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T Olsson

Publications and source records attributed to T Olsson.

At least 91 records · Page 5Linked to original sources
PubMed2000

On automatic determination of movement phases in manual transport during the precision grip.

Integrated movement and force analysis of the precision grip-lift sequence (grasping an object between index finger and thumb) is a useful tool in studies on manipulative hand functions. The everyday Manual Transport tasks, moving objects from one place to another, exhibits powerful test possibilities because it includes the precision grip. In this study, as a step towards the exploitation of these possibilities, we created an algorithm that extracts sequence of phases in this task. The mathematical and dynamical properties of the movement and force signals were used to determine the start and the end of each phase. The grip-lift synergy was quantified by the correlation coefficient during each phase. Eight patients with Parkinson's Disease (PD) and 10 healthy persons were studied. The PD patients were tested both in the medicated (ON) and the unmedicated (OFF) state. The object was lifted with the index finger and the thumb, moved a short distance, and put down on a shelf. The preliminary results of these experiments displayed significantly higher coordination between the grip and load forces in the initial phases, before the lift was completely established, than during the transport phases. This was evident both in PD patients and healthy subjects. This method provides an automatic analysis of the motor performance during an arm-hand movement that is important in daily life to aid in clinical diagnosis.

Algorithms↗
PubMed2000

HLA-DR15 is associated with lower age at onset in multiple sclerosis.

To date, more than a dozen studies have investigated the role of HLA genes in determining clinical course and disease severity in multiple sclerosis (MS); in each of these studies, however, patient sample size has been small, and no consistent pattern has emerged from the results. For the present study, we determined HLA class II genotypes and catalogued clinical and demographic data for a total of 948 patients, making our data set the largest ever used to investigate HLA genes in MS. Our goals were both to investigate the impact of HLA-DRB1 alleles on clinical course and disease severity in MS and to compare the frequencies of the established susceptibility allele DR15 in various clinicodemographic subgroups of MS patients. We found that, in addition to DR15, DR17 is positively associated with susceptibility to MS; that none of the HLA-DRB1 alleles influences course or outcome in MS; that carriers of DR15 are prone to MS development at an earlier age than noncarriers; and that differences in DR15 positivity rates, after stratification for diagnostic category and examination results, seem to reflect a gradient of phenocopy contamination, with rates increasing in proportion to the degree of clinical or paraclinical verification of the MS diagnosis.

Adult↗
PubMed1999

Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons.

We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis↗
PubMed1999

Non-MHC gene regulation of nerve root injury induced spinal cord inflammation and neuron death.

Spinal ventral root avulsion leads to an inflammatory response around lesioned motoneurons and the subsequent degeneration of a large proportion of the neurons. We demonstrate here differences in the regulation of cytokine mRNAs, microglia/macrophage activation, MHC expression and nerve cell survival in the two inbred rat strains DA and ACI. These strains have similar major MHC haplotypes, but differ in their non-MHC background genes. T cells were rare in the lesioned segments and depletion of T cells did not affect the response. Thus, non-MHC gene(s) regulate the inflammation and neuron death after nerve trauma by mechanisms not involving antigen-specific immune responses.

Animals↗
PubMed1999

Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis.

We here study the adjuvant properties of immunostimulatory DNA sequences (ISS) and coinjected cytokine-coding cDNA in suppressive vaccination with DNA encoding an autoantigenic peptide, myelin basic protein peptide 68-85, against Lewis rat experimental autoimmune encephalomyelitis (EAE). EAE is an autoaggressive, T1-mediated disease of the CNS. ISS are unmethylated CpG motifs found in bacterial DNA, which can induce production of type 1 cytokines in vertebrates through the innate immune system. Because ISS in the plasmid backbone are necessary for efficient DNA vaccination, we studied the effect of one such ISS, the 5'-AACGTT-3' motif, in our system. Treatment with a DNA vaccine encoding myelin basic protein peptide 68-85 and containing three ISS of 5'-AACGTT-3' sequence suppressed clinical signs of EAE, while a corresponding DNA vaccine without such ISS had no effect. We further observed reduced proliferative T cell responses in rats treated with the ISS-containing DNA vaccine, compared with controls. We also studied the possible impact of coinjection of plasmid DNA encoding rat cytokines IL-4, IL-10, GM-CSF, and TNF-alpha with the ISS-containing DNA vaccine. Coinjection of IL-4-, IL-10-, or TNF-alpha-coding cDNA inhibited the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding cDNA had no effect. Coinjection of cytokine-coding cDNA with the ISS-deficient DNA vaccine failed to alter clinical signs of EAE. We conclude that the presence of ISS and induction of a local T1 cytokine milieu is decisive for specific protective DNA vaccination in EAE.

