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Biomedical subjects

L R Olsen

Publications and source records attributed to L R Olsen.

15 recordsLinked to original sources
PubMed2006

Mental distress in the Danish general population.

OBJECTIVE: To present data on mental distress in the Danish general population using recently validated Hopkins symptom checklist (SCL) subscales and compare with data from other countries. To evaluate associations between mental distress and biopsychosocial factors. METHOD: Questionnaires were sent to a gender- and age-stratified random sample comprising 2040 Danes. Mean SCL subscale scores were calculated. Cases were defined in accordance with the traditional criteria, and Danish and US raw score cut-offs were compared. A multiple regression model was developed to describe associations between biopsychosocial factors and SCL scores. RESULTS: The response rate was 58%. The Danish mean scores were significantly higher than reported for a US non-patient sample, and Danish raw score cut-offs for caseness were higher. The Danish scores were closer to Nordic mean scores. Age, gender, social status, somatic disorder and traumatic life events in the past year in work life as well as personal life were significantly associated with the level of mental distress. SCL scores were compared with scores on the Major Depression Inventory. CONCLUSION: The SCL mean scores of the Danish general population were relatively high, but similar to data from the Nordic countries. Consequently, interpretation of the Danish SCL requires Danish norms and Danish cut-off scores for caseness.

Adult↗
PubMed2005

Modafinil augmentation in depressed patients with partial response to antidepressants: a pilot study on self-reported symptoms covered by the Major Depression Inventory (MDI) and the Symptom Checklist (SCL-92).

Treatment-resistant depression, i.e. partial or non response to antidepressants in spite of various treatment attempts with optimized doses and combinations, is rather common. With residual symptoms such as tiredness, anhedonia and concentration disturbances, the treatment strategy has often been to use monoamino-oxidase inhibitors (MAOIs). Their use, however, is limited due to interaction problems. Modafinil is recently developed wake-promoting drug with only minor side-effects. Pilot studies indicate that it appears to have an augmentation effect in treatment-resistant depression. This open-label study performed in the private psychiatric practice setting is the first to make a comprehensive evaluation of the target patient profile based on patient-reported symptoms. Modafinil in doses of 100-400 mg was administered as augmentation to ongoing antidepressant therapy in patients with partial response and suffering from hypersomnia. The total number of patients was 21 and 43% of these were responders (i.e. had a score reduction of >50% on the Major Depression Inventory (MDI) as well as remitters, i.e. the remission rate was 43%. At endpoint, the responders had psychological distress scores on the Symptom Checklist (SCL-92) on the level of the general Danish population. Baseline characteristics for responders were lower scores on depression, hostility, anxiety, somatization, obsession and psychoticism. Modafinil thus appears to be an appropriate augmentation to antidepressant treatment, leading to a remission rate of 43%. However, the results from this open-label study need ot be confirmed in a placebo-controlled trial.

Antidepressive Agents↗
PubMed2004

Prevalence of major depression and stress indicators in the Danish general population.

OBJECTIVE: To estimate the prevalence rate of major depression in the Danish general population by using the Major Depression Inventory (MDI), a validated self-rating scale fulfilling the symptomatic criteria in DSM-IV and ICD-10 for a depressive episode. METHOD: A booklet containing the MDI and a number of questions on psychosocial factors was sent to 2040 randomly selected Danish citizens. The sample was age- and gender-stratified. Mean MDI scores were calculated. Logistic regression analysis was used in order to produce a model for the influence of psychosocial factors. RESULTS: The response rate was 60%. The point prevalence of major depression was 3.3%. Among the tested predictors of depression were sociodemographic variables, alcohol and smoking habit, bodily pain, somatic diseases and traumatic life events. For a traumatic event in personal life over the past year odds ratio was 6.4 [2.7; 15.5], for overconsumption of alcohol odds ratio was 3.2 [1.5; 6.8]. While the gender difference in major depression rate was not found statistically significant, a significant (P < 0.05) gender difference of male to female of 1 : 2 was found when including minor depression. Of people identified as having a major depression only 13% were currently treated by a medical doctor. CONCLUSION: Major depression has a high prevalence in the Danish general population and seems to be undertreated. The gender difference was only found statistically significant when including minor depression, indicating that the female predominance is less pronounced in the more severe depression states.

