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Biomedical subjects

I Andersson

Publications and source records attributed to I Andersson.

At least 91 records · Page 5Linked to original sources

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↗

Diagnostic accuracy of lightscanning and mammography in women with dense breasts.

The diagnostic accuracy of lightscanning and mammography in 610 breasts with mammographically dense parenchymal patterns was investigated. Lightscanning identified 31 out of 36 cancers and mammography 32. Lightscanning and mammography were in agreement in 28 cases of cancer. One noninvasive lobular carcinoma was not identified by either modality. Four cancers were not correctly identified with lightscanning alone and 3 cancers with mammography alone. Of the 574 breasts without cancer, lightscanning falsely denoted 101 (18%) as possibly being cancerous (false-positives). The corresponding figure for mammography was 25 (4%). Thus, lightscanning, as performed in this study, has the same sensitivity as mammography in detecting cancer in mammographically dense breasts. However, its usefulness is limited by a low predictive value of a positive test (high rate of false-positives).

Adolescent↗

Ca2+ binding in proteins of the calmodulin superfamily: cooperativity, electrostatic contributions and molecular mechanisms.

In a large number of intracellular regulatory proteins of the calmodulin superfamily a pair of closely interacting helix-loop-helix Ca2+ binding sites ('EF hands') constitute the functional unit--an arrangement that enables cooperative binding. We have recently made detailed experimental studies of the binding of Ca2+ ions to calmodulin, its tryptic fragments TR1C and TR2C (which each constitute a globular domain of a pair of EF hands) and calbindin D9k. Macroscopic Ca2+ binding constants have been obtained over a range of ionic strengths (0 to 0.15 M KCl). For calmodulin the measurements indicate that the two separate globular domains TR1C and TR2C retain the Ca2+ binding properties they have in the intact molecule, with positive cooperativity within each domain. The absolute value of the free energy of interaction between the two sites in each domain, a measure of the cooperativity, increases with ionic strength and is greater than or equal to 10 kJ mol-1 at 0.15 M KCl. Two-dimensional 1H NMR studies show that the addition of KCl does not alter the conformation of the protein. In the case of calbindin D9k several categories of mutants have been studied. One group encompasses the effect of protein surface charges 5 to 15 A from the Ca2+ binding sites. Two-dimensional 1H NMR shows that neither the addition of KCl, nor mutations that neutralize the surface charges, change the protein conformation. Although the global structure of calbindin D9k is largely unchanged upon binding of calcium, the structure with only one cation bound is more similar to the (Ca2+)2 form. Interestingly, the dynamical properties of the Ca(2+)-free and the (Ca2+)2-forms of calbindin differ greatly. For example, the rate of NH/ND exchange of the Ca(2+)-free form is on average 200 times faster than that of the (Ca2+)2-form. The results obtained so far point to a non-negligible entropic contribution to the observed cooperativity of Ca2+ binding.

Amides↗

Coordination geometry for cadmium in the catalytic zinc site of horse liver alcohol dehydrogenase: studies by PAC spectroscopy.

Active site substituted Cd(II) horse liver alcohol dehydrogenase has been studied by Perturbed Angular Correlation of Gamma rays Spectroscopy during turnover conditions for benzaldehyde and 4-trans-(N,N-dimethylamino)cinnamaldehyde. The ternary complex between alcohol dehydrogenase NAD+ and Cl-, and the binary complex between alcohol dehydrogenase and orthophenanthroline have also been studied. The Nuclear Quadrupole Interaction parameters have been interpreted in terms of different coordination geometries for Cd(II) in the catalytic zinc site of the enzyme. Calculation of the nuclear quadrupole interaction for cadmium in the catalytic site of the enzyme with and without coenzyme, based upon the four coordinated geometries determined from X-ray diffraction, agrees with the experimentally determined values. The ternary complexes between enzyme, NAD+ and either Cl- or trifluoroethanol and the binary complex between enzyme and orthophenanthroline have almost identical spectral parameters which are not consistent with a four coordinated geometry, but are consistent with a five coordinated geometry. The non-protein ligands for the ternary complex with trifluoroethanol are suggested to be an alkoxide group and a water molecule. The Nuclear Quadrupole Interaction parameters for the productive ternary complex between enzyme, NADH and an aldehyde is consistent with the four coordinated geometry predicted from X-ray diffraction data having the carbonyl group of the aldehyde substituting the water molecule as ligand to the metal.

Alcohol Dehydrogenase↗

Breast carcinoma in situ in 167 women--incidence, mode of presentation, therapy and follow-up.

