[The quality of mammography scrutinized. Ongoing control mass screenings for breast cancer is necessary].
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Breast Neoplasms↗
Biomedical subjects
I Andersson
Publications and source records attributed to I Andersson.
[Home care of deep venous thrombosis].
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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↗
[600,000 women are examined by mammography per year. Every fifth of them refuses screening].
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Adult↗
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↗
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↗
Fibrosarcoma of the breast: mammographic findings in five cases.
The mammographic features of fibrosarcoma of the breast, a rare malignant tumor, have not been described. Accordingly, we reviewed the mammograms, pathology reports, and medical records of five women with this tumor. All cases had surgical biopsies and a diagnosis made by histologic evaluation. The age of the patients ranged from 48 to 79 years. Histologically, three of the five fibrosarcomas were thought to have arisen from phyllodes tumor, and four were palpable. On mammograms, the tumors were dense masses with largely indistinct margins, ranging from 1.5 to 7.0 cm in diameter. One contained calcified osseous elements suggesting osseous trabeculae. Although the osseous trabeculae in that tumor strongly suggested sarcoma, most of the tumors had a nonspecific appearance on mammograms. Fibrosarcomas of the breast have a nonspecific mammographic appearance. Surgical biopsy and histologic evaluation are necessary for definitive diagnosis.
Breast Neoplasms↗
Interval carcinomas in the Malmö Mammographic Screening Trial: radiographic appearance and prognostic considerations.
OBJECTIVE: Interval carcinoma is the term used to describe malignant breast tumors that are detected in the intervals between mammographic screenings. These tumors are important because they contribute significantly to breast cancer mortality in the screened population. MATERIALS AND METHODS: Two radiologists retrospectively reviewed the mammograms of the 96 interval carcinomas (17% of all malignant neoplasms in the screened group) that were detected during the 10-year Malmö Mammographic Screening Trial in Malmö, Sweden (average time between screenings, 21 months), including one sarcoma, 75 invasive carcinomas, and 20 noninvasive carcinomas. We recorded the interval between screening and detection, and noted the tumor's appearance on the prior screening mammogram and at the time of diagnosis; these data were correlated with histologic tumor type and the patients' mortality. The doubling time for tumor volume of the invasive carcinomas was estimated. RESULTS: Excluding the sarcoma, 72 carcinomas (75%) were detected within 18 months of screening. Retrospective review of the available preceding screening mammograms (94 cases) indicated that 10 tumors were missed (observer's error), 63 studies showed no tumor (true interval carcinomas), and 21 studies showed subtle signs of malignancy, mostly nonspecific densities or asymmetries (unrecognized sign). Of 66 invasive carcinomas in which doubling times for tumor volume could be calculated, 27 (41%) had doubling times of less than 100 days. At the end of the study, 20 of the 96 patients had died of breast cancer. CONCLUSION: Interval carcinomas in this series were dominated by comedo, medullary, and mucinous carcinomas that often had a nonspecific appearance (when present) on prior screening mammograms. The interval carcinomas also contained a subset of rapidly growing tumors with a grave prognosis.
Aged↗
The Christmas factor in obesity therapy.
The effect of Christmas time on body weight development was measured in 46 obese patients in maintenance therapy at the Obesity Unit of the Karolinska Hospital and in 76 hospital staff controls of similar sex and age distribution. In controls a statistically significant weight increase of 0.4 +/- 0.8 (s.d.) kg (P < 0.001) was found, whereas the mean increase in the obese patients of 0.6 +/- 2.4 kg was not statistically significant. Little variation in weight development over Christmas was found in controls, whereas the weight change in the obese group ranged from +6.1 to -8.8 kg over the 2-3 weeks. Seasonal variation in body weight has been attributed to circadian rhythms. Cultural food habits may also play a role.
Adult↗
Relation between lightscanning and the histologic and mammographic appearance of malignant breast tumors.
The relation between real-time transillumination (lightscanning) and the histologic appearance of 243 breast carcinomas was evaluated. Lightscanning mainly failed in identifying ductal and lobular carcinomas in situ. The result of lightscanning was also poor regarding small, invasive carcinomas. The absorption patterns in elastosis and scar tissue associated with carcinoma played no important role in the ability of lightscanning to identify a cancer. The relation between the lightscanning and mammographic appearance of 85 breast cancers from the same material was also evaluated. Lightscanning performed poorly in identifying tumors characterized by classifications as compared to tumors with other mammographic appearances. However, the difference was not significant.
Adolescent↗