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Biomedical subjects

I Andersson

Publications and source records attributed to I Andersson.

At least 19 recordsLinked to original sources

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

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

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

Reversed-phase liquid chromatographic determination of plasma levels of adriamycin and adriamycinol.

A method is given for the determination of adriamycin and its main metabolite, adriamycinol in plasma from cancer patients after administration of adriamycin as the free drug or as a complex with DNA. Adriamycin and adriamycinol are extracted in a column from 1 ml of plasma (pH 8.6) using a mixture of chloroform--1-heptanol (8:2). After re-extraction into phosphate buffer pH 2.2, the separation is performed as reversed-phase liquid chromatography on a LiChrosorb RP-2 (5 micron) column with a mobile phase of acetonitrile-water, acidified with phosphoric acid. The precision by quantitation with photometric detection was better than 5% within the range 50-300 ng/ml. Plasma levels of adriamycin and adriamycinol in a cancer patient are presented in this paper.

Chromatography, Liquid

Isolation and characterization of a butyrylesterase from human erythrocytes.

Human erythrocytes contain a butyrylesterase which, judging from the ease with which it can be solubilized, is present in the cytoplasm of these cells. This enzyme has been isolated and a number of its properties characterized. The purified enzyme hydrolyzed butyryl esters with both a lower Km and higher V than is seen with esters containing longer or shorter acyl groups. It has a molecular weight of 320 000 and an isoelectric point of 4.1. This low isoelectric point is apparently a result of the relatively high content of glutamic and aspartic acids. The stability of the isolated butyrylesterase has been examined under a number of different conditions. The enzyme is inhibited by low concentrations of Hg2+, Cd2+, Zn2+ and the organophosphorus compound Mipafox, but is insensitive to eserine. The properties of this butyrylesterase, including its ability to hydrolyze thiocholine esters at a relatively rapid rate (albeit with a high Km), are a mixture of those expected for an arylesterase and a cholinesterase.

Amino Acids

Breast hamartomas. An important entity in mammary pathology.

1. Fifteen cases of a rather distinct entity of tumour-like lesion in the breast are presented. 2. They have a distinct mammographic appearance and can be easily shelled out at surgery, leaving symmetrical breasts. 3. They are well-circumscribed lumps of varying size with a smooth surface. 4. Microscopically they show normal or dysplastic glandular structures of lobules and ducts, without neoplastic features, within a prominent fibrous stroma. The lesions appear to be closely related to adenolipomas.

Adolescent

Site-specific substituted cobalt(II) horse liver alcohol dehydrogenases. Preparation and characterization in solution, crystalline and immobilized state.

The specific substitution, using highly selective techniques, of catalytic and/or noncatalytic zinc ions by cobaltous ions in horse liver alcohol dehydrogenase (EC 1.1.1.1) has been studied with dissolved, crystalline and agarose-immobilised enzyme, in order to examine the effect of protein structure on the specificity of the metal exchange. The different binding sites can be clearly distinguished by the absorption spectra of their cobalt derivatives. In solution an anaerobic column chromatographic method made it possible to exchange half of the zinc in the enzyme by cobalt ions in a much shorter time than previous procedures. By raising the temperature in the exchange step, even the slowly exchanging zinc ions were substituted by cobalt, yielding products similar to cobalt alcohol dehydrogenases described earlier. Treatment of crystal suspensions of the enzyme with chelating agents (preferentially dipicolinic acid) gave an inactive protein with two zinc ions remaining bound. The enzyme could be reactivated by treatment of the crystalline protein with 5 mM zinc or cobaltous ions or by dialysis of dissolved inactive protein against 20 microM zinc or 1 mM cobaltous ions. Higher metal concentrations led to denaturation but the inactive protein could be crystallized from solution and then reactivated completely at higher metal concentrations. The preparation and absorption spectrum show that cobalt is bound specifically at the catalytic sites. Since metal substitution at these sites critically depends on the maintenance of the correct tertiary and quaternary structure, these must be preserved in the crystal lattice and partially altered in solution when the catalytic zinc ions are removed (or when excess of metal ions is applied), thus demonstrating the structure-stabilizing role of the catalytic metal ions. The enzyme immobilised on agarose, with unchanged content of active sites [Schneider-Bernlöhr et al. (1978) Eur. J. Biochem. 41, 475--484], was treated like the crystal suspensions. Although half of the zinc was removed, some activity remained. After reactivation with cobaltous ions, a loss of about 30% active sites was measured. Thus the apparently homogenous bound enzyme was rather heterogeneous in the properties of its catalytic metal binding sites. These results are taken as further proof for the dependence of the metal substitution on the proper tertiary and quaternary structure which is strained by multiple interactions in the covalently immobilised enzyme.

