Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been hypothesized that urinary urokinase and sialidase may play a role in urolithiasis. If these theories have substance it is to be expected that microorganisms may also affect these enzymes, since the association between urinary tract infection and renal stone formation is well known. It is generally assumed that Proteus mirabilis and Staphylococcus albus, which produce the urea-splitting enzyme urease, are responsible for stone formation. However, the importance of non-urease-producing microorganisms (Escherichia coli and Enterococcus) in urolithiasis is unclear. Spectrophotometric studies were therefore devised to clarify this problem. Microorganisms associated with infection-induced stones (Proteus mirabilis and Escherichia coli) respectively inhibited the urokinase and stimulated the sialidase activity. In contrast, microorganisms which were not associated with infection stones (Bacillus subtilis) had significantly less effect on urokinase and sialidase activity. This study may explain infection-induced stone formation and could open a completely new line of research.
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PMID:Effects of bacteria involved with the pathogenesis of infection-induced urolithiasis on the urokinase and sialidase (neuraminidase) activity. 146 76

The effect of a promoter (calcium) and an inhibitor (magnesium) of urolithiasis was spectrophotometrically studied on urokinase (0.45 IU) and sialidase (5 mM). Although these mineral did not affect the sialidase activity, total inhibition of urokinase activity was observed with either 0.05 M calcium chloride or 0.1 M magnesium chloride. This observation might explain why calcium and magnesium respectively function as a promoter and an inhibitor of stone formation.
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PMID:The effect of calcium and magnesium ions on urinary urokinase and sialidase activity. 153 Dec 76

Although many risk factors and theories exist in the literature for urinary stone formation, a hypothesis is suggested for the pathogenesis of renal stones. According to the matrix theory, a protein such as uromucoid activates the initial crystallisation process by promoting the formation of calcium oxalate and calcium phosphate crystals as well as clumping in whole urine. We put forward a theory whereby one of the most important factors in the matrix theory would be the composition and concentration of the protein. In support of this hypothesis, emphasis is placed on the activities of urokinase and sialidase.
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PMID:Pathogenesis of kidney stones. 180 56

Renal stone formation can be caused by many different and varied disturbances, some of which are poorly understood. The relationship between urinary infection and renal stone formation has not been completely clarified. It is argued that renal stones form primarily as a consequence of the hydrolysis of urea by the bacterial enzyme urease. However, no explanation is given for microorganisms that produce urease only occasionally or not at all. The question arises as to whether the infection-induced microorganisms might not be playing a double role in renal stone formation by not only producing urease, but also by affecting in vivo urokinase (UK) and sialidase (SA) activity. With this in mind, the effect of Escherichia coli on renal UK and SA activity has been studied in male rats with a normal diet. The renal UK (P = 0.208) and SA (P = 0.2135) activities did not differ significantly between the two kidneys of the same rat. In contrast, when drainage from one kidney of a rat was externally obstructed, the UK and SA activities differed significantly between kidneys (P < 0.015). An increase in UK (r = 0.6456, P < 0.0001) and SA (r = 0.7507, P < 0.0001) activity was observed over time in the obstructed kidney. Subcutaneous injections with E coli reduced the UK activity of the obstructed kidney significantly (p = 0.017). However, the SA activity remained the same (P = 0.3929).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pyelonephritis: renal urokinase and sialidase (neuraminidase) activity in rats fed a standard laboratory diet. 807 42

uK2t-PA is a hybrid plasminogen activator in which the epidermal growth factor-like domain of the urokinase-type plasminogen activator precedes the kringle 2 and catalytic domains of tissue-type plasminogen activator. The molecules are expressed in Chinese hamster ovary cells in two variant forms, a type II form in which only the protease domain is glycosylated, and a type I form in which both the kringle 2 and the protease domains carry N-acetyllactosamine type glycans. The two forms differed slightly in their affinity for fibrin and fibrinogen, which allowed their separation, but the stimulation of plasminogen activation of the type II form by fibrin was up to eight-fold lower than that of the type II form. The sensitivity to fibrin could be restored by treatment of the type I form with N-glycanase or sialidase. Enzymatic activity vs low molecular weight substrates was not influenced by the glycosylation of kringle 2.
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PMID:Functional effects of kringle 2 glycosylation in a hybrid plasminogen activator. 838 98

