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Biomedical subjects

J Dabrowski

Publications and source records attributed to J Dabrowski.

At least 91 records · Page 5Linked to original sources

Structures of fucose-containing ceramide pentasaccharides from the plasma of blood group O Le(a-b-) nonsecretors.

A minor, Lec blood-group inactive ceramide pentasaccharide double band fraction has been isolated from the plasma of blood group O Le(a-b-) nonsecretors. The two purified glycolipids were analysed by NMR spectroscopy, mass spectrometry and combined gas chromatography-mass spectrometry. The following structures could be established: GlcNAc(beta 1----3)Gal(beta 1----4)Glc(beta 1----1)Cer (I); Gal(beta 1----4) [Fuc(alpha 1----3)]GlcNAc(beta 1----3)Gal(beta 1----4)Glc(beta 1----1)Cer (II). It must be concluded that at least part of the secretor gene-independent plasmatic H type 2 blood-group activity can be attributed to glycosphingolipid I, whereas substance II, originally detected in cancerous tissue, also occurs in the plasma of healthy individuals.

ABO Blood-Group System↗

Immunochemistry of I/i-active oligo- and polyglycosylceramides from rabbit erythrocyte membranes. Determination of branching patterns of a ceramide pentadecasaccharide by 1H nuclear magnetic resonance.

1H NMR spectra of the ceramide hexasaccharide obtained after the removal of the terminal alpha-Gal and subterminal beta-Gal residues from the ceramide decasaccharide, Gal(alpha 1-3)Gal(beta 1-4)GlcNAc(beta 1-3)[Gal(alpha 1-3)Gal(beta 1-4)GlcNAc (beta 1-6)]Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer, showed that terminal and internal GlcNAc residues are differentiated by their chemical shifts. This finding enabled us to determine the primary structure of the title compound as Gal(alpha 1-3)Gal(beta 1-4)GlcNAc (beta 1-3)[Gal(alpha 1-3)Gal(beta 1-4)GlcNAc(beta 1-6)]Gal(beta 1-4)GlcNAc (beta 1-3)[Gal(alpha 1-3)Gal(beta 1-4)GlcNAc(beta 1-6)]Gal(beta 1-4)GlcNAc (beta 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer. Alternative branching of this oligosaccharide chain was excluded since the removal of all terminal alpha-Gal and penultimate beta-Gal residues yielded a ceramide nonasaccharide containing one terminal and two internal 1----3-linked GlcNAc residues, as well as two terminal 1----6-linked GlcNAc units. The intermediate degradation products of the ceramide deca- and pentadecasaccharides , viz. the ceramide octa- and dodecasaccharide , obtained by the removal of alpha-Gal residues only, as well as the linear ceramide heptasaccharide, Gal(alpha 1-3)Gal(beta 1-4)GlcNAc(beta 1-3) Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer, and ceramide hexasaccharide, Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)GlcNAc (beta 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer, were also investigated. The usefulness of the glycosylation-induced chemical shifts is discussed.

Animals↗

Structure elucidation by one- and two-dimensional 360- and 500-MHz 1H NMR of the oligosaccharide units of two glycoproteins isolated from alveoli of patients with alveolar proteinosis.

The structure of the oligosaccharide units of the glycoproteins of Mr 36,000 and 62,000 isolated from alveoli of patients with alveolar proteinosis have been determined by one- and two-dimensional 1H NMR spectroscopy at 500 and 360 MHz. Bi-, tri-, and tetraantennary glycans of N-acetyllactosaminic type have been found in high percentage. They are 1----6 monofucosylated and fully sialylated, the ratio NeuAc(2----3)/NeuAc X (2----6) increasing with increasing degree of branching.

Chemical Phenomena↗

[Effect of forskolin eyedrops on intraocular pressure in healthy males].

Suspensions of Forskolin in concentrations of 0.3; 0.6; and 1.0% decreased effectively the intraocular pressure of healthy subjects when instillated in the conjunctival sac. The suspensions were compared with placebo in double blind studies. The maximum effect was reached 3 hours after application of the 0.3% (22.8%) and 0.6% (27.8%) suspensions and 4 hours after the 1.0% (26.5%) suspension. The higher concentrations decreased the intraocular pressure to the same extent as the lowest concentration but the effect lasted longer: 4 hours after instillation of the 0.3% suspension, 5 hours after instillation of the 0.6% suspension and 7 hours after the 1.0% suspension. The suspensions were well tolerated. Subjective sensations like burning, itching and augmentated lacrimation were observed only in a minor amount and for a short period of time.

Adult↗

Congenital fascial dystrophy--a noninflammatory disease of fascia: the stiff skin syndrome.

Our patient's disease was similar to the persons with stiff skin syndrome described by Esterly and McKusick (1). Stony-hard indurations of the skin and deeper tissue were generalized but most pronounced in the buttocks, thighs, and legs, with limitation of joint mobility and particularly extensive contractures in the lower limbs. The disease was noticed when the patient was 18 months old, and was nonprogressive within a follow-up period of 12 years. There was no visceral involvement except functional impairment of the lungs, probably due to thickened thoracic fascia. Biochemical, histologic, and electron microscopic studies of the skin and muscle were not remarkable. In skin fibroblasts, collagen synthesis was increased and was accompanied by elevated activity of the prolylhydroxylase and lysylhydroxylase, whereas the transferases were not altered. The fascia was considerably thickened, but contained no inflammatory infiltrates. The significant electron microscopic finding was the presence of amianthoid-like collagen fibers in the fascia.

