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Biomedical subjects

I Andersson

Publications and source records attributed to I Andersson.

At least 73 records · Page 4Linked to original sources

An overview of the Swedish randomised mammography trials: total mortality pattern and the representivity of the study cohorts.

OBJECTIVES: To analyse the cause of death pattern in the cohorts of women included in the Swedish randomised mammography screening trials by comparing the groups of invited and control women both with each other and with the general population of Swedish women. SETTING: Since 1977 four randomised trials of mammography screening have been performed in Sweden: Malmö, Kopparberg and Ostergötland (the two county trial), Stockholm, and Gothenburg. DESIGN: Overview of four randomised mammography screening trials. RESULTS: The total numbers of deaths in the invited and control groups respectively were 15 695 and 11 887 corresponding to a relative risk (RR) of 1.00. There were no significant differences between the invited and control groups for cause-specific mortality, except for breast cancer. When the total mortality in the invited and the control groups was compared with that for Swedish women in general the standardised mortality ratio was close to 100. CONCLUSIONS: The cause of death pattern in the invited group was, except for breast cancer, very similar to that in the control group, showing that the groups were comparable. Similarly, the total mortality including breast cancer mortality in the control group was almost identical to that in Swedish women in general. The same was true, with the exception of breast cancer, for the invited group. These observations confirm that the trial cohorts are representative of Swedish women and indicate that the quantitative results from these trials may safely be generalised to the Swedish populations.

Adult↗

The Swedish randomised mammography screening trials: analysis of their effect on the breast cancer related excess mortality.

OBJECTIVE: To apply an indirect method for estimation of the breast cancer related excess mortality in the Swedish randomised mammography screening trials. SETTING: Randomised trials on mammography screening have, in Sweden, been performed in the counties of Kopparberg (W) and Ostergötland (E), the so called WE study, and in the three largest cities in Sweden, Stockholm (southern part), Gothenburg, and Malmö. An overview of the trials was presented in the Lancet in 1993 and included 156,911 women in the invited group and 125,866 in the control group. METHODS: The excess mortality in the breast cancer subgroups was estimated by indirect standardisation using official national cause of death statistics according to Statistics Sweden as a reference. RESULTS: The estimated reduction of the breast cancer related mortality was 24% for the whole group (40-74 years at randomisation). The corresponding figures for the age groups 40-49, 50-59, and 60-69 years were 6%, 28%, and 34% respectively. CONCLUSION: The results are very similar to those presented earlier based on the traditional comparison of the breast cancer mortality in the invited and in the control group. This analysis further strengthens previous reports on a beneficial effect of mammography screening, which is especially pronounced in the age group 50-69.

Adult↗

Meal patterns in obese and normal weight men: the 'Gustaf' study.

OBJECTIVE: To compare the reported meal patterns between obese and normal weight men. DESIGN: A dietary survey, by means of 12 repeated telephone-administered 24-hour dietary recalls, was conducted in obese and normal weight men. The study period was three months with all seven days of the week included. The contribution of intake types to the reported daily energy intake (EI) was studied as well as the circadian distribution of EI and the reported number of intakes. SUBJECTS: 86 obese men (BMI 37.7 +/- 4.4 kg/m2, mean +/- SD) from the waiting list of the outpatient clinic completed the study altogether with 61 normal weight men (BMI 23.0 +/- 1.9 kg/m2), randomly selected from the Stockholm County Census Bureau. All men were 20-60 years old. RESULTS: Results were analyzed for Group A = all men who completed the study and for Group B = the men who exceeded the CUT-OFF 1 limit for energy intake (reasonably true report as defined by Goldberg). The obvious under-reporters amounted to 73% of the obese and to 28% of the normal weight men. The meal patterns were similar for the obese and the normal weight men. The greatest contributors to EI in both groups were cooked meals, sandwich meals, snacks and breakfast-like meals. The circadian eating pattern was mainly the same in both obese and normal weight men. The reported number of intakes was 5.3 (median) per day in all obese men vs 5.6 in all the controls (P = 0.02), and in Group B 5.3 s 5.9 (P = 0.16) intakes. No specific "obese eating style' could be detected in this study.

Adult↗

Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes.

