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Biomedical subjects

E Persson

Publications and source records attributed to E Persson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Comparison of the Ca2+ binding properties of the gamma-carboxyglutamic acid-containing module of protein Z in the intact protein and in N-terminal fragments.

Protein Z is a vitamin K-dependent plasma protein of unknown function. Its modular structure is identical with those of factors VII, IX, X, and protein C. These proteins have an N-terminal gamma-carboxyglutamic acid (Gla)-containing module which binds six to ten Ca2+. In factors IX, X, and protein C, the adjacent epidermal growth factor (EGF)-like module binds one Ca2+ whereas the EGF-like module in protein Z does not. We have compared the Ca2+ binding properties of a fragment of protein Z comprising the Gla and N-terminal EGF-like modules (pZ-GlaEGFN) with those of intact protein Z and the isolated Gla module by measuring the Ca(2+)-induced quenching of the intrinsic protein fluorescence. The similar Ca2+ affinities of pZ-GlaEGFN and protein Z indicate that pZ-GlaEGFN has a native conformation and normal Ca2+ binding properties. A comparison of the Ca2+ binding to pZ-GlaEGFN with those to the corresponding fragments of factors IX, X, and protein C indicate that Ca2+ binding to the N-terminal EGF-like modules in the latter proteins does not influence the folding and Ca2+ binding properties of their Gla modules. Furthermore, the Ca(2+)-induced fluorescence enhancements of GlaEGF fragments from factors IX, X, and protein C appear to be caused by Ca2+ binding to the site in the EGF-like modules since it is not observed for pZ-GlaEGFN.

1-Carboxyglutamic Acid↗
PubMed1992

How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X.

Domains homologous to the epidermal growth factor (EGF) are important building blocks for extracellular proteins. Proteins containing these domains have been shown to function in such diverse biological processes as blood coagulation, complement activation, and the developmental determination of embryonic cell fates. Many of these proteins require calcium for their biological function. In the case of coagulation factors IX and X and anticoagulants proteins C and S, calcium has been found to bind to the EGF-like domains. We have now determined the three-dimensional structure of the calcium-bound form of the NH2-terminal EGF-like domain in coagulation factor X by two-dimensional NMR and simulated folding. Ligands to the calcium ion are the two backbone carbonyls in Gly-47 and Gly-64, as well as the side chains in Gln-49, erythro-beta-hydroxyaspartic acid (Hya) 63, and possibly Asp-46. The conserved Asp-48 is not a ligand in our present structures. The remaining ligands are assumed to be solvent molecules or, in the intact protein, ligands from neighboring domains. Other proteins interacting in a calcium-dependent manner may also contribute ligands. A comparison with the calcium-free form shows that calcium binding induces strictly local structural changes in the domain. Residues corresponding to the side chain ligands in factor X are conserved in many other proteins, such as the integral membrane protein TAN-1 of human lymphocytes and its developmentally important homolog, Notch, in Drosophila. Calcium binding to EGF-like domains may be crucial for numerous protein-protein interactions involving EGF-like domains in coagulation factors, plasma proteins, and membrane proteins. Therefore, there is reason to believe that this novel calcium site plays an important role in the biochemistry of extracellular proteins.

Amino Acid Sequence↗
PubMed1992

Three-dimensional structure of the apo form of the N-terminal EGF-like module of blood coagulation factor X as determined by NMR spectroscopy and simulated folding.

The three-dimensional structure of a 42-residue fragment containing the N-terminal EGF-like module of blood coagulation factor X was determined by means of 2D NMR spectroscopy and computer simulation. The spectroscopic data consisted of 370 NOE distances and 27 dihedral angle constraints. These were used to generate peptide conformations by molecular dynamics simulation. The simulations used a novel functional form for the constraint potentials and were performed with two time steps to ensure rapid execution. Apart from preliminary runs to aid assignment of NOEs, 60 runs resulted in 13 accepted structures, which have two antiparallel beta sheets, no alpha helices, and five tight turns. There is no hydrophobic cluster. The root mean square deviation for the backbone of the 13 conformations is 0.65 +/- 0.11 A against their mean conformation. About half of the side chains have well-defined structure. The overall conformation is similar to that of murine EGF.