In the city of Malmö, in southern Sweden, 1693 women were diagnosed as having breast carcinoma during 1976 through 1984. Of these, 167 women had pure in situ breast carcinoma (9.9%). One hundred and thirty-two had ductal carcinoma in situ (DCIS) alone or in combination with lobular carcinoma in situ (LCIS), intracystic carcinoma and/or Paget's disease of the nipple. Thirty-three had pure LCIS and two had pure intracystic carcinomas. The incidence of breast carcinoma in situ (CIS) in women 20 years of age or older was 18.7 per 10(5) woman years with high rates of DCIS for all ages above 40, whereas a decline in incidence rate was seen for LCIS in the postmenopausal age groups. The ratio of DCIS to LCIS was 4:1. Of the 132 patients with DCIS, 46% were asymptomatic and were diagnosed by mammography, 35% presented with clinical symptoms, and 19% of the cases were incidental findings in breasts operated on for benign lesions. Mammography had been performed on all patients with DCIS and contributed to diagnosis in 75%. Sixty-one per cent of all DCIS lesions had microcalcifications suspicious for carcinoma. Eighty-nine of 132 patients with DCIS underwent fine-needle aspiration biopsy (FNAB) before surgical biopsy. FNAB was suspicious or diagnostic for carcinoma in 57/89 (64%). Of 33 cases with LCIS all but one were incidental findings. In one of 28 cases with LCIS examined by mammography there was suspicion of carcinoma. Sixteen per cent of the patients with DCIS were treated by a breast-conserving operation (BCO), the remaining patients by mastectomy (ME) (52%) or subcutaneous mastectomy (SCM) (33%) with immediate reconstruction. Thirty-three per cent of the patients with LCIS were treated by BCO, the remaining patients by ME (18%) or SCM (49%) with immediate reconstruction. Only one patient had radiotherapy postoperatively. In 60% of all CIS cases where an excisional biopsy had been performed there were further foci of CIS in the final ME/SCM specimen. After a median follow-up of 7 years for the DCIS group, three patients out of 21 treated by BCO had invasive carcinoma appearing ipsilaterally. They were alive and without symptoms of recurrent disease 2.5 to 6 years following further surgery. One patient treated by SCM died from generalized ductal breast carcinoma. In the LCIS group (median follow-up 8 years) one patient out of 11 had an invasive tubular carcinoma diagnosed 4 years after BCO. Eight years later she was alive and well after bilateral SCM.

Adult↗

Crystallographic analysis of ribulose 1,5-bisphosphate carboxylase from spinach at 2.4 A resolution. Subunit interactions and active site.

The X-ray structure of the quaternary complex of ribulose 1,5-bisphosphate carboxylase/oxygenase from spinach with CO2, Mg2+ and a reaction-intermediate analogue (CABP) has been determined and refined at 2.4 A resolution. Cyclic non-crystallographic symmetry averaging around the molecular 4-fold axis and phase combination were used to improve the initial multiple isomorphous replacement phases. A model composed of one large subunit and one small subunit was built in the resulting electron density map, which was of excellent quality. Application of the local symmetry gave an initial model of the L8S8 molecule with a crystallographic R-value of 0.43. Refinement of this initial model was performed by a combination of conventional least-squares energy refinement and molecular dynamics simulation using the XPLOR program. Three rounds of refinement, interspersed with manual rebuilding at the graphics display, resulted in a model containing all of the 123 amino acid residues in the small subunit, and 467 of the 475 residues in the large subunit. The R-value for this model is 0.24, with relatively small deviations from ideal stereochemistry. Subunit interactions in the L8S8 molecule have been analysed and are described. The interface areas between the subunits are extensive, and bury almost half of the accessible surface areas of both the large and the small subunit. A number of conserved interaction areas that may be of functional significance have been identified and are described, and biochemical and mutagenesis data are discussed in the structural framework of the model.

Amino Acid Sequence↗

Lightscanning versus mammography for the detection of breast cancer in screening and clinical practice. A Swedish multicenter study.

State of the art lightscanning of the breast was tested against mammography in 2568 women in a Swedish multicenter study. The study was in two parts. One was in women with symptoms from the breasts (the clinical study) comprising 3178 examined breasts with 198 cancers; the other in asymptomatic women (the screening study) comprising 1909 examined breasts with 126 cancers. In women with symptoms from the breasts, lightscanning did not contribute to clinical examination and mammography. In the screening situation, it was poor to pick up small cancers. Mammography alone falsely diagnosed cancer in 6.9% of the patients whereas lightscan falsely diagnosed cancer in 19.1%. Lightscan was not better than mammography in young women. The study shows that lightscanning in its current form is inferior to standard mammography.

Adult↗

Comparison of the crystal structures of L2 and L8S8 Rubisco suggests a functional role for the small subunit.

Comparison of the crystal structures of the L2 and L8S8 forms of ribulose-1,5-bisphosphate carboxylase from Rhodospirillum rubrum and spinach respectively, reveals a remarkable similarity in the overall architecture of the L2 building blocks in the two enzymes. Within the L subunits, no large conformational differences such as domain-domain rotations were found. In spite of a somewhat different packing of the L subunits in the L2 dimer, the active sites of the two enzymes are highly conserved. Significant local conformational differences are, however, observed for the C-terminal part of the polypeptide chains as well as for loop 7, helix alpha 7, loop 8 and helix alpha 8 in the barrel domain. The small subunit forms extensive interactions with one of these alpha helices, alpha 8, in the spinach L8S8 enzyme. The loops are at the active site and one of them forms a phosphate binding site for the substrate. We suggest that the small subunit modulates substrate binding and, possibly, the carboxylation/oxygenation ratio by inducing conformational changes in the active site through interactions distant from this site.

Amino Acid Sequence↗

Symptoms and signs of thrombotic occlusion of atherosclerotic renal artery stenosis.

Twenty-four patients, with an occluded renal artery diagnosed at angiography or operation, in whom previous angiography had demonstrated an atherosclerotic renal artery stenosis, were compared with a group of patients with a renal artery stenosis that remained patent after a similar interval. The risk of occlusion was found to increase with age, the degree of stenosis and advanced generalised atherosclerosis. At the presumed time of occlusion few patients had symptoms which when present were vague and easily overlooked. The most suggestive sign of occlusion was a rise in serum creatinine which was seen in the majority of the patients.

Adult↗