Penicillin antibiotics are all produced from fermentation-derived penicillins because their chemical synthesis is not commercially viable. The key step in penicillin biosynthesis, in which both the beta-lactam and thiazolidine rings of the nucleus are created, is mediated by isopenicillin N synthase (IPNS), which binds ferrous iron and uses dioxygen as a cosubstrate. In a unique enzymatic step, with no chemical precedent, IPNS catalyses the transfer of four hydrogen atoms from its tripeptide substrate to dioxygen forming, in a single reaction, the complete bicyclic nucleus of the penicillins. We now report the structure of IPNS complexed with manganese, which reveals the active site is unusually buried within a 'jelly-roll' motif and lined by hydrophobic residues, and suggest how this structure permits the process of penicillin formation. Sequence analyses indicate IPNS, 1-aminocyclopropane-1-carboxylic acid oxidase and many of the 2-oxo-acid-dependent oxygenases contain a conserved jelly-roll motif, forming a new structural family of enzymes.

Acremonium↗

Dietary intake in head and neck irradiated patients with permanent dry mouth symptoms.

Radiotherapy of the head and neck region, which includes the major and minor salivary glands in the radiation field, usually leads to temporary or permanent xerostomia. This may affect eating and increase the risk of inadequate intake of energy and nutrients. The aim of the present study was to investigate the effects of radiotherapy-induced xerostomia on energy and nutrient intake in individuals treated for malignancies in the head and neck region. The dietary intake of 24 patients with a low chewing stimulated whole saliva flow rate (< 0.5 ml/min) and in age and sex matched controls with normal flow rate (> 1.0 ml/min) was recorded for 7 days. The average daily energy intake was nearly 300 kcal lower in the irradiated patients with dry mouth symptoms than in the control group. The mean intake in the former group was 1925 kcal per day whereas the control group had an intake of 2219 kcal per day. Irradiated patients with dry mouth symptoms had significantly lower mean intakes of vitamin A, beta-carotene, vitamin E, vitamin B6, folacine, iron and zinc than those in the control group. There was also a lower intake of vitamin C, but this was not statistically significant. The intake of vitamins A and C exceeded or reached the levels recommended in the Swedish Nutritional recommendations, but the average intakes of fibre, iron, beta-carotene, vitamin E, zinc, selenium, and iron did not reach recommended levels, in neither the experimental nor the control group. There was a slight positive correlation between energy intake and saliva secretion rate in the control group, but the energy intake was totally independent of variations in secretion rate in the irradiated patients with low secretion rate.

Aged↗

Determination of cause of death among breast cancer cases in the Swedish randomized mammography screening trials. A comparison between official statistics and validation by an endpoint committee.

Between 1976 and 1982, four randomized mammography screening trials started in five screening centres in Sweden, involving 282,777 women (156,911 invited and 125,866 controls) with the aim to study if invitation to screening reduced the breast cancer mortality. An overview of the trials was performed to reduce the confidence intervals for the relative risk estimates. All 1,296 deaths occurring in women with breast cancer detected after randomization were evaluated by an independent endpoint committee (EPC), consisting of four physicians who reviewed collected medical information that was blinded regarding mammography screening. If there was disagreement between the EPC members at the initial individual evaluation the final classification was made at consensus meetings. In only 6.9% (n = 89) of the cases was there disagreement as to whether breast cancer was or was not the underlying cause of death. It was also found that 'breast cancer as underlying cause of death' and 'breast cancer as underlying or contributory cause of death' according to Statistics Sweden resulted in relative risk estimates very similar to those based on the classification by the EPC. The study thus supports the use of official health statistics in the evaluation of randomized breast screening trials in Sweden.

Adult↗

Remoxipride shows low propensity to block functional striatal dopamine D2 receptors in vitro.

