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L K Hansen

Publications and source records attributed to L K Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1999

On clustering fMRI time series.

Analysis of fMRI time series is often performed by extracting one or more parameters for the individual voxels. Methods based, e.g., on various statistical tests are then used to yield parameters corresponding to probability of activation or activation strength. However, these methods do not indicate whether sets of voxels are activated in a similar way or in different ways. Typically, delays between two activated signals are not identified. In this article, we use clustering methods to detect similarities in activation between voxels. We employ a novel metric that measures the similarity between the activation stimulus and the fMRI signal. We present two different clustering algorithms and use them to identify regions of similar activations in an fMRI experiment involving a visual stimulus.

Algorithms↗
PubMed1999

Generalizable patterns in neuroimaging: how many principal components?

Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.

Algorithms↗
PubMed1999

Plurality and resemblance in fMRI data analysis.

We apply nine analytic methods employed currently in imaging neuroscience to simulated and actual BOLD fMRI signals and compare their performances under each signal type. Starting with baseline time series generated by a resting subject during a null hypothesis study, we compare method performance with embedded focal activity in these series of three different types whose magnitudes and time courses are simple, convolved with spatially varying hemodynamic responses, and highly spatially interactive. We then apply these same nine methods to BOLD fMRI time series from contralateral primary motor cortex and ipsilateral cerebellum collected during a sequential finger opposition study. Paired comparisons of results across methods include a voxel-specific concordance correlation coefficient for reproducibility and a resemblance measure that accommodates spatial autocorrelation of differences in activity surfaces. Receiver-operating characteristic curves show considerable model differences in ranges less than 10% significance level (false positives) and greater than 80% power (true positives). Concordance and resemblance measures reveal significant differences between activity surfaces in both data sets. These measures can assist researchers by identifying groups of models producing similar and dissimilar results, and thereby help to validate, consolidate, and simplify reports of statistical findings. A pluralistic strategy for fMRI data analysis can uncover invariant and highly interactive relationships between local activity foci and serve as a basis for further discovery of organizational principles of the brain. Results also suggest that a pluralistic empirical strategy coupled formally with substantive prior knowledge can help to uncover new brain-behavior relationships that may remain hidden if only a single method is employed.

Brain↗
PubMed1999

Enhancing the multivariate signal of [15O] water PET studies with a new nonlinear neuroanatomical registration algorithm.

This paper addresses the problem of neuro-anatomical registration across individuals for functional [15O] water PET activation studies. A new algorithm for three-dimensional (3-D) nonlinear structural registration (warping) of MR scans is presented. The method performs a hierarchically scaled search for a displacement field, maximizing one of several voxel similarity measures derived from the two-dimensional (2-D) histogram of matched image intensities, subject to a regularizer that ensures smoothness of the displacement field. The effect of the nonlinear structural registration is studied when it is computed on anatomical MR scans and applied to coregistered [15O] water PET scans from the same subjects: in this experiment, a study of visually guided saccadic eye movements. The performance of the nonlinear warp is evaluated using multivariate functional signal and noise measures. These measures prove to be useful for comparing different intersubject registration approaches, e.g., affine versus nonlinear. A comparison of 12-parameter affine registration versus non-linear registration demonstrates that the proposed nonlinear method increases the number of voxels retained in the cross-subject mask. We demonstrate that improved structural registration may result in an improved multivariate functional signal-to-noise ratio (SNR). Furthermore, registration of PET scans using the 12-parameter affine transformations that align the coregistered MR images does not improve registration, compared to 12-parameter affine alignment of the PET images directly.

Algorithms↗
PubMed1999

Regulation of the hepatocyte cell cycle by type I collagen matrix: role of cyclin D1.

