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)

This report concerns a 3-month-old girl with rapidly progressive psychomotor retardation, hepatomegaly, vacuolated lymphocytes, minimal bone dysplasia and normal excretion of acid mucopolysaccharides. A deficiency of acid beta-galactosidase was demonstrated in isolated leucocytes and in a liver biopsy. The diagnosis of generalized gangliosidosis due to deficiency of beta-galactosidase was also based on the absence of the enzyme activity from cultured fibroblasts. The diagnosis was confirmed on autopsy at 16 months by typical histology, electron microscopy and biochemistry of the organs. beta-galactosidase deficiency has been demonstrated in various clinical conditions ranging from generalized gangliosidosis with severe mental retardation to clinical pictures resembling Morquio's disease and normal intelligence. The heterogeneity of the clinical manifestations in beta-galactosidase deficiency could be explained by different residual activities of a structurally mutated enzyme towards its various substrates.
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PMID:Generalized gangliosidosis: acid beta-galactosidase deficiency with early onset, rapid mental deterioration and minimal bone dysplasia. 6 26

The cell-mediated immune response (CMI) to E6 and E4 fusion proteins of human papillomavirus type 16 (HPV-16), E6 fusion protein of HPV-18, and to control proteins similarly produced, was analysed in 29 patients with cervical intraepithelial neoplasia (CIN) and in 15 age-matched laboratory personnel using a lymphocyte proliferation assay (LPA). Compared to controls without any added proteins, a positive response (stimulation index greater than 2.0) to the highly purified E6 control protein was found in only one patient. Positive responses to the E4 control protein which contained beta-galactosidase were noted in three patients and two controls. With control proteins as baseline, the lymphocytes from nine patients (28%) and three laboratory personnel (20%) responded to at least on HPV fusion protein after 7 days in culture. Stimulation indices were low in both groups with a range of 2.06-4.69 and the difference in incidence of positive responses between the groups is not significant. Proliferative responses to HPV-1 and HPV-2 virion antigens were noted in 6/23 (26%) of the patients and 2/15 (18%) of the other group. No correlation between responsiveness and degree of dysplasia or presence of koilocytes was found in the patient group. The relevance of the low proliferative responses is discussed.
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PMID:Lymphoproliferative response to fusion proteins of human papillomaviruses in patients with cervical intraepithelial neoplasia. 255 32

The clinical and biochemical findings in 3 siblings with Morquio's disease type B (mucopolysaccharidosis (MPS) IV B) are presented. Their phenotype is characterised by short trunk dwarfism with kyphoscoliosis and thoracic deformity. Radiographic findings include general platyspondyly, dysplasia of the pelvis and epiphyseal abnormalities. The patients are of normal intelligence. In the urine of all 3 affected children abnormal oligosaccharide excretion was found by thin-layer chromatography and in 1 of them keratosulphaturia was detected. The clinical diagnosis was confirmed biochemically by demonstration of a profound deficiency of beta-galactosidase activity in cultured fibroblasts. The clinical picture is compared with that of other cases in the literature and the possible molecular basis of the different phenotypes of beta-galactosidase deficiency (variants of monosialo-ganglioside-1 (GM1)-gangliosidosis, Morquio's disease type B) is discussed.
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PMID:Morquio's disease type B (beta-galactosidase deficiency) in three siblings. 312 Mar 23

Preneoplastic mucosal changes were studied at six different time-points during dimethylhydrazine (DMH)-induced colorectal carcinogenesis in the rat. After 40 weeks of treatment, seven of 10 animals were bearing a total of 11 colorectal adenocarcinomas. The crypt cell production rate in the normal mucosa of DMH-treated animals was greatly increased in the left colon and rectum and further rose with the duration of the experiment. Focal disturbances of the mucosal architecture could be detected as early as 4 weeks after the initiation of DMH-treatment using a stereomicroscope. Their incidence was greatest in the left colon and rectum and increased strongly with the duration of carcinogen exposure. Characterization of these mucosal alterations, by means of conventional histology, morphometry after microdissection, cell kinetics, mucin histochemistry and quantitative enzyme histochemistry performed with serial sections, revealed mild epithelial dysplasia, a considerable elongation and dilatation of the crypts and a marked increase of the crypt cell production, including a shift of the main proliferative compartment from the basal to the medial crypt segment as well as the occurrence of mitotic figures in the luminal epithelium. In affected crypts, the goblet cells completely lacked sulphomucins and exclusively contained sialomucins. The activities of the enzymes diaminopeptidase IV (brush-border), succinate dehydrogenase (mitochondria) and acid beta-galactosidase (lysosomes) were markedly reduced. We conclude that these early mucosal alterations are indeed preneoplastic lesions and indicate the existence of the adenoma-carcinoma sequence in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of stereomicroscopically identified preneoplastic lesions during dimethylhydrazine-induced colonic carcinogenesis. 314 93

