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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Walking training of patients with hemiparesis at an early stage after stroke: a comparison of walking training on a treadmill with body weight support and walking training on the ground.

OBJECTIVE: To compare the effect of walking training on a treadmill with body weight support (BWS) and walking training on the ground at an early stage of rehabilitation in patients with hemiparesis after stroke. DESIGN: Randomized controlled experimental study. SETTING: Multicentre design; three departments of rehabilitation medicine. SUBJECTS: Seventy-three consecutive first stroke patients admitted to a rehabilitation clinic were randomized into a treatment group and a control group. INTERVENTIONS: The treatment group received walking training on a treadmill with BWS for 30 minutes, 5 days a week. The control group received walking training according to the Motor Relearning Programme (MRP) on the ground for 30 minutes 5 days a week, not including treadmill training. During the time in the rehabilitation department (about two months), all patients in the study also received professional stroke rehabilitation besides the walking training in the two groups. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM), walking velocity for 10 m, Functional Ambulation Classification (FAC), Fugl-Meyer Stroke Assessment and Berg's Balance Scale. The assessments were performed at admission, at discharge and at 10-month follow-up. RESULTS: There were no statistically significant differences between the groups at discharge or at the 10-month follow-up with regard to FIM, walking velocity, FAC, Fugl-Meyer Stroke Assessment, and Berg's Balance Scale. Patients in both groups improved in these variables from admission to the 10-month follow-up. CONCLUSIONS: Treadmill training with BWS at an early stage of rehabilitation after stroke is a comparable choice to walking training on the ground.

Adult↗
PubMed2001

Preimplantation genetic diagnosis (PGD): the Gothenburg experience.

BACKGROUND: A program for preimplantation genetic diagnosis of pre-embryos from patients with hereditary disorders was set up in our unit at Sahlgrenska University Hospital in 1994. The majority of the patients were carriers of X-chromosome linked disorders; a few patients were translocation carriers. In this paper we describe our experiences of our first 36 cycles, 30 gender determinations and six analyses of embryos with possible translocations. METHODS: Conventional hormone replacement treatment with intracytoplasmic sperm injection to fertilize the eggs followed by blastomere biopsy and fluorescent in situ hybridization at the eight cell stage was used for sexing as well as detection of translocations. RESULTS: Out of the 30 cycles in 13 patients for gender determination, blastomere biopsies could be carried out in 25 cycles. Transfer of normal female embryos (XX) was performed in 18 cycles, resulting in five pregnancies (pregnancy rate 27.8%) and an implantation rate of 20% per transfer. Three girls have been born. Hence the take home baby rate was 16.7% per transfer and 10% per started cycle. Six cycles (three patients) for detection of translocations in embryos were performed. Diagnosis was possible in four cycles. Transfer of normal embryos was carried out in one cycle. No pregnancy was achieved. CONCLUSION: Successful PGD in its clinical application demands close collaboration between a large group of specialists. Even so, the success rate is considerably lower than after conventional IVF or ICSI procedures. Taking into account the stress caused to the parents facing late interruption of pregnancy following conventional prenatal diagnosis we are convinced that this technique is well worthwhile continuing and refining.

Cytogenetic Analysis↗
PubMed2000

Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q- syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q-), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q- syndrome as well as in other 5q-deleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloid-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cell might be the primary target in most patients. Although in 9 patients no evidence of peripheral blood T-cell and only 1 case of B-cell involvement was found, the data herein support that 5q deletions occur in hematopoietic stem cells (HSCs) with a combined lympho-myeloid potential. First, in all investigated patients a minimum of 94% of cells in the minor CD34(+)CD38(-) HSC compartment were 5q deleted as determined by fluorescence in situ hybridization. Second, in 3 of 5 patients 5q aberrations were detected in a large fraction (25% to 90%) of purified CD34(+)CD19(+) pro-B cells. Furthermore, extensive functional characterization with regard to responsiveness to early-acting cytokines, long-term culture-initiating cells, and nonobese diabetic/severe combined immunodeficiency repopulating cells supported that MDS HSCs in 5q-deleted patients are CD34(+)CD38(-), but inefficient at reconstituting hematopoiesis.

Antigens, CD34↗
PubMed2000

Effects of the maze operation on health-related quality of life in patients with atrial fibrillation.