Adult↗
PubMed2004

The SCL-90 and SCL-90R versions validated by item response models in a Danish community sample.

OBJECTIVE: To evaluate the internal validity of the subscales of the combined SCL-90 and SCL-90R, the SCL-92, by item response analyses as compared with several previously reported factor analyses of this questionnaire in the literature. METHOD: The SCL-92 questionnaire was mailed to an age- and gender-stratified random sample of Danish citizens. The sample comprised 2040 individuals. The internal structure of the nine factors of the SCL-92 questionnaire was evaluated by Mokken-Loevinger analysis and Rasch analysis. RESULTS: In total, 1153 persons or 58% returned the questionnaire fully completed. Mokken analysis found all scales apart from the psychoticism scale acceptable. The Rasch analysis found most of the subscales to be robust. Minor problems were seen for the scales of phobic anxiety, obsession-compulsion and depression. Analysis of the Global Severity Index showed that the Rasch model was rejected for the full 92-item scale, but not for a scale consisting of the 63 items from the non-psychotic subscales. Spearman correlations among the subscales were all positive (range 0.34-0.79) and so were correlations between each of the subscales and the Global Severity Index (range 0.55-0.91). CONCLUSION: In this sample from the Danish general population the non-psychotic subscales, i.e. the subscales covering psychological distress were observed to function well. In a general population sample, the 63 non-psychotic items primarily appear to reflect one broad dimension of distress.

Humans↗
PubMed2003

The internal and external validity of the Major Depression Inventory in measuring severity of depressive states.

BACKGROUND: We have developed the Major Depression Inventory (MDI), consisting of 10 items, covering the DSM-IV as well as the ICD-10 symptoms of depressive illness. We aimed to evaluate this as a scale measuring severity of depressive states with reference to both internal and external validity. METHOD: Patients representing the score range from no depression to marked depression on the Hamilton Depression Scale (HAM-D) completed the MDI. Both classical and modern psychometric methods were applied for the evaluation of validity, including the Rasch analysis. RESULTS: In total, 91 patients were included. The results showed that the MDI had an adequate internal validity in being a unidimensional scale (the total score an appropriate or sufficient statistic). The external validity of the MDI was also confirmed as the total score of the MDI correlated significantly with the HAM-D (Pearson's coefficient 0.86, P < or = 0.01, Spearman 0.80, P < or = 0.01). CONCLUSION: When used in a sample of patients with different states of depression the MDI has an adequate internal and external validity.

Adult↗
PubMed2001

Structure of the Escherichia coli GlmU pyrophosphorylase and acetyltransferase active sites.

N-Acetylglucosamine-1-PO(4) uridyltransferase (GlmU) is a trimeric bifunctional enzyme that catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-GlcNAc. The X-ray crystal structure of Escherichia coli GlmU in complex with UDP-GlcNAc and CoA has been determined to 2.1 A resolution and reveals a two-domain architecture that is responsible for these two reactions. The C-terminal domain is responsible for the CoA-dependent acetylation of Glc-1-PO(4) to GlcNAc-1-PO(4) and displays the longest left-handed parallel beta-helix observed to date. The acetyltransferase active site defined by the binding site for CoA makes use of residues from all three subunits and is positioned beneath an open cavity large enough to accommodate the Glc-1-PO(4) acetyl acceptor. The N-terminal domain catalyzes uridyl transfer from UTP to GlcNAc-1-PO(4) to form the final products UDP-GlcNAc and pyrophosphate. This domain is composed of a central seven-stranded beta-sheet surrounded by six alpha-helices in a Rossmann fold-like topology. A Co(2+) ion binds to just one of the two independent pyrophosphorylase active sites present in the crystals studied here, each of which nonetheless binds UDP-GlcNAc. The conformational changes of the enzyme and sugar nucleotide that accompany metal binding may provide a window into the structural dynamics that accompany catalysis.

Acetyltransferases↗
PubMed2001

The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity.

BACKGROUND: A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major (moderate to severe) depression by the patients' self-reported symptoms. This Major Depression Inventory (MDI) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items. METHODS: The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as index of validity for the clinician's DSM-IV and ICD-10 diagnosis of major (moderate to severe) depression. The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms. RESULTS: The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92. The specificity varied between 0.82 and 0.86. When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic. LIMITATIONS: The sample of subjects was limited. Patients with psychotic depression were not included. CONCLUSION: The MDI was found to have a sensitivity and specificity which is acceptable. The questionnaire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score.