Rat hepatocytes adherent to a rigid film of type I collagen will spread and enter S phase, while those attached to collagen gel or a dried collagen substrate remain round and quiescent. The current studies were initiated to determine the mechanism by which these different substrates differentially influence cell cycle progression. Cyclin D1 mRNA and protein expression and associated kinase activity was low on dried collagen relative to collagen film. In contrast, cyclin E and cdk2 protein levels were similar on the two substrates. Although cyclin E and cdk2 were present, cells on dried collagen lacked cdk2 kinase activity. p27 protein levels did not differ between dried collagen and film, but more p27 was associated with cdk2 in cells on dried collagen than those on collagen film. Cyclin D1 expression on collagen film was inhibited by cytochalasin D and exoenzyme C3, suggesting a role for the GTP-binding protein, Rho, in regulating cyclin D1 expression. Cyclin D1 over-expression induced hepatocytes into S phase in the absence of cell shape change on dried collagen or collagen gel. These results demonstrate a novel, substrate-dependent mechanism for cyclin D1 expression in hepatocytes, and also demonstrate that cyclin D1 over-expression allows shape-independent S phase entry.

ADP Ribose Transferases↗
PubMed1999

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus.

OBJECTIVE: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and morphological abnormalities by ultrasonography in young diabetics. SUBJECTS AND METHODS: Among young IDDM patients less than 18 years old and living in the county of Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children matched for sex and age. Routine thyroid function parameters (thyroxine (T4), tri-iodothyronine (T3), T3 resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography. RESULTS: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of subclinical hypothyroidism were found. There were no significant differences in thyroid function variables or thyroid volume between diabetics and controls. Thyroid volume correlated significantly with age and weight in both groups. Among diabetics, 17 had thyroid autoantibodies (13 with TPOab, 14 with Tgab and 10 with both) compared with 2 children in the control group (P<0.001). Forty-four with IDDM as opposed to 11 of the controls (P<0.001) had morphological abnormalities at ultrasonography. Most of them had various degrees of hypoechogenicity thought to be a marker of thyroid autoimmunity. Among the 17 diabetics with autoantibodies, 10 had morphological abnormalities at ultrasonography. CONCLUSIONS: A high proportion of young IDDM patients without any clinical signs of thyroid disease have markers of thyroid autoimmunity. Many have thyroid autoantibodies, but even more have abnormalities by thyroid ultrasonography.

Adolescent↗
PubMed1999

Chest roentgenogram in the evaluation of heart defects in asymptomatic infants and children with a cardiac murmur: reproducibility and accuracy.

OBJECTIVES: To evaluate the reproducibility and the accuracy of pediatric radiologists' assessments of chest radiographs with respect to the presence or absence of heart defects in children with an asymptomatic heart murmur. DESIGN: Ninety-eight children, ages 1 month to 15 years (median, 30.1 months), referred for evaluation of a heart murmur were consecutively included. They all had a standard chest radiograph and a color Doppler echocardiograph (CDE) performed. Six specialists in pediatric radiology evaluated the chest radiographs independently on two occasions 6 months apart. The radiologists were asked to classify each set of films into one of two categories: heart disease or no heart disease. The outcome of the CDE was considered the definite diagnosis. kappa statistics were used to analyze the reproducibility of the radiologic assessments. Sensitivity, specificity, and the predictive value of a positive and a negative test were used for evaluation of the accuracy of the radiologic assessments. RESULTS: Mean intra- and interobserver kappa values were all <0.6, and the majority were <0.4. Mean sensitivity was 0.3 (range: 0.17-0.52), mean predictive value of a positive test was 0.4, implying that 60% of the positive assessments were falsely positive. Mean specificity was 0.86 (range: 0.75-0.93) and the mean predictive value of a negative test was 0.80 implying that 20% of the negative assessments were falsely negative. CONCLUSION: We found a low reproducibility, as well as a low accuracy, of the radiologic assessments of the chest radiographs of children with an asymptomatic heart murmur with respect to the presence or absence of heart disease. A false-positive radiologic assessment of the chest radiograph with respect to heart defects causes unnecessary anxiety and further examinations, whereas a false-negative assessment might result in omission of relevant investigations and proper identification of the heart defect. We cannot recommend the use of chest radiographs in the initial evaluation of the asymptomatic child with a heart murmur. If a heart defect cannot be excluded by clinical examination a CDE must be performed.

