| 1. |
- Delavaran, Hossein, et al.
(författare)
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Proximity of brain infarcts to regions of endogenous neurogenesis and involvement of striatum in ischaemic stroke.
- 2012
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical stroke trials with stem cell-based approaches aiming for trophic actions, modulation of inflammation and neuroprotection are ongoing. However, experimental studies also suggest that neuronal replacement by grafted neural stem cells (NSCs) and possibly by endogenous NSCs from the subventricular zone (SVZ) may restore function in the stroke-damaged striatum. To evaluate the potential clinical impact of these findings, we analyzed the spatial relationship of infarcts to the SVZ and the proportion of individuals with striatal lesions in a consecutive series of ischaemic stroke patients. METHODS: Patients aged 20-75 years with first-ever ischaemic stroke underwent DW-MRI of the brain within 4 days after stroke onset. We analyzed location, size, number of acute focal ischaemic abnormalities and their spatial relationship to the SVZ. Stroke severity was assessed using NIH Stroke Scale (NIHSS). RESULTS: Of 108 included patients, the distance from the nearest margin of the infarct(s) to the SVZ was ≤2 mm in 51/102 patients with visible ischaemic lesions on DW-MRI. Twenty-four patients had involvement of striatum. Eight of these had predominantly striatal lesions, that is >50% of the total ischaemic lesion volume was located in caudate nucleus and/or putamen. These 8 patients had a median NIHSS of 3. CONCLUSIONS: Many stroke patients have infarcts located close to the SVZ, providing some supportive evidence that optimized endogenous neurogenesis may have therapeutic potential. However, predominantly striatal infarcts are rare and tend to give mild neurological deficits, indicating that striatum should not be the primary target for neuronal replacement efforts in humans.
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| 2. |
- Delavaran, Hossein, et al.
(författare)
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Spontaneous Recovery of Upper Extremity Motor Impairment After Ischemic Stroke : Implications for Stem Cell-Based Therapeutic Approaches
- 2017
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Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 8:4, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that stem cell therapy (SCT) may improve sensorimotor recovery after stroke. Upper extremity motor impairment (UEMI) is common after stroke, often entailing substantial disability. To evaluate the feasibility of post-stroke UEMI as a target for SCT, we examined a selected sample of stroke patients potentially suitable for SCT, aiming to assess the frequency and recovery of UEMI, as well as its relation to activity limitations and participation restrictions. Patients aged 20–75 years with first-ever ischemic stroke, and National Institutes of Health Stroke Scale (NIHSS) scores 1–18, underwent brain diffusion-weighted MRI within 4 days of stroke onset (n = 108). Survivors were followed up after 3–5 years, including assessment with NIHSS, Fugl-Meyer assessment of upper extremity (FMA-UE), modified Rankin Scale (mRS), and Stroke Impact Scale (SIS). UEMI was defined as NIHSS arm/hand score ≥1. UEMI recovery was evaluated with change in NIHSS arm/hand scores between baseline and follow-up. Of 97 survivors, 84 were available to follow-up. Among 76 subjects (of 84) without recurrent stroke, 41 had UEMI at baseline of which 10 had residual UEMI at follow-up. The FMA-UE showed moderate-severe impairment in seven of 10 survivors with residual UEMI. UEMI was correlated to mRS (rs = 0.49, p < 0.001) and the SIS social participation domain (rs = −0.38, p = 0.001). Nearly 25% of the subjects with UEMI at baseline had residual impairment after 3–5 years, whereas about 75% showed complete recovery. Most of the subjects with residual UEMI had moderate-severe impairment, which correlated strongly to dependency in daily activities and social participation restrictions. Our findings suggest that SCT targeting post-stroke UEMI may be clinically valuable with significant meaningful benefits for patients but also emphasize the need of early prognostication to detect patients that will have residual impairment in order to optimize patient selection for SCT.
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| 3. |
- Lueth, M, et al.