Adult↗
PubMed2001

Purification, crystallization and preliminary X-ray data for Escherichia coli GlmU: a bifunctional acetyltransferase/uridyltransferase.

Crystals of Escherichia coli GlmU, a bifunctional enzyme catalyzing the acetylation of glucosamine-1-phosphate and uridylylation of N-acetylglucosamine-1-phosphate to produce UDP-GlcNAc, have been prepared in complex with coenzyme A and UDP-GlcNAc. These crystals belong to space group R32, with unit-cell parameters a = 104.5, c = 648.2 A, diffract to at least 2.1 A resolution and may contain two subunits of the trimeric enzyme per asymmetric unit.

Crystallization↗
PubMed2000

[Logbook. A possible method].

The European board of psychiatry recommends the use of a logbook and checklist. There has been discussion about the extent of registration--and the resources involved. We present a simple method of registering supervision. Trainees make a daily report of the amount of supervision received. The trial period was divided into two sections: March, April and May 1997; (training intensive) and June, July and August 1997; (holiday season). The trainees responded well to the logbook, the answering rate was 94.2% in the first period, 60.9% in the holiday season. Calculations based on the first period show that trainees receive supervision during 9.8% of their working hours (range 4.8-16.0). Twenty-nine percent of supervision is of the direct variety, where both trainer and trainee are present. This variety suffers during holiday season. This type of logbook provides an opportunity to be directed in training activities, with a minimum of resources involved.

Denmark↗
PubMed1998

Insertions into the beta3-beta4 hairpin loop of HIV-1 reverse transcriptase reveal a role for fingers subdomain in processive polymerization.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) displays a characteristic poor processivity during DNA polymerization. Structural elements of RT that determine processivity are poorly understood. The three-dimensional structure of HIV-1 RT, which assumes a hand-like structure, shows that the fingers, palm, and thumb subdomains form the template-binding cleft and may be involved in determining the degree of processivity. To assess the influence of fingers subdomain of HIV-1 RT in polymerase processivity, two insertions were engineered in the beta3-beta4 hairpin of HIV-1NL4-3 RT. The recombinant mutant RTs, named FE20 and FE103, displayed wild type or near wild type levels of RNA-dependent DNA polymerase activity on all templates tested and wild type or near wild type-like sensitivities to dideoxy-NTPs. When polymerase activities were measured under conditions that allow a single cycle of DNA polymerization, both of the mutants displayed 25-30% greater processivity than wild type enzyme. Homology modeling the three-dimensional structures of wild type HIV-1NL4-3 RT and its finger insertion mutants revealed that the extended loop between the beta3 and beta4 strands protrudes into the cleft, reducing the distance between the fingers and thumb subdomains to approximately 12 A. Analysis of the models for the mutants suggests an extensive interaction between the protein and template-primer, which may reduce the degree of superstructure in the template-primer. Our data suggest that the beta3-beta4 hairpin of fingers subdomain is an important determinant of processive polymerization by HIV-1 RT.

Amino Acid Sequence↗
PubMed1997

X-ray crystallographic studies of unique cross-linked lattices between four isomeric biantennary oligosaccharides and soybean agglutinin.

