screening instruments adequate for assessment of dementia in people from diverse backgrounds becomes increasingly important. The aim of the present study was to investigate diagnostic accuracy of the Rowland Universal Dementia Assessment Scale (RUDAS) in a multicultural sample and to calculate normative data as a basis for demographic adjustment of RUDAS scores. Methods:: The study was a prospective international cross-sectional multi-center study. Receiver operating characteristic curve analysis was used to examine diagnostic accuracy. Regression analysis was used to assess the impact of demographic variables. Results:: Data was collected from 341 cognitively intact participants and 80 people with dementia with a wide age- and educational range. Of the 421 included participants, 239 (57%) had immigrant background. The RUDAS had high diagnostic accuracy with an area under the curve (AUC) of 0.93. The optimal cut-off score was <25 (sensitivity 0.80, specificity 0.90). Regression analysis revealed that RUDAS scores were mainly affected by education and were unrelated to data collection site and immigrant status. Education-adjusted normative data was calculated as a basis for education adjustment of RUDAS scores. Applying education-adjusted RUDAS scores slightly but significantly improved diagnostic accuracy with an AUC of 0.95. Conclusion:: We found the RUDAS to have excellent diagnostic properties in our multicultural sample. However, we suggest that RUDAS scores should be adjusted for education to increase diagnostic accuracy and that the choice of cut-off score should be considered based on the clinical context and expected base rate of dementia.
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| 16. |
- Rastad, Cecilia, et al.
(författare)
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Patients´ Experience of Winter Depression and Light Room Treatment
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Background. There is a need for more knowledge on the effects of light room treatment in patients with Seasonal Affective Disorder (SAD) and to explore patients´ subjective experience of the disease and the treatment.Methods. This was a descriptive and explorative study applying qualitative content analysis. A purposeful sample of 18 psychiatric out- patients with a major depressive disorder with a seasonal pattern according to the DSM-IV and a pre-treatment score >12 on the 9-item Montgomery-Åsberg Depression self-rating scale was included (10 women and 8 men, aged 24-65 years). All patients had completed light room treatment (> 7/10 consecutive weekdays). Data was collected two weeks post-treatment using a semi-structured interview guide.Results. Patients described a profound struggle to adapt to seasonal changes during the winter. Everyday life was affected with reduced work capacity, social withdrawal and disturbed relations with family and friends. Different individual signs and symptoms marked the onset of the seasonal depression. The light room treatment resulted in a radical and rapid change for the better, with only mild and transient side effects. Patients worried about the risk of not being able to receive the light room treatment in future possible relapses.Discussion. The patients experienced a clear seasonal pattern with deterioration in sleep, daily rhythms, energy level, mood, activity and cognitive functioning. Light room treatment was described as one of the most effective and personally important coping strategies available, with improvement in all the major symptoms. The results indicate that light room treatment is essential for some patients´ ability to cope with winter depression.
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| 17. |
- Rastad, Cecilia, et al.
(författare)
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Patients' Experience of Winter Depression and Light Room Treatment.
- 2017
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Ingår i: Psychiatry Journal. - : Hindawi Limited. - 2314-4327 .- 2314-4335. ; 2017
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is a need for more knowledge on the effects of light room treatment in patients with seasonal affective disorder and to explore patients' subjective experience of the disease and the treatment. Methods. This was a descriptive and explorative study applying qualitative content analysis. A purposeful sample of 18 psychiatric outpatients with a major depressive disorder with a seasonal pattern and a pretreatment score ≥12 on the 9-item Montgomery-Åsberg Depression self-rating scale was included (10 women and 8 men, aged 24-65 years). All patients had completed light room treatment (≥7/10 consecutive weekdays). Data was collected two weeks after treatment using a semistructured interview guide. Results. Patients described a clear seasonal pattern and a profound struggle to adapt to seasonal changes during the winter, including deterioration in sleep, daily rhythms, energy level, mood, activity, and cognitive functioning. Everyday life was affected with reduced work capacity, social withdrawal, and disturbed relations with family and friends. The light room treatment resulted in a radical and rapid improvement in all the major symptoms with only mild and transient side effects. Discussion. The results indicate that light room treatment is essential for some patients' ability to cope with seasonal affective disorder.
