PubMed Health⌕ Search

Biomedical subjects

M Lindgren

Publications and source records attributed to M Lindgren.

At least 37 records · Page 2Linked to original sources
PubMed2000

The arithmetic mean of ratio-normalized experiments overestimates the true E/C ratio.

Biological assays often suffer from large systematic variation between sets of experiments. This variation is sometimes countered by normalizing the results of an "exposed" (E) experiment to that of a simultaneously performed "control" (C). We demonstrate that the arithmetic mean of such ratios overestimates the "true" E/C ratio. Fortunately, the overestimation may be calculated from experimentally accessible information, and it is generally possible to correct for this factor using formulas presented in this paper. We have studied the impact of this effect on a set of studies in the bioelectromagnetics literature and find that, although most results are weakened by the correction, few are significantly altered. Some of the papers used for our literature study are controversial; we believe that the present study may strengthen the quoted results by removing doubts about the statistical treatment of E/C ratios. Both false positives and negatives are possible if the proper correction is not made to the arithmetic mean of a set of E/C data. Realistic examples of erroneous statistical conclusions demonstrate that this is a real concern for E/C data which are marginal in both magnitude (mean < 2) and variance (standard deviation > 0.5).

Animals↗
PubMed2000

Cell-penetrating peptides.

The established view in cellular biology dictates that the cellular internalization of hydrophilic macromolecules can only be achieved through the classical endocytosis pathway. However, in the past five years several peptides have been demonstrated to translocate across the plasma membrane of eukaryotic cells by a seemingly energy-independent pathway. These peptides have been used successfully for the intracellular delivery of macromolecules with molecular weights several times greater than their own. Cellular delivery using these cell-penetrating peptides offers several advantages over conventional techniques because it is efficient for a range of cell types, can be applied to cells en masse and has a potential therapeutic application.

Amino Acid Sequence↗
PubMed2000

Semantic processing without conscious identification: evidence from event-related potentials.

Three event-related potential (ERP) experiments examined whether semantic content can be accessed from visually presented words that cannot be consciously identified. Category labels were shown to participants, followed by masked, briefly exposed words that were either exemplars of the category or not exemplars. The task was to verify the category, by guessing if necessary, and to identify the word, naming it if possible. Exposure durations were selected to allow identification in approximately half the trials. For identified words, there was a marked difference in the ERP response between in-category and out-of-category words because of an N400 component. For unidentified words, there was a similar although smaller difference. Conscious identification was defined using a variety of approaches: verbal report, 6-alternative forced choice, and binary categorization (in the context of the regression method; A. G. Greenwald, M. R. Klinger, & E. S. Schuh, 1995). By any definition, ERPs for unidentified words showed evidence of semantic processing. In addition, there were differences in the neuronal populations recruited to process above-threshold versus below-threshold words, suggesting qualitative differences.

Adult↗
PubMed2000

Spectroscopic probing of the influence of calcium and the gla domain on the interaction between the first EGF domain in factor VIIa and tissue factor.

The binding of factor VIIa (FVIIa) to tissue factor (TF) initiates blood coagulation. The binary complex is dependent on Ca2+ binding to several sites in FVIIa and is maintained by multiple contacts distributed throughout the various domains. Although the contributions from various residues and domains, including the Ca2+ coordination, to the global binding energy have been characterized, their importance for specific local interactions is virtually unknown. To address this aspect, we have attached four spectroscopic probes to an engineered Cys residue replacing Phe140 in soluble TF (sTF). This allows the monitoring of local changes in hydrophobicity and rigidity upon complex formation at the interface between the first epidermal growth factor-like (EGF1) domain of FVIIa and sTF. The fluorescent labels used sense a more hydrophobic environment and the spin labels are dramatically immobilized when FVIIa binds sTF. The results obtained with a 4-carboxyglutamic acid (Gla)-domainless derivative of FVIIa indicate that the Gla domain has no or minimal influence on the interaction between EGF1 and sTF. However, there is a difference in local Ca2+ dependence between Gla-domainless and full-length FVIIa.

Amino Acid Substitution↗
PubMed2000

Event-related potential findings in healthy extremely pre-term (< week 29) children at age 10.

Ten healthy extremely pre-term (EPT) children, born before gestational week 29, were tested at age 10 using mismatch negativity (MMN) and a three-tone odd-ball task; the results were then compared to age-matched full-term controls. We found no difference in MMN. By contrast, EPT children had generally shorter N1 latencies and larger P2 amplitudes, possibly indicating a more stimulus-driven response mode. However, P300 parameters, indicative of controlled attention, were unaffected.