Adjuvants, Immunologic↗
PubMed1999

Single-cell volume estimation by three-dimensional wide-field microscopy applied to astroglial primary cultures.

Astrocytes, which constitute a prominent part of the number and volume of brain cells, have a high capacity for controlling their volume, and astrocytic swelling is associated with a number of pathological states affecting the CNS. In order to understand the mechanisms for regulating cell volume in astrocytes better, it is of utmost importance to develop technical instrumentation and analysis methods capable of detecting and characterizing dynamic cell shape changes in a quantitative and robust way. For this purpose, a new method was developed to quantify changes in cell volume at the single-cell level. This method is based on three-dimensional (3D) fluorescence imaging obtained by optical sectioning. An automated image acquisition system was developed for the collection of two-dimensional (2D) microscopic images. A deblurring algorithm was implemented in order to restore the originally unfocused image content. Advanced image analysis techniques were applied for accurate and automated determination of cell volume. The sensitivity and reproducibility of the method was evaluated by using fluorescent beads. The techniques were applied to fura-2-labeled astroglial cells in primary culture exposed to hypo- or hyperosmotic stress. The results show that this method is valuable for determining volume changes in cells or parts thereof.

Animals↗
PubMed1999

Serotonin receptor subtype gene expression in the hippocampus of aged rats following chronic amitriptyline treatment.

The raphe-hippocampal 5-HT system plays a key role in the modulation of mood, memory and neuroendocrine responses. In the elderly, there is an increased incidence of disturbances of these functions. We examined the effects of ageing and of chronic antidepressant treatment upon 5-HT receptor subtype mRNA expression in the hippocampus and raphe of cognitively tested rats. Amitriptyline treatment decreased 5-HT1A receptor mRNA expression in the dorsal raphe nucleus of the aged rats (24% fall compared to saline treated controls, p<0.01) but not in the young rats. Neither age nor amitriptyline (10 mg/kg, i.p.) administration for 10 weeks altered 5-HT1A, 5-HT2A, 5-HT2C or 5-HT7 receptor mRNA expression in any hippocampal subregion. This suggests a difference in responsiveness to amitriptyline with ageing originating at the level of the raphe 5-HT1A autoreceptor gene expression.

Aging↗
PubMed1999

Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.

Adolescent↗
PubMed1999

Microsatellite polymorphisms in the gene promoter of monocyte chemotactic protein-3 and analysis of the association between monocyte chemotactic protein-3 alleles and multiple sclerosis development.

Monocyte chemotactic protein 3 (MCP-3) is a chemokine that attracts mononuclear cells, including monocytes and lymphocytes, the inflammatory cell types that predominate in multiple sclerosis lesions. We studied the possible association between the presence of a CA/GA microsatellite repeat polymorphism in the promoter/enhancer region of the MCP-3 gene and the occurrence of multiple sclerosis. DNA samples from 192 Swedish multiple sclerosis (MS) patients and 129 healthy controls were analysed by an automated fluorescent technique. In the whole sample population, five MCP-3 allele variants (MCP-3*A1 to MCP-3*A5) were detected with an allele frequency ranging between 0.3% and 46%. The individual MCP-3 allele frequencies did not differ significantly between MS patients and control individuals. The relative MS risk, attributable to HLA-DRB1*15 was 3.05 (chi2 = 22.25, p < 0.0001). The phenotype frequency (PF) of none of the MCP-3 alleles was significantly altered in the population of controls versus unselected MS patients. When MS patients and control subjects were stratified according to positivity for HLA-DRB1*15, the MCP-3*A4-associated risk for developing MS decreased to 0.36 (p = 0.011). In the stratified groups of patients who were negative for both HLA-DRB1*15 and HLA-DRB1*03, and hence possessed a lower risk to develop MS, the MCP-3*A2-associated risk for MS development decreased significantly (p = 0.018). We conclude that the MCP-3*A4 allele might protect against MS development on the background of the increased risk in HLA-DRB1*15+ individuals and the MCP-3*A2 allele seems protective in low-risk individuals, who are both negative for DRB1*03 and DRB1*15.