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| 18. |
- Theander, Sten, et al.
(författare)
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Schizophrenia in Medline 1950-2006: A bibliometric investigation.
- 2010
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 118, s. 279-284
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to perform a bibliometric study, and compare the quantity of publications on schizophrenia with the total medical literature in Medline during 57 years, 1950-2006. The annual additions of literature to Medline are continually increasing and form the Medline growth curve. Comparisons of the number of publications on schizophrenia, or any other disease, to this curve, may be used to estimate the research activity. Methods for the identification of relevant references to papers on schizophrenia were evaluated and three different samples were operationally defined, retrieved and counted. During 1950-2006, 16.28 million references were added to Medline. Nearly 68000, 0.42%, references were related to schizophrenia. The percentage of papers on schizophrenia among the psychiatric literature decreased from 5.2 to 2.6%. The present study indicates that the number of references on schizophrenia in Medline has followed the general increase of medical publications. This pattern differs compared to some other research fields such as dementia, HIV, and peptic ulcer. Samples of references on schizophrenia may be retrieved in Medline by operational definitions of search methods. The quantity of schizophrenia research during 57 years has kept pace with the total medical literature. One interpretation of the results is that more resources are needed to enhance research activities on schizophrenia.
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| 19. |
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| 20. |
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| 21. |
- Wetterberg, Lennart
(författare)
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Pharmacological and Toxic Effectsof Kryptopyrrole in Mice
- 1972
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Ingår i: Orthomolecular psychiatry. - 0317-0217. ; 1:2-3, s. 141-144
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Tidskriftsartikel (refereegranskat)abstract
- In view of the established correlations betweenclinical psychiatric measures and kryptopyrrole (2,4-dimethyl-3-ethylpyrrole), and the paucity ofknowledge concerning the mechanism underlyingthese correlations, a preliminary pharmacologicalinvestigation of the substance was undertaken,utilizing mice as the experimental animal.In mice, kryptopyrrole was found to havepronounced general behavioral, hypnotic, andhypothermic effects.
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| 22. |
- Wetterberg, Lennart
(författare)
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Psykiatrin och de psykiska sjukdomarna
- 2012
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Ingår i: Bredd och djup. - Strömstad : Strömstad Akademi. - 9789186607036 ; , s. 26-28
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 23. |
- Wetterberg, Ola, 1956, et al.
(författare)
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Saltviks Slip och Varv AB
- 2016
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Ingår i: Fiskebåtarna & Varven – Skeppsbyggarna 2. Lennart Bornmalm, Krister Bång, Christer Fredriksen (redaktörer). - Göteborg : Breakwater Publishing. - 9789186687366 ; , s. 382-413
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 24. |
- Zachau, Anne C, et al.
(författare)
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Leukocyte-derived microparticles and scanning electron microscopic structures in two fractions of fresh cerebrospinal fluid in amyotrophic lateral sclerosis: a case report.
