[Excellent results of mammography screening. Still balancing between cost-benefit analysis].
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Adult↗
Biomedical subjects
I Andersson
Publications and source records attributed to I Andersson.
Prevalence and control of foot-pad dermatitis in broilers in Sweden.
1. A cross-sectional observational study was carried out to investigate spatial, temporal and management aspects of foot-pad dermatitis in Swedish broilers. The efficacy of a control programme was evaluated. 2. Flock information on producer, breed, foodstuff manufacturer, region, abattoir, date of slaughter, age at slaughter, planned and actual stocking density was recorded. A total of 6988 flocks, representing approximately 110 million broilers was examined. A total of 175 broiler producers from 15 geographical regions is represented. 3. The total foot-pad score per flock ranged from 0 to 200, with a mean of 34.7 and a standard deviation of 40.9. 4. Simple linear regression analysis showed that the mean total score on a weekly basis decreased (P < 0.001) over time, mainly because of a decrease in the prevalence of severe foot-pad lesions. 5. There was an association (P < 0.05) between slaughterhouse, foodstuff supplier and geographic region respectively and the mean total foot pad score of the flocks slaughtered.
Abattoirs↗
Structure of a product complex of spinach ribulose-1,5-bisphosphate carboxylase/oxygenase.
The crystal structure of an activated complex of ribulose-1,5-bisphosphate carboxylase/oxygenase from spinach and its product 3-phosphoglycerate has been determined to 2.2 A resolution. The structure is of the open form with the active site accessible to the solvent as observed in the structures of the activated ligand-free enzyme and the complex of the activated enzyme with the substrate ribulose-1,5-bisphosphate. Two molecules of 3-phosphoglycerate are bound per active site. The phosphates of both molecules bind approximately at the same position as the phosphates of ribulose-1,5-bisphosphate or the six-carbon intermediate analogue 2-carboxyarabinitol-1,5-bisphosphate, but one product molecule is swung out from the active site with its carboxylate group pointing toward solution. The present structure points to direct participation of the active site side chain of lysine 175 in later stages of catalysis. This possibility is discussed in the light of mutagenesis studies.
Binding Sites↗
The structure of the complex between rubisco and its natural substrate ribulose 1,5-bisphosphate.
The three-dimensional structure of the complex of ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco; EC 4.1.1.39) from spinach with its natural substrate ribulose 1,5-bisphosphate (RuBP) has been determined both under activating and non-activating conditions by X-ray crystallography to a resolution of 2.1 A and 2.4 A, respectively. Under activating conditions, the use of calcium instead of magnesium as the activator metal ion enabled us to trap the substrate in a stable complex for crystallographic analysis. Comparison of the structure of the activated and the non-activated RuBP complexes shows a tighter binding for the substrate in the non-activated form of the enzyme, in line with previous solution studies. In the non-activated complex, the substrate triggers isolation of the active site by inducing movements of flexible loop regions of the catalytic subunits. In contrast, in the activated complex the active site remains partly open, probably awaiting the binding of the gaseous substrate. By inspection of the structures and by comparison with other complexes of the enzyme we were able to identify a network of hydrogen bonds that stabilise a closed active site structure during crucial steps in the reaction. The present structure underlines the central role of the carbamylated lysine 201 in both activation and catalysis, and completes available structural information for our proposal on the mechanism of the enzyme.
Calcium↗
Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA.
Monoclonal antibodies were raised against prostate-specific antigen (PSA) by immunization with purified free PSA, i.e. not in complex with any protease inhibitor (F-PSA) and PSA in complex with alpha1-anti-chymotrypsin (PSA-ACT). Epitope mapping of PSA using the established monoclonal antibody revealed a complex pattern of independent and partly overlapping antigenic domains in the PSA molecule. Four independent antigenic domains and at least three partly overlapping domains were exposed both in F-PSA and in the PSA-ACT complex, while one antigenic domain was specific for F-PSA. The different domains contained both continuous and discontinuous epitopes. The combination of antibodies recognizing antigenic domains exposed both in F-PSA and PSA-ACT made it possible to develop several highly sensitive sandwich immunoassays for determination of total PSA, i.e. F-PSA + PSA-ACT, with the same molar response for F-PSA and PSA-ACT. Assays specific for F-PSA (cross-reactivity between F-PSA and PSA-ACT < 1%) were developed by the combination of antibodies recognizing epitopes exposed only in F-PSA and antibodies recognizing epitopes exposed both in F-PSA and PSA-ACT.
Animals↗
Weight development, drop-out pattern and changes in obesity-related risk factors after two years treatment of obese men.
