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Biomedical subjects

G Larsson

Publications and source records attributed to G Larsson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Kinetic properties and stereospecificity of the monomeric dUTPase from herpes simplex virus type 1.

Kinetic properties of the monomeric enzyme dUTPase from herpes simplex virus type 1 (HSV) were investigated and compared to those previously determined for homotrimeric dUTPases of bacterial and retroviral origins. The HSV and Escherichia coli dUTPases are equally potent as catalysts towards the native substrate dUTP with a kcat/K(M) of about 10(7) M(-1) s(-1) and a K(M) of 0.3 microM. However, the viral enzymes are less specific than the bacterial enzyme. The HSV and E. coli dUTPases show the same stereospecificity towards the racemic substrate analogue dUTPalphaS (2'-deoxyuridine 5'-(alpha-thio)triphosphate), suggesting that they have identical reaction mechanisms.

Catalysis↗
PubMed1998

The solution NMR structure of a blue-green algae hepatotoxin, microcystin-RR--a comparison with the structure of microcystin-LR.

The microcystin-RR structures are compared with the structures of microcystin-LR in solution as well as in the crystal structure of the complex with protein phosphatase. The gross structures of the two peptides are similar, but with a more accentuated and compact saddle structure for microcystin-RR. The structural differences affect the hydrogen-bond pattern in the peptides and the location of the side chain of N-methyldehydroalanine, both of which are important for the ability of the peptide to form a tight complex with protein phosphatase. These structural differences may contribute to the observed differences in toxicity of microcystin-RR and microcystin-LR.

Cyanobacteria↗
PubMed1998

Growth and energy metabolism in aerobic fed-batch cultures of Saccharomyces cerevisiae: simulation and model verification.

A kinetic model of overflow metabolism in Saccharomyces cerevisiae was used for simulation of aerobic fed-batch cultivations. An inhibitory effect of ethanol on the maximum respiration of the yeast was observed in the experiments and included in the model. The model predicts respiration, biomass, and ethanol formation and the subsequent ethanol consumption, and was experimentally validated in fed-batch cultivations. Oscillating sugar feed with resulting oscillating carbon dioxide production did not influence the maximum respiration rate, which indicates that the pyruvate dehydrogenase complex is not involved as a bottleneck causing aerobic ethanol formation.

Aerobiosis↗
PubMed1998

The refined structure of dUTPase from Escherichia coli.

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase, E.C. 3.6. 1.23) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate and is involved in nucleotide metabolism and DNA synthesis. A crystal of the recombinant E. coli enzyme, precipitated from polyethylene glycol mixtures in the presence of succinate at pH 4.2, was used to collect synchrotron diffraction data to 1.9 A resolution, in space group R3, a = b = 86.62, c = 62.23 A. Mercury and platinum derivative data were collected at wavelengths to optimize the anomalous contribution. The resulting 2.2 A MIRAS phases differed from the final set by 40 degrees on average and produced an excellent map which was easy to interpret. The model contains 132 water molecules and refined to an R value of 13.7%. 136 residues have clear electron density out of 152 expected from the gene sequence. The 16 C-terminal residues are presumably disordered in the crystal lattice. The monomer is a 'jelly-roll' type, containing mostly beta-sheet and only one short helix. The molecule is a tight trimer. A long C-terminal arm extends from one subunit and encompasses the next one within the trimer contributing to its beta-sheet. Conserved sequence motifs common among dUTPases, previously suggested to compose the active site and confirmed in a recent study of the dUDP complex, are located at subunit-subunit interfaces along the threefold axis, in parts of the beta-sheet and in loop regions. A similar molecular architecture has recently been found in two other trimeric dUTPases.

Amino Acid Sequence↗
PubMed1998

The complete triphosphate moiety of non-hydrolyzable substrate analogues is required for a conformational shift of the flexible C-terminus in E. coli dUTP pyrophosphatase.

