| 51. |
- Norman, Holly, et al.
(författare)
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Myofibrillar protein and gene expression in acute quadriplegic myopathy
- 2009
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 285:1-2, s. 28-38
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Tidskriftsartikel (refereegranskat)abstract
- The dramatic muscle wasting, preferential loss of myosin and impaired muscle function in intensive care unit (ICU) patients with acute quadriplegic myopathy (AQM) have traditionally been suggested to be the result of proteolysis via specific proteolytic pathways. In this study we aim to investigate the mechanisms underlying the preferential loss of thick vs. thin filament proteins and the reassembly of the sarcomere during the recovery process in muscle samples from ICU patients with AQM. Quantitative and qualitative analyses of myofibrillar protein and mRNA expression were analyzed using SDS-PAGE, confocal microscopy, histochemistry and real-time PCR. The present results demonstrate that the transcriptional regulation of myofibrillar protein synthesis plays an important role in the loss of contractile proteins, as well as the recovery of protein levels during clinical improvement, myosin in particular, presumably in concert with proteolytic pathways, but the mechanisms are specific to the different thick and thin filament proteins studied.
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| 52. |
- Olsson, Emma, 1977-, et al.
(författare)
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Tyrosine transport in fibroblasts from healthy volunteers and patients with schizophrenia
- 2006
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Ingår i: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 393, s. 211-215
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant tyrosine transport across the fibroblast membrane, as measured by lower Vmax and/or lower Km is a repeated finding in patients with schizophrenia. The aim of this study was to investigate the importance of two major transporters, the L- and A-systems and tyrosine transport in fibroblast cell lines from patients with schizophrenia and healthy volunteers. Fibroblast cell lines, n=6 from healthy volunteers and n=6 from patients with schizophrenia, were included in the study. Uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in absence and presence of inhibitors. The uptake of tyrosine by the L-system was evaluated with the inhibitor 2-aminobicyclo heptane-2-carboxylic acid (BCH) and the A-system with the inhibitor nonmetabolized methyl-aminoisobutyric acid (MeAIB). Using [14-C] MeAIB the functionality of system A isoform 2, ATA2, was tested. BCH inhibited the uptake of tyrosine with 90%, showing that tyrosine transport in fibroblasts is mainly transported by the L-system. Not more than 10% could be contributed by the A-system. Excess of MeAIB did not influence tyrosine kinetics. Moreover, MeAIB kinetics did not differ between the patients and the controls. In conclusion, aberrant tyrosine transport observed in patients with schizophrenia is probably linked to the one of the L-systems and does not seem to involve the ATA2 transporter.
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| 53. |
- Parkkinen, L, et al.
(författare)
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Abundant glial alpha-synuclein pathology in a case without overt clinical symptoms.
- 2007
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 26:6, s. 276-83
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Tidskriftsartikel (refereegranskat)abstract
- Screening of 1,800 brains with alpha-synuclein (alphaS) immunohistochemistry revealed five cases with abundant glial cytoplasmic inclusions (GCIs) within the white matter of the brainstem. Surprisingly, retrospective clinical assessment showed that one of these subjects did not fulfil the currently recommended clinical consensus criteria for the multiple system atrophy (MSA). One of the hallmark lesions of MSA, alphaS-positive GCIs, were widespread and abundant in this atypical case that nonetheless lacked any significant neuronal loss. If the patient had met the clinical criteria for MSA, the neuropathological phenotype would have undeniably confirmed the clinically suggested diagnosis. However, lacking overt clinical signs of MSA, the neuropathological phenotype in this subject is prone to be variably denoted or overlooked. We would therefore like to advise neuropathologists to acknowledge these cases with "occult" alpha-synucleinopathy and to inform the clinicians of such a finding. Whether these cases represent a preclinical stage of MSA or simply a biological coincidence, is yet unknown. The observation of abundant GCIs in an asymptomatic subject is, however, important, because even if these cases are rare in number, their occurrence challenge the current presumption, whereby simply the number of alphaS-positive GCIs mediates the neuronal dysfunction responsible for the clinical symptoms of MSA.
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| 54. |
- Parkkinen, Laura, et al.
(författare)
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Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance.