OBJECTIVE: To describe a combined behavioural treatment program for obese men, the 'Gustaf' study, and to evaluate treatment success by the means of weight loss, drop-out analysis and changes in metabolic risk factors. SUBJECTS: Eighty-six men, aged 43 +/- 9 y (mean +/- s.d.) and BMI 37.7 +/- 4.4 kg/m2, from the waiting list of the outpatient clinic and men directly approaching the Obesity Unit. DESIGN: Combined, behavioural modification treatment, by the means of group sessions, for one hour every week over a two year period. MAIN OUTCOME MEASURES: Weight loss and changes in risk factors after completion of one and two years study and description of treatment success in the form of changes in metabolic risk factors. RESULTS: The one year drop-out rate was 22% and the cumulative rate after two years was 34%. Mean weight decreased significantly from start (121 kg) to one year (114 kg, P < 0.001) and to two years (115 kg, P < 0.001) in completers. Several metabolic risk factors (waist and hip circumferences, systolic blood pressure, serum cholesterol and plasma insulin) remained significantly decreased after two years of treatment. The complete metabolic syndrome was diagnosed in five men at onset, but in no one after two years. There was no difference in change of metabolic risk factors after one year between the men who lost 8-12% of initial body weight and those who lost more. CONCLUSION: Sixty-six% (57/86) of the obese men who started in the 'Gustaf' program were still in the program after two years. In spite of the relatively modest weight loss, the men maintained a large proportion of this weight loss and also maintained their improved metabolic risk factor pattern.
Adult↗
Updated overview of the Swedish Randomized Trials on Breast Cancer Screening with Mammography: age group 40-49 at randomization.
The purpose of this overview is to estimate more precisely the long-term effect of mammography screening by adding four more years of follow-up to women aged 40-49 years in the four Swedish trials on mammography screening. Data from the four, trials were merged and linked to the Swedish Cancer and Cause of Death Register for 1958-1993 and 1951-1993 respectively to identify date of breast cancer diagnosis and cause and date of death. The invited and control groups comprised 48,569 and 40,247 women respectively. At the December 1993 follow-up, 602 and 482 breast cancer cases were identified in the two groups respectively, of which 104 and 111 had breast cancer as the underlying cause of death. This corresponds to a relative risk (RR) of 0.77 (95% CI: 0.59-1.01) for the two groups. In the 40-44 age group at randomization, 94% of breast cancer patients in the study and 89% in the control group were diagnosed before the age of 50; however, among breast cancer deaths in this age group, only two in the invited and five in the control group died after age 50. At follow-up of women 40-44 years at randomization 208 women in the invited and 184 in the control group were reported to the Cancer registry with breast cancer. Out of these 195 (94%) and 163 (89%) respectively were reported before the age of 50. Further, the relative risk for the age group 40-44 years at randomization by age at follow-up was 1.11, 0.51 and 0.46 for the age groups 45-49, 50-54, and 55-59 at follow-up. This study shows a 23% reduction in the breast cancer mortality in women 40-49 years at randomization achieved from a median trial time of 7.0 years, a median follow-up time of 12.8 years, and a screening interval of 18-24 months. Almost all of the effect in the 40-44 year age group at randomization was due to screening before the age of 50.
Adult↗
Reduced breast cancer mortality in women under age 50: updated results from the Malmö Mammographic Screening Program.
This article provides additional follow-up data of two cohorts from the Malmö Mammographic Screening Trial (MMST). The first cohort, MMST I, contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932. Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988. The second cohort, MMST II, contained 17,786 women born between 1933 and 1945. Fifty four percent of these women were randomly invited to screening between 1978 and 1990. The remaining 46%--the control group--was invited to screening between 1991 and 1994. Nine screening rounds were completed in MMST I, and a mean of five rounds were completed in MMST II; the screening interval ranged from 18 to 24 months. The effect of screening on breast cancer mortality was assessed by pooling the two cohorts. At the end of follow-up--December 1993 for MMST I and December 1995 for MMST II--there was a statistically significant 36% reduction in breast cancer mortality in the intervention groups (relative risk = 0.64; 95% CI: 0.45-0.89; P = 0.009). A harm-benefit analysis showed, however, that for every two breast cancer deaths prevented, one clinically insignificant cancer was diagnosed; for each breast cancer death prevented, 63 cancer-free women had been called back for further examinations; and for every 20 lives saved, one radiation-induced breast cancer death may have occurred. Recommendations for screening must therefore weigh mortality benefits against these negative effects.
Breast Neoplasms↗
Comparative study of DNA-based immunization vectors: effect of secretion signals on the antibody responses in mice.
