Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have combined a receptor-mediated DNA delivery system with the endosomal lysis ability of adenovirus and shown that DNA can be delivered into primary hepatocytes, resulting in a high level of gene expression. When asialoorosomucoid conjugated with poly(L-lysine) was used to deliver the Escherichia coli beta-galactosidase gene into primary hepatocytes through binding with the hepatic asialoglycoprotein receptor, only a low level of beta-galactosidase was detectable, with less than 0.1% of the hepatocytes being transfected. This level of activity can be greatly enhanced by the cointernalization of the DNA.protein complex with a replication-defective adenovirus, resulting in 100% of the hepatocytes staining blue with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. Quantitative analysis of beta-galactosidase expression also showed a 1000-fold enhancement of activity. To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and demonstrated complete reconstitution of enzymatic activity. This method shows great promise for efficient gene delivery to the liver for correction of hepatic disorders.
 ...
PMID:Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. 838 12

Galactosialidosis is an autosomal recessive inherited metabolic disorder induced by the deficiency of beta-galactosidase and neuraminidase. It can be classified into the early infantile form, the late infantile form, and the juvenile/adult form, by clinical characteristics. This disease has been known to be caused by the lack of protective protein. The human protective protein is synthesized as a 54 kD precursor and then processed to the mature form, a heterodimer of 32 and 20 kD polypeptides. The mature protective protein forms a complex with beta-galactosidase and neuraminidase, stabilizing beta-galactosidase and activating neuraminidase. Recently, this protective protein was found to have other multiple functions including activities of carboxypeptidase, esterase and deamidase. The nature of abnormality of the protective protein in the three subtypes of galactosialidosis however has not yet been well elucidated. On the other hand, a cDNA of the protective protein was cloned, and point mutations in the protective protein gene were found in a Japanese family with the adult form, and in Canadian and Italian patients with the late infantile form. We also detected the same point mutation in two Japanese patients with the adult form. Discovery of the genetic defect in different subtypes of galactosialidosis will contribute to the study on the nature of abnormality in the protective protein itself.
 ...
PMID:[Genetic advances in galactosialidosis]. 841 8

Galactosialidosis (GS) is an autosomal recessive condition caused by combined deficiency of the lysosomal enzymes beta-galactosidase and alpha-neuraminidase. The combined deficiency has been found to result from a defect in protective protein/cathepsin A (PPCA), an intralysosomal protein which protects these enzymes from premature proteolytic processing. The most severe form of GS, the early-infantile form, results in early onset of edema, ascites, visceromegaly, and skeletal dysplasia. We report a case of early-infantile GS in a male infant who presented with nonimmune fetal hydrops (NIH), "coarse" facial appearance, massive fluid-filled inguinal hernias, multiple telangiectasia, and diffuse hypopigmentation; he subsequently developed visceromegaly. The diagnosis of GS was confirmed biochemically and the defect in PPCA characterized at the protein level. Examination of fetal peripheral blood smears sampled at 30 weeks gestation demonstrated vacuolation of lymphocytes, suggesting blood film examination may be a useful screening tool for cases of NIH where a metabolic disorder is suspected. Skeletal radiography at birth demonstrated punctate epiphyses of the femora, calcanei, and sacrum. We present a discussion of and differential diagnosis for this radiographic finding. To the best of our knowledge, this is the first case of early-infantile GS presenting with stippled epiphyses.
 ...
PMID:Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up. 1037 11