Amino Acid Sequence↗
PubMed1992

Sources of information, experiences and opinions on sexuality, contraception and STD protection among young Swedish students.

The aim of the investigation was to study sources of information on sexuality, contraceptives and STDs among young people as well as their experiences of and opinions on the matter. A questionnaire was distributed to 192 high-school pupils in the Stockholm area. The mean age of the participants was 17.4 years. The majority stated that school teachers and individual reading are the best sources of information. Female students more often relied on friends and family members than male students. Among those who had had their sexual debut, many stated that condom use was hard to practice.

Adolescent↗
PubMed1992

Sleep and wakefulness after treatment for craniopharyngioma in childhood; influence on the quality and maturation of sleep.

Craniopharyngiomas are situated in immediate vicinity of sleep regulating structures in the basal forebrain area, and the tumor and its treatment might influence the regulation of sleep and wakefulness. In 10 patients treated for craniopharyngioma nighttime sleep quality and daytime vigilance were examined with polygraphic sleep records and multiple sleep latency tests (MSLT). Two girls and 8 boys, 7.1-22.9 years of age, were studied after a follow-up time of 1.5-16.1 years postoperatively. The results were compared to those of 18 normal children. The regulation of the ultradian sleep rhythm was normal but the ability to maintain nighttime sleep was severely disturbed. The patients had an increased number of awakenings and spent long time awake during two recorded nights. Two patients had excessive daytime somnolence during this examination, one after severe sleep disturbance, the other without any known cause. The pattern of sleep and vigilance did not change in puberty in the expected fashion. The disturbances may well have an impact on the psychosocial situation of the patients.

Adolescent↗
PubMed1992

Immunohistochemical localization of platelet-derived growth factor receptors in the porcine uterus during the oestrous cycle and pregnancy.

The distribution of alpha- and beta-type receptors for PDGF was studied immunohistochemically in the uterus of cycling and pregnant pigs with well-documented hormonal status in order to determine a possible steroid hormone-dependence of its expression. Peroxidase-antiperoxidase (PAP) labelling at light microscopical level was done with rabbit polyclonal antisera recognizing either both alpha- and beta-type receptors (PDGFR-1), or selectively beta-type (PDGFR-3). Immunoreactivity to the PDGF-receptors of alpha- and beta-type (PDGFR-1) was present in all endometrial samples examined, being located principally on subepithelial stromal and endothelial cells, the wall of endometrial blood vessels and in the fetal placenta (trophoblast and adjoining blood capillaries). In the myometrium, the major reactive cells were the non-vascular smooth muscle cells, and to some extent, also those of the tunica media of major uterine vessels. No dramatic variations in the intensity of the reaction were noticed during the oestrous cycle. A very intense immunoreactivity was present at early pregnancy and at term, i.e. under major oestrogenic influence. The immunoreactivity to the PDGF-receptor antiserum R-3 (against beta-type) was similarly localized as that showed for R-1 antiserum, while of a weaker intensity. The results indicate the presence of PDGF receptors (alpha- and beta-type) in the endo- and myometrium of cycling and pregnant pigs, and that their expression seems to be accentuated under oestrogenic influence.

Animals↗
PubMed1992

Sleep and wakefulness in preadolescent children with deficits in attention, motor control and perception.

In 10 children with deficits in attention, motor control and perception (DAMP), the relation between daytime vigilance and night-time sleep quality was examined with polygraphic sleep recordings, multiple sleep latency tests and measurements of reaction times. Two girls and eight boys, 6-12 years of age were studied. Eighteen normal children served as controls. Normal sleep regulation and sleep quality was found, but the children with DAMP tolerated the recording procedure less well than the controls. Most patients did not suffer from increased daytime sleepiness, but at MSLT 3, patients had short sleep latencies as in daytime hypersomnolence. Reaction times were significantly longer among the patients than among the controls. It is proposed that the findings may be related to functional changes in the forebrain.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Sexual behaviour among youth clinic visitors in Sweden: knowledge and experiences in an HIV perspective.