Alcohol Oxidoreductases

Liquid chromatographic monitoring of daunorubicin and daunorubicinol in plasma from leukemic patients treated with daunorubicin or the daunorubicin-DNA complex.

Fifteen patients with acute nonlymphocytic leukemia have been randomized for treatment with daunorubicin (1.0--1.5 mg/kg) either as the free drug (for 45 min or 4 h) or as the drug bound to a DNA carrier (for 5--6 h). The correlation between plasma kinetics of daunorubicin and its main metabolite daunorubicinol and the different administration schedules of daunorubicin has been studied by reversed-phase liquid chromatography. Plasma concentration kinetics of daunorubicin as well as the daunorubicin-DNA complex was biphasic in character. Maximum plasma level of daunorubicin was found during the infusion period. Its concentration decreased rapidly when the infusion stopped and was below the detection limit of the analytical method 2--4 h later. The data suggests a slower disposition of the duanorubicin-DNA complex compared with the free drug.

Animals

Case report of a Swedish school health clinic.

The work in the school health services, which, according to regulations, should be only preventive, has developed into a mixture of preventive and curative care with strong features of social paediatrics and treatment of minor complaints. Together, the nurse and the physician make an important contribution to pupil welfare in school, providing a sense of security for children, teachers and parents. On the other hand, it is evident that the resources are not used optimally. Too much time and effort are spent on routine class examinations, which yield very little benefit, while other important tasks are neglected, e.g. co-ordination of treatment and education of chronically ill or handicapped children and health education of children and teachers. This study reports the health problems that a physician and nurse encounter during one year in their daily work at a medium sized school in a medium sized city in Sweden.

Adolescent

Breast cancer screening with mammography: a population-based, randomized trial with mammography as the only screening mode.

A population-based, randomized breast cancer screening project was undertaken using mammography alone. Of 17,447 invited women aged 50-69, 12,765 (73%) attended the screening. On the basis of the screening films, malignancy was suspected in 405 women (3.2%) who were recalled for complete mammography. Additional films showed that the suspicion of malignancy was false in 194 women. The remaining 211 women (1.7%) were referred for clinical and cytological examination. Of these, 159 had surgery. Breast cancer was proved in 97 women, corresponding to a prevalence rate of 7.6/1000. Fifty-three (55%) of the carcinomas were either in situ or invasive with a diameter of less than or equal to 1 cm. Axillary metastases were found in 19 patients (19.6%). Cancers detected at screening were significantly less advanced than those in the control group. There was a remarkably high frequency of tubular carcinoma among cancers detected at screening.

Aged

Lesions of the dorsal renal artery in surgery for renal pelvic calculus. A potential cause of renovascular hypertension.

2 cases of lesions of the dorsal renal artery in surgery for renal pelvic calculus are described. In 1 of the cases hypertension developed. Anatomic factors and previous operations predispose to this complication. An arterial complication should be suspected when hypertension develops postoperatively. The blood pressure of patients with known renal vascular complications should be checked repeatedly for several months postoperatively. The diagnosis is radiological, renal angiography being the definite procedure although a reduction of kidney size observed at urography may indicate the vascular lesion.

Adult

Mammary hamartomas.

Five cases of mammary hamartoma are described, with special reference to the radiographic features. Hamartomas are well circumscribed lesions composed of normal or dysplastic mammary tissue. They are probably more common than has been anticipated from the literature and are important because they may be confused with other well circumscribed tumors, such as cystosarcoma phyllodes. The radiographic characteristics of hamartoma allows a tentative diagnosis in most cases.

Adult