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 granulocytes of a patient with generalized pustular psoriasis (GPP) were found to have impaired ability to fix iodine after ingestion of yeast particles. Since hexose monophosphate shunt (HMS) activity was increased and the contents of 3 other lysosomal enzymes, beta-glucuronidase, N-acetyl-beta-glucosaminidase and lysozyme, were within normal range, the impaired iodination appeared to be due to a selective defect of myeloperoxidase (MPO) activity within the phagocytic cells. The deficient iodination was accompanied by a decreased intracellular killing of E. coli and C. albicans. Since hexose monophosphate shunt activity was enhanced and azide and cyanide inhibited the intracellular killing of E. coli only moderately, the patient's granulocytes may possess azide- and cyanide-resistant, MPO-independant microbicidal systems coupled to the oxidative metabolism. Assessment of granulocyte iodination and enzyme contents of the relatives of the patient revealed no hereditary transmission. Since GPP is characterized by the development of subcorneal pustules containing granulocytes, the MPO-deficiency may be the cause of or enhance the development of the disease.
 ...
PMID:Function of granulocytes with deficient myeloperoxidase-mediated iodination in a patient with generalized pustular psoriasis. 17 20

Mycophenolic acid (MPA) is a fermentation product of a penicillium mould which has shown antitumour acitivity in certain animal models. It blocks nucleic acid synthesis by interfering with the interconversions of inosine monophosphate (IMP), xanthine monophosphate (XMP) and guanine monophosphate (GMP) thereby inhibiting growth and/or replication of tumour cells. In vivo activity depends on the presence of a beta-glucuronidase which is abundant in the cell wall of epithelial tissues. Encouraged by results obtained in earlier clinical trials, we have studied 28 patients with psoriasis, 21 in double-blind fashion. A comparison of disease severity in patients before and after receiving MPA versus patients receiving placebo clearly showed the superiority of drug over placebo. The mean severity score of patients receiving MPA as an initial course of therapy improved by 56% versus 9% in patients receiving placebo. Patients receiving MPA after an initial course of placebo therapy showed improvement in their mean severity score averaging 86%. Those patients receiving placebo after an initial course of MPA showed worsening of their mean severity score averaging 70%. Overall, about 75% of MPA treated patients have shown good to excellent responses, and toxicity appears low. Evidence suggests that MPA may be very useful in treating severe psoriasis.
 ...
PMID:Mycophenolic acid in psoriasis. 34 42

Mycophenolic acid, a new chemotherapeutic agent for the treatment of psoriasis, is known to be rapidly conjugated on absorption and to circulate largely in the form of its glucuronide conjugate. Since this metabolite does not readily penetrate intact cells and is cleaved by the enzyme beta-glucuronidase to yield free mycophenolic acid, the ability of preparations of mouse skin to cleave mycophenolic glucuronide was studied. The time course of mycophenolic acid liberation by such preparations and the dependence upon the amount of enzyme preparation were demonstrated. Preparations of mouse skin and mouse liver, kidney, spleen, lung, heart and small intestine were assayed for beta-glucuronidase activity using p-nitrophenyl-beta-D-glucuronide as substrate. Skin yielded preparations with higher beta-glucuronidase activity per/mg protein than any of the other organs tested. When expressed on the basis of beta-glucuronidase activity recovered per milligram of tissue DNA, skin, liver and kidney showed higher levels than the other organs tested.
 ...
PMID:Cutaneous beta-glucuronidase: cleavage of mycophenolic acid by preparations of mouse skin. 92 1

Macrophages derived from circulating blood monocytes of psoriatic patients demonstrated an enhanced release of beta-glucuronidase and lysozyme compared with macrophages from healthy subjects. The relationship of cell activation to the pathogenesis of psoriasis is discussed.
 ...
PMID:Increased macrophage activity in psoriasis. 241 Oct 73