OBJECTIVE: To study the knowledge and experience of sexuality, contraception and sexually transmitted diseases among sexually active adolescents in Sweden. SUBJECTS: Youth clinic visitors. SETTING: Seventy-four youth clinics from all over the country of Sweden. METHODS: A questionnaire with 17 multiple choice and nine open questions was distributed to all visitors at participating youth clinics during a 2-month period. RESULTS: A total of 9277 young persons answered the questionnaire. Their mean age was 17.5 years. Ninety-three percent were females. Knowledge on STD and STD protection was wide-spread and good. Chlamydia and HIV was recognised as STDs by 90% and 87% respectively. More than 99% knew of the condom method as a means for STD protection. Knowledge on contraceptive methods for pregnancy protection was also good. Ninety-three percent of the investigated adolescents had had coitus. Nine percent had experienced pregnancies and 17% STDs. The mean number of life-time sexual partners was 3.2. CONCLUSIONS: In spite of good knowledge on preventive measures among Swedish youth clinic visitors their sexual behaviour carriers risks for future health. Further interventions are needed to minimise these risks.

Adolescent↗
PubMed1991

Protein structural requirements for Ca2+ binding to the light chain of factor X. Studies using isolated intact fragments containing the gamma-carboxyglutamic acid region and/or the epidermal growth factor-like domains.

Coagulation factor X is a multidomain proenzyme of a serine protease. Calcium ions bind to the vitamin K-dependent gamma-carboxyglutamic acid (Gla) residues and to a site in the NH2-terminal of two epidermal growth factor (EGF)-like domains. To study structure-function relationships in the NH2-terminal part of factor X and to determine the structure of isolated domains, we have developed methods that allow the subsequent isolation of the first or both EGF-like domains with or without an attached Gla domain from controlled proteolytic digests of the protein. The Ca2(+)-induced changes of the intrinsic protein fluorescence were measured to elucidate whether the isolated fragments retain their native conformation. Changes in the fluorescence caused by Ca2+ binding were found to result from perturbations of the environment of the Trp residue in position 41. Calcium ion binding to the Gla-containing region linked to the NH2-terminal EGF-like domain was identical with that to intact factor X, indicating a native orientation of the ligand binding groups in the fragment. In contrast, the isolated Gla peptide had a lower affinity for Ca2+, suggesting that the NH2-terminal EGF-like domain serves as a scaffold for the folding of the Gla region. Similarly, the presence of the Gla region was found to increase the affinity of the Gla-independent site in the first EGF-like domain for Ca2+. The metal ion-induced resistance against chymotryptic cleavage COOH-terminal of Tyr-44 in intact factor X is similar in the isolated fragment that contains the Gla region linked to one EGF-like domain, indicating a native conformation of the fragment in the presence of Ca2+. Furthermore, the Gla-independent metal ion binding site binds Ca2+ but does not appear to bind Mg2+.

1-Carboxyglutamic Acid↗
PubMed1991

The gamma-carboxyglutamic acid and epidermal growth factor-like domains of factor X. Effect of isolated domains on prothrombin activation and endothelial cell binding of factor X.

Factor Xa is the enzymatically active constituent of the prothrombinase complex, which catalyzes the conversion of prothrombin to thrombin. We have isolated fragments, from tryptic digests of factor X, that consists of the gamma-carboxyglutamic acid (Gla) region linked to one or two epidermal growth factor (EGF)-like domains. Calcium ion binding measurements indicated that these fragments have a native conformation. The factor X-GlaEGF fragments inhibit factor Xa-induced blood clotting in a manner suggesting that they compete with factor Xa for phospholipid binding sites. The same conclusion was reached when thrombin generation was studied in a system of purified components (factor Xa, factor Va, prothrombin, phospholipid, and Ca2+). There was no evidence for a strong interaction between the EGF-like domains of factor Xa and factor Va in either system. However, experiments in the purified system without phospholipid indicated a direct, albeit weak, interaction between the Gla region of factor Xa and factor Va and between the COOH-terminal EGF-like domain of factor Xa and factor Va. Using domain-specific Fab fragments, we have confirmed that the conformation of the serine protease region alters dramatically upon activation of factor X. Furthermore, we have demonstrated that the conformation of the Gla region is affected by the activation, whereas the EGF-like domains appear to be unaltered. The association constant for factor X binding to endothelial cells was two orders of magnitude lower than that for binding of factor IX to these cells. Binding of the Gla and GlaEGF fragments suggested Gla-mediated binding to phospholipid rather than binding to a specific receptor.

