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Biomedical subjects

T Samuelsson

Publications and source records attributed to T Samuelsson.

30 records · Page 2Linked to original sources

Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome.

The concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients with adult respiratory distress syndrome (ARDS). The mean level was 163 +/- 85 (SD) micrograms/L and significantly increased (p less than 0.001) compared with the levels in control subjects (19 +/- 18 micrograms/L). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in ARDS, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. No relation was seen between BAL fluid ECP or MPO and degree of complement consumption, suggesting that other mechanisms besides complement activation may underlie granulocyte activation in ARDS. Lavage ECP levels correlated strongly with the severity of lung damage defined by pulmonary oxygenation index (PaO2/inspired fraction of O2). Activation of eosinophils, neutrophils, and the complement system is not specific for ARDS but was also observed in patients after major surgery, but at a significantly lower level (p less than 0.001). It is concluded that eosinophil activation is part of the inflammatory process in the lung in ARDS. The association observed between elevated lavage fluid levels of ECP and reduced pulmonary function in ARDS might reflect a pathophysiologic role for ECP and other cytotoxic eosinophil products in this syndrome and should be evaluated.

Adult

Volume substitution and treatment with prostaglandin E1 in a porcine model of endotoxaemia-induced pulmonary and cardiovascular failure.

The effects of prostaglandin E1 (PGE1) and volume substitution (5% albumin) on pulmonary haemodynamics and oxygen transport were evaluated in a porcine model of pulmonary and cardiovascular failure. Albumin was infused i.v. to maintain baseline mean left atrial pressure throughout the experiments. Ten pigs received endotoxin + albumin and showed ten-fold increase in venous admixture, 90% increased extravascular lung water and 25% fall in cardiac output. Oxygen delivery and base excess decreased significantly and four pigs died. In ten other endotoxin-albumin-treated pigs PGE1 infusion (0.25 micrograms X kg-1 X min-1) was begun after established pulmonary and cardiovascular dysfunction, for closer mimicking of clinical use. The raised pulmonary vascular resistance thereafter normalized and extravascular lung water increased by only 15%, but the increase in venous admixture was not influenced. Cardiac output was maintained at baseline. PGE1 prevented further derangement of oxygen delivery and base excess. All the animals survived. The clinical implications may be that volume infusion, even optimally titrated, is not optimum treatment in endotoxemic pulmonary and cardiovascular failure. PGE1 added to optimum volume treatment may be a useful adjuvant in endotoxaemia.

Albumins

The predictive and discriminative value of biologically active products of eosinophils, neutrophils and complement in bronchoalveolar lavage and blood in patients with adult respiratory distress syndrome.

To determine whether biologically active products of eosinophils, neutrophils and complement contribute to the development of adult respiratory distress system (ARDS) we measured eosinophil cationic protein (ECP), lactoferrin (LF) and C3a in bronchoalveolar lavage (BAL) and blood by means of radioimmunoassays. Seventeen patients served as controls. Fifteen patients were studied before and after major surgery to evaluate the influence of the surgical procedure, and 12 patients with ARDS were investigated 4-12 h after the onset of the disease. Major surgery per se significantly increased ECP in BAL, LF in serum and C3a in BAL and plasma. ECP, LF and C3a levels in BAL and blood were all significantly higher in ARDS patients as compared with levels in controls and those observed after major surgery. The higher ECP levels in BAL were associated with the more severe ARDS as was also the case for C3a in BAL and plasma and LF in serum. One out of 15 patients subjected to major surgery developed ARDS postoperatively and had very high levels of ECP, LF and C3a in BAL and blood at sampling 3 h prior to onset of ARDS, and these levels were similar to those observed in ARDS patients. One out of 12 ARDS patients died from the disease and this patient had the highest level of ECP in BAL and serum. Our results strongly support the role of activated polymorphonuclears, and notably the activated eosinophils, in the pathogenesis of ARDS. Evidence is also presented that ECP can be used as a predictor of impending ARDS.

Adult

Treatment with prostaglandin E1 in a porcine model of early adult respiratory distress syndrome.

The effects of treatment with PGE1 were evaluated in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms X kg-1 X h-1) for 6 h. Thirteen pigs were given endotoxin, and 11 pigs were treated with a continuous infusion of PGE1, 0.25 microgram X kg-1 X min-1 for 4 h, beginning 2 h after start of endotoxin and established lung injury. Four pigs served as controls and receiving only PGE1 (0.25 microgram X kg-1 X min-1) during the whole observation period of 6 h. PGE1 treatment did not influence the decline in platelet and polymorphonuclear cell counts, whereas it markedly decreased the pulmonary hypertension induced by endotoxaemia. The increased extravascular lung water returned towards baseline after institution of PGE1. The increased venous admixture was not significantly influenced by PGE1. Treatment with PGE1 induced an exacerbated hypotensive state in the endotoxaemic animals primarily due to vasodilation. The decline in cardiac output and oxygen delivery noted in endotoxaemic pigs were not influenced by PGE1 and survival was not improved. Although one should be extremely careful in extrapolating these data to the clinical situation the results from the present study suggest the need for optimum volume replacement when starting PGE1 infusion in endotoxin-induced ARDS.

Alprostadil

Cloning and nucleotide sequence analysis of transfer RNA genes from Mycoplasma mycoides.