Alleles↗
PubMed1999

Genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9.

The immunization of inbred Dark Agouti (DA) rats with an emulsion containing homogenized spinal cord and CFA induces chronic relapsing experimental autoimmune encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis. We report here the first genome-wide search for quantitative trait loci regulating EAE in the rat using this model. We identified one quantitative trait locus on chromosome 9, Eae4, in a [DA(RT1av1) x BN(RT1n)]F2 intercross showing linkage to disease susceptibility and expression of mRNA for the proinflammatory cytokine IFN-gamma in the spinal cord. Eae4 had a larger influence on disease incidence among rats that were homozygous for the RT1av1 MHC haplotype (RT1av1 rats) compared with RT1n/av1 rats, suggesting an interaction between Eae4 and the MHC. Homozygosity for the DA allele at markers in Eae4 and in the MHC was sufficient for EAE. Thus, Eae4 is a major genetic factor determining susceptibility to EAE in this cross of DA rats. In addition, there was support for linkage to phenotypes of EAE on chromosomes 1, 2, 5, 7, 8, 12, and 15. The chromosome 12 region has been shown previously to predispose DA rats to arthritis, and the chromosome 2 region is syntenic to Eae3 in mice. We conclude that Eae4 and probably the other identified genome regions harbor genes regulating susceptibility to neuroinflammatory disease. The identification and functional characterization of these genes may disclose critical events in the pathogenesis of multiple sclerosis; understanding these events could be essential for the development of new therapies against the disease.

Animals↗
PubMed1999

Chronic amitriptyline administration increases serotonin transporter binding sites in the hippocampus of aged rats.

The effects of ageing and of chronic antidepressant treatment upon 5-HT transporter sites ([3H]paroxetine binding) in the rat hippocampus was examined. [3H]paroxetine binding to transporter sites was decreased with ageing in the hippocampus of control rats (38% decrease in dentate gyrus and CA4). Amitriptyline (10 mg/kg, i.p.) had no significant effect on [3H]paroxetine binding in 10 months old rats, but increased binding sites in 24 months rats in all hippocampal subregions (greatest increase of 109% in CA1 compared to saline controls). These data indicate an age-related decrease in hippocampal serotonin transporter sites and upregulation of these sites following 10 weeks of amitriptyline. The observed increase in transporter sites following amitriptyline may contribute to the general lower effectiveness of tricyclic antidepressants with ageing.

Aging↗
PubMed1999

Amelioration of experimental allergic neuritis by sodium fusidate (fusidin): suppression of IFN-gamma and TNF-alpha and enhancement of IL-10.

The immunomodulating antibiotic drug fusidic acid and its sodium salt sodium fusidate (fusidin) ameliorate several organ-specific immunoinflammatory diseases. Because preliminary observations suggest that fusidin may also exert a beneficial effect in Guillain-Barré syndrome (GBS), here we have studied the effects of fusidin on actively induced experimental autoimmune neuritis (EAN) in rats, a known animal model for GBS. Both prophylactic and therapeutic treatment with fusidin (4 mg/rat day ip) markedly ameliorated the clinical course of the disease compared to vehicle-treated animals. The beneficial effects were associated with profound modifications of the capacity of these rats to produce and release pro- and anti-inflammatory cytokines such as IFN-gamma, TNF-alpha and IL-10, which are important in regulating the development of EAN.

Animals↗
PubMed1999

5-Hydroxytryptamine and glutamate modulate velocity and extent of intercellular calcium signalling in hippocampal astroglial cells in primary cultures.