Brain Damage, Chronic↗
PubMed2000

Cognitive intervention in unemployed individuals with reading and writing disabilities.

Sixty native-born Swedish unemployed participants with reading and writing disabilities (R&WD) participated in a 20-week educational program aimed at improving reading and writing, verbal memory, self-confidence, and flexibility of perspectives. They were tested with a comprehensive battery (interviews, questionnaires, neuropsychological tests, and tests of academic achievement) before and after the intervention. Sixteen controls, matched for sex, age, education, and nonverbal IQ, participated in the pre- and posttest sessions but received only standard unemployment interventions. The educational program participants' performance in tests assessing spelling, decoding of letters, self-confidence, and flexibility improved significantly in comparison with the controls after the intervention. A significantly larger number of the participants had obtained work or started a regular education than expected. A substantial proportion of unemployed participants have R&WD and it appears that an intensive but fairly short educational program can improve their accessibility to the labor market and their motivation for study.

Aged↗
PubMed1999

EPR mapping of interactions between spin-labeled variants of human carbonic anhydrase II and GroEL: evidence for increased flexibility of the hydrophobic core by the interaction.

Human carbonic anhydrase II (HCA II) interacts weakly with GroEL at room temperature. To further investigate this interaction we used electron paramagnetic resonance (EPR) spectroscopy to study HCA II cysteine mutants spin-labeled at selected positions. From our results it is evident that protein-protein interactions can be specifically mapped by site-directed spin-labeling and EPR measurements. HCA II needs to be unfolded to about the same extent as a GuHCl-induced molten-globule intermediate of the enzyme to interact with GroEL. The interaction with GroEL includes interactions with outer parts of the HCA II molecule, such as peripheral beta-strands and the N-terminal domain, which have previously been shown to be rather unstable. As a result of the interaction, the rigid and compact hydrophobic core exhibits higher flexibility than in the molten globule, which is likely to facilitate rearrangements of misfolded structure during the folding process. The degree of binding to GroEL and accompanying inactivation of the enzyme depend on the stability of the HCA II variant, and nonspecific hydrophobic interactions appear to be most important in stabilizing the GroEL-substrate complex.

Amino Acid Substitution↗
PubMed1999

Electroencephalographic effects of intravenous nicotine--a dose-response study.

RATIONALE: It has often been demonstrated that both tobacco abstinence and nicotine have effects on the EEG power spectrum and components of the event-related potentials. In contrast, few attempts have been made to establish the dose-response relationship between nicotine and EEG parameters. OBJECTIVES: The aim of this study was to investigate the dose-response relationship for EEG and auditory oddball P300 parameters over a wide range of intravenously infused nicotine doses. METHOD: Fourteen regular smokers who had abstained from nicotine for at least 12 h were given intravenous infusions of 0, 3.5, 7, 14 and 28 micrograms/kg nicotine over 10 min in a single-blind randomised cross-over design. Parallel recordings of spontaneous EEG, auditory P300 and heart rate, as well as venous blood sampling were made before, during and after nicotine administration. RESULTS: Linear dose-related decreases of delta and theta power were found, along with increases in alpha2 power and alpha peak frequency. Alpha1, beta and P300 parameters were unaffected. CONCLUSION: Our results are consistent with nicotine-dependent changes in EEG measures indicative of arousal.

Cross-Over Studies↗
PubMed1999

Properties of spin and fluorescent labels at a receptor-ligand interface.

Site-directed labeling was used to obtain local information on the binding interface in a receptor-ligand complex. As a model we have chosen the specific association of the extracellular part of tissue factor (sTF) and factor VIIa (FVIIa), the primary initiator of the blood coagulation cascade. Different spectroscopic labels were covalently attached to an engineered cysteine in position 140 in sTF, a position normally occupied by a Phe residue previously characterized as an important contributor to the sTF:FVIIa interaction. Two spin labels, IPSL [N-(1-oxyl-2,2,5, 5-tetramethyl-3-pyrrolidinyl)iodoacetamide] and MTSSL [(1-oxyl-2,2,5, 5-tetramethylpyrroline-3-methyl)methanethiosulfonate], and two fluorescent labels, IAEDANS [5-((((2-iodoacetyl)amino) ethyl)amino)naphthalene-1-sulfonic acid] and BADAN [6-bromoacetyl-2-dimethylaminonaphthalene], were used. Spectral data from electron paramagnetic resonance (EPR) and fluorescence spectroscopy showed a substantial change in the local environment of all labels when the sTF:FVIIa complex was formed. However, the interaction was probed differently by each label and these differences in spectral appearance could be attributed to differences in label properties such as size, polarity, and/or flexibility. Accordingly, molecular modeling data suggest that the most favorable orientations are unique for each label. Furthermore, line-shape simulations of EPR spectra and calculations based on fluorescence depolarization measurements provided additional details of the local environment of the labels, thereby confirming a tight protein-protein interaction between FVIIa and sTF when the complex is formed. The tightness of this local interaction is similar to that seen in the interior of globular proteins.

