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Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 433 records · Page 24Linked to original sources

Direct photoaffinity labeling of the catalytic site of mouse ribonucleotide reductase by CDP.

Ribonucleotide reductase reduces all four ribonucleoside diphosphates to the deoxyribonucleotides required for DNA synthesis. The enzyme is composed of two nonidentical subunits, M1 and M2. The 89-kilodalton M1 subunit contains at least two allosteric sites which, by binding nucleotide effectors, regulate the catalytic activity and substrate specificity of the enzyme. We now show that in addition, protein M1 contains a substrate-binding (catalytic) site which is specifically photolabeled after UV irradiation in the presence of the natural substrate, [32P]CDP. The photolabeling of protein M1 by [32P]CDP required the presence of the second subunit, protein M2, and ATP, the positive allosteric effector for CDP reduction. The negative effectors, dATP, dGTP, and dTTP, inhibited the photolabeling of wild type protein M1. Deoxy-ATP did not inhibit the labeling of a mutant protein M1 that is resistant to feedback inhibition by dATP. In addition, hydroxyurea and 4-methyl-5-aminoisoquinoline thiosemicarbazone, two inhibitors of ribonucleotide reductase which affect protein M2, also inhibited the [32P]CDP labeling of protein M1. These data provide new insights into the role and interaction of the two ribonucleotide reductase subunits, proteins M1 and M2, and the mechanism of action of the allosteric effectors.

Affinity Labels↗

Joint fluid leukocytosis of patient with rheumatoid arthritis Computer analysis of possible explanative factors.

The relationship between joint fluid leukocytosis and some clinical and laboratory parameters (disease duration, ESR, maximal titres of rheumatoid factor and of antinuclear factors, blood leukocytosis and sex) was studied in 27 consecutive patients with seropositive rheumatoid arthritis. The concentration of leukocytes was significantly higher in the synovial fluid than in peripheral blood. Variations of joint fluid leukocytosis could, however, not be explained by disease duration, actual ESR, maximal rheumatoid factor or antinuclear factor titres, concentration of blood leukocytes, or sex. It is suggested that a possible correlation between joint fluid leukocytosis and the listed parameters of rheumatoid arthritis may be too complex for analysis by a linear multiple regression model in samples of the present size.

Adult↗

Joint fluid leukocytosis of patients with rheumatoid arthritis evidence for neutrophil and monocyte chemotaxis in vivo.

The cell picture of the synovial fluid of fourteen patients with rheumatoid arthritis was studied in smears contrasted with the May-Grünwald-Giemsa stain. The cytology was dominated by neutrophils, many with signs of necrobiosis. The mononuclear cells displayed signs of proliferation and differentiation. Comparison with the immobile erythrocyte provided evidence that the accumulation of leukocytes in the synovial fluid of patients with rheumatoid arthritis was due to active leukocyte migration, presumably stimulated random movement and chemotaxis.

Arthritis, Rheumatoid↗

Brain amino acids measured by intracerebral dialysis in portacaval shunted rats.

Changes in brain amino acid uptake and metabolism have been proposed as a possible etiological factor in hepatic encephalopathy. By use of a brain dialysis technique (a thin tube implanted in the brain of the living animal), the extracellular amino acid concentrations in the striatum of portacaval (PC)-shunted and sham-operated rats were measured. Leucine, phenylalanine, methionine, and glutamine were increased two- to sixfold in the PC-shunted rats, whilst no changes were seen for GABA, valine, glutamate, or isoleucine, confirming previous reports. Aspartate levels were 350% higher in the PC-shunted rats, and this rise, as well as that of phenylalanine, was significantly correlated with the lower motor activity observed in the PC-shunted rats, suggesting a possible importance of these amino acids in the etiology of hepatic encephalopathy. The amino acid concentrations measured in whole blood demonstrated the well-known pattern of low levels of branched-chain amino acids and increased concentrations of phenylalanine, glutamine, and histidine.

Amino Acids↗

The role of the MA-sensitive leukocyte chemotaxis in rheumatoid arthritis. A randomized double-blind clinical trial of griseofulvin treatment.