Many hypotheses have been proposed for renal stone formation. It has been argued that with infection-induced renal stones the hydrolysis of urea by bacterial urease increases urinary pH, with consequent stone formation. Unfortunately, this theory is not applicable to the micro-organisms that do not produce urease (e.g. Escherichia coli). It has been recently reported that E. coli reduces the urinary urokinase activity of male rats, but does not influence the urinary sialidase activity. This study has now been expanded to the urease-producing bacteria Proteus mirabilis, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Micrococcus luteus. Subcutaneous injections with these bacteria were found to significantly (P < 0.003) reduce the UK activity of extrarenally obstructed kidneys. The urease-producing mammalian skin bacterium, M. luteus, was, however, the exception (P = 0.1079). In contrast to S. epidermidis, P. aeruginosa and M. luteus (P < 0.0213), P. mirabilis and S. aureus had no effect on renal sialidase activity (P < 0.4047). These results may explain why Proteus species are predominant in infection-induced renal stones. According to the urokinase-sialidase hypothesis, a decrease in urinary urokinase activity should increase the uromucoid levels, whilst no effect on the urinary sialidase activity should favour conversion of urinary uromucoid to mineralizable matrix. These conditions may lead to renal stone formation. An increase in urinary pH resulting from urease-producing micro-organisms will increase salt precipitation on the uromucoid. It is thus concluded that urease-producing bacteria may play a double role in renal stone formation.
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PMID:In vivo effects of urease-producing bacteria involved with the pathogenesis of infection-induced urolithiasis on renal urokinase and sialidase activity. 883 91

In the experimental metastasis assay certain animals, from groups of similarly treated animals, develop more lung metastases than expected from random chance alone. This clustering of metastases is characterized by a power function relationship, sigma(2) = amu(b), between the variance, sigma(2), and mean, mu, of the numbers of lung metastases per animal (a and b are constants). To determine whether this clustering could be an artifact of experimental metastasis, whether it could be influenced by different experimental conditions, and to attempt to clarify its cause, 22 published data sets from experimental metastasis utilizing 2,145 mice, as well as 8 data sets from spontaneous metastasis utilizing 1,020 mice were analyzed. In these experiments cell cloning, cell-cell fusion, treatment with a protein kinase C inhibitor, treatment with cell adhesion compounds, and transfection with either the ras oncogene, the sialidase gene, or the urokinase sense and antisense genes were used to influence metastasis. They employed 14 different cell lines and 6 different strains of inbred mice. Clustering of metastasis was evident in animals from the spontaneous metastasis assays as well as from the experimental metastasis assays. It was apparent whether mice were injected with tumor cells derived from clones or from cell lines. Clustering was demonstrated within each data set, regardless of the experimental conditions employed. A single variance to mean power function (with a = 2.2 and b = 1.51) characterized the clustering in the 30 data sets. The regional distribution of blood flow through lungs and other organs is nonuniform, exhibiting a fractal symmetry on change of scale. This symmetry implies that the variance of a region's blood flow is related to its mean by the same power function as was observed with metastasis. Indeed, measurements of blood flow from isolated canine lungs yield b = 1.56, similar to the corresponding figure from murine lung metastasis. These findings lend support to the hypothesis that the observed clustering of metastases is a consequence of fractal variations in lung blood flow.
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PMID:Clustering of murine lung metastases reflects fractal nonuniformity in regional lung blood flow. 1072 73

Administration of quercetin, a common polyphenolic component of many vascular and edible plants including vegetables, fruits and tea significantly reduced the tumor volume in rats induced for mammary carcinoma using dimethyl benz (a) anthracene (DMBA). Dose response was assessed, by treating the animals with different doses (15-45 mg/kgbw) of quercetin and 25 mg/kgbw was taken as effective dose. Quercetin was administered as an intra tumoral injection once a week for 4 weeks. Serum levels of carcino embryonic antigen (CEA), a potent marker for tumor growth and invasion was significantly decreased on quercetin treatment. Quercetin caused a significant decrease in the activities of acid phosphatase and Cathepsin D in serum of experimental animals. Activities of lysosomal enzymes- (beta-D galactosidase, beta-D glucuronidase, beta-D glucosidase and sialidase), in serum and tissue were significantly altered in DMBA animals compared to control animals. However, quercetin treatment caused no significant change in lysosomal enzyme activities in tissues, whereas the activities were significantly lowered in serum. Partial purification of tissue type plasminogen activator (t-PA) from the tumor and kidney showed increased activity in the DMBA induced animals. Serum urokinase, -like plasminogen activator (u-PA) was also increased in animals with tumor, indicating tumor invasion. Administration of quercetin caused a significant decrease of both t-PA and u-PA. In conclusion, the present study suggests the possible role of quercetin in primary and invasive mammary tumor treatment. The above observations in vivo warrant further studies, due to the easy availability, common occurrence and low toxicity of this dietary bioflavonoid.
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PMID:Suppression of tumor growth and invasion in 9,10 dimethyl benz(a) anthracene induced mammary carcinoma by the plant bioflavonoid quercetin. 1684 95