New group of leukotrienes formed by initial oxygenation at C-15.
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Biomedical subjects
Publications and source records attributed to B Samuelsson.
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A ganglioside named GM1b (Hirabayashi, Y., Taki, T., and Matsumoto, M. (1979) FEBS Let. 100, 253-257) with a sugar composition identical with that of GM1, II3 alpha NeuAc-GgOse4Cer (Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal(3 leads from 2 alpha NeuAc) beta 1 leads to 4G1c beta 1 leads to 1'ceramide), isolated from rat ascites hepatoma was further characterized. In contrast to GM1, the sialic acid in this ganglioside was susceptible to clostridial sialidase in the absence of bile salts. Based on the sequential enzymic hydrolysis, permethylation analysis and direct probe mass spectrometric analysis, the structure of this ganglioside is determined to be: NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal beta 1 leads to 4Glc leads to ceramide. The structure of this ganglioside is identical with that biosynthesized in vitro (Stoffyn, A., Stoffyn, P., and Yip, M. C. M. (1975) Biochim. Biophys. Acta 409, 97-103).
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In the nervous tissue of miniature pig, type Göttingen, three fucosyl-containing gangliosides are major gangliosides. All three were found in dorsal-root ganglia and spinal cord, but only two of them in the forebrain. The concentrations of these gangliosides were increased in chloroquine intoxication. Their chemical structures were determined by component analysis, partial acid and enzymatic degradation and assay of the partially methylated sugars after hydrolysis, reduction and acetylation. Mass spectrometric analysis of the intact gangliosides as permethylated, permethylated-reduced and permethylated-reduced-silylated derivatives confirmed the following structures of the three gangliosides. (See Formula in text).
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Leukotrienes B4, C4, and D4, members of a recently discovered family of substances biosynthesized from arachidonic acid, were found to have potent microvascular actions in the hamster cheek pouch. When applied topically to the vascular network, leukotrienes C4 and D4 caused an intense constriction of arterioles, being similar to angiotensin in potency in this respect. The vasoconstriction induced by leukotrienes C4 and D4 was short-lived, and it was consistently followed by a marked and dose-dependent extravasation of macromolecules from postcapillary venules. Histamine did not constrict arterioles, but it elicited leakage of plasma, although on a molar basis it was no more than 1/1000th as potent as the leukotrienes. When used in the same concentration range as leukotrienes C4 and D4, leukotriene B4 did not evoke vasoconstriction or promote plasma leakage. On the other hand, leukotriene B4 caused a conspicuous and reversible adhesion of leukocytes to the endothelium in postcapillary venules. Our findings that leukotrienes induce microcirculatory alterations in vivo, closely resembling the early events in the acute inflammatory response, imply that leukotrienes, formed in several blood-borne and tissue-bound cells, may mediate important microcirculatory adjustments to noxious stimuli.
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We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate-traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(-7)M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at greater or equal to 2.5 x 10(-5)M, but not at lower concentrations. Thus, since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, it is suggested that these mediators could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.
Ninety-six persons, living in Gothenburg, Sweden, on the first of January 1978 and known by the health services as cases of neurofibromatosis, were investigated concerning clinical and genetic aspects of the disease. Close relatives were also interviewed and examined. The diagnostic criteria were operationally defined according to number of café-au-lait spots and/or neurofibromas. The prevalence of neurofibromatosis was estimated to be 0.02%. The following findings were made in the patients: axillary freckling (48%), neurological symptoms (30%), epilepsy (3-9%), sarcoma (4%), pheochromocytoma (3%), osseous dysplasias (12%), subnormal intelligence (45%) and psychiatric symptoms (33%). The genetic analysis revealed a dominantly inherited disease with full penetrance and a very high mutation frequency, at least 4.3 X 10(-5). Questions commonly encountered during counselling are discussed.