Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberration of IgA-bearing B lymphocytes in patients with IgA nephropathy has been investigated. Twelve patients with IgA nephropathy demonstrated a marked increase of IgA-bearing lymphocytes in peripheral blood, while ten patients with chronic proliferative glomerulonephritis without mesangial deposition of IgA showed normal amounts of IgA-bearing lymphocytes. The increase of IgA-bearing lymphocytes reflected that of IgA-producing lymphocytes, since lymphocytes obtained from patients with IgA nephropathy restored a high percentage of IgA-bearing cells in vitro after treatment with trypsin. Quantitation of IgA-bearing lymphocytes in peripheral blood is a useful method for screening of patients with IgA nephropathy.
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PMID:Increase of IgA-bearing lymphocytes in peripheral blood from patients with IgA nephropathy. 31 81

To investigate the response of urinary active and inactive kallikrein excretion to sodium depletion in golmerulonephritic (GN) patients, we measured the excretion of urinary active and inactive kallikreins in 10 primary GN patients before and after a low sodium (17 mEq/day), constant potassium (40 mEq/day) diet. They ranged in age from 24 to 47 years with 7 men and 3 women. The etiology included 4 IgA nephropathy, 4 mesangial proliferative GN, 1 minimal change disease and 1 focal sclerosis. The active urinary kallikrein activity was measured by assay of its enzymatic activity on synthetic chromogenic substrate S-2266. The urinary inactive kallikrein excretion was determined indirectly by substracting active kallikrein activity from total kallikrein activity. The latter was measured after trypsin activation of inactive kallikrein. The results showed a significant increase in total and active urinary kallikrein excretion following a low salt diet. Yet, the inactive urinary kallikrein excretion and the ratio of active/total kallikrein excretion showed no significant change. There was no correlation between active and inactive urinary kallikrein excretion either before or after a low sodium, constant potassium diet. These findings suggest that the renal kallikrein-kinin system of GN patients responds normally to the stimulation of sodium depletion.
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PMID:Effect of sodium depletion on urinary excretion of active and inactive kallikrein in glomerulonephritic patients. 167 3

A nuclear antigen is recognized by autoantibodies in the sera of some patients with IgA nephropathy. Using these autoantibodies as a reagent, this antigen was purified 77.2-fold by ammonium sulfate fractionation, DEAE chromatography and Sepharose 6BCL gel filtration. The antigenicity of this antigen was sensitive to trypsin but resistant to RNase and DNase, suggesting that the antigenic determinant resided in protein and not nucleic acids. This antigen was inactivated at 56 degrees C for 3 h. Isoelectrophoretic focussing showed that the pI was below 4. The immunoblotting (Western transfer) assay showed a single polypeptide (69,000 Daltons) which proved to be a reactive antigen.
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PMID:Characterization of an acidic nuclear protein recognized by autoantibodies in sera from patients with IgA nephropathy. 349 Sep 36

Monocytes of 95 patients with chronic glomerulonephritis (ch.g.) tested in vitro demonstrated characteristics of activation in proliferative, and of functional suppression in mesangiocapillary glomerulopathy. Fc and C3 receptor function studied by rosette assay and metabolic potential measured by the NBT reduction test constituted result patterns. Receptor tests were supplemented with their counterparts after monocyte triggering with heat-inactivated sera and in case of NBT assay - stimulation with zymosan. Membranous, minimal change, mesangial and focal glomerulonephritis monocytes presented less specific configurations of data than those of proliferative and mesangiocapillary, with a uniform increase of trypsin-resistant Fc receptor activity. There was no appreciable correlation between the presence of circulating immune complexes (c.i.c.) in patient sera and parameters tested. The mesangiocapillary "suppression pattern" suggests mononuclear phagocyte defect in this glomerulopathy.
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PMID:Activity of circulating monocytes in patients with chronic glomerulonephritis. 383 78