- 2008
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 115:4, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- In Parkinson's disease (PD) and dementia with Lewy bodies (DLB) alpha-synuclein (alphaS) pathology is seen that displays a predictable topographic distribution. There are two staging/categorization systems, i.e. Braak's and McKeith's, currently in use for the assessment of alphaS pathology. The aim of these diagnostic strategies in pathology is, in addition to assess the stage/severity of pathology, to assess the probabilities of the related clinical symptomatology i.e. dementia and extrapyramidal symptoms (EPS). Herein, we assessed the applicability of these two staging/categorization systems and the frequency of dementia and EPS in a cohort of 226 alphaS-positive-subjects. These subject were selected from a large autopsy sample (n = 1,720), irrespective of the clinical presentation, based on the detection of alphaS-immunoreactivity (IR) in one of the most vulnerable nuclei; in the dorsal motor nucleus of vagus, substantia nigra and basal forebrain. The frequency of alphaS-IR lesions in this large cohort was 14% (248 out of 1,720). If applicable, each of the 226 subjects with all required material available was assigned a neuropathological stage/category of PD/DLB and finally the neuropathological data was analyzed in relation to dementia and EPS. 83% of subjects showed a distribution pattern of alphaS-IR that was compatible with the current staging/categorization systems. Around 55% of subjects with widespread alphaS pathology (Braak's PD stages 5-6) lacked clinical signs of dementia or EPS. Similarly, in respect to those subjects that fulfilled the McKeith criteria for diffuse neocortical category and displaying only mild concomitant Alzheimer's disease-related pathology, only 48% were demented and 54% displayed EPS. It is noteworthy that some subjects (17%) deviated from the suggested caudo-rostral propagation suggesting alternative routes of progression, perhaps due to concomitant diseases and genetic predisposition. In conclusion, our results do indeed confirm that current staging/categorization systems can readily be applied to most of the subjects with alphaS pathology. However, finding that around half of the subjects with abundant alphaS pathology remain neurologically intact is intriguing and raises the question whether we do assess the actual disease process.
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| 55. |
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| 56. |
- Pikkarainen, Maria, et al.
(författare)
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Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions visualized with ubiquitin-binding protein p62 immunohistochemistry.
- 2008
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 67:4, s. 280-98
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Tidskriftsartikel (refereegranskat)abstract
- Genetic, clinical, and neuropathologic heterogeneity have been observed in frontotemporal lobar degeneration with ubiquitin (Ubq)-positive inclusions (FTLD-U) and FTLD-U with motor neuron disease. Here, the distribution and morphologic features of neuronal and glial inclusions in the brains of 20 FTLD-U and 2 FTLD-U/motor neuron disease cases were assessed using immunohistochemistry for Ubq-binding protein p62. Eighteen cases displayed TAR DNA-binding protein 43-immunoreactive lesions and were classified as Types 3 (neuronal cytoplasmic inclusions and neurites; 72%), 2 (primarily neuronal cytoplasmic inclusions; 17%), or 1 (primarily neurites; 11%) FTLD-U. The distribution of p62-immunoreactivity varied considerably in each type. Of 4 unclassifiable cases, 2 displayed p62-immunoreactive lesions suggestive of FTLD-U with a mutation in the charged multivesicular body protein 2B gene; 1 suggested basophilic inclusion body disease, and 1 was of a type not previously described. By immunohistochemistry for Ubq-binding protein p62, the distribution of abnormalities was wider than expected; in approximately half of the cases, there were p62-positive but TAR DNA-binding protein 43-negative inclusions in the cerebellum, a region not previously considered to be affected. In other regions, TAR DNA-binding protein 43-, Ubq-, and Ubq-binding protein p62 labeling of inclusions was variable. Whether variations in inclusion morphologies, immunoreactivity, and topographic distribution are due to methodologic factors, different stages of inclusion and disease evolution, different disease entities or biologic modifications of the same disease are presently unclear.
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| 57. |
- Rafiefard, Farideh, et al.