(författare)
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Lectin histochemistry of the gastric mucosa in normal and Helicobacter pylori infected guinea-pigs
- 2005
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Ingår i: Journal of Molecular Histology. - : Springer Science and Business Media LLC. - 1567-2379 .- 1573-6865. ; 36:1-2, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori attaches via lectins, carbohydrate binding proteins, to the carbohydrate residues of gastric mucins. Guinea-pigs are a suitable model for a H. pylori infection and thus the carbohydrate composition of normal and H. pylori infected gastric mucosa was investigated by lectin histochemistry. The stomach of all infected animals showed signs of an active chronic gastritis in their mucosa, whereas no inflammation was present in the control animals. The corpus-fundus regions of the controls showed heterogeneous WGA, SNA-I, UEA-I and HPA binding in almost all parts of the gastric glands. While these lectins labelled the superficial mucous cells and chief cells heterogeneously, the staining of the parietal cells was limited to WGA and PHA-L. Mucous neck cells reacted heterogeneously with UEA-I, HPA, WGA and PHA-L. In the antrum, the superficial mucous cells and glands were stained by WGA, UEA-I, HPA, SNA-I or PHA-L. WGA, UEA-I, SNA-I and HPA labelled the surface lining cells strongly. The mucoid glands reacted heterogeneously with WGA, UEA-I, HPA, SNA-I and PHA-L. In both regions, the H. pylori infected animals showed similar lectin binding pattern as the controls. No significant differences in the lectin binding pattern and thus in the carbohydrate composition between normal and H. pylori infected mucosa could be detected, hence H. pylori does not induce any changes in the glycosylation of the mucosa of the guinea-pig. This unaltered glycosylation is of particular relevance for the sialic acid binding lectin SNA-I as H. pylori uses sialic acid binding adhesin for its attachment to the mucosa. As sialic acid binding sites are already expressed in the normal mucosa H. pylori can immediately attach via its sialic acid binding adhesin to the mucosa making the guinea-pig particularly useful as a model organism.
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| 4. |
- Moran, A P, et al.
(författare)
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The relationship between O-chain expression and colonisation ability of Helicobacter pylori in a mouse model
- 2000
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Ingår i: Pathogens and Disease. - 2049-632X. ; 29:4, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- The influence of lipopolysaccharide (LPS) O-polysaccharide chain production on the colonisation ability of Helicobacter pylori in four mouse models (NMRI, C57BL/6, CBA/Ca, and BALB/cA mice) was studied. H. pylori strains that produced smooth-form LPS (S-LPS) detectable in silver-stained electrophoretic gels colonised mice. In contrast, a laboratory-passaged strain G50 and the culture collection strain CCUG 17874 did not colonise mice; the former strain produced low amounts of O-chains only detectable in immunoblotting but not in silver-stained gels, whereas the latter produced rough-form LPS (R-LPS) without O-chains. Furthermore, a galE isogenic mutant, which produced R-LPS, did not colonise mice. However, after repeated broth culture, strains G50 and CCUG 17874 produced S-LPS detectable in silver-stained gels and were capable of colonising mice. Consistent with the production of O-chains, all colonising strains produced Lewis (Le) antigens, Le(x) and/or Le(y). Except for low expression of Le(y) by non-colonising G50, reflecting low production of O-chains, all other non-colonising strains and the galE mutant lacked expression of Le antigens consistent with their production of R-LPS. Lectin typing of strains supported these findings, and also showed that lectin types did not differ before and after colonisation. The low level of O-chain production and Le antigen expression by the non-colonising G50 may not be sufficient to aid colonisation. Examination of protein profiles of H. pylori strains before inoculation showed that protein expression was not significantly different between colonising and non-colonising strains. These results show that S-LPS production with O-chain expression is required by H. pylori for colonisation in a number of mouse models and that care should be taken with inoculating H. pylori strains that loss of O-chains does not occur during subculturing.
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| 5. |
- Pearson, Kevin, et al.