Polymorphonuclear leukocyte (PMN) chemotaxis is thought to play an essential role in the pathogenesis of rheumatoid arthritis. PMN chemotaxis is in part sensitive to microtubule antagonists (MAs), e.g. colchicine. The antimycotic antibiotic griseofulvin inhibits the MA-sensitive PMN chemotaxis in vitro in concentrations far below those obtained in serum during antimycotic therapy. The role of the MA-sensitive chemotaxis in rheumatoid arthritis could thus be elucidated by a clinical trial of griseofulvin treatment. Griseofulvin (n = 20) was tested in a randomized double-blind study versus placebo (m = 19) during one year in patients with rheumatoid arthritis of mild-moderate activity. No beneficial effect of griseofulvin treatment was noted on clinical symptoms or laboratory parameters of rheumatoid arthritis. Moreover, the placebo-treated patients showed more improvement than the griseofulvin-treated patients. It is therefore suggested that the MA-sensitive chemotaxis plays a reparative role in the inflammatory lesions of rheumatoid arthritis.

Adult↗

Respiratory alkalosis early after stroke: its relation to loco-motor function.

In 27 acute stroke patients with hemi-motor deficit blood gases (paO2, paCO2 and blood pH) were determined within 72 hours and related to level of consciousness, site of brain lesion, findings of haemorrhage into the cerebral spinal fluid, extent of motor impairment and concomitant medical disorders. Sixteen subjects were followed for three weeks with repeated blood-gas sampling and assessment of motor control. Respiratory alkalosis occurred in 37%, hypoxia in 7% but acidosis in none. Blood gas abnormalities were significantly and positively associated only with the extent of motor impairment. Only small changes in blood gases were found during the three weeks follow-up. Initial findings of respiratory alkalosis predicted poor motor recovery during the follow-up period.

Aged↗

The effect of tamoxifen in intermediate alpha 1-antitrypsin deficiency associated with the phenotype PiSZ.

Three patients, one with lung disease and two with liver disease, with intermediate alpha 1-antitrypsin (AAT) deficiency phenotype PiSZ, (plasma AAT concentration approximately 1/3 of normal) were treated with the anti-oestrogen drug, tamoxifen, for 2-24 months. Patients responded with 50-70% increases in plasma AAT concentrations. Progress of emphysema appeared to be retarded in one case but no improvement in liver function was recorded in the other two patients.

Aged↗

Direct photoaffinity labeling of an allosteric site on subunit protein M1 of mouse ribonucleotide reductase by dTTP.

The protein M1 subunit of ribonucleotide reductase contains at least two allosteric nucleotide binding sites that control the capacity of the enzyme to reduce ribonucleotides to the deoxyribonucleotides required for DNA synthesis. Direct photoaffinity labeling of partially purified protein M1 from mouse T-lymphoma (S49) cells was observed after UV irradiation in the presence of dTTP at 0 degrees C. The relative molar incorporation of nucleotide per subunit was 4-8%. Competition experiments showed that the dTTP was bound to an allosteric domain genetically and kinetically defined as the substrate specificity site of the enzyme. An altered protein M1 isolated from a thymidine-resistant mutant cell line showed significantly decreased photoincorporation of dTTP, consistent with the fact that its CDP reductase activity is resistant to feedback inhibition by dTTP. Specific photolabeling of several other proteins with pyrimidine and purine nucleotides was also found, indicating the general usefulness of direct photoaffinity labeling in the study of enzymes involved in nucleotide and nucleic acid metabolism.

Affinity Labels↗

Hyperosmolar non-ketotic coma in diabetic stroke patients.

Hyperosmolar non-ketotic coma in diabetes is a life-threatening condition. We describe three patients, aged 59-67 years, who developed hyperosmolar coma during the first ten days after admission for stroke. Common to all three were normal plasma osmolality and slightly elevated plasma creatinine levels on admission, treatment with diuretics, parenteral dextrose administration before and low urinary glucose output during the coma. In the five days preceding the coma, total fluid deficits were 3.8, 6.5 and 9.4 1, respectively. In one patient the rate of glucose delivery had clearly exceeded utilization during adequate insulinization, in another a marked reduction in urinary glucose output preceded extreme hyperglycaemia and coma. Two of the three patients died, both from extensive thrombus formation in cerebral arteries and multiple emboli to the lungs. We conclude that enhanced endogenous glucose production and reduced renal clearance of glucose may contribute to precipitate hyperosmolar non-ketotic coma. A close monitoring of fluid and dextrose administration seems mandatory in diabetic stroke patients, in particular if renal function is impaired or if diuretics are given. Insulin treatment should be considered in all diabetic patients during the first days after a stroke.