As part of an investigation of the tRNA genes of Mycoplasma mycoides, two HindIII fragments of mycoplasma DNA comprising 0.4 and 2.5 kilobases (kb), respectively, were cloned in pBR322 and their nucleotide sequences determined. Only one tRNA gene was found in the 0.4 kb fragment, the gene for tRNAArg with the anticodon TCT, while the 2.5 kb fragment contained nine different tRNA genes arranged in a cluster which presumably constitutes a transcriptional unit. The clustered tRNA genes, with their respective anticodons, were as follows: Arg (ACG), Pro (TGG), Ala (TGC), Met (CAT), Ile (CAT), Ser (TGA), fMet (CAT), Asp (GTC), and Phe (GAA).

Base Sequence

Unconventional reading of the glycine codons.

We have used a protein-synthesizing in vitro system programmed with the phage message MS2-RNA to investigate the ability of glycyl-tRNAs with different anticodons to read the glycine codons. Under conditions of no competition, when the glycyl-tRNA analyzed was the only source of glycine for protein synthesis, each of the isoacceptors tested, tRNA1Gly (anticodon CCC), tRNA2Gly (anticodon N/UCC), tRNA3Gly (anticodon GCC) from Escherichia coli, and tRNAGly (anticodon UCC) from Mycoplasma mycoides, could read all of the glycine codons in the MS2 coat protein cistron (GGU, GGC, GGA, and GGG). However, tRNA1Gly seemed to have difficulties reading through the whole cistron. Experiments in which two glycyl-tRNAs competed for the same codon showed that the mycoplasma tRNAGly (anticodon UCC) was almost as efficient in the unorthodox reading of the codons GGU and GGC as it was in conventional reading. It would seem to be the only tRNAGly present in Mycoplasma mycoides and our results are consistent with this finding since the mycoplasma tRNAGly appears to have been designed to read all four glycine codons with approximately equal efficiency. The competition experiments furthermore showed that E. coli tRNA1Gly (anticodon CCC) reads the codon GGA more efficiently than it reads GGU and GGC suggesting that the mispair C . A between the wobble position of the anticodon and the third codon position might have appreciable stability.

Amino Acid Sequence

Codon reading and translational error. Reading of the glutamine and lysine codons during protein synthesis in vitro.

The reading of glutamine and lysine codons during protein synthesis in vitro has been investigated using an MS2-RNA-programed system derived from Escherichia coli. Under conditions when either glutaminyl-tRNA1Gln (s2UUG) or glutaminyl-tRNA2Gln (CUG) was the only source of glutamine for protein synthesis both tRNAs were able to read the glutamine codons CAA and CAG as indicated by the incorporation of labeled glutamine into the pertinent coat protein tryptic peptides. On the other hand, when the two glutamine tRNAs competed for the codon CAA the reading efficiency of the anticodon s2UUG, which reads the codon according to the wobble rules, was almost 40 times higher than that of the competing anticodon CUG, which reads the codon by "two out of three," i.e. it cannot form a regular base pair with the third codon position. In reading the codon CAG the anticodon CUG was approximately eight times more efficient than the anticodon s2UUG. The lysyl-tRNA1Lys (CUU) could not alone sustain any detectable coat protein synthesis in the MS2 system indicating that there was no significant reading of the lysine codon AAA. This conclusion is supported by the outcome of experiments where lysyl-tRNA1Lys (CUU) and lysyl-tRNA2Lys (s2UUU) competed for the codon AAA. The reading efficiency of the anticodon CUU was less than 1% of that of the competing s2UUU which represents the limit of resolution of our experimental system. When the two lysine tRNAs competed for the codon AAG the anticodon CUU was about four times more efficient than s2UUU. These results are discussed in the context of the two out of three hypothesis, which attempts to relate the frequency of such reading to the hydrogen bonding properties of the codon nucleotides.

Bacterial Proteins

Glomerulonephritis in infections with Yersinia enterocolitica O-serotype 3. I. Evidence for glomerular involvement in acute cases of yersiniosis.

Signs of damage to the glomerular basement membrane appearing as haematuria and proteinuria have been observed in 16 cases of proven acute yersiniosis. The infecting agent was Yersinia enterocolitica serotype O:3 in all. In a few cases a transient deterioration of the renal function was observed. The renal symptoms were not related to the acute febrile state, but seemed to appear about 14 days after the onset of yersiniosis and to be reversible in the observation period. Infection with other microorganisms known as nephritogenic was not found in spite of attempts to do so. Kidney biopsy was performed in one case and immunofluorescence microscopy showed deposits of immunoreactants. Based on these observations we suggest that acute glomerulonephritis can be included in the spectrum of complications of infection with Yersinia enterocolitica serotype O:3. The frequency of complicating glomerulonephritis in yersiniosis could not be estimated from this study.

Adolescent

Aberrations of the classic codon reading scheme during protein synthesis in vitro.

Using a protein synthesizing in vitro system programmed with MS2-RNA, the ability of alanine tRNAs with the anticodons U*GC (U* represents 5-oxyacetic acid uridine monophosphate) and IGC to read the alanine codons in the coat protein cistron of MS2 has been determined both under conditions of no competition, where the alanyl-tRNA used was the only aminoacylated tRNAAla present in the system, and in experiments where the two alanyl-tRNAs were competing against each other. Under conditions of no competition, each of the anticodons can read all four alanine codons. However, when the anticodons compete for the codon GCC, the anticodon IGC, which can read all three positions of the codon according to the rules of Watson-Crick base pairing, is considerably more efficient than U*GC, which misreads the codon by reading only the first two positions and presumably disregards the third nucleotide of the codon. The outcome of the competition experiments also reveals two apparent violations of the wobble restrictions: the anticodon U*GC reads the codon GUU almost as effectively as does the anticodon IGC, and IGC is almost as effective as U*GC in reading the codon GCG.

Alanine-tRNA Ligase