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

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that focal glomerulosclerosis (FGS) is analogous to atherosclerosis. Because monocytes and their derivatives are involved in the latter, these cells may be involved in the development of the former. To investigate this possibility a combined histochemical and ultrastructural study of FGS was done. Sections from 13 biopsies showing FGS were stained for either nonspecific esterase or lysozyme to detect monocytes and their derivatives. These include foam cells (lipid-containing macrophages) in which there was positive cytoplasmic staining for both nonspecific esterase and lysozyme. Twenty-one of 29 glomeruli (72%) with segmental sclerotic lesions contained monocytes and/or foam cells, whereas only 18 of 251 glomeruli (7%) without the lesions demonstrated these cells (p less than 0.0001). The mean number of monocytes and/or foam cells in segmentally sclerotic glomeruli was 2.0 +/- 1.7 compared with 0.2 +/- 0.3 for uninvolved glomeruli (p less than 0.01). In glomeruli with sclerotic lesions foam cells predominated over monocytes. Neutral lipid was observed focally and segmentally in 29 of 35 biopsies with FGS. Electron microscopy in 23 biopsies consistently demonstrated intracapillary cells with monocytic features but few foam cells in very early lesions characterized by epithelial cell changes but no or minor glomerular tuft alterations. With progression, the relative number of monocytes declined but foam cells were observed more frequently. These results suggest that monocytes and their derivatives are involved in the development of FGS.
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PMID:Monocytes and focal glomerulosclerosis. 279 89

Asymptomatic low molecular weight proteinuria, a disease recently reported by Suzuki et al. [1985], was found in five boys, two pairs of brothers and a sporadic patient aged 3 to 11 years. Their urinary proteins contained 56% to 67% of proteins of less than 40,000 mol wt, defined as low molecular weight proteins by Suzuki et al. [1985], an indication that proximal tubular reabsorption of these proteins is impaired in these patients. Their glomerular function tests and intravenous urography were normal. An attempt was made to identify urinary low molecular weight proteins in these patients, using Western blotting analysis of the protein bands separated by sodium dodecylsulfate polyacrylamide gel electrophoresis. All five proteins tested were detected: alpha 1-acid glycoprotein (mol wt 44,000), alpha 1-microglobulin (mol wt 33,000), retinol-binding protein (mol wt 21,000), lysozyme (mol wt 14,000), and beta 2-microglobulin (mol wt 11,800). The latter two proteins had been identified in the disease by other means by Suzuki et al. [1985], while the other three were newly identified. Light microscopic studies of renal biopsy specimens from these patients revealed in three of four patients tested focal global or segmental glomerular sclerosis with scattered intratubular casts and focal tubular atrophy. Immunofluorescence staining of the renal biopsy specimens for the five proteins revealed some in the lumens of the proximal tubules and in the casts in the distal or collecting tubules, while only retinol-binding protein was found in the epithelial cytoplasm of the proximal tubules.
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PMID:Asymptomatic low molecular weight proteinuria: studies in five patients. 330 34

Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) of urinary proteins was performed in 56 children with nephrotic syndrome during relapse, of whom 31 had their urines tested within 2 months of the onset of disease. The urines of all 32 steroid-sensitive [presumed minimal change nephrotic syndrome (MCNS)] patients revealed albumin and transferrin bands only; whereas 19 steroid-resistant children with focal glomerular sclerosis showed additional excretion of IgG and low molecular weight proteins (lysozyme, beta 2-microglobulin). This mixed pattern of proteinuria was also detected in 5 other steroid-resistant patients, 3 of whom were Africans with MCNS on biopsy and 2 who were Indians and not biopsied. Findings in patients studied within 2 months of presentation were identical to those investigated later in the course of the disease. SDS PAGE analysis of urine, which appears to distinguish steroid-responsive from steroid-resistant patients may provide a valuable adjunct to the management of childhood nephrotic syndrome.
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PMID:Sodium dodecyl sulphate polyacrylamide gel electrophoresis of urinary proteins in steroid-responsive and steroid-resistant nephrotic syndrome in children. 769 97