The effect of remoxipride ((S)(-)3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenzam ide) on dopamine D2 receptor-mediated inhibition of cAMP formation in rat striatal tissues pieces was established together with that of a number of other dopamine D2 receptor antagonists. The action of remoxipride, three other substituted benzamides, (-)-sulpiride, raclopride and NCQ 298 ((S)-3-iodo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5,6-dimethoxysalicylam ide mesylate) and haloperidol, a butyrophenone, was studied in the presence of (I) (+/-) SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) hydrochloride (100 microM) plus pergolide (1 microM) or (II) forskolin (1 microM) plus dopamine (100 microM). In addition, four of the metabolites of remoxipride: FLA 797 ((S)-3-bromo-N[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-6- methoxybenzamide), NCR 181 ((S)(-)-5-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-6- methoxybenzamide tartrate), NCQ 436 ((S)(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5,6-dihydroxy-2- methoxybenzamide semioxalate) and NCQ 469 ((S)(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-hydroxy-2,6- dimethoxybenzamide hydrochloride), mainly found in rodents, were studied using test system I. The results demonstrate that remoxipride is significantly weaker in blocking functional striatal dopamine D2 receptors than either of the reference compounds studied and three of the four metabolites. The studies also demonstrate that dopamine D1 and D2 receptor interactions at the level of cAMP formation in the striatum are independent of action potentials or Ca2+.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

B- and T-cell responses in congenic mice to repeat sequences of the malaria antigen Pf332: effects of the number of repeats.

The Plasmodium falciparum antigen Pf332 comprises degenerated 11-amino-acid repeats with regularly spaced pairs of glutamic acid. Epitopes formed by such repeats are recognized by polyclonal and monoclonal antibodies that interfere with the life cycle of the blood stages of the malaria parasite. In order to study the immunogenicity of one such Pf332 repeat sequence (SVTEEIAEEDK), fusion proteins containing ZZ (two IgG binding domains of staphylococcal protein A) and dimers, trimers or tetramers of the malarial sequence were injected into mice. To analyse possible major histocompatibility complex class II restrictions of the immune response, mice of different H-2 haplotypes were used. A significant antibody response was elicited by administration of all the three fusion proteins in mice expressing the I-Ak allele (B10.BR, B10.A(2R) and B10.A(4R)) whereas B10 and C57BL/6 (H-2b) mice were low responders. In comparison, B10.D2 (H-2d) mice were low responders to fusion proteins with 2 or 3 repeats but responded well to the protein containing 4 repeats. Lymph node cells from B10.BR (H-2k) mice, primed in vivo with ZZ-fusion proteins containing either 2 or 4 repeats, proliferated in vitro in response to repeat sequences fused to ZZ or to an unrelated fusion partner, as well as to a synthetic peptide containing less than two repeats. In contrast, a response of lymph node cells from B10.D2 (H-2d) mice was only obtained when a fusion protein containing 4 repeats was used both for in vivo priming and in vitro restimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Nitrogen saturation induced during winter by experimental NH4NO3 addition to a forested catchment.

To investigate the potential risk of 'nitrogen saturation' in Scandinavian boreal forests, the authors are experimentally adding 30-50 kg N ha(-1) year(-1) as NH4NO3 in precipitation to an entire 0.52-ha 80-year-old spruce forested catchment at Gårdsjön, near Gothenburg on the Swedish west coast. NO3 concentrations in runoff increased from 0 to about 7 microeq liter(-1) (maximum pulse of 43 microeq liter(-1)). The increase occurred in winter; during the April-October growing season, NO3 concentrations were very low. The speed of the response suggests that these forests are already close to saturation.

Journal Article↗

Detection of breast cancer in women after augmentation mammoplasty using fluorine-18-fluorodeoxyglucose-PET.

UNLABELLED: The purpose of this study was to determine the feasibility of FDG-PET imaging in women with silicone implant augmentation mammoplasties where mammographic detection of breast cancers is challenging due to the implants' radiodensity, which can obscure tumor visualization. METHODS: FDG-PET imaging was performed in two women with augmentation mammoplasties and small palpable breast abnormalities. Mammograms with and without breast displacement were also performed. RESULTS: PET clearly demonstrated focal FDG accumulation in the suspicious breasts, corresponding to tumors of less than 1.5 cm in diameter. There was no degradation of image quality by the implants and no need for breast displacement views. By contrast, implant displacement mammograms were necessary to fully delineate the tumors. CONCLUSION: While mammograms with displacement views represent the initial choice for imaging the augmented breast, FDG-PET can image tumors in the augmented breast without implant displacement and without obvious degradation of image quality by the implant. FDG-PET warrants additional evaluation as an adjunctive study in the augmented breast, particularly when displacement mammographic views are not adequate or are impossible to perform due to peri-implant capsule formation.