BACKGROUND: Maze surgery for atrial fibrillation (AF) is a curative therapy, but its effect on health-related quality of life has not been studied. METHODS AND RESULTS: Maze operations were performed in 48 patients with drug-refractory AF. The majority of patients (80%) had lone AF, and the primary indication for surgery in all patients was AF. The SF-36 Health Survey was used to assess quality of life before operation and at 6 months and 1 year after surgery. Twenty-five patients were available for the 1-year follow-up and completed all questionnaires. Before maze surgery, the SF-36 scores were significantly lower than in the general Swedish population, reflecting significant impairment in well-being, physical and social functioning, and mental health. After maze surgery, the quality of life was significantly improved at 6 months and at 1 year on all scales except for bodily pain, which, however, was not significantly decreased before surgery. At both 6 months and 1 year after maze surgery, quality of life, measured by the SF-36, reached the levels of the general Swedish population. CONCLUSIONS: The maze operation can significantly improve the health-related quality of life in selected groups of patients with both paroxysmal and chronic AF refractory to antiarrhythmic therapy.

Adult↗
PubMed2000

Nuclear receptor-DNA binding specificity: A COMBINE and Free-Wilson QSAR analysis.

Specific binding of transcription factors to DNA is crucial for gene regulation. We derived models for the binding specificity of transcription factors of the nuclear receptor family to DNA using two QSAR methods: a Free-Wilson-like method and COMparative BINding Energy (COMBINE) analysis. The analysis is based on experimental data for the interaction of 20 mutant glucocorticoid receptor DNA-binding domains with 16 different response elements in a total of 320 complexes (Zilliacus, J.; Wright, A. P.; Carlstedt-Duke, J.; Nilsson, L.; Gustafsson, J. A. Proteins 1995, 21, 57-67). The predictive abilities of the models obtained by the two methods are similar. The COMBINE analysis indicates that the most important properties for determining binding specificity for this dataset are the changes upon binding of the solvation free energies of the bases that are mutated in the dataset and the electrostatic interactions of the mutated nucleotides with certain charged amino acids. Further important descriptors are the changes of solvation free energy and surface area of the side chain of the mutated residue. It is clear, however, that there are additional features important for the specificity of binding that are not included in the models, such as differences in interfacial hydration of the complexes.

Algorithms↗
PubMed2000

Tachyarrhythmias and triggering factors for atrial fibrillation after coronary artery bypass operations.

BACKGROUND: We evaluated the role of supraventricular arrhythmias and assessed clinical predictors of atrial fibrillation (AF) that developed after coronary artery bypass operations. METHODS: Eighty patients, with a mean age of 65.8 years, underwent 24-hour Holter monitoring preoperatively and for 4 consecutive days postoperatively, or until clinically documented AF, for analysis of the number of premature beats and tachyarrhythmias. Atrial areas and atrial peptides were measured preoperatively and postoperatively. RESULTS: Twenty-nine of 80 (36.3%) patients had postoperative AF. Preoperatively, the maximal supraventricular premature beats per minute were higher in the AF group (p = 0.02). The body mass index and total amount of cardioplegia were lower (p = 0.02 and p = 0.006, respectively), and withdrawal of beta-blockers postoperatively more frequent (p = 0.001) in the AF group, but atrial areas and atrial peptides did not differ. CONCLUSIONS: Frequent supraventricular premature beats preoperatively may indicate a propensity for AF. A larger amount of cardioplegia during the cross-clamp period may reduce the risk of postoperative AF. Further studies are mandatory to clarify why patients with lower body mass index were more prone to AF.

Aged↗
PubMed2000

Conformational dynamics of a 5S rRNA hairpin domain containing loop D and a single nucleotide bulge.

Molecular modeling and molecular dynamics have been employed to study the conformation and flexibility of a 15-nucleotide fragment of the plant 5S rRNA containing loop D and a single uridine bulge. Two different model built initial structures were used: one with the bulge localized inside the helical stem and another with the bulge pointing out from the helix. Several independent 700-ps-long trajectories in aqueous solution with Na(+) conterions were produced for each starting structure. The bulge nucleotide inside the helix stayed in two main conformations, both of which affected the geometry of the stem part opposite the bulge. When the bulge nucleotide was located outside the helix, we found high base mobility and local backbone flexibility. The dynamics of the hydrogen bond network and conformational changes from a direct to a water mediated hydrogen bond in the sheared G-A basepair in the tetraloop was described. Our results correlate with lead ion induced cleavage patterns in 5S rRNA. Sites resistant to nonspecific lead cleavage appeared in all our simulations as the most rigid fragments independent of the localization of the bulge nucleotide.

