| 1. |
- Belichenko, P, et al.
(författare)
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Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy.
- 1994
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Ingår i: Epilepsy research. - 0920-1211. ; 18:3, s. 233-47
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Tidskriftsartikel (refereegranskat)abstract
- Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.
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| 2. |
- Beyan, Huriya, et al.
(författare)
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Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans
- 2012
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 22:11, s. 2138-2145
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Tidskriftsartikel (refereegranskat)abstract
- A major concern in common disease epigenomics is distinguishing causal from consequential epigenetic variation. One means of addressing this issue is to identify the temporal origins of epigenetic variants via longitudinal analyses. However, prospective birth-cohort studies are expensive and time consuming. Here, we report DNA methylomics of archived Guthrie cards for the retrospective longitudinal analyses of in-utero-derived DNA methylation variation. We first validate two methodologies for generating comprehensive DNA methylomes from Guthrie cards. Then, using an integrated epigenomic/genomic analysis of Guthrie cards and follow-up samplings, we identify interindividual DNA methylation variation that is present both at birth and 3 yr later. These findings suggest that disease-relevant epigenetic variation could be detected at birth, i.e., before overt clinical disease. Guthrie card methylomics offers a potentially powerful and cost-effective strategy for studying the dynamics of interindividual epigenomic variation in a range of common human diseases.
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| 3. |
- C:son Silander, H, et al.
(författare)
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Surgical treatment for epilepsy: a retrospective Swedish multicenter study.
- 1997
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Ingår i: Acta neurologica Scandinavica. - 0001-6314. ; 95:6, s. 321-30
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Tidskriftsartikel (refereegranskat)abstract
- The characteristics of patients suffering from drug resistant epilepsy, including the results of the preoperative evaluation and epilepsy surgery were retrospectively analyzed in a Swedish multicenter 10-year cohort of children and adults. Altogether 152 patients (65 children and 87 adults) treated during the period 1980-1990 in three epilepsy centers were included and followed-up 2 years after surgery. Median age at onset of seizures was 4 years for the children and 12 years for the adults. A localization related epilepsy was present in 85% of the children and in 95% of the adults. The mean number of seizure types in the children was 1.7 (range 1-4) and in the adults 1.8 (range 1-4). The median monthly seizure frequency was 52 and 15 for children and adults respectively. Resective surgery was performed in 143 cases (94 temporal, 31 extratemporal, 9 multilobar and 9 major resection procedures) and palliative procedures in 16 cases (13 callosotomies and 3 stereotactic amygdalotomies). Postoperative neurological deficits were detected in 9% of the patients after temporal lobe resections and in 15% of the patients after extratemporal and multilobar resection procedures. Two years after resective surgery 53% of the children and 49% of the adults were seizure free. Another 25% of the patients had a more than 50% reduction of seizure frequency. In the postoperative non seizure free group of patients there was a negative correlation between decrease in weighted seizure severity and decrease in seizure frequency. This finding stresses the need for including other parameters than seizure frequency when evaluating the outcome of epilepsy surgery.
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| 4. |
- Edström, Dag, et al.
(författare)
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Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome
- 2023
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Ingår i: Respiratory Research. - 1465-9921. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 10 6 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.
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| 5. |
- Eriksson, S H, et al.
(författare)
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Widespread microdysgenesis in therapy-resistant epilepsy--a case report on post-mortem findings.
