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Biomedical subjects

B Samuelsson

Publications and source records attributed to B Samuelsson.

At least 199 records · Page 11Linked to original sources

Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation.

Arachidonic acid plays a central role in a biological control system where such oxygenated derivatives as prostaglandins, thromboxanes, and leukotrienes are mediators. The leukotrienes are formed by transformation of arachidonic acid into an unstable epoxide intermediate, leukotriene A4, which can be converted enzymatically by hydration to leukotriene B4, and by addition of glutathione to leukotriene C4. This last compound is metabolized to leukotrienes D4 and E4 by successive elimination of a gamma-glutamyl residue and glycine. Slow-reacting substance of anaphylaxis consists of leukotrienes C4, D4, and E4. The cysteinyl-containing leukotrienes are potent bronchoconstrictors, increase vascular permeability in postcapillary venules, and stimulate mucus secretion. Leukotriene B4 causes adhesion and chemotactic movement of leukocytes and stimulates aggregation, enzyme release, and generation of superoxide in neutrophils. Leukotrienes C4, D4, and E4, which are released from the lung tissue of asthmatic subjects exposed to specific allergens, seem to play a pathophysiological role in immediate hypersensitivity reactions. These leukotrienes, as well as leukotriene B4, have pro-inflammatory effects.

Animals↗

Neurofibromatosis in monozygotic twins: a case report.

A case report is given of a pair of monozygotic twin girls with neurofibromatosis caused by a new mutation. The symptomatology was dominated by a neurofibrosarcoma on the leg of one twin and by a large plexiform neurofibroma on the neck of the other twin. Otherwise, the disease showed similar, although not identical or mirror-image distribution of subcutaneous neurofibromas and café-au-lait spots. The twins had identical HLA and blood group antigens and the same chromosome aberration. These case reports indicate that nonhereditary factors may influence the manifestations of neurofibromatosis. A review of the literature on monozygotic twins with neurofibromatosis is given.

Adult↗

Metabolism of leukotriene A4 by an enzyme in blood plasma: a possible leukotactic mechanism.

Cell-free mammalian plasma transformed leukotriene A4 into leukotriene B4. This conversion originated from a soluble enzymatic activity. Heating at 56 degrees C or digestion of plasma with a proteolytic enzyme eliminated formation of leukotriene B4 but not other diastereomeric dihydroxyicosatetraenoic acids formed by nonenzymatic hydrolysis of leukotriene A4. Plasma from several mammals, including guinea pigs, pigs, cows, sheep, rabbits, rats, dogs, and humans, exhibited a qualitatively similar activity. Maximal production of leukotriene B4 occurred in guinea pig plasma near a pH of 7.6; metabolic capacity approached saturation at a substrate concentration of 10 microM. Leukotriene A4 anion was transformed but not its methyl ester. The results suggest that conversion of leukotriene A4 by an enzyme in blood plasma of mammals may provide local gradients of the chemotactic substance leukotriene B4. High interfacial concentrations of leukotriene B4 between the vascular endothelium and leukocytes could facilitate their diapedesis and accumulation at inflammatory sites.

Animals↗

Amblyopia in 4-year-old children treated with grating stimulation and full-time occlusion; a comparative study.

We have compared the effects on visual acuity and binocular functions of grating stimulation (CAM therapy) and full-time occlusion in 38 4-year-old, previously untreated amblyopic children. The patients were divided into subgroups with regard to amblyopia type and fixation pattern. We found that grating stimulation was slightly better than occlusion in improving visual acuity of anisometropic amblyopes with central fixation, but that both types of therapy were equally effective in strabismic amblyopia with central fixation and in amblyopia with eccentric fixation. However, maximal treatment effects were not reached with grating stimulation alone, as shown at follow-up after continued conventional therapy. Grating stimulation may be regarded as a valuable method at the initiation of treatment, particularly in anisometropic amblyopia, but it has to be supplemented with occlusion, which still must be regarded as the prime form of amblyopia therapy.

Amblyopia↗

Renal transplantation across a blood group barrier--'A2' kidneys to 'O' recipients.

The outcome of 11 renal transplants with kidneys from blood group A2 donors to blood group O recipients is reported. Eight grafts had a satisfactory function, three early losses were noted: one acute rejection after four weeks, two technical failures. The longest survival is four years, the patient died from septicaemia with a functioning graft. Obviously, the blood group A2-O incompatibility is not an obstacle to successful organ transplantation.