Adolescent↗
PubMed1999

Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes.

Cyclin D1 is widely believed to regulate progression through G1 phase of the cell cycle, and previous studies have shown that this protein is induced during hepatocyte proliferation in culture and in vivo. In this study, the role of cyclin D1 in the cell cycle of primary rat hepatocytes was further examined. Following epidermal growth factor stimulation, cyclin D1 was upregulated at time points corresponding to the mitogen restriction point, and this was associated with enhanced cyclin D1-associated kinase activity. To test whether cyclin D1 expression was sufficient to promote mitogen-independent progression through the G1-S transition, we constructed a replication-defective adenovirus that overexpressed human cyclin D1. Transfection with the cyclin D1 vector but not a control vector resulted in hepatocyte DNA synthesis in the absence of growth factor that was similar to that seen in mitogen-treated cells. Furthermore, cyclin D1 transfection led to activation of downstream biochemical events, including cyclin A and proliferating cell nuclear antigen expression and cyclin E- and cyclin A-associated kinase activation. These results suggest that cyclin D1 expression is sufficient to promote progression of hepatocytes through the G1 restriction point.

Adenoviridae↗
PubMed1999

Induction of the metabolism of midazolam by rifampin in cultured porcine hepatocytes: preliminary evidence for CYP3A isoforms in pigs.

The induction of putative CYP3A isoforms in cultured porcine hepatocytes was evaluated by measurement of midazolam metabolism, a model substrate of the CYP3A family. The induction was also studied at the molecular level by quantitation of mRNA and protein levels, by Northern blotting and Western blotting, respectively. Pretreatment with rifampin (50 microM) resulted in a 5.5- to 9-fold higher rate of midazolam metabolism when compared with control cultures. No induction was observed when the cultures were pretreated with 50 microM dexamethasone. A 12-fold increase in the CYP3A mRNA signal (approximately 2.4 kB) was observed in induced cultures over control cultures. Microsomal proteins were separated by SDS-polyacrylamide gel electrophoresis and detected by immunoblotting with a polyclonal antibody raised against human CYP3A4. The immunoblots showed the presence of four bands in microsomes prepared from pig livers, with two bands (51.5 and 52 kD) that showed intense staining. Microsomes prepared from a pig pretreated with rifampin showed marked induction of these two bands. Immunoblotting of microsomes from rifampin-induced cultures also showed significantly greater intensity than in control cultures. Our results indicate that rifampin, but not dexamethasone, is an inducer of midazolam hydroxylase in pig hepatocytes. This induction may be regulated at the transcriptional level as detected by an increase in mRNA with a CYP3A oligonucleotide probe. Finally, there appears to be a multiplicity of the CYP3A isoforms in pig hepatocytes, similar to that observed in humans and rats.

Animals↗
PubMed1998

Quantitative analysis of ultrasound B-mode images of carotid atherosclerotic plaque: correlation with visual classification and histological examination.

This paper presents a quantitative comparison of three types of information available for 52 patients scheduled for carotid endarterectomy: subjective classification of the ultrasound images obtained during scanning before operation, first-and second-order statistical features extracted from regions of the plaque in still ultrasound images from three orthogonal scan planes and finally a histological analysis of the surgically removed plaque. The quantitative comparison was made with the linear model and with separation of the available data into training and test sets. The comparison of subjective classification with features from still ultrasound images revealed an overall agreement of 60% for classification of echogenicity and 70% for classification of structure. Comparison of the histologically determined relative volume of soft materials with features from the still images revealed a correlation coefficient of r = -0.42(p = 0.002). for mean echogenicity of the plaque region. The best performing feature was of second order and denoted Contrast (r = -0.5). Though significant, the latter correlation is probably not strong enough to be useful for clinical prediction of relative volume of soft materials for individual patients. Reasons for this is discussed in the paper, together with suggestions for improvements.

