Biomedical subjects

I Dahlqvist

Publications and source records attributed to I Dahlqvist.

8 recordsLinked to original sources

PubMed1999

A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx.

Cone snails are gastropod mollusks of the genus Conus that live in tropical marine habitats. They are predators that paralyze their prey by injection of venom containing a plethora of small, conformationally constrained peptides (conotoxins). We report the identification, characterization, and structure of a gamma-carboxyglutamic acid-containing peptide, conotoxin epsilon-TxIX, isolated from the venom of the molluscivorous cone snail, Conus textile. The disulfide bonding pattern of the four cysteine residues, an unparalleled degree of posttranslational processing including bromination, hydroxylation, and glycosylation define a family of conotoxins that may target presynaptic Ca2+ channels or act on G protein-coupled presynaptic receptors via another mechanism. This conotoxin selectively reduces neurotransmitter release at an Aplysia cholinergic synapse by reducing the presynaptic influx of Ca2+ in a slow and reversible fashion. The three-dimensional structure, determined by two-dimensional 1H NMR spectroscopy, identifies an electronegative patch created by the side chains of two gamma-carboxyglutamic acid residues that extend outward from a cavernous cleft. The glycosylated threonine and hydroxylated proline enclose a localized hydrophobic region centered on the brominated tryptophan residue within the constrained intercysteine region.

1-Carboxyglutamic Acid↗

PubMed1997

Calcium-binding properties of the third and fourth epidermal-growth-factor-like modules in vitamin-K-dependent protein S.

Protein S is a plasma glycoprotein requiring vitamin K for normal biosynthesis and functioning as a cofactor of activated protein C, a regulator of blood coagulation. Protein S contains four modules that are similar to the epidermal growth factor (EGF) precursor. Qualitative Ca2+-binding experiments have indicated that the EGF-module region of bovine protein S harbors high-affinity Ca2+-binding sites. We have chemically synthesized the third and fourth EGF modules from human protein S, which both have the sequence motif associated with Ca2+-binding and Asp/Asn beta-hydroxylation. Both modules were folded to a native conformation, as judged by immunochemical experiments and NMR spectroscopy. Ca2+ binding to the modules was monitored with 1H-NMR spectroscopy. At physiological pH and 0.15 M NaCl, each module was found to have a single Ca2+-binding site with low affinity, i.e. Kd values of 6.1 mM for the third and 8.6 mM for the fourth EGF module. At low salt conditions the Ca2+ affinities are 5.2 mM and 0.6 mM, respectively. This Ca2+ affinity is similar to that of the isolated N-terminal EGF module from coagulation factors IX and X. The very high affinity Ca2+ binding to the EGF-module region of protein S thus appears to be due to the influence of neighboring modules.

Amino Acid Sequence↗

PubMed1993

The effect of aspartate hydroxylation on calcium binding to epidermal growth factor-like modules in coagulation factors IX and X.

Hydroxylation of aspartic acid to erythro-beta-aspartic acid (Hya) occurs in epidermal growth factor (EGF)-like modules in numerous extracellular proteins with diverse functions. Several EGF-like modules with the consensus sequence for hydroxylation bind Ca2+, and it has therefore been suggested that the hydroxyl group is essential for Ca2+ binding. To determine directly the influence of beta-hydroxylation on calcium binding in the EGF-like modules from coagulation factors IX and X, we have now measured calcium binding to both the fully beta-hydroxylated and the non-beta-hydroxylated modules of the two proteins. At low ionic strength, the Hya-containing module of factor X has a slightly higher Ca2+ affinity, but at physiological salt concentrations this difference is no longer significant for either factor IX or X. Analysis of the 1H NMR chemical shift differences between the hydroxylated and nonhydroxylated factor X modules show that hydroxylation has no effect on the domain fold. Furthermore, measurements on factor IX show that hydroxylation has no effect on the Ca2+/Mg2+ specificity of the ion binding site. We conclude that the hydroxyl group is not a direct ligand for the calcium ion in these EGF-like modules, nor is it essential for high-affinity Ca2+ binding.

Amino Acid Sequence↗

PubMed1983

The use of thiol-disulphide exchange chromatography for the automated isolation of alpha 1-antitrypsin and other plasma proteins with reactive thiol groups.

A method has been developed for the rapid isolation of alpha 1-antitrypsin and other thiol proteins from plasma by an automated chromatography system. The thiol-proteins are initially bound to matrix-linked activated thiol-compounds by an SH-SS interchange reaction. The mixed disulphides are then reduced in two steps and subfractionated by passage through Blue-Sepharose and AH-Sepharose columns. The rate of the interchange reactions varies with the microenvironment of the reacting thiols. alpha 1-Antitrypsin is recovered with 95% purity in 60% yield within two days from 1 l of plasma.

Blood Proteins↗

PubMed1982

Incidence of hypothyroidism occurring long after iodine-131 therapy for hyperthyroidism.

We have studied the long-term incidence of hypothyroidism in 4,473 formerly hyperthyroid patients given I-131 therapy between 1951 and 1975. The mean age at the first I-131 treatment was 56 yr. Six percent developed hypothyroidism within one year of therapy, and 72% within 26 yr. Prior antithyroid medication did not affect the incidence of hypothyroidism. Patients cured with one dose of I-131 had a lower cumulative long-term incidence of hypothyroidism than those requiring more than one dose.

Adolescent↗

PubMed1981

Cure rate after 131I therapy for hyperthyroidism.

The cure rate of hyperthyroidism after 131I therapy was analysed in 4 473 patients, aged between 14 and 91 years, treated between 1951 and 1975. Despite unchanged treatment principles, the cumulative incidence of cure increased for each 5-year period. Within the first 4 months 34 per cent of the patients with diffuse thyroid glands treated during 1951-1955 were cured, as compared with 59 per cent of those treated 1971-1975, i.e. an increment by a factor of 1.7. The corresponding figures for patients with nodular thyroid glands were 23 and 54 per cent, respectively, or a factor of 2.3.

Adolescent↗

PubMed1980

Malignant thyroid tumors after iodine-131 therapy: a retrospective cohort study.

We studied the incidence of malignant thyroid tumors after 131I therapy in 2727 patients with hyperthyroidism and in 273 euthyroid patients with cardiac disease. The patients were all adults, with a mean age of 57 years. The 131I therapy was given between 1951 and 1965. The mean follow-up period was 13 years for the hyperthyroid patients (15 years for the 85 per cent surviving for more than five years) and six years for the cardiac patients (12 years for the 41 per cent surviving for more than five years). The incidence of malignant thyroid tumors was based on a search of the Swedish Cancer Registry for the occurrence of such tumors in any of the 3000 patients. At present there is no increased incidence of malignant thyroid tumors after 131I therapy (four cases observed versus 3.2 cases expected).

Female↗

PubMed1978

A method for determining bone mineral content using Fourier image reconstruction and dual source technique.

The basic principles of a quantitative tomographic technique for bone mineral determination are considered. The bone mineral content could be evaluated from a single reconstruction using projection data from two different energies. Beam hardening effects and photon counting statistics are studied by computer simulation and found to be the limiting factors in precision and accuracy.

Bone and Bones↗