- 2012
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Ingår i: Journal of medical case reports. - : Springer Science and Business Media LLC. - 1752-1947. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Introduction: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder characterized by degeneration of motoneuron cells in anterior spinal horns. There is a need for early and accurate diagnosis with this condition. In this case report we used two complementary methods: scanning electron microscopy and fluorescence-activated cell sorting. This is the first report to our knowledge of microparticles in the cerebrospinal fluid of a patient with amyotrophic lateral sclerosis. Case presentation: An 80-year-old Swedish man of Caucasian ethnicity presented to our facility with symptoms of amyotrophic lateral sclerosis starting a year before his first hospital examination, such as muscle weakness and twitching in his right hand progressing to arms, body and leg muscles. Electromyography showed classical neurophysiological findings of amyotrophic lateral sclerosis. Routine blood sample results were normal. A lumbar puncture was performed as a routine investigation and his cerebrospinal fluid was normal with regard to cell count and protein levels, and there were no signs of inflammation. However, scanning electron microscopy and fluorescence-activated cell sorting showed pronounced abnormalities compared to healthy controls. Flow cytometry analysis of two fractions of cerebrospinal fluid from our patient with amyotrophic lateral sclerosis was used to measure the specific binding of antibodies to CD42a, CD144 and CD45, and of phosphatidylserine to lactadherin. Our patient displayed over 100 times more phosphatidylserine-positive microparticles and over 400 times more cell-derived microparticles of leukocyte origin in his cerebrospinal fluid compared to healthy control subjects. The first cerebrospinal fluid fraction contained about 50% more microparticles than the second fraction. The scanning electron microscopy filters used with cerebrospinal fluid from our patient were filled with compact aggregates of spherical particles of lipid appearance, sticking together in a viscous batter. The quantitative increase in scanning electron microscopy findings corresponded to the flow cytometry result of an increase in leukocytederived microparticles. Conclusions: Microparticles represent subcellular arrangements that can influence the pathogenesis of amyotrophic lateral sclerosis and may serve as biomarkers for underlying cellular disturbances. The increased number of leukocyte-derived microparticles with normal cell counts in cerebrospinal fluid may contribute to the amyotrophic lateral sclerosis inflammatory process by formation of immune complexes of prion-like propagation, possibly due to misfolded proteins. The two complementary methods used in this report may be additional tools for revealing the etiology of amyotrophic lateral sclerosis, for early diagnostic purposes and for evaluation of clinical trials, long-term follow-up studies and elucidating the pathophysiology in amyotrophic lateral sclerosis.
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| 25. |
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| 26. |
- Åberg, Karolina, et al.
(författare)
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Support for schizophrenia susceptibility locus on chromosome 2q detected in a Swedish isolate using a dense map of microsatellites and SNPs
- 2008
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-485X. ; 147B:7, s. 1238-44
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Tidskriftsartikel (refereegranskat)abstract
- Extended pedigrees are not only very useful to identify disease genes for rare Mendelian conditions, but they may also help unravel the genetics of complex diseases such as schizophrenia. In this study we performed genome-wide multipoint non-parametric linkage (NPL) score calculations using 825 microsatellites and 5,366 single nucleotide polymorphisms (SNPs), respectively, and searched for haplotypes shared by affected individuals, in three multiplex families including 29 genotyped affected individuals which in total contains 49 relative pairs useful for linkage studies. The most consistent results for microsatellites and SNPs were observed on 2q12.3-q14.1 (NPL scores 2.0, empirical P-value 0.009). However, the overall highest NPL score was observed on chromosome 2q33.3 using SNPs (NPL score 2.2, empirical P-value 0.007). Other chromosomal regions were detected on 5q15-q22.1, with microsatellites (NPL scores 1.7, empirical P-value 0.021) and with SNPs (NPL scores 2.0, empirical P-value 0.010) and on 5q23.1 (NPL score 1.9, empirical P-value 0.012) and 8q24.1-q24.2 (NPL score 2.1, empirical P-value 0.009) when using SNPs. The analysis of extended pedigrees allowed the search for haplotypes inherited identical by decent (IBD) by affected individuals. In all regions with NPL score >1.9 we found haplotypes inherited IBD by multiple cases. However, no common haplotypes were found for affected individuals in all families. In conclusion our NPL results support earlier findings suggesting that 2q and possibly 5q and 8q contain susceptibility loci for schizophrenia. Haplotype sharing in families helped to delimit the detected regions that potentially are susceptibility loci for schizophrenia.
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| 27. |
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