Base Pairing↗
PubMed2000

On the truncation of long-range electrostatic interactions in DNA.

Long-range interactions are known to play an important role in highly polar biomolecules like DNA. In molecular dynamics simulations of nucleic acids and proteins, an accurate treatment of the long-range interactions are crucial for achieving stable nanosecond trajectories. In this report, we evaluate the structural and dynamic effects on a highly charged oligonucleotide in aqueous solution from different long-range truncation methods. Two group-based truncation methods, one with a switching function and one with a force-switching function were found to fail to give accurate stable trajectories close to the crystal structure. For these group-based truncation methods, large root mean square (rms) deviations from the initial structure were obtained and severe distortions of the oligonucleotide were observed. Another group-based truncation scheme, which used an abrupt truncation at 8. 0 A or at 12.0 A was also investigated. For the short cutoff distance, the conformations deviated far away from the initial structure and were significantly distorted. However, for the longer cutoff, where all necessary electrostatic interactions were included, the trajectory was quite stable. For the particle mesh Ewald (PME) truncation method, a stable DNA simulation with a heavy atom rms deviation of 1.5 A was obtained. The atom-based truncation methods also resulted in stable trajectories, according to the rms deviation from the initial B-DNA structure, of between 1.5 and 1.7 A for the heavy atoms. In these stable simulations, the heavy atom rms deviations were approximately 0.6-1.0 A lower for the bases than for the backbone. An increase of the cutoff radius from 8 to 12 A decreased the rms deviation by approximately 0.2 A for the atom-based truncation method with a force-shifting function, but increased the computational time by a factor of 2. Increasing the cutoff from 12 to 18 A for the atom-based truncation method with a force-shifting function requires 2-3 times more computational time, but did not significantly change the rms deviation. Similar rms deviations from the initial structure were found for the atom-based method with a force-shifting function and for the PME method. The computational cost was longer for the PME method with a cutoff of 12. 0 A for the direct space nonbonded calculations than for the atom-based truncation method with a force-shifting function and a cutoff of 12.0 A. If a nonperiodic boundary, e.g., a spherical boundary, was used, a considerable speedup could be achieved. From the rms fluctuations, the terminal nucleotides and especially the cytidines were found to be more flexible than the nonterminal nucleotides. The B-DNA form of the oligonucleotide was maintained throughout the simulations and is judged to depend on the parameters of the energy function and not on the truncation method used to handle the long-range electrostatic interactions. To perform accurate and stable simulations of highly charged biological macromolecules, we recommend that the atom-based force-shift method or the PME method should be used for the long-range electrostatics interactions.

Base Sequence↗
PubMed2000

Molecular dynamics of the anticodon domain of yeast tRNA(Phe): codon-anticodon interaction.

We have studied the effect of codon-anticodon interaction on the structure and dynamics of transfer RNAs using molecular dynamics simulations over a nanosecond time scale. From our molecular dynamical investigations of the solvated anticodon domain of yeast tRNA(Phe) in the presence and absence of the codon trinucleotides UUC and UUU, we find that, although at a gross level the structures are quite similar for the free and the bound domains, there are small but distinct differences in certain parts of the molecule, notably near the Y37 base. Comparison of the dynamics in terms of interatomic or inter-residual distance fluctuation for the free and the bound domains showed regions of enhanced rigidity in the loop region in the presence of codons. Because fluorescence experiments suggested the existence of multiple conformers of the anticodon domain, which interconvert on a much larger time scale than our simulations, we probed the conformational space using five independent trajectories of 500 ps duration. A generalized ergodic measure analysis of the trajectories revealed that at least for this time scale, all the trajectories populated separate parts of the conformational space, indicating a need for even longer simulations or enhanced sampling of the conformational space to give an unequivocal answer to this question.

Anticodon↗
PubMed2000

Monitoring of respiratory rate in postoperative care using a new photoplethysmographic technique.

