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Biomedical subjects

L Dorland

Publications and source records attributed to L Dorland.

At least 73 records · Page 4Linked to original sources
PubMed1990

Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency.

Deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is a common inherited defect in energy metabolism. Characterization of the mRNA encoding MCAD in a Dutch MCAD-deficient patient revealed an A----G change at nucleotide position 985 of the MCAD mRNA coding region. This point mutation results in the substitution of a glutamic acid for a lysine at amino acid position 304 of the mature protein. The single base change was not found in any wild-type MCAD mRNAs. A mutant allele-specific oligonucleotide probe was used in a hybridization analysis of amplified genomic DNA of MCAD-deficient family members, a carrier, and normal individuals. The hybridization analysis specifically identified individuals who were heterozygotes or homozygotes. In addition to the point mutation, a significant proportion of the index patient's MCAD mRNA contained a variety of deletions and insertions as a result of exon skipping and intron retention. The missplicing occurred in multiple regions throughout the MCAD mRNA. Analysis of the patient's MCAD gene in the regions where the missplicing occurred most frequently did not reveal a mutation in the splicing acceptor or donor sites. Therefore, the molecular characterization of this family revealed a crucial point mutation in the MCAD gene and an unusual abnormality in MCAD pre-mRNA splicing.

Acyl-CoA Dehydrogenase↗
PubMed1990

Secondary carnitine deficiency.

For any given tissue the normal carnitine content is that which is necessary for an optimal rate of long-chain fatty acid oxidation. Tissues especially rich in carnitine are liver, muscle and heart. The endogenous rate of carnitine biosynthesis from lysine and methionine is not known to be influenced by fluctuations in the levels of the parent amino acids, as exemplified by hypermethioninaemic patients. Inadequate dietary supply of carnitine, leading to a deficiency, may occur in vegetarians and especially in subjects on total parenteral nutrition. Premature babies are especially at risk in this respect, and this has led to the addition of carnitine to solutions for intravenous alimentation. It has been suggested that carnitine plays an important role in the intramitochondrial regulations of coenzyme A homeostasis by expelling short-chain and medium-chain acyl groups from the mitochondrion in the form of acylcarnitines. These esters are preferentially excreted into the urine and thus result in a depletion of the body's carnitine stores. Important conditions in this respect are the inherited organic acidurias and disorders of fatty acid oxidation. Urinary acylcarnitines can be identified by indirect gas chromatographic or direct mass spectrometric methods. Patients on haemodialysis treatment will lose carnitine in the dialysis fluid, whereas excessive urinary losses of free and acetylated carnitine occur in the Fanconi syndrome. Secondary carnitine deficiency may be accompanied by a moderate degree of muscular dysfunction. Reassuringly, however, no signs of hepatic or cardiac involvement, as often seen in primary carnitine deficiency, have been observed.

Adolescent↗
PubMed1988

Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I.

A sensitive and accurate isotope dilution assay using electron capture negative ion mass fragmentography was developed for succinylacetone in amniotic fluid, plasma and urine. The method utilizes (D4)-5(3)-methyl-3(5)-isoxasole propionic acid as internal standard. Sample pretreatment consisted of oximation at pH less than 2 to 5(3)-methyl-3(5)-isoxasole propionic acid, clean up using liquid partition chromatography and further derivatization to the pentafluorobenzyl ester. Control values in plasma revealed a mean means = 0.044 mumol/l, range = 0.005-0.163 mumol/l, in urine means = 0.15 mumol/l, range 0.01-0.40 mumol/l corresponding to means = 0.03 mumol/mmol creat., range 0.01-0.14 mumol/mmol creat., and in amniotic fluid means = 0.016 mumol/l, range = 0.001-0.030 mumol/l. The utility of the method was demonstrated by quantification of succinylacetone in urine from patients with hereditary tyrosinemia type I (n = 8, excretion range 2.60-493.3 mumol/l corresponding to 0.67-197.3 mumol/mmol creat.) and in two amniotic fluid samples from fetuses affected with this disorder (concentration of succinylacetone 0.085 and 1.50 mumol/l, respectively). Maternal urine from a woman carrying an affected fetus did not show elevated urinary succinylacetone excretion.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Fast atom bombardment/collisional activation mass spectrometry of beta-D-mannosyl-(1----4)-beta-D-N-acetylglucosaminyl (1----N) urea and related compounds.

A new compound, obtained during the isolation of oligosaccharides from the urine of two brothers affected with inherited beta-mannosidase deficiency, has been investigated using fast atom bombardment ionization and MS/MS techniques. The compound could be characterized as an N-acetylglucosamine molecule linked to a hexose and a urea molecule.

Disaccharides↗
PubMed1987

Urinary excretion of 2-methyl-2,3-butanediol and 2,3-pentanediol in patients with disorders of propionate and methylmalonate metabolism.

Urine samples from patients with propionic acidemia and from a patient with methylmalonic acidemia contained unknown non-acidic metabolites by gas chromatography/mass spectrometry after ethyl acetate extraction. It could be demonstrated by mass spectrometric studies and by synthesis of reference compounds that the major metabolite was 2-methyl-2,3-butanediol, while smaller amounts of 2,3-pentanediol were also present. These diols were present in abnormal amounts in these patients during attacks of metabolic decompensation.

Acidosis↗
PubMed1986

1,6-Anhydro-beta-D-glucopyranose (beta-glucosan), a constituent of human urine.

When screening for abnormal urinary saccharides with one-dimensional thin-layer chromatography, an unknown component was observed in a position just above that of xylose. This compound was studied by gas chromatography-mass spectrometry and identified as the anhydro sugar beta-glucosan. It was observed in approximately 20% of all urine samples investigated by thin-layer chromatography. Excretory levels varied widely from zero up to 5.3 mmol/l. No correlation with age or disease could be established. The compound was thought to be of exogenous origin.

