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Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 487 records · Page 27Linked to original sources

Glutathione-dependent hydrogen donor system for calf thymus ribonucleoside-diphosphate reductase.

Purified calf thymus ribonucleoside-diphosphate reductase (2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1), showed an absolute requirement for a dithiol as hydrogen donor, whereas the natural monothiol glutathione (GSH) was inactive per se. However, a protein partially purified from thymus coupled the oxidation of GSH to the formation of deoxyribonucleotides by ribonucleotide reductase. In analogy with the ribonucleotide reductase system of Escherichia coli this protein was called glutaredoxin [Holmgren, A. (1976) Proc. Natl. Acad. Sci. USA 73, 2275-2279]. Thymus glutaredoxin had the following properties: (i) its molecular weight determined by gel chromatography was about 12,000; (ii) it was active iwth ribonucleotide reductase in the presence of GSH, NADPH, and glutathione reductase but had no activity with NADPH and thioredoxin reductase; and (iii) it was immunologically different from thioredoxin because it did not bind to antithioredoxin immunoadsorbents. Experiments on the crossreactivity of thymus and E. coli ribonucleotide reductases and the corresponding thioredoxin and glutaredoxin systems showed essentially no specificity for the homologous thioredoxin but a high species specificity for the homologous glutaredoxin.

Animals↗

Organ cultures of human fetal hepatocytes in the study of extra-and intracellular alpha1-antitrypsin.

The rate of synthesis of alpha 1-antitrypsin has been studied in organ cultures of fetal human liver. By de novo synthesis, alpha 1-antitrypsin of the same electrophoretic mobility and molecular size as plasma alpha 1-antitrypsin was produced. Synthetic rate was comparable to in vivo conditions and was suppressed by cycloheximide, colchicine and neuraminidase. By increasing alpha 1-antitrypsin levels in cultre medium, suppression of alpha 1-antitrypsin release from the intra-to the extracellular site was achieved, i.e., synthesis does not proceed autonomously. This suppression was preceded by a temporary enhancement of synthesis. Both effects were found to be independent of degree of sialylation of add-d alpha 1-antitrypsin. In contrast to alpha 1-antitrypsin released in tissue culture, the intracellular protein, as analyzed by crossed immunoelectrophoresis of Triton X-100 extracts from fetal liver, was found to occur partly as slowly moving peaks. Whether these peaks represent proforms or incompletely glycosylated precursors of export alpha 1-antitrypsin or complexes with proteases remains unsettled. A variety of other plasma proteins are released in organ cultures making the system suitable for study of factors regulating plasma protein synthesis.

Culture Media↗

Production of protein HC by human fetal liver explants.

Human fetal lever explants were found to secrete protein HC into the medium in molar amounts comparable to those of albumin, alpha 1-antitrypsin and orosomucoid. Incorporation of a radioactive amino acid from the medium into the secreted protein HC demonstrated de novo synthesis. The secreted protein HC had the same size and electrophoretic mobility as protein HC of plasma and urine and gave a reaction of immunochemical identity with the protein in these biological fluids.

Alpha-Globulins↗

Purification and characterization of cytoplasmic thioltransferase (glutathione:disulfide oxidoreductase) from rat liver.

An enzyme catalyzing thiol-disulfide interchange of glutathione and disulfides and the reaction between glutathione and thiosulfate esters has been purified 40 000-fold from rat liver cytosol. The enzyme, named thioltransferase (Askelöf, P., Axelsson, K., Eriksson, S., & Mannervik, B. (1974) FEBS Lett. 38, 263--267), was homogeneous in several electrophoretic systems, had an isoelectric point at pH 9.6, and contained 8.6% (w/w) carbohydrate. The catalytic activity had a distinct optimum at pH 7.5. A series of substrates was tested at a constant glutathione level; the kcat values (at 4mM glutathione) were all in the range of about 10(4) min-1. The substrates included mixed disulfides of glutathione, other low-molecular-weight disulfides, S-sulfocysteine and S-sulfoglutathione, and peptide disulfides such as insulin, oxytocin, ribonuclease, and the mixed disulfide of glutathione and egg-white lysozyme. The enzymatic reaction was inhibited by an excess of glutathione (greater than 4mM).

Animals↗

Catalytic effects by thioltransferase on the transfer of methylmercury and p-mercuribenzoate from macromolecules to low molecular weight thiol compounds.