OBJECTIVE: Photoplethysmography (PPG) is a non-invasive optical technique that measures variations in skin blood volume and perfusion. The PPG signal contains components that are synchronous with respiratory and cardiac rhythms. We undertook this study to evaluate PPG for monitoring patients' respiratory rate in the postoperative care unit, using a new prototype device. We compared it with the established technique, transthoracic impedance (TTI). METHODS: PPG signals from 16 patients (ASA classes 1-2, mean age 43 years) who were recovering from general anaesthesia after routine operations were recorded continuously for 60 minutes/patient. The respiratory synchronous part of the PPG signal was extracted by using a bandpass filter. Detection of breaths in the filtered PPG signals was done both visually and by using an automated algorithm. In both procedures, the detected breaths were compared with the breaths detected in the TTI reference. RESULTS: A total of 10,661 breaths were recorded, and the mean +/- SD respiratory rate was 12.3 +/- 3.5 breaths/minute. When compared with TTI, the rates of false positive and false negative breaths detected by PPG (visual procedure) were 4.6 +/- 4.5% and 5.8 +/- 6.5%, respectively. When using the algorithm for breath detection from PPG, the rates of false positive and false negative breaths were 11.1 +/- 9.7% and 3.7 +/- 3.8%, respectively, when compared to TTI. Lower respiratory rates increased the occurrence of false-positive breaths that were detected by the PPG using visual identification (p < 0.05). The same tendency was seen with the automated PPG procedure (p < 0.10). CONCLUSIONS: Our results indicate that PPG has the potential to be useful for monitoring respiratory rate in the postoperative period.

Adult↗
PubMed2000

Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens.

Acellular pertussis vaccines (Pa) protect against severe pertussis in children. However, serum antibody responses decline quickly after immunization. Studies in animal models suggest that cell-mediated immunity also contributes to protection against Bordetella pertussis, and it has already been demonstrated that Pa induce T cells that secrete type-1 and type-2 cytokines in children. In this study we examined the persistence of the T cell response and the effect of booster immunization in 4-6-year-old children. Cell-mediated immunity to B. pertussis antigens was detected in a high proportion of children more than 42 months after their last immunization. Peripheral blood mononuclear cells (PBMC) from the majority of children secreted interferon-gamma (IFN-gamma) and a smaller proportion IL-5, in response to specific antigen stimulation in vitro. However, following booster immunization, significantly higher concentrations of IL-5, but not IFN-gamma, were produced by PBMC in response to B. pertussis antigens. Furthermore, plasma IL-4 and IL-5 concentrations were increased, whereas IFN-gamma concentrations were reduced following booster immunization. It has been suggested that childhood immunization with Th2-inducing vaccines may predispose some children to atopic disease. Although we found that pertussis toxin (PT)-specific IgE was significantly increased after booster immunization in both atopic and non-atopic children, the levels of IgE to common allergens and the prevalence of positive skin prick test were unaffected by the booster vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis antigens, booster vaccination with Pa does not appear to be a risk factor for allergy.

Allergens↗
PubMed2000

Caenorhabditis elegans lin-25: a study of its role in multiple cell fate specification events involving Ras and the identification and characterization of evolutionarily conserved domains.

Caenorhabditis elegans lin-25 functions downstream of let-60 ras in the genetic pathway for the induction of the 1 degrees cell fate during vulval development and encodes a novel 130-kD protein. The biochemical activity of LIN-25 is presently unknown, but the protein appears to function together with SUR-2, whose human homologue binds to Mediator, a protein complex required for transcriptional regulation. We describe here experiments that indicate that, besides its role in vulval development, lin-25 also participates in the fate specification of a number of other cells in the worm that are known to require Ras-mediated signaling. We also describe the cloning of a lin-25 orthologue from C. briggsae. Sequence comparisons suggest that the gene is evolving relatively rapidly. By characterizing the molecular lesions associated with 10 lin-25 mutant alleles and by assaying in vivo the activity of mutants lin-25 generated in vitro, we have identified three domains within LIN-25 that are required for activity or stability. We have also identified a sequence that is required for efficient nuclear translocation. We discuss how lin-25 might act in cell fate specification in C. elegans within the context of models for lin-25 function in cell identity and cell signaling.

Amino Acid Sequence↗
PubMed2000

Peripheral blood concentrations of inhibin B are elevated during gonadotrophin stimulation in patients who later develop ovarian OHSS and inhibin A concentrations are elevated after OHSS onset.