(författare)
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Genotyping of respiratory syncytial virus (RSV) group A in Stockholm, Sweden, using PCR and two-dimensional melting curve analysis
- 2008
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 116:4, s. 317-22
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Tidskriftsartikel (refereegranskat)abstract
- Genotyping of respiratory syncytial (RS) virus group A, by means of a novel method based on PCR, FRET (fluorescence resonance energy transmission) detection and two-dimensional melting curve analysis, was carried out on 80 RS virus samples of group A collected in Stockholm from 1976 to 2005. The Tm values were assessed for three different genotypes (GA2, GA5 and GA7) circulating in Sweden. Two pairs of probes were used and results of subsequent data analysis were plotted in a two-dimensional system. The results obtained were compared to genotyping using conventional nucleotide sequencing and phylogenetic tree analysis. It was found that the new assay was able to correctly identify genotype in about 89% of the isolates; it identified the remaining 11% as untypeable and as candidates for conventional nucleotide sequencing. The new method constitutes a complement to nucleotide sequencing and could be useful in studies of large numbers of samples in epidemiological studies.
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| 58. |
- Rydberg, L, et al.
(författare)
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ABO antigen expression in graft tissue: is titration against donor erythrocytes relevant?
- 2007
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 84:12 Suppl, s. S10-2
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Tidskriftsartikel (refereegranskat)abstract
- ABO-incompatible living donor renal transplantation has become an accepted treatment for end-stage renal disease. Two main factors appear to be important when crossing the ABO barrier, the donor organ A/B antigen expression and the amount of recipient anti-A/B antibody. Antigen expression depends on the ABO blood group and subgroup and may vary in different tissues and cells. The amount of recipient anti-A/B antibody, determined by titration, is very variable. One major drawback with titration is the lack of conformity between different laboratories, making comparisons difficult. For clinical use, the anti-A/B antibody titration technique has to be simple, rapid, and cheap, in addition to being accurate. Although there is a need for more standardized procedures for determination of ABO antibodies, existing techniques are sufficient in the clinical care of patients. To illustrate the variation in susceptibility of different graft tissues to ABO antibodies, in this paper we describe a case of an ABO-incompatible combined liver and kidney transplantation.
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| 59. |
- Røe, Oluf Dimitri, et al.
(författare)
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Genome-wide profile of pleural mesothelioma versus parietal and visceral pleura : the emerging gene portrait of the mesothelioma phenotype
- 2009
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:8, s. e6554-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignant pleural mesothelioma is considered an almost incurable tumour with increasing incidence worldwide. It usually develops in the parietal pleura, from mesothelial lining or submesothelial cells, subsequently invading the visceral pleura. Chromosomal and genomic aberrations of mesothelioma are diverse and heterogenous. Genome-wide profiling of mesothelioma versus parietal and visceral normal pleural tissue could thus reveal novel genes and pathways explaining its aggressive phenotype. METHODOLOGY AND PRINCIPAL FINDINGS: Well-characterised tissue from five mesothelioma patients and normal parietal and visceral pleural samples from six non-cancer patients were profiled by Affymetrix oligoarray of 38 500 genes. The lists of differentially expressed genes tested for overrepresentation in KEGG PATHWAYS (Kyoto Encyclopedia of Genes and Genomes) and GO (gene ontology) terms revealed large differences of expression between visceral and parietal pleura, and both tissues differed from mesothelioma. Cell growth and intrinsic resistance in tumour versus parietal pleura was reflected in highly overexpressed cell cycle, mitosis, replication, DNA repair and anti-apoptosis genes. Several genes of the "salvage pathway" that recycle nucleobases were overexpressed, among them TYMS, encoding thymidylate synthase, the main target of the antifolate drug pemetrexed that is active in mesothelioma. Circadian rhythm genes were expressed in favour of tumour growth. The local invasive, non-metastatic phenotype of mesothelioma, could partly be due to overexpression of the known metastasis suppressors NME1 and NME2. Down-regulation of several tumour suppressor genes could contribute to mesothelioma progression. Genes involved in cell communication were down-regulated, indicating that mesothelioma may shield itself from the immune system. Similarly, in non-cancer parietal versus visceral pleura signal transduction, soluble transporter and adhesion genes were down-regulated. This could represent a genetical platform of the parietal pleura propensity to develop mesothelioma. CONCLUSIONS: Genome-wide microarray approach using complex human tissue samples revealed novel expression patterns, reflecting some important features of mesothelioma biology that should be further explored.
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| 60. |
- Schmitt, A, et al.
(författare)
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How a neuropsychiatric brain bank should be run : a consensus paper of Brainnet Europe II.
- 2007
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 114:5, s. 527-37
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Tidskriftsartikel (refereegranskat)abstract
- The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.
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