(författare)
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The evolution of epilepsy surgery in tuberous sclerosis in Sweden: A national registry study
- 2023
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Ingår i: Seizure. - 1532-2688. ; 112, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThis study aimed to characterize the Swedish cohort of surgically treated patients with TSC and explore differences in preoperative investigation and outcome over time.MethodsData on patient and seizure characteristics were retrieved from the Swedish National Epilepsy Surgery Register. Two-year follow-up results were compared between the years 1997–2010 and 2011–2018. Preoperative investigations were re-evaluated.ResultsEighteen tuberectomies and seven callosotomies were identified. Seizure freedom after tuberectomy was achieved in 11 % (1/9) 1997–2010 and 56 % (5/9) 2011–2018. The number of tuberectomies increased each decade. Patients operated on in 1997–2010 had higher seizure frequency (median 175 seizures/month vs. 102) and incidence of infantile spasms (4/9 vs. 1/9, none after 2011). There was a trend towards surgery at a younger age (median 86 months 1997–2010 vs. 48 months 2011–2018). None with >200 seizure/month, SEGA, or history of infantile spasms achieved seizure freedom. Two patients underwent anterior callosotomy (1992 and 1994) and became free of drop attacks. Five callosotomies were performed between 2011 and 2013, one patient became free of drop attacks. Two complications with new neurological deficits were reported. The median age at surgery was higher in the callosotomy group (14 years) than in the tuberectomy group (5 years).ConclusionSeizure freedom after tuberectomy in patients with TSC has increased over time in our cohort. Signs of a heavier disease burden were more frequently observed 1997–2010 and associated with worse outcomes. Callosotomy operations were prevalent at the beginning of the 2010s.
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| 6. |
- Sjunnesson, Håkan, et al.
(författare)
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Comparative study of Helicobacter pylori infection in guinea pigs and mice - elevation of acute-phase protein C3 in infected guinea pigs
- 2001
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Ingår i: Pathogens and Disease. - 2049-632X. ; 30:2, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- Eighteen Dunkin-Hartley guinea pigs and 50 NMRI mice were inoculated with Helicobacter pylori and the infection followed by culture, histopathology, antibody response, and plasma levels of the acute-phase proteins albumin, C3, and transferrin for up to 7 weeks. The immune response to H. pylori surface proteins was studied by an enzyme immunoassay (EIA) and Western immunoblot and the plasma levels of albumin, C3, and transferrin were analyzed by single radial immunodiffusion. Guinea pigs had a more severe gastritis and a higher EIA immune response than NMRI mice. Serum C3 levels were elevated in infected guinea pigs after 3 and 7 weeks indicating a systemic inflammatory response and a possible link between H. pylori infection and extragastric manifestations such as vasculitis associated with atherosclerosis. Serum cholesterol levels were analyzed in guinea pigs at 7 weeks and indicated a higher level in H. pylori-infected than in control animals, but this difference was not statistically significant.
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| 7. |
- Sjunnesson, Håkan, et al.
(författare)
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Five month persistence of Helicobacter pylori infection in guinea pigs
- 2003
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 111:6, s. 634-642
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Tidskriftsartikel (refereegranskat)abstract
- Seven Dunkin-Hartley guinea pigs were infected with the Sydney strain of H. pylori (SS1). Gastric histopathology was evaluated and serum antibody response to H. pylori cell-surface proteins was analysed by enzyme immunoassay (EIA) and immunoblot. Tissue and faecal samples from five control animals were analysed for the presence of naturally occurring Helicobacter spp. infection by culture and Helicobacter genus-specific PCR. The H. pylori infection persisted for 5 months, in most animals accompanied by a histologically severe antral gastritis, exhibiting focal degeneration and necrosis of gastric crypt epithelium. Increased numbers of mitotic figures were observed in the gastric epithelium, indicating a regenerative process. Infected animals displayed specific antibodies towards H. pylori cell-surface proteins in immunoblot, whereas EIA was of dubious value creating false-positive results. Serum complement C3 and cholesterol levels appeared to be elevated in infected animals. Helicobacter spp. infection was not detected in the control animals. The persistent infection, accompanied by severe gastritis and a prominent serum antibody response, and the apparent absence of a natural Helicobacter spp. infection makes the guinea pig model useful in H. pylori research.
