Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two brothers with oligosymptomatic mucopolysaccharidosis VII were observed from age 11 8/12 to 16 years, and 15 1/2 to 19 years, respectively. Asymptomatic thoracic kyphosis and mild scoliosis were the prominent clinical features. Herniae, hepatosplenomegaly, corneal clouding and shortness of stature were absent. Both had Alder type granulations in polymorphonuclear leukocytes and to a lesser degree in monocytes. Ultrastructural analysis of blood leukocytes revealed polymorphous inclusions of probably more than one class of organic substances. Radiological signs were mild, confined to the spine and consisted of irregularities of upper and lower vertebral plates, of vertebral flattening and some osteophytic changes. Both patients excreted excessive amounts of acid mucopolysaccharides in urine and also globoside. Cultured skin fibroblasts of both patients contained metachromatic granules, had only approx. 10% of normal beta-glucuronidase activity and degraded sulfated mucopolysaccharides at a slower than normal rate. Sera of the patients had none or minimal beta-glucuronidase activity, the mother's serum had subnormal and the father's serum low-normal activity. The older brother is the oldest known case of mucopolysaccharidosis VII. As this hereditary disorder may take a remarkably mild clinical course, beta-glucuronidase-deficient juveniles may exist undetected in the general population.
...
PMID:Unusually mild course of beta-glucuronidase deficiency in two brothers (mucopolysaccharidosis VII). 10 85

Heteropolymeric beta-glucuronidases are detected in somatic cell hybrids between mouse cells and human fibroblasts deficient in beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31) by electrophoresis and column chromatography. Specific antisera against human beta-glucuronidase prepared in mice recognize these heteropolymeric beta-glucuronidases. Our results demonstrate that synthesis of mutant subunits of variant beta-glucuronidase continues in deficient human fibroblasts; these mutant subunits of human beta-glucuronidase retain the ability to associate with normal subunits of mouse beta-glucuronidase to form the enzymatically and immunologically active tetramer. These studies demonstrate the usefulness of interspecific cell hybrids for study of structural gene mutations of polymeric enzymes, such as those of beta-glucuronidase in mucopolysaccharidosis type VII.
...
PMID:Detection of active heteropolymeric beta-glucuronidase in hybrids between mouse cells and human fibroblasts with beta-glucuronidase deficiency. 26 46

An enzyme immunoassay for human beta-glucuronidase was developed to determine the presence or absence of antigenically cross-reactive material (CRM) in patients with beta-glucuronidase deficiency mucopolysaccharidosis. This assay provided a sensitive means of measuring the primary interaction between the enzyme molecule and antibody but required neither pure antigen nor monospecific antiserum, an important consideration, since neither of these was available. Goat antiserum to partially purified human placenta beta-glucuronidase did not recognize differences in normal enzyme from human placenta, liver, fibroblasts, or blood platelets. CRM was identified in fibroblast extracts from all four of the unrelated beta-glucuronidase-deficient patients studied, but titration patterns indicated genetic heterogeneity among these four mutant proteins. Fibroblast enzymes from two obligate heterozygotes were distinguishable immunologically from normal enzyme. The enzyme immunoassay was also used to compare human enzyme with liver enzyme from other mammalian species. CRM was present in liver extracts of all species tested, but the liver enzymes, except for the rabbit, were weakly cross-reactive. We conclude that despite certain limitations, the enzyme immunoassay for human beta-glucuronidase is useful and that all four beta-glucuronidase-deficient patients studied possess CRM.
...
PMID:Human beta-glucuronidase deficiency mucopolysaccharidosis: identification of cross-reactive antigen in cultured fibroblasts of deficient patients by enzyme immunoassay. 40 8

In 24 men aged 32 to 58 years with precancerous states of the larynx, i.e., leukoplakia, papillomas and pachydermia the peripheral blood lymphocytes were cytochemically stained for N-acetyl-beta-glucosaminidase, beta-glucuronidase, acid phosphatase and glycogen; and the neutrophils were stained for alkaline phosphatase, myeloperoxidase and lipids. The results were expressed in terms of the absolute counts of reaction-positive cells and of the activity index score. The serum immunoglobulins IgG, IgA and IgM were also determined by Mancini's method. The results obtained were compared with those in 20 healthy men aged 20 to 30 years. The patients exhibited elevated numbers of N-acetyl-beta-glucosaminidase and beta-glucuronidase-positive lymphocytes. A characteristic feature was an increase in the absolute counts of lymphocytes with diffuse and granular-diffuse types of cytochemical reaction for all enzymes studied. The number of cells with the granular type of enzymatic reaction (intact enzyme-positive lysosomes) was significantly diminished. These cytochemical alterations were accompanied by a significant increase in the serum IgA level. These results are discussed with reference to the lymphoid system response to tissues of precancerous lesions of the larynx. So far as the neutrophils are concerned the patients exhibited significant intracellular deficiency of beta-glucuronidase and decrease in the lipid content as well as an elevated alkaline phosphatase activity. The possible significance of the beta-glucuronidase deficiency in neutrophils for the diminished cytotoxic response of these cells against the tumor and precancerous lesion cells is discussed.
...
PMID:Lymphocytes, neutrophils and serum immunoglobulins in patients with precancerous states of the larynx. 44 57

