Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of three lysosomal enzymes were measured from the lymphocytes and granulocytes of patients with multiple sclerosis and of controls. The activity of acid phosphatase was increased in the granulocytes and that of beta-glucuronidase in the lymphocytes of MS patients in remission, as compared to those in relapse. No marked increases were observed in the activity of acid proteinase. These findings suggest that a number of lysosomal enzymes in both lymphocytes and granulocytes can be activated during demyelinating processes for reasons unknown at the moment.
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PMID:Lysosomal enzymes in the lymphocytes and granulocytes of patients with multiple sclerosis. 87 47

The neuropathology of 3 cases of acute multiple sclerosis was correlated with biochemical analyses. Astrocytosis was a characteristic feature of the diffuse demyelinating lesions in one case and lymphocytic cuffing characterized the well-defined plaques present in the white matter of the other two cases. No abnormalities were found in the protein or lipid composition of isolated myelin, despite a wide range of recovery. Nevertheless, the gel electrophoretic protein pattern of white matter adjacent to plaque areas showed selective loss of myelin basic protein. Lysosomal acid proteinase and beta-glucuronidase levels were very significantly increased in all white matter samples in which astrocytosis was a major neuropathological feature. Levels were less markedly raised in samples containing discrete active plaques. Enzyme changes were also found in the apparently normal white matter of 2 of the cases. Acid proteinase activity was in the normal range but the activities of beta-glucuronidase and acetylcholine esterase were elevated. The significance of these results in relation to glial cell activity in the early stages of demyelination is discussed.
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PMID:Myelin composition in acute and chronic multiple sclerosis in relation to cerebral lysosomal activity. 97 13

The change in activity of lysosomal hydrolases in the brain tissue of patients with demyelinating disease has been suggested to reflect the demyelination process. In this study we measured neutral proteinase (NP), acid proteinase (AP), and beta-glucuronidase (BG) activities in CSF of 32 patients with multiple sclerosis (MS) (remitting, remitting and relapsing, or chronic progressive course of the disease), 62 controls, and 4 patients with chronic inflammatory disease of central nervous system (ID). Samples from MS patients were taken at different clinical conditions of the disease during the 22-month follow-up. Elevated NP activity was found in patients with relapsing course of MS and also in patients with ID (P less than 0.05). NP activity correlated with the number of leucocytes in CSF of both MS (P less than 0.005, r = 0.50) and control (P less than 0.05, r = 0.21) patients. AP activity decreased in the MS group, especially in patients with remitting or remitting and relapsing courses of the disease (P less than 0.05), but even more in patients with ID (P less than 0.01). During the follow-up the increase in NP activity seemed to be associated with the clinical relapses of MS patients. Other enzymes did not fluctuate with the disease. This study suggests that the change in activity of lysosomal hydrolases is not specific for MS. The increase in NP activity in CSF is associated with clinical relapse of individual MS patients during the follow-up and may indicate immunological activation of the demyelination process in the brain. The large intra- and interindividual variation in enzyme activities in the CSF, however, makes the use of these enzymes difficult for diagnosis of MS and follow-up of MS activity.
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PMID:Lysosomal hydrolases in cerebrospinal fluid of multiple sclerosis patients. A follow-up study. 330 15

Culture of thioglycollate-elicited rat peritoneal macrophages in the presence of derivatized, non-ingestible, bovine CNS material results in a release of the lysosomal marker enzyme beta-glucuronidase that is both dose- and time-dependent. Concomitant with enzyme secretion, lactic acid is secreted in a manner that is also dose- and time-dependent. The secretion of lactic acid represents an increased dependence on anaerobic glycolysis by the aerobic phagocyte cultures and is paralleled by an increase in cytoplasmic lactate dehydrogenase. When unbuffered media are used, the secretion of lactic acid is accompanied by a drop in the pH of the culture medium. Culture of the cells in the presence of the pyruvate dehydrogenase stimulator, dichloroacetate, inhibits the formation of lactic acid and the resulting drop in pH. Suspensions of multilamellar myelin undergo turbidity changes and aggregation in acidic media. Initial rates of turbidity changes follow a titration curve with an apparent pKa of 6.0. Because of the sensitivity of the myelin lamellae to an acidic microenvironment, it is suggested that a local hyperlactemia, with the resulting decrease in interstitial pH, may be a major pathological process in cell-mediated inflammatory demyelination. Antihyperlactemics, such as dichloroacetate, may therefore provide a new therapeutic approach to minimizing myelin degeneration in multiple sclerosis and in other CNS disorders characterized by inflammatory demyelination.
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PMID:Secretion of lactic acid by peritoneal macrophages during extracellular phagocytosis. The possible role of local hyperacidity in inflammatory demyelination. 359 69