Binding Sites↗
PubMed1999

Dyslexia among Swedish prison inmates in relation to neuropsychology and personality.

Several investigations have reported high frequencies of reading and writing disabilities in criminal populations. The aims of the present study were to assess the frequency of dyslexia among Swedish prison inmates and to relate dyslexia to other indices of neuropsychological functions. Sixty-three prison inmates with Swedish as their native language, age 19 to 57 years, were examined by interviews, tests of academic achievement, and neuropsychological assessment. Twenty-six (41%) were diagnosed as dyslexic. As expected, the dyslexic group performed more poorly on verbal tests as compared to the normal readers among the prison inmates, but they also performed more poorly on tests measuring nonverbal abilities. The dyslexic group had higher frequencies of paranoid and avoidant personality disorders compared to the nondyslexics. They also reported higher levels of anxiety and suspicion and a lower degree of socialization. Previous studies report low IQ to be associated with criminal propensity, supporting the interpretation that a double handicap (dyslexia and low IQ) increases the risk of entering a criminal career and remaining in it.

Adult↗
PubMed1998

The relationship between stress-coping and vasomotor symptoms in postmenopausal women.

OBJECTIVE: The objective was to assess whether menopausal women with vasomotor symptoms had a lower stress-coping than menopausal women without symptoms and if stress-coping changed when vasomotor symptoms had been effectively treated with estrogens. The objective was also to assess whether menopausal women, effectively treated for vasomotor symptoms, had a higher neuroticism score than women without such symptoms. METHODS: Two groups of physically and mentally healthy postmenopausal women were recruited from the outpatient clinic at the Department of Obstetrics and Gynaecology, University Hospital of Linköping, Sweden. Sixteen women with vasomotor symptoms (target group) were treated with oral 17 beta-estradiol, 2 mg/day during 3 months. A comparison group was formed comprising 17 women without vasomotor symptoms. The Kupperman Index was used to cover menopausal characteristics in all women at baseline as well as at the second visit after 3 months. Stress-coping was measured by means of the Stress Coping Inventory, which is an instrument developed to measure of the individual's appraisal of having adaptive resources for handling stressful situations. At the second visit all women were also asked to complete the Eysenck Personality Inventory. RESULTS: Women in the target group had a significantly lower stress-coping than women in the comparison group at baseline as well as after 3 months. Stress-coping did not change after estrogen therapy, although the vasomotor symptoms had virtually disappeared. Women in the target group successfully treated for vasomotor symptoms, had a significantly higher neuroticism score compared to the comparison group. CONCLUSIONS: Differences in behaviour patterns and personality are probably two reasons why some women report or seek advice due to vasomotor symptoms and some women do not. Stress-coping in women with moderate to severe vasomotor symptoms is unaffected by estrogens.

Adaptation, Psychological↗
PubMed1998

Purification of a galanin degrading 70 kDa metallo-peptidase from bovine spinal cord.

Galanin is a 29/30 amino acids long neuroendocrine peptide, acting as an inhibitory modulator in the spinal cord. Several studies show that galanin is involved in control of pain threshold and acts synergistically with morphine, hence, inhibition of galanin degradation may be a pharmaceutical target for treatment of pain. In this study we have designed an 11 amino acids long substrate based on the first 10 N-terminal amino acids of galanin (this part contains the major pharmacophores of galanin), with a N-terminal fluorescent marker, anthranilic acid, and a C-terminal internal fluorescence quencher, 3-nitrotyrosine, coupled to the epsilon-amino group of the linker Lys11. Using this substrate to detect galanin degradation, we have purified a membrane bound galanin inactivating metallo-peptidase from bovine spinal cord. This enzyme, cleaving galanin between Trp2 and Thr3, is a novel 70 kDa, Zn2+ dependent metallo-peptidase.

Animals↗
PubMed1998

Effects of nicotine in a bimodal attention task.

Fifteen male users of oral snuff participated in an experiment where we used an auditory-visual vigilance task to study nicotine effects on P300 and response parameters. Quantitative EEG was also studied. Fifteen male nonusers served as controls. We found some decrease of response times and a tendency towards improved signal detection. P300 parameters were not affected in this study. Quantitative EEG analysis indicated an expected increase of arousal, as the activity within the alpha band shifted towards higher frequencies.