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| 8. |
- Sjunnesson, Håkan
(författare)
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Helicobacter pylori-induced gastritis in guinea pigs: Model development, diagnostic methods and comparison with mouse protocols
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori is a gram-negative spiral-shaped bacterium that colonizes the human stomach and causes gastric inflammation, gastric and duodenal peptic ulcers, gastric cancer and MALT-lymphoma. A novel guinea pig model of H. pylori infection was developed. Infection was induced by oral inoculation and was confirmed by cultivation from the stomach mucosa. The infection led to severe gastric inflammatory changes and a detectable serum antibody response similar to that in humans. When infected by H. pylori, guinea pigs were found to develop more severe gastritis than mice. The infection induced an acute-phase response in guinea pigs, as revealed by the elevated serum C3 levels obtained, and appeared to cause elevated serum cholesterol levels, suggesting a possible link between H. pylori infection and cardiovascular disease. The effects on H. pylori-infected guinea pigs of dietary supplements consisting of a combination of antioxidant vitamins and selenium were evaluated. Animals receiving these supplements displayed a lesser density of H. pylori colonization in the stomach than control animals and their gastric inflammation appeared to be suppressed. It was concluded that in order to obtain optimal gastric inflammation in the guinea pig model the antioxidant levels in the feed should be kept low. H. pylori infection in guinea pigs was followed for a five-month period. It was found to persist and to be accompanied by severe gastric inflammation. Control animals tested for Helicobacter by use of culture methods and a genus-specific PCR protocol were found to be free of natural Helicobacter infection. Methods of monitoring H. pylori colonisation were evaluated in both mice and guinea pigs. Of two commercial H. pylori faeces-antigen tests assessed in mice, a test based on monoclonal antibodies displayed 100% accuracy, whereas a polyclonally based test sometimes gave false positive results, probably by cross-reacting with a natural murine Helicobacter infection. Indigenous Helicobacter ganmani infection in the mouse colony was detected by PCR-denaturing gradient gel electrophoresis. The polyclonal antibody test was found to cross-react in vitro with several non-pylori Helicobacter species, including species reported in humans. Analyses of faecal samples from guinea pigs, in contrast to mice, by the use of an antigen test or PCR methods were found unable to detect the H. pylori infection. In conclusion, the investigation considers the development and optimisation of experimental H. pylori infection in guinea pigs, and also explores different methods of monitoring the infection. The study shows the guinea pig to be a viable model for studying H. pylori-related gastric and possible extra-gastric manifestations.
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| 9. |
- Sjunnesson, Håkan, et al.
(författare)
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High intake of selenium, beta-carotene, and vitamins A, C, and E reduces growth of Helicobacter pylori in the guinea pig
- 2001
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Ingår i: Comparative Medicine. - 1532-0820. ; 51:5, s. 418-423
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Helicobacter pylori is a human gastroduodenal pathogen associated with type-B gastritis and gastric cancer. Low gastric tissue antioxidant levels are believed to increase the risk of developing gastric cancer. We investigated whether dietary antioxidant levels protect against infection and type-B gastritis in H. pylori-infected guinea pigs. METHODS: Dunkin-Hartley guinea pigs infected for 6 weeks with H. pylori were fed diets with various antioxidant levels. Stomach specimens were cultured, and gastritis was graded from 0 to 3. RESULTS: Supplementation with vitamins A, C, and E and with selenium yielded H. pylori recovery from 17% of challenged animals, compared with 43% of those fed a control diet. Gastritis was scored at 0.33 and 0.93, respectively. Supplementation with only vitamin C or astaxanthin had less effect on gastritis and recovery rate. In a second experiment, gastritis score in a group given vitamins A, C, E, and selenium and beta-carotene was 2.25 and in a control group, it was 2.57. The H. pylori recovery rate was 75 and 100%, respectively, with fewer colonies from animals given antioxidant supplementation (P < 0.05). CONCLUSIONS: A combination of antioxidants can protect against H. pylori infection in guinea pigs. In animal studies, antioxidant intake should be low to optimize development of H. pylori-associated disease. Furthermore we established that H. pylori causes severe gastritis in guinea pigs.
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| 10. |
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