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388 results on '"Sly, W. S."'

16. Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII

Author

Vervoort, R., Islam, M. R., Sly, W. S., Zabot, M. T., Kleijer, W. J., Chabas, A., Fensom, A., Young, E. P., Liebaers, I., and Lissens, W.

Subjects
Adult, DNA, Complementary, Base Sequence, Hydrops Fetalis, RNA Splicing, DNA Mutational Analysis, Molecular Sequence Data, Infant, Newborn, Mucopolysaccharidosis VII, Fibroblasts, Polymerase Chain Reaction, Gene Frequency, Chlorocebus aethiops, Animals, Humans, Point Mutation, Amino Acid Sequence, Genetic Testing, RNA, Messenger, Alleles, Cells, Cultured, Polymorphism, Single-Stranded Conformational, Research Article, Glucuronidase
Abstract

Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. We used reverse-transcription-PCR-SSCP and direct sequencing to screen for mutations in the human beta-glucuronidase cDNA of 17 MPS VII patients with severe presentation of the disease. Mutations resulting in an unstable mRNA were detected in genomic DNA with direct sequencing of the PCR-amplified beta-glucuronidase exons. We found extensive genetic heterogeneity in MPS VII alleles: in addition to 6 or 12 previously reported mutations (L176F, R216W, R357X, R382C, W507X, and W627C), we detected 14 undescribed mutations in the beta-glucuronidase coding region that produce MPS VII alleles (G136R, E150K, S312X, Y320S, Y320C, H351Y, R382H, R374C, R435P, R477W, G572D, Y508C, K606N and 1900 delta GA). The mutations in hydropic fetuses were widely scattered in the beta-glucuronidase gene. Analysis of three polymorphic sites of the mutant alleles (1766T/C, 1972C/T and a new 1091+27C/G polymorphism) allowed exclusion of identity by descent for some recurrent mutations. Three of four mutations introducing a premature translation stop codon were found to affect mRNA abundance and/or structure. Expression studies provided evidence for the causal relationship between each of the mutations found in MPS VII alleles and the enzyme deficiency, in that all mutations identified exhibited markedly reduced enzyme activity expressed in COS7 cells following transfection with the mutant cDNA.

Published
1996

45. Differential expression of cytoplasmic carbonic anhydrases, CA I and II, and membrane-associated isozymes, CA IX and XII, in normal mucosa of large intestine and in colorectal tumors.

Author

Kivela, A J, Saarnio, J, Karttunen, T J, Kivelä, J, Parkkila, A K, Pastorekova, S, Pastorek, J, Waheed, A, Sly, W S, Parkkila, T S, and Rajaniemi, H

Abstract

This study compares the localization of carbonic anhydrase isozymes (CA) I and II and that of IX and XII in normal large intestine and in colorectal tumors. Immunohistochemical studies were performed on 69 colorectal lesions. While the normal mucosa of the large intestine showed high expression for CA I and II, the intensity of the immunostaining for both isozymes decreased in benign lesions and was very weak in malignant tumors. The reciprocal pattern of expression observed for these cytoplasmic isozymes and transmembrane CA IX and XII in intestinal tissue specimens supports the suggestion that CA IX and XII may be functionally involved in tumor progression to malignancy and/or in invasion. By contrast, while CA I and II are prominent in normal colorectal mucosa, where they play a role in regulation of pH homeostasis and water and ion transport, loss of expression of these cytoplasmic isozymes consistently accompanies progression to malignant transformation. [ABSTRACT FROM AUTHOR]

Published
2001

46. Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous A619V mutation.

Author

Yamada, Y, Kato, K, Sukegawa, K, Tomatsu, S, Fukuda, S, Emura, S, Kojima, S, Matsuyama, T, Sly, W S, Kondo, N, and Orii, T

Subjects
BONE marrow transplantation, MUCOPOLYSACCHARIDOSIS treatment, GENETIC mutation
Abstract

A 12-year-old girl with Sly disease (mucopoly- saccharidosis VII; β-glucuronidase deficiency), who is homozygous for the A619V mutation, had a successful allogeneic BMT, donored by an HLA-identical unrelated female to replace the deficient enzyme. Within 5 months after BMT, the enzyme activity of the recipient’s lymphocytes increased to normal range. No signs of acute or chronic GVHD were observed. For the successive 31 months post-BMT, β-glucuronidase activity in her lymphocytes was maintained at almost normal levels and excretion of glycosaminoglycans in the urine was greatly diminished. Ultrastructural findings demonstrated no abnormal vacuoles and inclusion bodies in the cytoplasm of her rectal mucosal cells. Coincident with the restoration of the enzyme activity, clinical improvement was dramatic. Especially notable were improvements in motor function. The patient was able to walk alone for a long time without aid, and she even became able to ride a bicycle and take a bath. In addition, recurrent infections of the upper respiratory tract and the middle ears decreased in frequency and severity, and dyspnea on exertion, severe snoring and vertigo have substantially improved. Thus, allogeneic BMT in this patient produced a better quality of life and provided a more promising outlook. [ABSTRACT FROM AUTHOR]

Published
1998
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