Ovarian hyperstimulation syndrome (OHSS) is a serious side-effect of controlled ovarian stimulation. Inhibin A and inhibin B, as putative predictors of OHSS development in the same stimulation cycle, were evaluated. A cohort of 428 in-vitro fertilization (IVF) patients was followed. Fifteen patients with severe OHSS were compared with matched (age, follicle number) controls. Serum samples were obtained at five time points from the start of ovarian stimulation until >/= 3 days post-embryo transfer and analysed with specific enzyme-linked immunosorbent assays. Inhibin A in the OHSS group showed a continuous increase with a significant elevation 3 days prior to oocyte aspiration (ASP-3) and onwards. Maximal concentrations were detected at embryo transfer and the concentrations remained high at >/= 3 days post-embryo transfer. Inhibin A concentrations in the control group showed a transient elevation (significant increase at ASP and embryo transfer). Inhibin A in the OHSS group was significantly higher than in controls only at the time point where OHSS had developed (>/= 3 days post-embryo transfer), and declined during OHSS treatment. Overall, there was a positive correlation between the number of follicles and inhibin A concentrations at ASP-3 until embryo transfer in the control group but not in the OHSS group. The concentrations of inhibin B in both groups increased from the start of ovarian stimulation, with peak values at ASP-3, and then a decline. Inhibin B was significantly higher in OHSS patients at ASP-3 and at ASP. Inhibin B at ASP-3 was correlated with the total number of follicles in both the OHSS group and the control group.

Adult↗
PubMed2000

Incidence of congenital malformations in children born after ICSI.

The aim of this study was to determine the incidence of congenital malformations in a complete cohort of children born after intracytoplasmic sperm injection (ICSI). The medical records were retrieved for 1139 infants, 736 singletons, 200 sets of twins and one set of triplets. The total number of infants with an identified anomaly was 87 (7.6%), 40 of which were minor. The incidence of malformations in children born after ICSI was also compared with all births in Sweden using data from the Swedish Medical Birth Registry and the Registry of Congenital Malformations. For ICSI children, the odds ratio (OR) for having any major or minor malformation was 1.75 [95% confidence interval (CI) 1.19-2.58] after stratification for delivery hospital, year of birth and maternal age. If stratification for singletons/twins was also done, the OR was reduced to 1.19 (95% CI 0.79-1.81). The increased rate of congenital malformations is thus mainly a result of a high rate of multiple births. The only specific malformation which was found to occur in excess in children born after ICSI was hypospadias (relative risk 3.0, exact 95% CI 1. 09-6.50) which may be related to paternal subfertility.

Chromosome Aberrations↗
PubMed2000

Carbon dioxide and nisin act synergistically on Listeria monocytogenes.

This paper examines the synergistic action of carbon dioxide and nisin on Listeria monocytogenes Scott A wild-type and nisin-resistant (Nis(r)) cells grown in broth at 4 degrees C. Carbon dioxide extended the lag phase and decreased the specific growth rate of both strains, but to a greater degree in the Nis(r) cells. Wild-type cells grown in 100% CO(2) were two to five times longer than cells grown in air. Nisin (2.5 microg/ml) did not decrease the viability of Nis(r) cells but for wild-type cells caused an immediate 2-log reduction of viability when they were grown in air and a 4-log reduction when they were grown in 100% CO(2). There was a quantifiable synergistic action between nisin and CO(2) in the wild-type strain. The MIC of nisin for the wild-type strain grown in the presence of 2.5 microg of nisin per ml increased from 3.1 to 12.5 microg/ml over 35 days, but this increase was markedly delayed for cultures in CO(2). This synergism between nisin and CO(2) was examined mechanistically by following the leakage of carboxyfluorescein (CF) from listerial liposomes. Carbon dioxide enhanced nisin-induced CF leakage, indicating that the synergistic action of CO(2) and nisin occurs at the cytoplasmic membrane. Liposomes made from cells grown in a CO(2) atmosphere were even more sensitive to nisin action. Liposomes made from cells grown at 4 degrees C were dramatically more nisin sensitive than were liposomes derived from cells grown at 30 degrees C. Cells grown in the presence of 100% CO(2) and those grown at 4 degrees C had a greater proportion of short-chain fatty acids. The synergistic action of nisin and CO(2) is consistent with a model where membrane fluidity plays a role in the efficiency of nisin action.

Anti-Bacterial Agents↗
PubMed2000

Association studies of candidate genes in bipolar disorders.

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Adult↗