An 18-year-old boy showed childhood onset of mental retardation, neurogenic muscle atrophy with hyperreflexia, Marfan-like features, multiple epiphyseal dysplasia, increased urinary excretion of dermatan sulfate, and decreased lysosomal enzyme activities in beta-galactosidase, beta-glucuronidase, and N-acetyl-beta-D-glucosaminidase. This case may be a new syndrome, the combination of neurogenic muscle atrophy with lysosomal enzyme deficiencies.
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PMID:Juvenile neurogenic muscle atrophy with lysosomal enzyme deficiencies: new disease or variant of mucopolysaccharidosis? 618 76

This report describes a third mucopolysaccharidosis in animals: canine mucopolysaccharidosis VII. The affected dog was the offspring of a father-daughter mating. Weakness in the rear legs was evident at 8 weeks of age and became progressively worse. He had a large head, a shortened maxilla, and corneal granularities. Most joints were extremely lax, easily subluxated, with joint capsules that were swollen and fluctuant. The dog was alert and had apparently normal pain perception. At 13 months of age, there was radiographic evidence of extensive skeletal disease including bilateral femoral head luxation, abnormalities in the shape and density of the carpal and tarsal bones, radiolucent lesions of the epiphyseal regions of most long bones, and cervical vertebral dysplasia and platyspondylia. The electrophoretic pattern of precipitated glycosaminoglycans indicated a predominance of chondroitin sulfate. The animal died suddenly from gastric dilatation. There was generalized hepatomegaly, thickening of the atrioventricular heart valves, and generalized polyarthropathy. Vacuolated cytoplasm was observed in hepatocytes, keratocytes, fibroblasts, chondrocytes and cells of the synovial membrane, retinal pigment epithelium, and cardiac valves. Neurons had cytoplasmic vacuoles. Electron microscopy demonstrated membrane-bound cytoplasmic inclusions in polymorphonuclear leukocytes, hepatocytes, synovium, heart valves and spleen. The activities of 12 lysosomal hydrolases were determined in liver from the affected and control dogs: beta-glucuronidase (EC 3.2.1.31), beta-hexosaminidases A and B (EC 3.2.1.30), alpha-hexosaminidase (EC 3.2.1.-), alpha-L-iduronidase (EC 3.2.1.76), alpha-galactosidase A (EC 3.2.1.22), beta-galactosidase (EC 3.2.1.23), arylsulfatases A and B (EC 3.1.6.1), acid alpha-mannosidase (EC 3.2.1.24), acid beta-mannosidase (EC 3.2.1.25), and N-acetyl-D-galactosamine-6-sulfate sulfatase (EC 3.1.6.-).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-glucuronidase deficiency in a dog: a model of human mucopolysaccharidosis VII. 643 80

Morquio B disease was found in a 15-year-old Japanese boy who presented with progressive generalized skeletal dysplasia without neurological manifestations. Mild keratan sulfaturia was found, and beta-galactosidase was deficient in fibroblasts. Gene analysis revealed two mutant alleles, 83Tyr-->His (Y83H) and 482Arg-->Cys (R482C). The former expressed a low enzyme activity (2-5% of normal), and the latter expressed no detectable enzyme activity.
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PMID:Clinical and molecular analysis of a Japanese boy with Morquio B disease. 758 49