The molecular mechanism of substrate analogue interaction with Escherichia coli dUTPase was investigated, using the non-hydrolyzable 2'-deoxyuridine 5'-(alpha,beta-imido)triphosphate (alpha,beta-imido-dUTP). Binding of this analogue induces a difference in the far UV circular dichroism (CD) spectrum arguing for a significant change in protein conformation. The spectral shift is strictly Mg2+-dependent, does not appear with dUDP instead of alpha,beta-imido-dUTP and is not elicited if the flexible C-terminal arm is deleted from the protein by limited tryptic digestion. Involvement of the C-terminal arm in alpha,beta-imido-dUTP binding is consistent with the finding that this analogue protects against tryptic hydrolysis at Arg-141. Near UV CD of ligand-enzyme complexes reveals a characteristic difference in the microenvironments of enzyme-bound dUDP and alpha,beta-imido-dUTP, a difference not observable in C-terminally truncated dUTPase. The results suggest that (i) closing of the active site during the catalytic cycle, through the movement of the C-terminal arm, requires the presence of the complete triphosphate moiety of the substrate in complex with Mg2+, and (ii) after catalytic cleavage the active site pops open to facilitate product release.

Binding Sites↗
PubMed1998

Sense of coherence, quality of life, and function among elderly hip fracture patients.

The aim was to study whether sense of coherence (SOC) had any predictive power in patients with hip fractures regarding length of stay in hospital, state of confusion and health, functional ability, quality of life, and municipal home-help service. A total of 73 patients admitted from their own homes participated (mean age 80.4 years). The patients were followed during a 4-month period. Acute confusional state was diagnosed using a Swedish version of the NEECHAM Confusion Scale. SOC and self-rated functional health status were assessed during the hospitalization period and one month after discharge; Quality of Life Index (QLI) and instrumental daily activities (SPE) were assessed four months after discharge. Focusing on the differences in outcome between persons with a stronger vs a weaker SOC, there were few significant differences in physical status between the subgroups. However, the persons with a weaker SOC stayed longer in the hospital and reported a significantly lower score on the NEECHAM Confusion Scale, as well as more discomfort and disability symptoms related to communication, mental, and emotional status. Furthermore, these persons had less favorable scores on the overall QLI and subscales respectively, and on all subscales measuring instrumental daily activities. The persons with a weaker SOC were significantly more dependent on assistance before admission to the hospital than those with a stronger SOC. The conclusions drawn from the study indicate that persons with a stronger SOC seem to cope in a better way with their situation after a hip fracture.

Activities of Daily Living↗
PubMed1998

Cancer patient and staff ratings of the importance of caring behaviors and their relations to patient anxiety and depression.

Patient and staff ratings of the importance of caring behaviours (Caring Assessment Instrument, CARE-Q) were studied and related to ratings of patient levels of anxiety and depression (Hospital Anxiety and Depression Scale) in 53 cancer patient-staff dyads. Both groups perceived anticipatory and comforting behaviours to be among the three most important. Patients considered staff explanation and facilitation as well as anticipation to be more important than did staff. Staff rated accessibility and comforting as more important than did patients. Patient and staff ratings of the importance of staff accessibility were negatively correlated. Thus, patient and staff 'did not agree strongly on the importance of several types of caring behaviours. Neither patient nor staff ratings of the importance of caring behaviours were associated with their ratings of the levels of anxiety or depression of specific patients. The results suggest that patient-staff communication requires specific knowledge and skills to make staff accurately judge what is important in making patients feel cared for.

Adult↗
PubMed1998

Quality of life in patients with endocrine tumors of the gastrointestinal tract: patient and staff perceptions.

Patient and staff perceptions regarding the importance of selected quality-of-life (QoL) aspects and patient ratings of their present QoL (EORTC QLQ-C30) were investigated. The study comprised 17 patients with endocrine tumors of the gastrointestinal tract and their staff, paired in dyads. Both patients and staff rate physical aspects of life (e.g., "wash yourself, dress, eat, etc.," "have a good health," "not have pain") as most important for experiencing a good QoL. Staff considered work as more important for experiencing a good QoL than did patients. Patients rated their QoL as relatively good and were more satisfied with certain QoL aspects than staff perceived them to be. Staff did not accurately judge a certain patient's satisfaction with various QoL aspects, which suggests that there is room for staff to improve their understanding of these aspects. There were no significant mean value differences between patient and staff ratings of patient anxiety and depression, but no significant correlations within dyads. This suggests that the communication between patients and staff could be improved in this respect.