Six male non-smoking subjects treated for psoriasis with topical applications of pure coal tar or 4% coal tar-containing ointment were examined in order to assess the genotoxic risk associated with this type of therapy. Mutagenicity in urine samples collected before and during the coal tar therapy was evaluated in the plate incorporation assay on Salmonella typhimurium strain TA98 in the presence of S9 mix and beta-glucuronidase. Total urinary polycyclic aromatic hydrocarbon (PAH) levels were evaluated in parallel by high resolution gas chromatography/mass spectrometry. In addition, sister chromatid exchanges and chromosomal aberrations were also analysed in peripheral blood lymphocytes collected before, during and after the end of the coal tar applications. The results suggest that urinary mutagenicity levels as well as the frequencies of chromosome aberrations and sister chromatid exchanges in lymphocytes are related to the levels of exposure to coal tar. Moreover the kinetics of repair of chromosome damage in relation to different exposure levels and the capacity of the urinary mutagenicity assay to correctly identify the exposure to significant levels of PAH are discussed.
 ...
PMID:Chromosomal alterations in peripheral blood lymphocytes, urinary mutagenicity and excretion of polycyclic aromatic hydrocarbons in six psoriatic patients undergoing coal tar therapy. 264 86

Scales from patients with nonpustular psoriasis were investigated for the presence of peptides capable of activating functional activities in human polymorphonuclear leukocytes (PMNL). Two compounds with similar molecular weight (12,500 and 15,000) were isolated which markedly stimulated PMNL functional activities including chemotaxis, generation of superoxide radical anion (O-2), and liberation of beta-glucuronidase as a marker enzyme. As revealed by ion-exchange and subsequent radioimmunoassay followed by chromatofocusing, one peptide proved to be the desarginated form of the complement split product C5ades arg. No C5a was detectable. As a second psoriatic scale chemotaxin we isolated an anionic neutrophil-activating peptide (ANAP) which shows a single isoelectric point at pH 6.8. This peptide shares some of the characteristics of epidermal cell-derived thymocyte-activating factor and interleukin 1 and, as shown by deactivation experiments, it cross-reacts with a monocyte-derived cytokine. The 2 newly described neutrophil-activating peptides (C5ades arg and ANAP) may play an important role in the psoriatic tissue reaction.
 ...
PMID:Identification of C5ades arg and an anionic neutrophil-activating peptide (ANAP) in psoriatic scales. 301 8

Chemotactic migration, production of superoxide anion (O2-), and the release of beta-glucuronidase from azurophilic granules were determined in polymorphonuclear leukocytes (PMN) from 135 patients with infectious (e.g., pyoderma, acne conglobata, erysipelas) as well as noninfectious (psoriasis) skin diseases. Purified C5a and the formylated tripeptide FMLP were used as stimuli. In addition, longitudinal profiles of PMN activities were performed at daily intervals in several patients. There was a complete absence of PMN responses (chemotaxis, O2--production, and enzyme release) specifically induced by C5a in 25 patients suffering from various inflammatory diseases of the skin. In these patients PMN responsiveness for the tripeptide FMLP was either normal or increased. The C5a-dependent defect of PMN was transient and correlated with disease activity. When normal PMN were incubated with sera from C5a-defective patients, no inherent stimulatory or inhibitory activities compared to control sera were seen. Pretreatment of normal PMN in vitro with various concentrations of C5a failed to completely deactivate PMN without affecting FMLP dependent functions. These observations demonstrate the presence of a functional defect in circulating PMN during acute cutaneous inflammation. The in vitro experiments suggest transient blocking of C5a-dependent PMN functions by a cell-bound factor which seems not to be C5a or C5adesarg.
 ...
PMID:Transient absence of C5a-specific neutrophil function in inflammatory disorders of the skin. 316 55