Biopsy↗

Proton-nuclear magnetic resonance study of peracetylated derivatives of ten oligosaccharides isolated from human milk.

Proton-nuclear magnetic resonance (NMR) spectra of peracetylated derivatives of ten structurally related oligosaccharides isolated from human milk were measured for solutions in CDCl3 at 360 MHz. The following oligosaccharides were investigated: Gal beta 1 leads to 4Glc-ol (1), GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc-ol (2), Gal beta 1 leads to 4GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc-ol (3), Gal beta 1 leads to 3GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc-ol (4), Gal beta 1 leads to 3GlcNAc(4 comes from 1Fuc alpha) beta 1 leads to 3Gal beta 1 leads to 4Glc-ol (5), Fuc alpha 1 leads to 2Gal beta 1 leads to 3GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc-ol (6), Fuc alpha 1 leads to 2Gal beta 1 leads to 3GlcNAc(4 comes from 1Fuc alpha)beta 1 leads to 3Gal beta 1 leads to 4Glc-ol (7), Fuc alpha 1 leads to 2Gal beta 1 leads to 4Glc-ol(3 comes from 1Fuc alpha) (8), and a 1:3 mixture of Fuc alpha 1 leads to 2Gal beta 1 leads to 4Glc-ol (9) and Gal beta 1 leads to 4Glc-ol(3 comes from 1Fuc alpha) (10). Owing to the strong downfield shifts of the resonances of protons linked to acetoxylated carbons, the problems of signal overlap are less severe and the spin systems of all constituent sugar residues can be assigned fully. The sites of glycosidic linkage can be recognized by the high-field position of the signals of protons linked to those sites; for example, type 1 (Gal beta 1 leads to 3GlcNAc) and type 2(Gal beta 1 leads to 4GlcNAc) saccharide chains can be distinguished. The sequence can be established by observing a nuclear Overhauser effect involving the anomomeric and the aglyconic proton.

Acetylation↗

Unexpected similarity of the structures of the weakly toxic amanitin (S)-sulfoxide and the highly toxic (R)-sulfoxide and sulfone as revealed by proton nuclear magnetic resonance and X-ray analysis.

The three-dimensional structures of the slightly toxic diastereomeric (S)-sulfoxide of 6'-O-methyl-alpha-amanitin [6'-O-Me-alpha-ama (S)-sulfoxide, 4] and of the corresponding highly toxic sulfone 5 have been determined by X-ray diffraction analysis. The same derivatives along with 6'-O-methyl-alpha-amanitin [O-Me-alpha-ama (R)-sulfoxide, 3] and the corresponding thioether (O-Me-alpha-ama sulfide, 6] have been investigated in dimethyl sulfoxide solutions by 360-MHz 1H NMR spectroscopy including nuclear Overhauser effects (NOE). In addition alpha-amanitin (2) has been reinvestigated by this high-resolution method involving the identification of the ABMX systems of the tryptophan, cysteine, and asparagine and discrimination between the glycine residues. The structures of compounds 2-6 are compared with the structure of beta-amanitin which was solved previously by X-ray structure analysis. The results are (1) the structures in the crystalline state of the (S)-sulfoxide 4 and sulfone 5 are practically identical and (2) in dimethyl sulfoxide solution the structures of compounds 4 and 5 are likewise identical with each other and with those of the (R)-sulfoxide 3 and the thioether 6. The general structure of the peptide backbone of the alpha-amanitin derivatives investigated here almost corresponds to that of beta-amanitin (1), the main difference being a rotated plane of the peptide bond between the asparagine and cysteine residue. In order to explain the lack of high toxicity in the (S)-sulfoxide 4 we tentatively suggest alternative hydrogen bonding of a donor from the protein, or displacement of the R oxygen to the S oxygen of a hydrogen bond donor. This alternative bonding or displacement might not occur in the sulfoxide 4. Other explanations which include local conformational changes in the inhibitors or a difference between the SO and SO2 local dipoles are also possible.

Amanitins↗

Structural analysis of glycosphinoglipids by high-resolution 1H nuclear magnetic resonance spectroscopy.

The carbohydrate composition of eight glycosphingolipids--glucosylceramide, lactosylceramide, lacto-N-triaosylceramide, neolactotetraosylceramide, IV3Gal alpha neolactotetraosylceramide, globotriaosylceramide, globoside (P-antigen), and Forssman glycolipid (IV3GalNAc alpha GbOse4Cer)--derived from different sources was analyzed by 1H nuclear magnetic resonance at 360 MHz in dimethyl-d6 sulfoxide as solvent. The resonances of all H-1 and H-2 protons as well as those of most of the H-3 and H-4, and of some H-5 protons, of the sugar rings were assigned with the aid of spin decoupling difference spectroscopy. They show regularities related to the type, anomeric configuration, site of glycosidic linkage, and sequence of the component sugars glucose, galactose, glucosamine, and galactosamine. These regularities are thus suited for elucidation of hitherto unknown structure of more complex glycosphingolipids.

Acetylgalactosamine↗