Thiol agarose and glyceraldehyde-3-phosphate dehydrogenase were blocked with methylmercury or p-mercuribenzoate. The exchange of mercurials between the thiol-containing polymers and glutathione or dithioerythritol was investigated. The activity of glyceraldehyde-3-phosphate dehydrogenase was inhibited by blocking thiol-groups with the mercury compounds. Inhibition was reversible when a short period of inactivation was used. Inactivation for longer periods resulted in reduced regain of enzyme activity. The activity was in part regained when either of the 2 thiol compounds was added. Thioltransferase, known to catalyze thiol-disulfide exchange reactions, increased the regain of glyceraldehyde-3-phosphate dehydrogenase activity to nearly the original value. Here, thioltransferase is proposed to catalyze the transfer of organomercurial from one thiol complex to another. Some consequences of the observations in vivo are discussed.

Animals↗

Complete reversibility of paraneoplastic acanthosis nigricans after operation.

A patient with widespread acanthosis nigricans is described. No abdominal tumour was found. Explorative thoracotomy disclosed numerous enlarged lymph glands containing squamous cell carcinoma. The left lung was removed but meticulous search did not disclose any tumour. The glands were removed as radically as possible. After the operation the skin improved and the lesions have disappeared completely. The observation time is over three years.

Acanthosis Nigricans↗

The development of mucosal changes after gastric surgery for ulcer disease.

The development of morphological changes in the body mucosa after partial gastrectomy for ulcer disease according to Billroth I and II was studied early (within 3 years) and late (10-24 years) postoperatively with gastroscopy and forceps biopsies. The morphological findings in the body mucosa of the operation specimens and biopsies from the stomas were compared. The effect of time, ulcer disease, operation procedure, sex, and age was studied. In duodenal ulcer patients, with significantly less pronounced inflammatory mucosal changes in the operation specimen, partial gastrectomy caused acute and chronic gastritis to the same degree as seen in gastric ulcer patients within 3 years postoperatively. Duodenal ulcer patients also developed mucosal atrophy, cystic dilatation of the gastric glands, and intestinal metaplasia by time to an extent not significantly different from what was found in gastric ulcer patients. No correlation could be found between the mucosal changes and factors like age, sex, or operation procedure. Mucosal atrophy, chronic gastritis, and intestinal metaplasia are regarded as possible features of malignant transformation. If this concept is true, our findings may explain why stump carcinoma is frequently reported with the same incidence independent of preoperative ulcer disease or anastomotic procedure.

Acute Disease↗

Allosteric regulation of calf thymus ribonucleotide reductase.

Ribonucleotide reductase was purified 3400-fold from calf thymus. The enzyme preparation was essentially free of kinases and phosphatases and therefore allowed a conclusive study of the allosteric regulation of a eukaryotic ribonucleotide reductase to be made for the first time. Comparable maximal activities were obtained for the reduction of all four ribonucleotide substrates in the presence of their optimal stimulatory effectors. These and other results strongly argue for the existence of only one ribonucleotide reductase in mammalian cells. No reduction was observed in the absence of effector. The reduction of CDP and UDP both required ATP, with no stimulatory effect of any other nucleoside triphosphate. The only activator of GDP reduction was dTTP and the only activator of ADP reduction was dGTP. Reduction of the purine ribonucleotides was further stimulated by ATP but only in combination with dTTP or dGTP. The reduction of all four ribonucleotides was strongly inhibited by dATP, the inhibition being partly released by ATP. The data can be integrated into a scheme which links ribonucleotide reduction to DNA synthesis.

Allosteric Regulation↗

Smoking and intermediate alpha1-antitrypsin deficiency and lung function in middle-aged men.

Lung function was evaluated in a representative population sample of 50-year-0ld men living in one Swedish city. Twenty-four smoking and 15 non-smoking men heterozygous for alpha1-antitrypsin deficiency--that is, with the protease-inhibitor (Pi1 phenotype MZ--were carefully matched for weight and smoking habit with Pi M controls. The pulmonary function of non-smoking Pi MZ subjects did not differ from that of non-smoking Pi M controls. In contrast, smoking heterozygotes showed a significant loss of elastic recoil, enlarged residual volumes, and increased closing capacity but no signs of obstructive ventilatory impairment. Most smoking Pi MZ individuals reported mild exertional dyspnoea.

Homozygote↗