Aged↗

Commentary on the reduced urinary noradrenaline excretion following cold stress and exercise in physically trained rats.

Urinary catecholamine excretions of rats trained by swimming or running were compared with those of cold-acclimated rats and controls i.e. sedentary warm-acclimated rats. During cold stress the trained rats excreted less noradrenaline (NA) than did controls. In fact rats trained by swimming excreted less NA than did cold-acclimated rats, while rats trained by running excreted about the same amount as did cold-acclimated rats. 2 h of swimming increased the urinary catecholamine (CA) excretion of all groups but trained rats excreted less NA than did controls and cold-acclimated rats, which had excretions of similar magnitude. The NA excretions of the two trained groups never deviated statistically from each other. It is concluded that concerning NA requirement in order to maintain homeostasis, training produces "cross tolerance" to cold stress but cold-acclimation does not produce "cross tolerance" to acute exercise. Furthermore the positive effect of training on NA excretion during the stress of cold or that of acute exercise seems essentially to be an effect of increased locomotor activity as such regardless of the type of training. It is also suggested that increased levels of locomotor activity of the rat may be of importance for seasonal acclimation of the species by increasing its tolerance to cold.

Animals↗

Oro-gastro-intestinal inhibition of hypernatremia-induced drinking in the goat.

Reduction of drinking by slow (5 ml/min) administration for 20 min of nearly body-warm (35 degrees C) and cold (15 degrees C) water into the mouth, the abomasum, or the duodenal bulb was studied in goats made thirsty by the simultaneous i.v. infusion of hypertonic (2 M) NaCl at 2 ml/min. During the control experiments the drinking response to corresponding infusion of 1.7 M NaCl was recorded. This in order to eliminate the possible influence on the results of a postabsorptive thirst inhibition which would occur if the administered water was completely absorbed already during the saline infusion. The entrance of warm water into the mouth or into the abomasum caused about 20%, and into the duodenal bulb about 30% reduction of drinking during the infusion of hypertonic NaCl. The corresponding reduction for cold water was when introduced into the mouth and duodenal bulb about 50% and into the abomasum about 60%. Cold water also considerably delayed the onset of drinking. The inhibition obtained during cold water administration was partially compensated for by increased post-infusional drinking. As regards the sensory input underlying preabsorptive inhibition of thirst, it is concluded that (regardless of distension, swallowing, and other mechanical factors) the entrance of pure water into various parts of the alimentary tract contributes to reduce the thirst drive. In addition, stimulation of oral, gastric, and duodenal cold receptors obviously diminish the urge to drink considerably.

Animals↗

Potentiation of antidiuretic response to systemic angiotensin II by elevation of CSF NaCl concentration.

The antidiuretic effect of the simultaneous intracerebroventricular (ICV) infusion of 0.24 M NaCl (0.02 ml/min) and intravenous (i.v.) infusion of angiotensin II (12 ng/kg X min) was studied in hydrated goats, and was compared to the antidiuretic effects of the separate infusions. The combined infusions inhibited the water diuresis for 30 min, whereas the separate infusions only reduced the water diuresis by 25% (ICV NaCl) and by 50% (i.v. angiotensin). The combined infusions increased the urine osmolality on the average by 415%. Corresponding increases induced by ICV NaCl and by i.v. angiotensin were 100 and 160%. The results suggest that systemic angiotensin II and elevated CSF NaCl concentration interact and potentiate each other as stimuli for antidiuretic hormone secretion. It is postulated that this synergism may help to preserve body water in hypovolemic conditions associated with hyperactivity of the renal renin-angiotensin system.

Angiotensin II↗