Soybean agglutinin (SBA) (Glycine max) is a tetrameric GalNAc/Gal-specific lectin which forms unique cross-linked complexes with a series of naturally occurring and synthetic multiantennary carbohydrates with terminal GalNAc or Gal residues [Gupta et al. (1994) Biochemistry 33, 7495-7504]. We recently reported the X-ray crystal structure of SBA cross-linked with a biantennary analog of the blood group I carbohydrate antigen [Dessen et al. (1995) Biochemistry 34, 4933-4942]. In order to determine the molecular basis of different carbohydrate-lectin cross-linked lattices, a comparison has been made of the X-ray crystallographic structures of SBA cross-linked with four isomeric analogs of the biantennary blood group I carbohydrate antigen. The four pentasaccharides possess the common structure of (beta-LacNAc)2Gal-beta-R, where R is -O(CH2)5COOCH3. The beta-LacNAc moieties in the four carbohydrates are linked to the 2,3-, 2,4-, 3,6-, and 2,6-positions of the core Gal residue(s), respectively. The structures of all four complexes have been refined to approximately 2.4-2.8 A. Noncovalent lattice formation in all four complexes is promoted uniquely by the bridging action of the two arms of each bivalent carbohydrate. Association between SBA tetramers involves binding of the terminal Gal residues of the pentasaccharides at identical sites in each monomer, with the sugar(s) cross-linking to a symmetry-related neighbor molecule. While the 2,4-, 3,6-, and 2,6-pentasaccharide complexes possess a common P6422 space group, their unit cell dimensions differ. The 2, 3-pentasaccharide cross-linked complex, on the other hand, possesses the space group I4122. Thus, all four complexes are crystallographically distinct. The four cross-linking carbohydrates are in similar conformations, possessing a pseudo-2-fold axis of symmetry which lies on a crystallographic 2-fold axis of symmetry in each lattice. In the case of the 3,6- and 2,6-pentasaccharides, the symmetry of their cross-linked lattices requires different rotamer orientations about their beta(1,6) glycosidic bonds. The results demonstrate that crystal packing interactions are the molecular basis for the formation of distinct cross-linked lattices between SBA and four isomeric pentasaccharides. The present findings are discussed in terms of lectins forming unique cross-linked complexes with glycoconjugate receptors in biological systems.

Carbohydrate Conformation↗
PubMed1996

The nucleoside analog-resistant E89G mutant of human immunodeficiency virus type 1 reverse transcriptase displays a broader cross-resistance that extends to nonnucleoside inhibitors.

The alteration of a glutamic acid (E) to a glycine (G) amino acid residue at position 89 (E89G alteration) in the human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to several nucleoside analog inhibitors. Because the nonnucleoside inhibitor-binding pocket is adjacent to the deoxynucleoside triphosphate substrate-binding site, the impact of the E89G reverse transcriptase has decreased susceptibility to TIBO R82150, nevirapine, and to a lesser extent, delavirdine. Human immunodeficiency viruses bearing the same mutation displayed decreased susceptibility to inhibition by these compounds in a cell culture virus replication assay.

Anti-HIV Agents↗
PubMed1995

Circular dichroism and Fourier transform infrared spectroscopic studies on the secondary structure of Saccharomyces cerevisiae and Escherichia coli phospho enolpyruvate carboxykinases.

The secondary structure of Saccharomyces cerevisiae and Escherichia coli phospho enolpyruvate (PEP) carboxykinases was quantitatively examined using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies. From CD analyses, values of 24% alpha-helix and 38% beta-sheet were obtained for the E. coli enzyme, while the corresponding values for the S. cerevisiae PEP carboxykinase were 20% and 36%. Analysis of the amide I' infrared band indicated 20% alpha-helix and 36% beta-sheet for the S. cerevisiae enzyme, while for the E. coli protein values of 40% beta-sheet and between 9 and 36% alpha-helix could be inferred. It is concluded that the bacterial enzyme has more secondary structure elements than the yeast protein. No alteration of the CD or FTIR spectra was detected upon substrate or metal ion binding to any enzyme.

Circular Dichroism↗
PubMed1993

The structure of the MnIIADP-nitrate-lyxose complex at the active site of hexokinase.

The coordination scheme of Mn2+ in the hexokinase-MnIIADP-nitrate-lyxose complex has been determined by electron paramagnetic resonance (EPR) spectroscopy with 17O-enriched ligands. Nitrate binds to the active site of hexokinase when MnIIADP and a sugar substrate or analogue are present. The binding of nitrate enhances inhibition by glucose when ADP is present and narrows the EPR signals of the enzyme-bound MnIIADP complex in the presence of sugar substrates or analogues. Experiments using regiospecifically 17O-enriched ADP, 17O-enriched nitrate, and 17O-enriched water establish the coordination scheme of Mn2+. The EPR experiments show that ADP is a beta-monodentate ligand and that nitrate binds directly to Mn2+. Four water molecules complete the coordination sphere of the enzyme-bound Mn2+. The dissociation constant (Kd approximately 8 mM) of nitrate for the complex with enzyme, MnIIADP, and lyxose was obtained from titration experiments. These results suggest that nitrate-stabilized, dead-end complexes of hexokinase may be useful in stabilizing the closed conformation of this "hinge-bending" enzyme for crystallographic experiments.

Adenosine Diphosphate↗