In continuation of our previous studies, which demonstrated a decreased glutathione peroxidase (GSH-Px) activity of erythrocytes from multiple sclerosis (MS) patients the activity of some enzymes regulating the peroxide level (GSH-PX and glutathione reductase (GSSG-Rd)) in leucocytes and erythrocytes respectively, the selenium level of whole blood and the beta-glucuronidase activity of serum (marker of lysosomal membrane damage) were assayed in this group of patients. GSH-Px activity in lymphocytes and granulocytes from MS patients was significantly (2 alpha smaller than or equal to 0.01) decreased by 35-50%. Erythrocyte glutathione reductase activity was only insignificantly decreased in MS patients. Erythrocyte GSH-Px : GSSG-Rd ratio was 11.0 for the control group, but 8.0 for the MS group. The selenium content of whole blood and serum from Danish MS patients was normal. The selenium level in erythrocytes from Danish MS patients was however higher than the selenium level in erythrocytes from controls.
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PMID:Leucocyte glutathione peroxidase activity and selenium level in multiple sclerosis. 742 Jan 26

Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in oral tolerance induction for intervention in an autoimmune disease, multiple sclerosis. Recombinant L. casei which express surface-anchored tetanus toxin fragment C (TTFC) were generated. Quantitative analysis by flow cytometry demonstrated a high level of cell wall-bound expression of TTFC and immunogenicity was demonstrated by parenteral immunization with whole cell extracts of the recombinants. A series of expression vectors was constructed to secrete human myelin basic protein (hMBP) or hMBP as a fusion protein with beta-glucuronidase from Escherichia coli. These heterologous products produced by L. casei were detected in the growth medium and parenteral immunization with this medium evoked antibodies against hMBP, confirming that secretion indeed had occurred. Based on the different localization of the heterologous proteins, lactobacilli expressing surface-anchored TTFC are ideally suited for the induction of antibody responses, whereas lactobacilli that secrete myelin proteins can be used for the induction of peripheral T-cell tolerance. In conclusion, the specific technology described here allows the construction of a wide array of safe live recombinant lactobacilli which may prove to be useful in oral intervention strategies for the prevention of infectious diseases or treatment of autoimmune diseases.
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PMID:Instruments for oral disease-intervention strategies: recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis. 1036 44

Gene therapy in the brain has focused mainly on neurons (gray matter), with little comparable research on white matter. In this study, injections into mice cerebral white matter of mice were done to assess the distribution of gene transfer with recombinant feline immunodeficiency virus vectors expressing either beta-galactosidase or beta-glucuronidase. Our results show that vectors were preferentially distributed along the white matter of the external capsule, which was the site of vector injection as confirmed by horseradish peroxidase labeling. Moreover, we found gene transfer almost exclusively to NeuN(+) cells lining the external capsule, which then robustly secreted recombinant beta-glucuronidase throughout the white matter of the entire external capsule on the injected side. These results may have application to lysosomal storage diseases with widespread central nervous system deficits, and other disorders such as multiple sclerosis and human immunodeficiency virus dementia.
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PMID:Transduction of neurons lining the cerebral external capsules in mice with feline immunodeficiency virus based vectors. 1458 96

Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP(139-151)). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP(72-85) significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP(72-85) fused to the marker enzyme beta-glucuronidase (beta-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis.
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PMID:Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens. 1458 76

For the last 15 yr, a great deal of knowledge has been accumulated on health beneficial factors, protein and nonprotein, of bovine milk fat globule membrane (MFGM). Among the health-beneficial components of the MFGM are cholesterolemia-lowering factor, inhibitors of cancer cell growth, vitamin binders, inhibitor of Helicobacter pylori, inhibitor of beta-glucuronidase of the intestinal Escherichia coli, xanthine oxidase as a bactericidal agent, butyrophilin as a possible suppressor of multiple sclerosis, and phospholipids as agents against colon cancer, gastrointestinal pathogens, Alzheimer's disease, depression, and stress. All of the above compel us to consider bovine MFGM as a potential nutraceutical.
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PMID:Invited review: Bovine milk fat globule membrane as a potential nutraceutical. 1595 91

Enzyme activity changes in reagent and neoplastic glia are examined. In the case of reagent glia, considerably increased ADPase, ATPase and AMPase values have been observed in experimental elective parenchymal necrosis in the rat, in hypertrophic astrocytes from recent plaques in multiple necrosis, in demyelinisation associated with cyanide encephalopathy, and in reagent astrocytes surrounding tumours and arteriosclerosis sites. Depressed ATPase values have been observed in experimental oedema, as compared with increased TPPase in human oedema. BuChE and ChE activity disappears in both oligodendro- and astroglia near old cerebral infarct sites, whereas there is marked BuChE activity peripherally to multiple sclerosis plaques and in areas of phenylpyruvic oligophrenia demyelinisation. In neoplastic glia, ADPase is clearly evident in malignant gliomas, ATPase is related to the extent of the cell body, AMPase is positive in medulloblastoma cell cytoplasm and beta-glucuronidase increases in anaplasia. Above-normal ChE activity has been observed in astrocyte tumors, while BuChE is greater than that of AChE. Phosphorylase reaction is intense in astrocytoma and in glioblastoma giant cells. Phosphoglucomutase values are below-normal in tumours, except in the case of ependymoma, while both phosphohexoisomerase and hexokinase display increased activity in atypical forms.
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PMID:[Histochemical demonstration of glial enzyme activity. II. Reagent and neoplastic glia]. 1734 Aug 8


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