Adult↗
PubMed1997

Solvent-induced toxic encephalopathy: electrophysiological data in relation to neuropsychological findings.

Male subjects with type 2A (n = 12) and 2B (n = 12) solvent-induced toxic encephalopathy and a reference group of healthy men (n = 12) without previous solvent exposure were studied using quantitative EEG and event-related potentials from an odd-ball and a dual-task paradigm. Subjects with toxic encephalopathy of types 2A and 2B showed markedly lower P300 amplitudes than did controls in both paradigms. In the relatively complex dual-task setting, subjects with 2A and 2B showed lower signal detection than did controls.

Brain Diseases↗
PubMed1997

VEGF and tPA co-expressed in malignant glioma.

Neovascularisation and migration of tumour cells are two features of highly malignant glioma. Vascular endothelial growth factor (VEGF) and tissue plasminogen activator (tPA) seem to be of importance in the process of malignancy. In the present study a topographical co-expression of tPA mRNA and VEGF mRNA (VEGF121 and VEGF165 isoforms) was demonstrated in the tumour edge of a rat malignant glioma, using in situ hybridisation. No signs of co-expression was seen in the normal brain tissue. In the normal brain the forms of VEGF mainly expressed were VEGF121, VEGF165, and VEGF189. Further studies are required to show whether VEGF and tPA are produced by the same tumour cells and to elucidate the role of this co-expression.

Animals↗
PubMed1996

Restitution of neurophysiological functions, performance, and subjective symptoms after moderate insulin-induced hypoglycaemia in non-diabetic men.

The restoration of cognitive function was studied in 10 healthy men aged 26 years (25.5 +/- 1.2 years; mean +/- SD) after insulin-induced hypoglycaemia (arterialized blood glucose 2.5 +/- 0.4 mmol l-1) for 62 +/- 8 min. Another group of six men participated in a single blind sham study for comparison. The hypoglycaemic event caused a significant increase (p = 0.006) in serum adrenaline levels. Ratings of adrenergically mediated symptoms increased during hypoglycaemia (p = 0.006), as did neuroglycopenic symptoms (p = 0.002), although neuroglycopenia ratings increased in both studies. During hypoglycaemia, P300 amplitudes in a relatively demanding visual search task decreased (p = 0.02), whereas easier tasks were unaffected. The amplitudes were restored after 40 min of normoglycaemia. Reaction time deteriorated after restoration of normoglycaemia, suggesting an effect of hypoglycaemia on learning. Thus, hypoglycaemia at a blood glucose level that is common among patients treated with insulin causes clear cognitive dysfunction, although restoration of the cognitive dysfunction to normal was fast.

Adult↗
PubMed1995

Mapping the folding intermediate of human carbonic anhydrase II. Probing substructure by chemical reactivity and spin and fluorescence labeling of engineered cysteine residues.

Several conformation-sensitive parameters have shown that human carbonic anhydrase II exists as a stable and compact equilibrium folding intermediate of molten globule type. In this study we have continued a previously initiated mapping of the intermediate structure. Cys residues were engineered, one at a time, into various regions of the protein structure, so as to obtain chemically reactive probes and handles for spectroscopic probes. These probes were used to specifically report on conformational changes accompanying the folding process. Thus, the accessibility of the introduced Cys residues to specific chemical labeling by radioactive iodoacetate was used to monitor the stability and compactness of the substructure surrounding each Cys residue. In addition, a spin-label (nitroxide radical) and a fluorescent probe (IAEDANS) were attached to the inserted SH-groups to give complementary information. The mobility of the spin-label was used to indicate local changes in structure, and the fluorophore was used to probe local changes in polarity at various stages of unfolding. Much of the predominant beta-structure, consisting of 10 beta-strands extending throughout the entire molecule, appears to be compact and largely intact in the intermediate. Thus, beta-strands 3-7, probed at positions 68, 97, 118, 123, 206, and 245, seem to have a native-like structure in the folding intermediate. In contrast, a more flexible structure is found around positions 56, 176, and 256 in the peripheral beta-strands 1, 2, and 9, showing that the stability of the secondary structure in the intermediate state is less in the outer parts of the protein. A hydrophobic region, containing beta-strands 3-5, seems to be remarkably stable and is not ruptured until strong denaturing conditions (5 M GuHCl) are applied. The stability of this hydrophobic beta-core appears to increase toward the center. This stable region is contained in the middle of a sequentially continuous antiparallel structure that spans beta-strands 2-6, suggesting that this part might represent a site where folding is initiated.

Carbonic Anhydrases↗