Arteriosclerosis↗
PubMed1997

Concentrations of blood and hair mercury and serum PCBs in an Ojibwa population that consumes Great Lakes region fish.

OBJECTIVE: This paper describes an exposure assessment of an American Indian population using blood and hair samples as indicators of mercury and polychlorinated biphenyl exposure from the consumption of fish taken from the Great Lakes region. METHODS: Questionnaires regarding fish consumption were completed by 89 Ojibwa tribal members. Mercury concentrations were determined in human hair and blood samples, and polychlorinated biphenyl concentrations were determined in serum. RESULTS: Fish were consumed at the highest rates in April, May, June, and July. Lake trout, whitefish, and walleye were the preferred fish consumed by 91.4% of the respondents. Concentrations of blood mercury were all below 55 micrograms/L (ppb), while concentrations of mercury in hair were all less than 3 mg/L (ppm). Hair mercury concentrations were correlated with the previous year's fish consumption (p = .05). Dental amalgams and blood mercury concentrations were also significantly correlated (p < .002). Serum polychlorinated biphenyl concentrations, determined as the sum of 89 congeners, were all below 9.6 ppb total polychlorinated biphenyls. Subject age and total serum polychlorinated biphenyls were correlated (p < .001). CONCLUSIONS: The concentrations of mercury and polychlorinated biphenyls in this Ojibwa population were relatively low, but several individuals were identified as having elevated concentrations and additional testing may be warranted. Since the accumulation of contaminants was related to fish consumption and age, a long-term monitoring program that assesses chronic exposure to fish diets would be beneficial.

Adolescent↗
PubMed1996

Repeated sequences from the Arabidopsis thaliana genome function as enhancers in transgenic tobacco.

Sixteen segments of Arabidopsis thaliana DNA that function as enhancers in transgenic tobacco plants were isolated using the pROA97 enhancer cloning vehicle and library transformation of Nicotiana tabacum. The sequences were compared for AT content, homology, repeated motifs, and expression pattern in transgenic N. tabacum. The sequences were average with respect to the AT content of A. thaliana DNA. They could be placed into seven homology groups. Five of the sequences are single-copy sequences. The remaining eleven sequences represent two homology groups. Homology Group I contains seven sequences with minor differences. Homology Group II contains four sequences with minor differences. Two repeated motifs were identified (5'-CCTCT-3' and 5'-AAGGAT-3'). Both repeated motifs are found in other plant enhancers, and in the promoter region of the cauliflower mosaic virus 35S gene. In the 35S gene TATA region, the motifs can form two alternative stem-loop structures. The TATATAA sequence is located in the loop region of both stem-loop structures.

Arabidopsis↗
PubMed1996

[Myxedema--an early model for hormone research].

Myxoedema, later known as hypothyroidism, was first described in England in 1873. During the following years it was thought that the disease was caused by a lesion in the nervous system. However, towards the end of the century it was established that the thyroid gland produced an essential substance later known as a hormone. An efficient treatment was introduced, consisting of different forms of tissue extracts. The thyroid gland and myxoedema became a model for the development of the concept of internal secretion. Norwegian physicians were well informed about the scientific advances and quickly accepted the new principles of treatment. This article describes the first Norwegian reference to the disease and its treatment.

Female↗
PubMed1995

[Pediatric evaluation of children with heart murmurs].