1-Carboxyglutamic Acid↗
PubMed1991

Sexual experience, abortion and sexually transmitted diseases among young women at a contraceptive clinic.

All visitors who during one year visited a contraceptive clinic in the Solna district of Stockholm County and were below the age of 26 were asked to fill in a questionnaire and offered a test for C. trachomatis. Three hundred and six women (97%) participated. Ninety percent had at some time used oral contraceptives and 91% had experience of condom use. One-fifth of the whole group had undergone one or more legal abortions, and one fourth had experience of a sexually transmitted disease (STD). The most common STD experienced was chlamydia, followed by condyloma. The actual prevalence of chlamydia in the group was 6%. Sexual contacts were often made early in on-going steady relations. Forty-two percent admitted casual sex, but the number of life-time partners was five or less among the majority.

Abortion, Legal↗
PubMed1990

1H NMR assignment and secondary structure of the Ca2(+)-free form of the amino-terminal epidermal growth factor like domain in coagulation factor X.

Blood coagulation factor X is composed of discrete domains, two of which are homologous to the epidermal growth factor (EGF). The N-terminal EGF like domain in factor X (fX-EGFN), residues 45-86 of the intact protein, contains a beta-hydroxylated aspartic acid and has one Ca2(+)-binding site. Using 2D NMR techniques, we have made a full assignment of the 500-MHz 1H NMR spectrum of Ca2(+)-free fX-EGFN. On the basis of this assignment and complementary NOESY experiments, we have also determined the secondary structure of Ca2(+)-free fX-EGFN in water solution. Residues 45-49 are comparatively mobile, whereas residues 50-56 are constrained by two disulfide bonds to one side of an antiparallel beta-sheet involving residues 59-64 and 67-72. Another antiparallel beta-sheet involves residues 76-77 and 83-84. A small, parallel beta-sheet connects residues 80-81 and 55-56 and thereby orients the two antiparallel beta-sheets relative to each other. Four beta-turns are identified, involving residues 50-53, 56-59, 64-67, and 73-76. Residues 78-82 adopt an extended bend structure. On the basis of secondary structure and the location of the three disulfide bonds, we find that Asp 46, Asp 48, and Hya 63 are sufficiently close to each other to form a Ca2(+)-binding site. However, the amino terminus of the Ca2(+)-free form of fX-EGFN is not part of a triple-stranded beta-sheet as in other EGF like peptides. Differences and similarities between fX-EFGN and murine EGF with respect to secondary structure and conformational shifts are discussed.

Amino Acid Sequence↗
PubMed1990

Release of lipoprotein lipase and hepatic lipase activities. Effects of heparin and a low molecular weight heparin fragment.

Unfractionated heparin and a low molecular weight heparin fragment (LMWH, mean molecular weight 5000) were compared with respect to the ability to release lipoprotein lipase (LPL) and hepatic lipase (HL) from tissue binding sites. The investigations were carried out in vivo and in vitro in man and in the rat. The in vivo release of LPL activity was greater with heparin in both species. The release of HL activity was equal with both heparins in man, but greater with unfractionated heparin in the rat. In the in vitro studies the LMWH fragment consistently released more LPL activity from the tissues investigated, i.e. fat, skeletal muscle and heart muscle. With isolated adipocytes, however, we could not demonstrate any difference between the two heparins with respect to their lipase-releasing effect. In liver tissue homogenate the two heparins showed the same ability to release HL activity. It is concluded that not only biochemical differences between the two heparins are of importance for the difference in the lipolytic effect. The possibility of different rheological behaviours of the two heparins in the capillary lumen, which might partly explain the greater in vivo lipolytic effects of heparin, is discussed. It is suggested that LMWH enters the tissue preparation more readily in vitro, thereby exerting a greater lipase-releasing effect than heparin.

Adipose Tissue↗