Using serum-coated zymosan, the generation of reactive oxidants by measurement of chemiluminescence was shown to be significantly enhanced in isolated peripheral psoriatic neutrophils compared to normal controls. This response was observed irrespective of whether zymosan was opsonized with fresh autologous or normal AB serum. However, this increased activity was reduced with zymosan was opsonized with serum that was preheated at 56 degrees C for 30 min. There was no statistical correlation of chemiluminescence activity with degranulation of beta-glucuronidase in either normal or psoriatic subjects. In addition, chemiluminescence produced by normal cells was significantly increased when zymosan was opsonized with psoriatic serum. The plasma membrane-bound enzyme, NAD(P)H oxidase, which produces superoxide in response to phagocytic stimulation, was significantly increased in psoriatic neutrophils compared to normal controls. These data add further evidence for activated neutrophils in psoriasis.
 ...
PMID:Enhanced chemiluminescence production by phagocytosing neutrophils in psoriasis. 339 84

The urinary mutagenicity and the excretion of polycyclic aromatic hydrocarbons (PAH) in three non-smoking male patients, treated for psoriasis with cutaneous applications of crude coal tar, were analysed. Mutagenicity of the urinary extracts was measured by the plate incorporation assay using Salmonella typhimurium strains TA 98 and TA 100 in the presence of liver S9 fraction from Aroclor-induced rats with or without beta-glucuronidase. After concentration, hydrolysis and reduction of the urine sample, PAH levels were measured by high resolution gas chromatography/mass spectrometry. Following cutaneous treatment with coal tar, the urine of all three subjects showed noticeable levels of PAH and/or metabolites and marked mutagenicity both on strain TA 98 and TA 100 in the presence of S9 fraction. The addition of beta-glucuronidase increased the mutagenicity of the urinary extracts, the maximum values being attained on strain TA 100 in the presence of both microsomal fraction and deconjugating enzymes. The mutagenicity of urinary extracts from subjects treated therapeutically with crude coal tar was correlated (r = 0.788, P less than 0.01) with the total PAH levels in their urine. The PAH excreted in urine were mainly low molecular weight compounds, while benzo[a]anthracene was present in scarce amounts and the excretion of benzo[a]pyrene did not increase following the cutaneous exposure to the crude coal tar.
 ...
PMID:Mutagenic activity and polycyclic aromatic hydrocarbon levels in urine of humans exposed to therapeutical coal tar. 369 8

In vitro degranulation of polymorphonuclear leukocytes, which were stimulated either with synthetic chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine, FMLP) or with C3b-opsonized zymosan as a promotor of phagocytosis, was studied in 66 patients with psoriasis, 18 lesion-free psoriatics, 18 healthy subjects, and 14 other dermatological disorder controls. Stimulated release of lysozyme (from specific granules and azurophil granules) and beta-glucuronidase (from azurophil granules) in the presence of both FMLP and serum-activated zymosan was markedly reduced in patients with actively spreading guttate psoriatic lesions, in whom relapse of lesions lasted for less than 1 month and papules involved about 13-25% of skin surface. In contrast, stimulated degranulation was within normal range in active plaque psoriasis, stationary plaque psoriasis, symptomless psoriatics, and patients with disseminated eczema. Spontaneous release of lysozyme and beta-glucuronidase (background) was found to be not different in all groups studied; however, patients with active guttate psoriasis had significantly lower total lysozyme activity than those with active and stationary plaque psoriasis as well as psoriatics in the remission. These data are in favor of in vivo activation of neutrophils in active guttate psoriasis by some factors related to the early relapse of the lesions. This results in a possible combination of the following phenomena: (1) in vivo partial degranulation of neutrophils; (2) induction of "unresponsiveness state" of these cells to subsequent in vitro stimulation; and/or (3) migration of highly responsive neutrophils to skin lesions, which leaves in the circulation the subpopulation less reactive to chemotactic and phagocytic stimuli.
 ...
PMID:Decreased extracellular release of granule enzymes from in vitro-stimulated polymorphonuclear leukocytes in guttate psoriasis. 371 May 63


1 2 Next >>