Adult↗
PubMed1998

Refinement of the questionnaire 'quality of care from the patient's perspective' using structural equation modelling.

In 1994, the questionnaire 'Quality of Care from the Patient's Perspective' (QPP) was developed using a conventional factor analytical approach (Wilde et al. 1994). The items and conceptual framework of this questionnaire were derived from a theoretical model, which, in turn, was developed from qualitative patient interviews, using a grounded theory method of analysis (Wilde et al. 1993). The aims of this study were to develop further the dimensionality of the QPP using structural equation modelling combined with advances in factor analysis modelling, and to refine the instrument. This comparatively new methodology extracts more information out of questionnaire data and is considered to be superior to traditional scaling methods. The sample consisted of 611 somatic inpatients from four departments at a Swedish hospital. Data collected with the QPP were explored with the new tool tracing the dimensions postulated in the theoretical model underlying the QPP. A nested factor model was developed fulfilling statistical criteria for adjustment between model and data. The model consists of a general factor and 16 subordinate factors. Most of the original QPP scales were reproduced with the new statistical technique. However, some content changes were made which appear to bring the QPP scales closer to patients' meaning representations of the area. Some changes were also made to the response format, changes which appear to strengthen the psychometric properties of the instrument. The refined QPP will hopefully contribute to a more differentiated picture of quality of care when applied in the field. All scales, items, and response formats of the revised QPP are presented in an appendix.

Adult↗
PubMed1998

Cough-induced leak-point pressure--a valid measure for assessing treatment in women with stress incontinence.

BACKGROUND: Presently available urodynamic methods are of little use for assessing the severity of urinary stress incontinence or for evaluating of treatment, Cough-induced leak-point pressure may prove to be a more useful urodynamic method in these respects. A vaginal anti-incontinence device was used to validate this new urodynamic method. AIM: The primary aim was to determine the extent to which cough-induced leak-point pressure was affected by the vaginal device. Secondary aims were to study the short-term effects of the vaginal device on leakage and urinary flow, and to relate the change in cough-induced leak-point pressure to the change in leakage as expressed by a short-term pad test. METHODS: In a prospective study of 22 women with a history of stress incontinence, the effect of a new vaginal anti-incontinence device (Conveen Continence Guard) on cough-induced leak-point pressure, a short-term pad test and urinary flow was studied. RESULTS: Cough-induced leak-point pressure increased from 99.9 to 138.9 cm H2O, while leakage, measured by a short-term pad test, decreased from 22.7 to 3.3 g when using the device. Urinary flow was not significantly reduced by the device. CONCLUSIONS: Cough-induced leak-point pressure is a valid, quantitative, dynamic measure of urethral closure function which can be used to study the effects of treatment in patients with stress incontinence. The vaginal device is effective for treatment of stress incontinence in the short-term, without reducing urinary flow.

Adult↗
PubMed1997

dUTPase from the retrovirus equine infectious anemia virus: specificity, turnover and inhibition.

The kinetic properties of dUTPase from equine infectious anemia virus (EIAV) were investigated. K(M) (1.1 +/- 0.1 microM) and k(cat) (25 s(-1)) were found to be independent of pH in the neutral pH range. Above pH 8.0, K(M) increases slightly. Below pH 6.0, the enzyme is rapidly deactivated. Detergent was found to enhance activity, leaving K(M) and k(cat) unaffected. Compared to the Escherichia coli dUTPase, the EIAV enzyme is equally potent in hydrolyzing dUTP, but less specific. Inhibition of the viral enzyme by the nucleotides dTTP, dUMP and a synthetic analogue, 2'-deoxyuridine 5'-(alpha,beta-imido)triphosphate, is stronger by one order of magnitude.

Animals↗
PubMed1997

A longitudinal study of birth control and pregnancy outcome among women in a Swedish population.