The effects of 5-hydroxytryptamine or glutamate treatment on mechanically induced intercellular calcium waves were studied in gap junction-coupled astroglial cells using rat astroglial-neuronal primary cultures from hippocampus. Imaging software was developed to study amplitude, velocity and extent of wave propagation. Velocity software was designed to find the cell contours automatically and to calculate travelled distance and time-delay of the calcium wave as it propagates from the stimulated cell to all other cells. Propagation analyses were performed to calculate the area of wave propagation. Mechanical stimulation of a single astroglial cell induced an intercellular calcium wave spreading from cell to cell in the astroglial syncytium. When registering the appearances of calcium signals in individual cells along the wave path upon re-stimulation of the same cell, 44.7% of the cells responded with similar calcium signal appearances the second time as the first time. A second wave from the opposite direction resulted in similar calcium signal appearances in 27.3% of the studied cells. Both amplitude and velocity of the calcium signal decreased most prominently in the first part and showed a later flattening out. Treatment with 5-hydroxytryptamine or glutamate for 20-30 s before mechanical stimulation increased the velocity of the calcium waves. 5-Hydroxytryptamine treatment for varying times decreased the propagation area of the calcium waves. In contrast, glutamate treatment increased the propagation area.

Animals↗
PubMed1999

Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats.

Housing rats in an enriched environment after focal brain ischemia improves functional outcome without changes in infarct volume, suggesting neuroplastic changes outside the lesion. In this study, permanent occlusion of the middle cerebral artery was followed by housing in an enriched or a standard environment. Nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression were determined by in situ hybridization two to 30 days after middle cerebral artery occlusion. Stroke induced a decrease in nerve growth factor-induced gene A messenger RNA expression in cortical areas outside the ischemic lesion and in the CA1 subregion of the hippocampus two to three days after ischemia. This decrease was more prolonged with environmental enrichment, lasting until 20 days. However, 30 days after focal cerebral ischemia, environmental enrichment increased nerve growth factor-induced gene A expression compared to standard housing. A reduction of hippocampal glucocorticoid receptor (type II) messenger RNA two to 12 days after stroke in standard housed rats was restored by environmental enrichment. These data suggest that improved functional outcome induced by environmental enrichment after middle cerebral artery occlusion is associated with dynamically altered expression of nerve growth factor-induced gene A messenger RNA in brain regions outside the ischemic lesion, and sustained levels of hippocampal glucocorticoid receptor messenger RNA expression.

Animals↗
PubMed1999

Adrenal steroid dysregulation in dystrophia myotonica.

OBJECTIVE: To evaluate circulating adrenal steroid hormones, cortisol diurnal rhythm and the negative feedback function of the cortisol axis in patients with dystrophia myotonica (DyM), a disease where metabolic disturbances, peripheral insulin insensitivity and cognitive dysfunction are common features. DESIGN: Morning serum levels of dehydroepiandrosterone sulphate, androstenedione, 17 alpha-hydroxy progesterone and cortisol; morning serum levels of testosterone and insulin; diurnal rhythm of saliva cortisol; and an overnight dexamethasone suppression test, together with a cognitive screening test in men with DyM and in controls. SETTING: Outpatient clinic in co-operation with Umeå University Hospital. SUBJECTS: Fifteen men with DyM and 13 age-matched controls. MAIN OUTCOME MEASURES: Adrenal steroid hormone levels, diurnal rhythm of saliva cortisol, dexamethasone suppression test and Mini Mental State Examination scores. RESULTS: Morning serum levels of dehydroepiandrosterone sulphate, androstenedione and 17 alpha-hydroxy progesterone were significantly decreased in DyM after inclusion of age and body mass index in multiple regression analyses (48, 26 and 32% decreases, respectively). An abnormal diurnal rhythm of saliva cortisol was present in all patients, mean saliva cortisol levels being significantly increased (33%) in DyM patients. Dexamethasone suppressibility did not differ between groups. DyM patients scored significantly lower on the Mini Mental State Examination (P < 0.001). CONCLUSIONS: These results indicate an abnormal adrenal steroid hormone secretion in DyM, which may contribute to peripheral insulin sensitivity as well as cognitive impairment in these patients.

17-alpha-Hydroxyprogesterone↗