Adult↗

Formation of the active site of ribulose-1,5-bisphosphate carboxylase/oxygenase by a disorder-order transition from the unactivated to the activated form.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) catalyzes the key first step in photosynthetic CO2 fixation, the reaction that incorporates CO2 into sugar. In this study, refined crystal structures of unactivated tobacco RuBisCO and activated RuBisCO from spinach and tobacco, in complex with the reaction-intermediate analog 2-carboxyarabinitol 1,5-bisphosphate (CABP), are compared. Both plant enzymes are hexadecameric complexes of eight large and eight small subunits with a total relative molecular mass of approximately 550,000. The comparison of activated and unactivated forms of RuBisCO provides insight into the dynamics of action of this enzyme. The catalytic site, which is open to the solvent in the unactivated enzyme, becomes shielded in the activated CABP complex. This shielding is accomplished by a 12-A movement of the active-site "loop 6" (residues 331-338) and a disorder-order transition of three loops near the active-site entrance, the N terminus, the C terminus, and a loop comprising residues 64-68. All these residues belong to the catalytic large subunit. Domain rotations of about 2 degrees are observed, also tightening the active-site cleft. These observations provide an explanation for the extremely tight binding (Kd < or = 10(-11) M) of the CABP molecule. A striking correlation exists between crystallographic temperature factors in the activated enzyme and the magnitude of the atomic movement upon activation.

Amino Acid Sequence↗

Breast cancer screening with mammography: overview of Swedish randomised trials.

Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, based on 282,777 women followed for 5-13 years in randomised trials in Malmö, Kopparberg, Ostergötland, Stockholm, and Gothenburg, reveals a 24% (95% confidence interval 13-34%) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation ("breast cancer as underlying cause of death" or "breast cancer present at death"). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1. The largest reduction of breast cancer mortality (29%) was observed among women aged 50-69 at randomisation. Among women 40-49 there was a non-significant 13% reduction. In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up. After 8 years there was a difference in favour of the invited women. There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group. Among women aged 70-74 years screening seems to have had only a marginal impact.

Adult↗

Crystal structure of activated tobacco rubisco complexed with the reaction-intermediate analogue 2-carboxy-arabinitol 1,5-bisphosphate.

The crystal structure of activated tobacco rubisco, complexed with the reaction-intermediate analogue 2-carboxy-arabinitol 1,5-bisphosphate (CABP) has been determined by molecular replacement, using the structure of activated spinach rubisco (Knight, S., Andersson, I., & Brändén, C.-I., 1990, J. Mol. Biol. 215, 113-160) as a model. The R-factor after refinement is 21.0% for 57,855 reflections between 9.0 and 2.7 A resolution. The local fourfold axis of the rubisco hexadecamer coincides with a crystallographic twofold axis. The result is that the asymmetric unit of the crystals contains half of the L8S8 complex (molecular mass 280 kDa in the asymmetric unit). The activated form of tobacco rubisco is very similar to the activated form of spinach rubisco. The root mean square difference is 0.4 A for 587 equivalent C alpha atoms. Analysis of mutations between tobacco and spinach rubisco revealed that the vast majority of mutations concerned exposed residues. Only 7 buried residues were found to be mutated versus 54 residues at or near the surface of the protein. The crystal structure suggests that the Cys 247-Cys 247 and Cys 449-Cys 459 pairs are linked via disulfide bridges. This pattern of disulfide links differ from the pattern of disulfide links observed in crystals of unactivated tobacco rubisco (Curmi, P.M.G., et al., 1992, J. Biol. Chem. 267, 16980-16989) and is similar to the pattern observed for activated spinach tobacco.

Binding Sites↗

Prokaryotic calcium-binding protein of the calmodulin superfamily. Calcium binding to a Saccharopolyspora erythraea 20 kDa protein.

The EF-hand calcium-binding protein from Saccharopolyspora erythraea has been shown, using 113Cd NMR, to possess three Cd(2+)-ion binding sites. This indicates that of the four EF-hand motifs in the molecule, one (probably site 2) is unable to bind Cd(2+)-ions. Data from the titration of the protein with Ca2+, in the presence of Quin2, were fitted to a curve calculated on the assumption that the protein contains three high affinity Ca2+ binding sites, two of which (pK1 = 8.0, pK2 = 9.0) are strongly cooperative, and one single site (pK3 = 7.5). Preliminary 1H NMR experiments indicate marked structural changes upon Ca(2+)-binding.

Binding Sites↗