Cytochemical investigations performed in 24 men with precancerous states of the larynx, i.e. leukoplakia, papillomas and pachydermia, indicated that the peripheral blood neutrophils from these patients exhibit a significant intracellular deficiency of beta-glucuronidase activity and of total lipids, as well as an increased alkaline phosphatase activity. Acid phosphatase and N-acetyl-beta-glucosaminidase activities did not differ significantly between patients and normal controls. In the authors' opinion, the neutrophil beta-glucuronidase deficiency might be a specific disturbance of neutrophils in the precancerous states and the cancer of the larynx. The possible significance of this disturbance and the subsequent decrease of antitumor immune reactivity are discussed.
...
PMID:The enzymatic equipment of neutrophils in patients with precancerous states of the larynx. 63 1

To simplify the process of transfection of human fibroblasts and to acquire a suitable number of transformants, we investigated experimental conditions of electric pulse-induced transfection of human fibroblasts using origin-defective simian virus 40 DNA (SV40 (ori-) DNA). Voltage, pulse duration, number of pulses and the concentration of SV40 (ori-) DNA led to the formation of 10 to 30 foci/25 cm2 6 weeks after transfection, using 2 to 3 x 10(6) cells and a square wave pulse generator. Optimal condition was determined to be 2 or 3 pulses at a voltage of 1500 to 2000 V/0.4 cm with 30 microseconds pulse width, using 2 micrograms of linearized SV40 (ori-) DNA. With this approach we developed human transformed fibroblasts cell lines with all types of mucopolysaccharidoses. The transformed fibroblasts grew rapidly and the saturation density exceeded that of the parental cells. All the transformed cell clones expressed T antigen, and deficiency in specific enzymes was conserved. A point mutation which occurred in the human beta-glucuronidase gene in a patient with mucopolysaccharidosis type VII was also conserved.
...
PMID:Optimization of electroporation for transfection of human fibroblast cell lines with origin-defective SV40 DNA: development of human transformed fibroblast cell lines with mucopolysaccharidoses (I-VII) 131 88

Genetic disorders affecting the central nervous system (CNS) can potentially be treated by gene transfer using vectors which infect and express genes in post-mitotic neurons. Herpesviruses establish latent infections in neurons during which only one viral gene (LAT) is expressed, thus the LAT promoter may express foreign genes in latently infected CNS cells. Expression of a beta-glucuronidase gene driven by the LAT promoter was tested in mice lacking this enzyme, which are a model for a human genetic disease affecting the CNS (mucopolysaccharidosis VII, Sly disease). Cells expressing the missing enzymatic activity were present in the trigeminal ganglia and brainstems of latently infected animals, up to four months post-inoculation, demonstrating the potential of this approach for the long-term expression of foreign genes in the CNS.
...
PMID:Herpesvirus vector gene transfer and expression of beta-glucuronidase in the central nervous system of MPS VII mice. 133 72

We report on a 20-year-old male with a beta-glucuronidase (GUSB) deficiency mucopolysaccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder-type granulations in his polymorphonuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane-limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross-reactive material towards anti-GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease.
...
PMID:Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a chronic variant with an oligosymptomatic severe skeletal dysplasia. 145 83

An inherited deficiency of beta-glucuronidase in humans, mice and dogs causes mucopolysaccharidosis VII (Sly syndrome), a progressive degenerative disease that reduces lifespan (to an average of 5 months in mice) and results from lysosomal storage of undegraded glycosaminoglycans in the spleen, liver, kidney, cornea, brain and skeletal system. Bone marrow transplantation in mutant mice provides a source of normal enzyme ('cross-correction'), which substantially improves the clinical condition and extends the average lifespan to 18 months. Gene therapy by transfer of a beta-glucuronidase gene into mutant haematopoietic stem cells is an alternative approach, but it is not known whether the low expression of vector-transferred genes in vivo would be sufficiently effective. Here we show that retroviral vector-mediated transfer of the gene to mutant stem cells results in long-term expression of low levels of beta-glucuronidase which partially corrects the disease by reducing lysosomal storage in liver and spleen.
...
PMID:Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer. 146 45

We identified two different exonic point mutations causing beta-glucuronidase (beta G1) deficiency in two Japanese patients with mucopolysaccharidosis type VII (MPSVII). Enzyme assay of lysates of the lymphocytes and cultured fibroblasts showed little residual activity. The beta G1-specific mRNA levels were normal, as determined by northern blot analysis. Mutated cDNA clones, including the entire coding sequence, were isolated using the polymerase chain reaction (PCR) products derived from beta G1-deficient fibroblasts. Sequence analysis of the full-length mutated cDNAs showed C----T transitions, which resulted in a single Ala619----Val change (case 1, a 24-year-old male) and a Arg382----Cys change (case 2, a 7-year-old female). The former change was revealed by a loss of the cleavage site for the Fnu4HI in the mutated cDNA. On the basis of the loss of Fnu4HI restriction site, the patient (case 1) was a homozygote with this mutation. The mutational change in patient 2 was confirmed by direct sequencing and by demonstrating heterozygosity for the mutation in her parents. The Ala619----Val and Arg382----Cys mutations each disrupt a different domain which is highly conserved among human, rat, and Escherichia coli beta G1s. Each of these two amino acid changes reduced the beta G1 activity of the corresponding mutant beta G1 expressed following transfection of COS cells with expression vectors harboring the mutated cDNAs.
...
PMID:Mucopolysaccharidosis type VII: characterization of mutations and molecular heterogeneity. 170 66


1 2 3 4 5 6 7 8 9 10 Next >>

---