The presence of a signal sequence preceding the gene encoding a target antigen in a DNA vaccine should facilitate secretion of the in vivo translated antigen. The immune responses elicited upon injection with such a vector could differ from those induced by the same vector lacking a signal sequence. In the present study, the humoral responses elicited in mice immunized with two plasmids, either containing or lacking the human tissue plasminogen activator signal sequence, were compared. Both plasmids encode the chimeric antigen ZZN4, containing a malaria antigen Pf332-derived sequence (N4) linked to a bacterial fusion partner (ZZ). In vitro transfection of COS cells with each plasmid and treatment of the transfectants with brefeldin A confirmed that secretion of ZZN4 via the endoplasmic reticulum and Golgi pathway only occurred in cells transfected with the signal peptide-encoding plasmid. Repeated intramuscular injections of mice with either of the plasmids elicited comparable antibody responses to ZZN4 with regard to kinetics, specific IgG levels and persistence. These results indicate that in vivo transfection of muscle cells by either of these two plasmids generated comparable levels of antigen available for B-cell recognition and for uptake by antigen-presenting cells, despite the differential intracellular targeting of the encoded antigen. The relevance of these findings for the design of DNA vaccine vectors is discussed.
Animals↗
Virucidal treatment of blood protein products with UVC radiation.
The virus safety of blood derivatives continues to be of concern, especially with respect to nonenveloped and/or heat-stable viruses. Previously, we demonstrated that treatment of whole plasma, AHF concentrate or fibrinogen with short wavelength ultraviolet light (UVC) results in the inactivation of > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), hepatitis A virus (HAV) and porcine parvovirus (PPV), each of which is nonenveloped. Protein recovery was enhanced greatly by inclusion of the flavonoid, rutin, added prior to UVC exposure to quench reactive oxygen species. We now report on the treatment of albumin and intravenous immune globulin (IVIG) isolated by a previously described, integrated chromatographic method. Albumin was treated with either 0.1 or 0.2 J/cm2 UVC in the presence of 0.8 or 1.6 mM rutin; IVIG was treated with either 0.05 or 0.1 J/cm2 UVC in the presence of 0.5 or 1.0 mM rutin. Our results show that > or = 10(6.9) ID of EMCV and PPV were inactivated under each of the conditions studied except the treatment of albumin with 0.1 J/cm2 UVC in the presence of 1.6 mM rutin where 10(4.3) ID of EMCV and > or = 10(6.9) ID of PPV were killed. It appears that the sensitivity of PPV to UVC exceeds that of EMCV and that virus kill with UVC is higher in IVIG than in albumin. In the absence of rutin, UVC increased the extent of aggregation of both albumin and IVIG by two- to three-fold. With rutin present, the increase in albumin aggregation was reduced, and it was virtually eliminated by subsequent processing on Sephacryl S-200, a step in the existing procedure designed to remove aggregates. The increase in aggregation of IVIG appeared to be eliminated on inclusion of either 0.5 mM or 1 mM rutin. We conclude that both albumin and IVIG can be treated with UVC to inactivate > or = 10(6) ID of nonenveloped viruses. The inclusion of rutin during treatment helps protect against protein aggregation.
Blood Proteins↗
A common structural basis for the inhibition of ribulose 1,5-bisphosphate carboxylase by 4-carboxyarabinitol 1,5-bisphosphate and xylulose 1,5-bisphosphate.
Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the carboxylation of ribulose 1,5-bisphosphate. The reaction catalyzed by Rubisco involves several steps, some of which can occur as partial reactions, forming intermediates that can be isolated. Analogues of these intermediates are potent inhibitors of the enzyme. We have studied the interactions with the enzyme of two inhibitors, xylulose 1,5-bisphosphate and 4-carboxyarabinitol 1,5-bisphosphate, by x-ray crystallography. Crystals of the complexes were formed by cocrystallization under activating conditions. In addition, 4-carboxyarabinitol 1,5-bisphosphate was soaked into preformed activated crystals of the enzyme. The result of these experiments was the release of the activating CO2 molecule as well as the metal ion from the active site when the inhibitors bound to the enzyme. Comparison with the structure of an activated complex of the enzyme indicates that the structural basis for the release of the activator groups is a distortion of the metal binding site due to the different geometry of the C-3 hydroxyl of the inhibitors. Both inhibitors induce closure of active site loops despite the inactivated state of the enzyme. Xylulose 1,5-bisphosphate binds in a hydrated form at the active site.
Binding Sites↗
[Overestimated cost savings by mammographic screening].
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Cost Savings↗
Large structures at high resolution: the 1.6 A crystal structure of spinach ribulose-1,5-bisphosphate carboxylase/oxygenase complexed with 2-carboxyarabinitol bisphosphate.
Ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) from spinach is a hexadecamer (L8S8, Mr = 550,000) consisting of eight large (L, 475 residues) and eight small subunits (S, 123 residues). High-resolution data collection on crystals with large unit cells is not a trivial task due to the effect of radiation damage and the large number of overlapping reflections when conventional data collection methods are used. In order to minimise these effects, data on rubisco were collected with a giant Weissenberg camera at long crystal to image-plate distances at the synchrotron of the Photon Factory, Japan. Relative to conventional data sets, this experimental arrangement allowed a 20 to 30-fold reduction of the X-ray dose/exposure time for data collection. This paper describes the refined 1.6 A crystal structure of activated rubisco complexed with a transition state analogue, 2-carboxyarabinitol-bisphosphate. The crystallographic asymmetric unit contains an L4S4 unit, representing half of the molecule. The structure presented here is currently the highest resolution structure for any protein of comparable size. Refinement of the model was carried out by restrained least squares techniques without non-crystallographic symmetry averaging. The results show that all L and S subunits have identical three-dimensional structures, and their arrangement within the hexadecamer has no intrinsic asymmetry. A detailed analysis of the high-resolution maps identified 30 differences in the sequence of the small subunit, indicating a larger than usual heterogeneity for this nuclear encoded protein in spinach. No such differences were found in the sequence of the chloroplast encoded large subunit. The transition state analogue is in the cis conformation at the active site suggesting a key role for the carbamate of Lys201 in catalysis. Analysis of the active site around the catalytically essential magnesium ion further indicates that residues in the second liganding sphere of the metal play a role in fine-tuning the acid-base character and the position of the residues directly liganded to the metal.
Amino Acid Sequence↗
[Some glipses from the history of mammography: from radiography of preparations to general screening].
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Europe↗
Obesity treatment and attrition: no relationship to obesity level.
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Adult↗
The Gustaf study: repeated, telephone-administered 24-hour dietary recalls of obese and normal-weight men--energy and macronutrient intake and distribution over the days of the week.
OBJECTIVE: A dietary survey of obese and control men was conducted through 24-hour dietary recalls administered by telephone at 12 times selected randomly over a period of 3 months. Energy and macronutrient intake and distribution were studied for all days of the week. SUBJECTS: Eighty-six obese men, 20 to 60 years old, body mass index (BMI) = 37.7 +/- 4.4 (mean +/- standard deviation) from the waiting list of the outpatient clinic and 6I normal-weight (BMI = 23.0 +/- 1.9), age-matched men selected randomly from the Stockholm County Census Bureau. MAIN OUTCOME MEASURES: Energy and macronutrient intake, intakes by energy tertiles, and distribution over the days of the week. STATISTICAL ANALYSES: Nonparametric tests were used because of skewed distribution of most food data. RESULTS: A median daily energy intake of 2,700 kcal was found in both groups. The obese men reported a higher protein (P < .001) and a lower alcohol (P < .001) intake than the control subjects. Both groups reported a maximum intake of energy and macronutrients on Saturdays. When separated into tertiles according to reported energy intake, the obese men in tertile 3 reported a higher intake from fat (% energy, P < .001) and a lower intake from protein (P < .01) compared with men in tertile 1. Normal-weight men intertile 3 reported a higher intake fat (% energy, P < .01) compared with men intertile 1. CONCLUSIONS: When reported energy intake was compared with calculated total daily energy expenditure, there was a greater discrepancy in the obese group than in the control group. The normal-weight men may have had a special interest in food and health, and this group may not reflect the population at large.
Adult↗
Structural transitions during activation and ligand binding in hexadecameric Rubisco inferred from the crystal structure of the activated unliganded spinach enzyme.
Activation of ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco; EC 4.1.1.39) by CO2 involves carbamylation of Lys 201 and the subsequent binding of a magnesium ion to complete the active site. The refined crystal structure of activated Rubisco shows that the magnesium ligands are Asp 203, Glu 204, the carbamate of Lys 201, and three water molecules. Structural differences between the unactivated and activated forms are minimal. Substrate binding replaces water ligands around the metal and triggers substantial structural changes in loops covering the active site. This leads to a contraction and tightening of the structure of the large subunits with the movements transmitted to and modulated by the small subunits.
Crystallography, X-Ray↗
Ferryl intermediates of catalase captured by time-resolved Weissenberg crystallography and UV-VIS spectroscopy.
Various enzymes use semi-stable ferryl intermediates and free radicals during their catalytic cycle, amongst them haem catalases. Structures for two transient intermediates (compounds I and II) of the NADPH-dependent catalase from Proteus mirabilis (PMC) have been determined by time-resolved X-ray crystallography and single crystal microspectrophotometry. The results show the formation and transformation of the ferryl group in the haem, and the unexpected binding of an anion during this reaction at a site distant from the haem.
Binding Sites↗