Adolescent↗
PubMed1986

A 500-MHz 1H-n.m.r. study of oligosaccharides derived from gangliosides by ozonolysis-alkaline fragmentation.

The structural-reporter-group resonances in the 1H-n.m.r. spectra of a series of ganglioside-derived oligosaccharides are completely assigned. The three different types of sialic acid residues which may occur in these compounds could be adequately characterized. They are distinguishable on the basis of the set of chemical shifts of their H-3a and H-3e atoms. The mutual influence of GalNAc beta-(1----4) and Neu5Ac alpha-(2----3), both linked to the same Gal residue, on the 1H-n.m.r. parameters of each other, reflects a well-defined solution conformation, which is held to be responsible for the resistance of this "internal" sialic acid towards various sialidases.

Animals↗
PubMed1985

Octanoylglucuronide excretion in patients with a defective oxidation of medium-chain fatty acids.

Octanoyl-beta-D-glucuronide was identified in the urine of five patients with hypoketotic hypoglycemia and dicarboxylic aciduria due to a defective beta-oxidation of medium-chain fatty acids. Two subjects who ingested large amounts of medium-chain triglycerides also excreted large amounts of the glucuronide. The substance was extracted from the urine with ethyl acetate and analyzed by: (1) gas chromatography/mass spectrometry (GC-MS) of the trimethylsilyl derivative and (2) preparative one-dimensional thin-layer chromatography followed by enzymatic hydrolysis with beta-glucuronidase and again GC-MS. A quantitative analysis was performed indirectly by measuring the urinary bound octanoate after the removal of octanoylcarnitine. Octanoylglucuronide represents an additional mechanism for the detoxification of octanoate; its formation may be of help for the maintenance of carnitine homeostasis in patients with medium-chain acyl-CoA dehydrogenase deficiency.

Acyl-CoA Dehydrogenase↗
PubMed1985

Studies on the interaction of Clostridium perfringens sialidase with sialic acid linked to the internal galactose in monosialogangliotetraosyl ceramide.

Investigation of the action of highly purified Clostridium perfringens sialidase on ganglioside II3Neu5Ac-Gg4Cer and its oligosaccharide II3Neu5Ac-Gg4, in the presence and absence of sodium cholate, extend earlier results obtained with impure enzyme fractions. Sialidase labeled with 125I was found to bind to various ganglioside substrate micelles, including II3Neu5Ac-Gg4Cer, and to mixed ganglioside-sodium cholate micelles. No binding occurred between the enzyme and the ganglioside-derived oligosaccharide II3Neu5Ac-Gg4, even when radioactive II3Neu5Ac-Gg4-[3H]ol was used. The binding of sialidase to micellar substrate is a condition for enzymic hydrolysis. Correspondingly, II3Neu5Ac-Gg4Cer and II3Neu5Ac-Gg4Cer-sodium cholate micelles were hydrolyzed by the enzyme but II3Neu5Ac-Gg4 was not. Ganglioside oligosaccharide analogues containing an amino function at the reducing terminus or between two oligosaccharide chains, II3Neu5Ac-Gg4-NH2 and (II3Neu5Ac-Gg4)2NH, were hydrolyzed in the absence of cholate. A synthetic analogue of II3Neu5Ac-Gg4Cer containing only the fatty acid moiety and not the sphingosine residue (I1-deoxy-I1-stearamido-II3-monosialo-gangliotetraitol ) behaved as the ganglioside in the presence and absence of sodium cholate.

Chemical Phenomena↗
PubMed1984

The identification of terminal alpha (1----3)-linked galactose in N-acetyllactosamine type of glycopeptides by means of 500-MHz 1H-NMR spectroscopy.

500-MHz 1H-NMR spectroscopy was employed to study two N-acetyllactosamine-type glycopeptide fractions which were derived from a bovine thyroglobulin preparation (Cummings, R.D., and Kornfeld, S. (1982) J. Biol. Chem. 257, 11230-11234). By this method, their branches were found to be terminated either by NeuAc in alpha (2----6)-linkage or by Gal in alpha (1----3)-linkage. For the first time, the Gal alpha (1----3) Gal beta (1----4) GlcNAc beta (1----.) sequence is characterized by 1H-NMR to occur in N-glycosidic carbohydrate chains of glycoproteins. Moreover, this approach made possible the branch localization of such a unit. Microheterogeneity with respect to the presence of alpha-linked Gal or NeuAc in terminal position of a certain branch in one of the preparations, could be adequately assessed in terms of structures by 1H-NMR.

Amino Sugars↗
PubMed1984

The structure of sialyl-glycopeptides of the O-glycosidic type, isolated from sialidosis (mucolipidosis I) urine.

Sialyl-glycopeptides containing an O-glycosidically linked tetrasaccharide chain were obtained from the urine of a patient suffering from mucolipidosis I. Isolation of these compounds was achieved by gel filtration, ion-exchange chromatography and preparative paper chromatography. Their structures were determined by a combination of carbohydrate and amino acid analysis, dansylation, periodate oxidation, methylation studies, enzymatic hydrolysis and 1H-NMR spectroscopy, to be as follows: (formula; see text) wherein R = peptide linked through -Thr-, -Ser-Thr- or -Thr-Ser-. The finding of these glycopeptides in urine shows that mucolipidosis I is characterized by a general "glycoprotein-specific" sialidase deficiency. The possibility of the existence of a human endo-alpha-N-acetylgalactosaminidase is discussed.

Amino Acids↗