The prevalence of contraception and pregnancy outcome in the same women, at 19, 24, and 29 years of age, was assessed in a longitudinal cohort study using a postal questionnaire technique. A one-in-four random sample of all women born in 1962 and resident in the city of Göteborg in 1981, was obtained from the population register (n = 656). Respondents from 1981 were re-assessed in 1986 and 1991. Four hundred thirty women (66%) answered the questionnaire on all three occasions and are included in the analysis. Contraceptive usage was as follows (at 19, 24, and 29 years of age, respectively): oral contraception (OC) 47%/51%/22%; intrauterine device 3%/11%/19%; barrier methods 12%/12%/20%; depot gestagen 0/0.2%/0.4%; no contraception 39%/26%/25%. OCs had been taken at some time by 93%. Reasons give for cessation of OC were: contraception not required 10%/21%/20%; fear of OC 28%/32%/35%; menstrual disorder 17%/13%/14%; weight increase 20%/16%/15%; mental side effects 14%/ 21%/20%; desire to become pregnant 7%/33%/52%. Pregnancy outcome was as follows: Ever pregnant 17%/42%/ 71%; children 5% had 1-2 children/27% had 1-3 children/ 59% had 1-5 children; 12%/25%/30% > or = 1 legal abortion; 3%/8%/15% > or = 1 miscarriage; and > or = 1 ectopic pregnancy 0.2%/1.2%/2.1%. On all three survey occasions, more than 97% of the legal abortions were performed < or = 12 weeks gestation. The complication rate following legal abortion was 7%. The proportion of live births to the total number of pregnancies was 25%, 45%, and 61%. The relationship between method of contraception, history of pregnancy, legal abortion, and smoking habits was analyzed in detail. Despite the availability of effective contraception, the ratio of legal abortions to live births was high. Fear of side effects was the commonest reason for discontinuing OC.

Adult↗
PubMed1997

Tolterodine--a new bladder selective muscarinic receptor antagonist: preclinical pharmacological and clinical data.

Tolterodine is a new, potent and competitive muscarinic receptor antagonist in clinical development for the treatment of urge incontinence and other symptoms of unstable bladder. Tolterodine has a high affinity and specificity for muscarinic receptors in vitro and it exhibits a selectivity for the urinary bladder over salivary glands in vivo. A major active metabolite, (PNU-200577) the 5-hydroxymethyl derivative of tolterodine, has a similar pharmacological profile. Based on pharmacological and pharmacokinetic data, it has been concluded that this metabolite contributes significantly to the therapeutic effect of tolterodine. The bladder selectivity demonstrated by tolterodine and PNU-200577 in vivo cannot be attributed to selectivity for a single muscarinic receptor subtype. Moreover, this favourable tissue-selectivity seems to occur also in humans. Tolterodine is well tolerated and it exerts a marked effect on bladder function in healthy volunteers. Phase II data indicate that tolterodine is an efficacious and safe treatment for patients with idiopathic detrusor instability or detrusor hyperreflexia. An optimal efficacy/side-effect profile is obtained with tolterodine, at a dosage of 1 or 2 mg twice daily, which seems to have less propensity to cause dry mouth than the currently available antimuscarinic drugs.

Animals↗
PubMed1997

Expression, purification and characterization of the homeodomain of rat ISL-1 protein.

Isl-1 is a member of a family of Homeodomains containing proteins that possess an N-terminal pair of zinc binding LIM domains. The Isl-1 gene in rat codes for a protein that binds to the insulin gene enhancer and is also involved in regulation of amylin and proglucagon genes. A DNA sequence coding for 66 amino acid residues containing the C-terminal homeodomain fragment of Isl-1 was expressed as a soluble protein in Escherichia coli. Here, we describe a procedure which allows the rapid native purification of recombinant homeodomain protein fused to an N-terminal tag of six histidines. The purified homeodomain showed DNA-binding activity to its cognate DNA sequence. An enhanced binding activity is observed in the presence of a reducing agent in electrophoretic mobility shift assays. The DNA binding was further characterized by circular dichroism spectroscopy. Addition of DNA to the homeodomain did not change the overall secondary structure content, but the thermal and chemical denaturing profiles were altered. A stabilization of the secondary structure was observed upon DNA binding. The free energy of unfolding at 23 degrees C was 7 kJ mol(-1) in absence of DNA and 29 kJ mol(-1) in the presence of DNA.

Animals↗