- 2002
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Ingår i: Acta neuropathologica. - 0001-6322. ; 103:1, s. 74-7
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Tidskriftsartikel (refereegranskat)abstract
- Microdysgenesis is a subtle malformation, which is often found in specimens from epilepsy surgery. It is, however, not clear whether the changes are focal or diffuse. A recent autopsy case offered an opportunity to investigate whether microdysgenesis found after temporal lobe surgery was focal or widespread in the brain. The entire brain of a 20-year-old patient who died suddenly and unexpectedly was examined histologically. Microdysgenesis had previously been diagnosed after a left temporal lobectomy performed because of therapy-resistant seizures. A light microscopic examination was performed on specimens stained with Luxol-fast blue-cresyl violet and polyclonal antibodies to glial fibrillary acidic protein. Widespread microdysgenesis with irregular nerve cell distribution in the cortex and an increased number of nerve cells in cortical layer I and in the white matter was found in the right temporal and parietal lobes and bilaterally in the frontal and occipital lobes. The post-mortem examination confirmed the previous diagnosis of microdysgenesis and showed that the changes were widespread in a patient who was operated on because of focal epilepsy.
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| 6. |
- Eriksson, s, et al.
(författare)
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Surgical treatment of epilepsy--clinical, radiological and histopathological findings in 139 children and adults.
- 1999
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Ingår i: Acta neurologica Scandinavica. - 0001-6314. ; 99:1, s. 8-15
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Tidskriftsartikel (refereegranskat)abstract
- The present study relates clinical and radiological data to histopathological diagnoses in the first 139 patients (children and adults) in the G?teborg Epilepsy Surgery series. Temporal lobe resections were most common (54.0%) followed by frontal lobe (18.0%) and multilobar resections (11.5%). All histopathological specimens were re-evaluated in connection with this study. Parenchymal malformations and atrophic-gliotic lesions were the most common histopathological findings. Microdysgenesis was more common than major malformations (24.5% versus 11.5%). When the MRI scans were blindly re-evaluated the MRI findings correlated with histopathological diagnosis in all of the vascular malformations, in 77.8% of the tumours, in 76.5% of the cases with hippocampal sclerosis but only in 28.6% of the major cortical development malformations. Hemispherectomies carried the best seizure outcome prognosis followed by temporal lobe resections (75.0% versus 57.3% seizure free 2 years after surgery). Vascular malformations carried the best, and microdysgenesis the worst prognosis (76.9% versus 39.4% seizure free).
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| 7. |
- Fadista, Joao, et al.
(författare)
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Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:38, s. 13924-13929
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism.
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| 8. |
- Nordborg, Claes, 1946, et al.
(författare)
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Microdysgenesis in surgical specimens from patients with epilepsy: occurrence and clinical correlations.
- 1999
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - 0022-3050. ; 67:4, s. 521-4
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Tidskriftsartikel (refereegranskat)abstract
- Malformations of cortical development are commonly associated with epilepsy. In the first 139 consecutive patients in the G?teborg epilepsy surgery series, parenchymal malformations were found in 56. 1% of the children and in 23.1% of the adults. Microdysgenesis (MDG), which was the most common parenchymal malformation, was found in 35. 1% of the children and in 16.7% of the adults. The aim of this study was to identify clinical characteristics of patients with MDG. Mental retardation was found to be significantly more common in patients with major parenchymal malformations and in patients with MDG compared with patients without parenchymal malformations. Patients with major parenchymal malformations as well as patients with MDG also had a significantly earlier onset of seizures than patients without parenchymal malformations, also when adjusting for mental retardation. Patients with MDG were in these clinical aspects shown to closely resemble patients with major malformations. These findings suggest that MDG is a pathoanatomical entity of clinical relevance, with implications both in mental retardation and in epileptogenesis.
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| 9. |
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| 10. |
- Silander, Hans C.-Son, et al.
(författare)
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[Surgical treatment is efficient in epilepsy]
- 1997
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Ingår i: Läkartidningen. - 0023-7205. ; 94:24, s. 2283-6
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Forskningsöversikt (refereegranskat)abstract
- Epilepsy surgery has a very long tradition, and recent advances in diagnostic and surgical procedures have enabled a number of patients with drug-resistant epilepsy to be treated successfully. In addition to the conventional clinical work-up, candidates for epilepsy surgery undergo evaluation by a multidisciplinary team using a battery of neuroimaging and neurophysiological procedures. Such teams have been established at all six university hospitals in Sweden.
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