ABO Blood-Group System↗

On the mechanism of biosynthesis of leukotrienes and related compounds.

[10D-3H; 3-14C]- and [10L-3H; 3-14C]arachidonic acids were incubated with human polymorphonuclear leukocytes and with human platelets. Leukotriene B4 and 5(S),12(S)-dihydroxy-6trans,8cis,10trans,14-cis-eicosatetraenoic acid (5,12-DHETE) were isolated and the 3H/14C ratios determined. It could be concluded that the 10D (pro-R)-hydrogen is eliminated in the conversion of 5(S)-hydroperoxy-6trans,8-cis,11cis,14cis-eicosatetraenoic acid into leukotriene A4 whereas in the conversion of arachidonic acid into 5,12-DHETE the 10L (pro-S)-hydrogen is lost. Incubation of the doubly labeled arachidonic acids with human platelets confirmed and extended previous data on the stereochemistry of the hydrogen removal from C-10 during the conversion into 12(S)-hydroperoxy-5cis,8cis,10trans,14cis-eicosatetraenoic acid, i.e., the 10L (pro-S)-hydrogen is eliminated and the 10D (pro-R)-hydrogen retained.

Arachidonic Acid↗

A novel leukotriene produced by stimulation of leukocytes with formylmethionylleucylphenylalanine.

Stimulation of human polymorphonuclear leukocytes with the chemotactic peptide formylmethionylleucylphenylalanine led to the formation of a novel leukotriene: 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraen-1,20-dioic acid. This dihydroxydicarboxylic acid is derived from omega-oxidation of 5(S),12(R),dihydroxy-6,8,10,14-eicosatetradienoic acid (leukotriene B4). The intermediate 5(S),12(R),20-trihydroxy-6,8,10,14-eicosatetraenoic acid was also isolated from these incubations. The two metabolites of leukotriene B4 exhibit chemotactic properties for human polymorphonuclear leukocytes but are less active in this respect than the parent compound.

Arachidonic Acids↗

Effect of leucotrienes C4, D4, prostacyclin and thromboxane A2 on isolated human cerebral arteries.

The effects of leucotrienes C4 (LTC4), D4 (LTD4), Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were studied on superfused human cerebral artery strips. LTC4 and LTD4 neither contracted nor relaxed the strips. PGI2 caused a dose-dependent relaxation from 0.2 nmol to 0.8 nmol. When given simultaneously with a vasoconstrictor substance, PGI2 had an almost complete inhibitory effect. TXA2 caused a dose-dependent contraction from 0.03 nmol to 0.15 nmol. Also, TXA2 was more potent than 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) with a contraction threshold of about 0.1 nmol. Prostaglandin E1 (PGE1), H2 (PGH2), and F2a (PGF2a) had contraction thresholds of about 1 nmol. Only a stable endoperoxide analogue (EPA), was more potent than TXA2, with a contraction threshold of 0.005 nmol. The possible role of these substances in producing ischaemic manifestations after subarachnoidal haemorrhage (SAH) is discussed.

Aged↗

Localization and characteristics of transglutaminase in the rabbit and human eye.

Transglutaminases (transamidases; endo-gamma-glutamine: zeta-lysine transferases) are calcium-dependent enzymes, which cross-link proteins by introducing covalent zeta-(gamma-glutaminyl)lysine pseudopeptide bonds between the molecules. The distribution and characteristics of transglutaminase in both human and rabbit eyes have been studied. Transglutaminase activity was measured with an isotope technique based on the enzyme catalysed incorporation of 14C-putrescine into casein. Electrophoretic characteristics were studied using agarose gel electrophoresis combined with a specific fluorescent activity staining procedure based on the transglutaminase catalysed incorporation of monodansylthiacadaverine into casein. A thrombin-independent enzyme, indistinguishable from the guinea pig liver transglutaminase with regard toi electrophoretic mobility, was found in the choroid/pigment epithelium and ciliary body of the human eye while the lens, retina, iris and vitreous humour did not contain detectable amounts. The lens and the choroid/pigment epithelium of the rabbit eye tissues contained high activities while the activity in the extract from the combined ciliary body/iris was low but measurable.

Aged↗