N-Acetylgalactosamine-6-sulfate sulfatase (GALNS) catalyzes the first step of intralysosomal keratan sulfate (KS) catabolism. In Morquio type A syndrome GALNS deficiency causes the accumulation of KS in tissues and results in generalized skeletal dysplasia in affected patients. We show that in normal cells GALNS is in a 1.27-MDa complex with three other lysosomal hydrolases: beta-galactosidase, alpha-neuraminidase, and cathepsin A (protective protein). GALNS copurifies with the complex by different chromatography techniques: affinity chromatography on both cathepsin A-binding and beta-galactosidase-binding columns, gel filtration, and chromatofocusing. Anti-human cathepsin A rabbit antiserum coprecipitates GALNS together with cathepsin A, beta-galactosidase, and alpha-neuraminidase in both a purified preparation of the 1. 27-MDa complex and crude glycoprotein fraction from human placenta extract. Gel filtration analysis of fibroblast extracts of patients deficient in either beta-galactosidase (beta-galactosidosis) or cathepsin A (galactosialidosis), which accumulate KS, demonstrates that the 1.27-MDa complex is disrupted and that GALNS is present only in free homodimeric form. The GALNS activity and cross-reacting material are reduced in the fibroblasts of patients affected with galactosialidosis, indicating that the complex with cathepsin A may protect GALNS in the lysosome. We suggest that the 1.27-MDa complex of lysosomal hydrolases is essential for KS catabolism and that the disruption of this complex may be responsible for the KS accumulation in beta-galactosidosis and galactosialidosis patients.
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PMID:Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate. 891 Apr 59

RAS mutations arise at high frequency (20-40%) in both acute myeloid leukemia and myelodysplastic syndrome (which is considered to be a manifestation of preleukemic disease). In each case, mutations arise predominantly at the N-RAS locus. These observations suggest a fundamental role for this oncogene in leukemogenesis. However, despite its obvious significance, little is known of how this key oncogene may subvert the process of hematopoiesis in human cells. Using CD34+ progenitor cells, we have modeled the preleukemic state by infecting these cells with amphotropic retrovirus expressing mutant N-RAS together with the selectable marker gene lacZ. Expression of the lacZ gene product, beta-galactosidase, allows direct identification and study of N-RAS-expressing cells by incubating infected cultures with a fluorogenic substrate for beta-galactosidase, which gives rise to a fluorescent signal within the infected cells. By using multiparameter flow cytometry, we have studied the ability of CD34+ cells expressing mutant N-RAS to undergo erythroid differentiation induced by erythropoietin. By this means, we have found that erythroid progenitor cells expressing mutant N-RAS exhibit a proliferative defect resulting in an increased cell doubling time and a decrease in the proportion of cells in S + G2M phase of the cell cycle. This is linked to a slowing in the rate of differentiation as determined by comparative cell-surface marker analysis and ultimate failure of the differentiation program at the late-erythroblast stage of development. The dyserythropoiesis was also linked to an increased tendency of the RAS-expressing cells to undergo programmed cell death during their differentiation program. This erythroid lineage dysplasia recapitulates one of the most common features of myelodysplastic syndrome, and for the first time provides a causative link between mutational activation of N-RAS and the pathogenesis of preleukemia.
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PMID:Mutant N-RAS induces erythroid lineage dysplasia in human CD34+ cells. 910 20

Brachyolmia refers to a form of skeletal dysplasia characterized by general platyspondyly without significant epiphyseal, metaphyseal or diaphyseal changes in long bones. Three, possibly four, types of brachyolmia have been defined: Type I-Hobaeck-Toledo type. Type II-Maroteaux and Type III. We report a patient with brachyolmia and present the clinical and radiological findings. A 15-year-old boy presented to our Outpatient Department because of his short stature. His height, weight, head circumference and arm span were 127 cm (< 3rd percentile), (3rd percentile) 39 kg, 55 cm (50th-75th percentile), and 142 cm respectively, and his upper segment/lower segment ratio was 0.91. His neck and trunk were short. He had severe kyphoscoliosis. Slit-lamp examination was normal. Radiologic features included platyspondyly in cervical, thoracic and lumbar vertebrae as well as kyphoscoliosis. Bilateral coxa valga and mild acetabular irregularities were noticed on pelvic radiographies. Levels of chondroitin and heparan sulphate as well as the glycosaminoglycan/creatinine ratio were elevated in the 24-hour urine specimen. The activities of N-acetylgalactosamine-6-sulphatase, beta-galactosidase and beta-hexosaminosidase were all normal in fibroblast culture. Although the x-ray findings of this patient are consistent with both Types I and III, recessive inheritance and glycosaminoglycan anomalies point to Type I brachyolmia.
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PMID:A case of brachyolmia. 933 23


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