In order to analyse the non-specialized paediatrician's ability to evaluate children with a heart murmur and the consequences of this evaluation for the need of further investigations, we made a prospective and consecutive study concerning 100 children who were referred for initial evaluation of a heart murmur. Based on the clinical evaluation, the children were assigned to one of the three categories of "no heart disease" "heart disease" or "definite heart disease". Within two months each child underwent a complete colour Doppler echocardiographic study. Except for one child with an insignificant peripheral pulmonary artery stenosis, 53% of the children were correctly diagnosed as having no heart disease. We conclude that clinical evaluation without laboratory tests performed by paediatricians without any special training in cardiology could correctly acquit half of the children of heart disease, with no need for further investigation.

Age Factors↗
PubMed1995

Identification of a homologous heparin binding peptide sequence present in fibronectin and the 70 kDa family of heat-shock proteins.

This study was undertaken to characterize the potential heparin affinity of an amino-acid sequence within the 70 kDa heat-shock family of proteins (HSPs) that shares homology with a heparin-binding sequence present in the carboxy-terminus of fibronectin (FN), defined by the synthetic peptide, FN-C/H-II (KNNQKSEPLIGRKKT). To first define the heparin binding sequence within FN-C/H-II, solid phase binding assays were performed using overlapping, short (7 amino acids) synthetic peptides corresponding to the amino-acid sequence within FN-C/H-II. Only the sequence LIGRKKT bound [3H] heparin, and the LIGRKKT peptide blocked heparin binding to intact fibronectin by 47% (+/- 0.4, p < 0.001). A computer-generated homology search revealed that two members of the 70 kDa HSP family, HSP70 and HSC70, contain the sequences LIGRK and LIGRR, respectively. Examination of heparin binding using affinity chromatography indicated that while native HSC70 binds heparin, native HSP70 does not. Treatment of the heparin-unbound fraction with heat or urea led to enhanced HSP70 binding to heparin affinity columns. Soluble LIGRKKT peptide or anti-FN-C/H-II IgG also significantly inhibited heparin binding to HSC70 that had been purified by heparin affinity chromatography. Finally, Western blot analysis of HSC70 purified by heparin affinity chromatography demonstrated that polyclonal anti-FN-C/H-II IgG could recognize HSC70. These data demonstrate that LIGRK or LIGRR represent a a common heparin binding motif in fibronectin, HSP70, and HSC70, and are consistent with a proposed role for heparin or similar polyanionic structures in the function of the 70 kDa heat-shock proteins.

Amino Acid Sequence↗
PubMed1995

Refined crystal structure of lysozyme from the rainbow trout (Oncorhynchus mykiss).

Lysozymes (E.C. 3.2.1.17) are well characterized ubiquitous enzymes that have an antibacterial effect. The lysozymes from rainbow trout (RBTL) (Oncorhynchus mykiss) could be particularly interesting in aquaculture since they show higher activity than egg-white lysozyme and lysozymes from other fish species against a variety of pathogenic bacteria. Two lysozymes, I and II, differing only in a single amino acid, were purified from the kidney of rainbow trout and shown to belong to the c-type class of lysozymes. The type II form was shown to be much more potent against a variety of bacteria than the type I enzyme. We have grown crystals from a mixture containing about 80% type I and 20% type II lysozyme from rainbow trout, and solved the X-ray crystal structure. The crystals are trigonal with a = 76.68, c = 54.46 A and space group P3(1)21. The phase problem was solved by the molecular-replacement method, and the structure was refined to an R-factor of 17.4% using data to 1.8 A resolution. The crystal structure shows that the three-dimensional structure of rainbow trout lysozyme is very similar to the previously solved structures of other c-type lysozymes. The single polypeptide of 129 amino acids is folded into two domains separated by a deep cleft which contains the active site. Secondary-structure elements, four alpha-helices and a three-stranded beta-sheet, are located in the same sequential positions as in the hen, turkey and human enzymes. The beta-sheet is found to be common for structures of both c- and g-type lysozymes. We suggest that differences in antibiotic activity of the two forms of RBTL are probably due to small differences in the hydophobicity of a small surface region.

Journal Article↗