9 research outputs found

    Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

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    Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT. © 1999 Cancer Research Campaign © 1999 Cancer Research Campaig

    Alpha-mannosidosis in the guinea pig: A new animal model for lysosomal storage disorders

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    Alpha-mannosidosis is a lysosomal storage disorder resulting from deficient activity of lysosomal alpha-mannosidase. It has been described previously in humans, cattle, and cats, and is characterized in all of these species principally by neuronal storage leading to progressive mental deterioration. Two guinea pigs with stunted growth, progressive mental dullness, behavioral abnormalities, and abnormal posture and gait, showed a deficiency of acidic alpha-mannosidase activity in leukocytes, plasma, fibroblasts, and whole liver extracts. Fractionation of liver demonstrated a deficiency of lysosomal (acidic) alpha-mannosidase activity. Thin layer chromatography of urine and tissue extracts confirmed the diagnosis by demonstrating a pattern of excreted and stored oligosaccharides almost identical to that of urine from a human alpha-mannosidosis patient. Widespread neuronal vacuolation was observed throughout the CNS, including the cerebral cortex, hippocampus, thalamus, cerebellum, midbrain, pons, medulla, and the dorsal and ventral horns of the spinal cord. Lysosomal vacuolation also occurred in many other visceral tissues and was particularly severe in pancreas, thyroid, epididymis, and peripheral ganglion. Axonal spheroids were observed in some brain regions, but gliosis and demyelination were not observed. Ultrastructurally, most vacuoles in both the CNS and visceral tissues were lucent or contained fine fibrillar or flocculent material. Rare large neurons in the cerebral cortex contained fine membranous structures. Skeletal abnormalities were very mild. Alpha-mannosidosis in the guinea pig closely resembles the human disease and will provide a convenient model for investigation of new therapeutic strategies for neuronal storage diseases, such as enzyme replacement and gene replacement therapies.Allison C Crawley, Margaret Z Jones, Lynda E Bonning, John W Finnie and John J Hopwoo

    History and Development of Food-Based Attractants

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