Although renal biopsy is the definitive investigation in kidney disorders and is particularly helpful in distinguishing steroid-responsive nephrotic syndrome (SRNS) from focal glomerulosclerosis (FGS), it is attended by a small risk to the patient. Accordingly, noninvasive tests have been used to predict the response to steroids and the underlying renal histologic diagnosis in nephrotic syndrome. The performance of these tests has, however, not been encouraging. We have therefore compared the reliability of the conventional selectivity index (SI) of serum and urinary transferrin and immunoglobulin G (IgG) against other tests of urinary proteins, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), and isoelectric focusing (IEF). SI, SDS PAGE, and IEF were carried out in children with nephrotic syndrome within 2 months of clinical presentation. Thirty-one children who had SRNS were compared with 26 who had biopsy-proved FGS and who were steroid resistant. SDS PAGE and IEF revealed excretion of albumin and transferrin only, with homogeneous anionic charge, respectively, in SRNS but unrestricted excretion of additional proteins IgG, beta2-microglobulin, and lysozyme with heterogeneity of electrical charge in FGS. With SDS PAGE and IEF we were able to predict all children who had SRNS and FGS; the SI test predicted all steroid-resistant patients with FGS but was able to predict only 41.7% of the patients with SRNS. Therefore the negative predictive value for steroid response was 58.8% by SI and 100% by SDS PAGE and IEF; the positive predictive value was 100% by SI, SDS PAGE, and IEF. We illustrate the value of SDS PAGE in guiding management in a further seven children with FGS in whom there was either an initial discordance between renal biopsy results and steroid responsiveness or when biopsy was delayed. Accordingly, SDS PAGE and IEF of urinary proteins appear to be useful tests in the diagnosis and management of SRNS and FGS.
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PMID:Comparison of noninvasive methods for distinguishing steroid-sensitive nephrotic syndrome from focal glomerulosclerosis. 901 90

Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid-sensitive cis-aconityl linker. All free amino groups of the lysozyme were used for drug attachment to achieve intact excretion of the doxorubicin-aconityl-lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be regenerated through acidification of the urine. First, the doxorubicin-aconityl-lysozyme conjugate was tested in rats for its target specificity and general toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/- 3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on heart, liver and lung but caused severe renal damage (proteinuria, N-acetylglucosaminidase excretion and glomerulosclerosis). None of the rats injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second, we tested whether doxorubicin could be released from the conjugate in the bladder through acidification of the urine and if the released doxorubicin could still exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1) and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was released from the conjugate in the group with acidified urine (15 +/- 7% versus 1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a specific delivery of doxorubicin to the urinary bladder combined with a reduced toxicity of doxorubicin in the kidneys can be achieved by coupling this anti-tumor drug to the low-molecular weight protein lysozyme via an acid-labile linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved by acidification of the urine. This technology, after further optimization, may provide an interesting tool for the treatment of bladder carcinoma.
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PMID:Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity. 1199 90

Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications. The purpose of this study was to examine the novel coumarin-aspirin compound XLF-III-43 in the inhibition of AGE formation in diabetic nephropathy. In vitro analysis showed XLF-III-43 in a dose-dependent manner decreased glucose induced formation of glycation adducts on albumin and inhibited AGE-lysozyme crosslinking. The streptozotocin-induced diabetic rats were used to investigate the beneficial effects of XLF-III-43 treatment on diabetic nephropathy. Administration of XLF-III-43 significantly decreased (P<0.05) blood urea nitrogen and urinary albumin excretion. Moreover, XLF-III-43 ameliorated kidney hypertrophy, mesangial expansion and glomerulosclerosis in diabetic rats relative to untreated model group. These data correlated with decreased both AGE and downstream markers of AGE stress (TGF-beta1, CTGF, fibronectin and collagen IV fibrolysis) in kidneys of diabetic rats. These data support further development of XLF-III-43 for prevention of nephropathy via inhibition of AGE formation consequent to chronic hyperglycemia.
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PMID:XLF-III-43, a novel coumarin-aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products. 1989 8

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