A study on the clinical effects of urokinase in patients with IgA nephropathy is described. Three different methods of administration, including single, continuous, and mixed administration, were employed in this study. Measurements of plasminogen, plasmin and alpha 2-plasmin inhibitor levels in plasma were performed during the course of urokinase administration in patients with IgA nephropathy and chronic proliferative glomerulonephritis. Measurements of alpha 1-anti-trypsin and alpha 2-macroglobulin levels were also performed in these patients. Urinalysis was performed both before and after administration of urokinase. It was demonstrated that a single shot of urokinase induced a significant fibrinolytic activity in patients with IgA nephropathy, and that a single shot of urokinase was effective in improving proteinuria and/or hematuria in patients with IgA nephropathy. It is concluded that a single shot of urokinase may be useful for treatment of patients with IgA nephropathy.
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PMID:Effects of a "single shot" of urokinase on fibrinolytic activities in patients with IgA nephropathy. 653 1

Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori. We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN.
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PMID:Helicobacter pylori antigen in the glomeruli of patients with membranous nephropathy. 936 60

This study was performed to analyze the structural variety of O-glycans on the IgA1 hinge in IgA nephropathy (IgAN). The IgA1 fragments containing the hinge glycopeptide (33-mer hinge peptide core (HP) + O-glycans) were separated from 13 IgAN patients, eight healthy control subjects, and 11 patients with other primary glomerulonephritides by pyridylethylation, trypsin treatment, and Jacalin affinity chromatography. Because of the use of Jacalin, only the Gal beta 1-3GalNAc residue containing IgA was analyzed. The molecular weights (MW) of the IgA1 fragments treated by the following sequential treatment by exoglycosidases were estimated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: (1) Sialidase treatment: the MW of the two observed peaks A and B were compatible with (A) HP + 4GalNAc + 4Gal and (B) HP + 5GalNAc + 4Gal. (2) Sialidase and galactosidase: the MW of the two identified peaks a and b were consistent with (a) HP + 4GalNAc and (b) HP + 5GalNAc. (3) Sialidase, galactosidase, and alpha-N-acetylgalactosaminidase. All subjects revealed one peak, indicating the 33-mer IgA1 hinge peptide core. The intensity rate of peak B/A was significantly decreased in the IgAN group (mean +/- SD, 1.01 +/- 0.08) compared with the negative control subjects (healthy group, 1.15 +/- 0.06, P = 0.0048; other glomerulonephritis group, 1.13 +/- 0.10, P = 0.0049; Scheffe's F test). These results suggested the presence of a defect in the Gal and/or GalNAc residues in the IgA1 hinge glycopeptides in IgAN.
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PMID:Analyses of IgA1 hinge glycopeptides in IgA nephropathy by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. 955 59

Human serum immunoglobulin IgA1 is produced in bone marrow and interacts with specific cellular receptors that mediate biological events. In this study, we have analyzed the detailed glycoform structure of the human serum IgA1 Fc O-glycosylated hinge region by electrospray ionization liquid mass spectrometry. The IgA1 fragments containing the hinge glycopeptide were separated from 4 IgA nephropathy patient (IgAN) pooled sera, 10 non-IgAN pooled sera with other primary glomerulonephritides, and 5 healthy control subject pooled sera by trypsin treatment and Jacalin affinity chromatography. The molecular weights of IgA1 hinge glycopeptide were estimated using mass spectrometry, and 13 sialo and 8 asialo glycopeptide groups were identified. The results obtained clearly showed a decrease of GalNAc, Gal, and sialic acid in IgAN compared with non-IgAN and normal controls, and those strongly suggested the possibility that the decreased galactosylation and sialylation of the IgA1 hinge result in its glomerular deposition in IgAN.
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PMID:Direct evidence for decreased sialylation and galactosylation of human serum IgA1 Fc O-glycosylated hinge peptides in IgA nephropathy by mass spectrometry. 1077 13

Leukocyte accumulation in the kidney is observed in patients with IgA nephropathy. Chemokines are a large family of cytokines chemotactic for leukocytes and have been shown to be upregulated in renal diseases. We previously reported that the gene expression of lymphotactin, a sole member of C chemokine subfamily, is enhanced in an animal model of crescentic glomerulonephritis, but its expression in human renal diseases is totally unknown. In the present study, we investigated the expression of mRNAs of lymphotactin and some other chemokines in IgA nephropathy. The expression of mRNAs for three chemokines, lymphotactin, MCP-1, and MIP-1beta, in renal cortex was increased and the levels of lymphotactin and MCP-1 mRNAs were statistically higher in patients with glomerular crescents than in those without crescents. These levels also correlated with tubulointerstitial changes and urinary protein excretion. Glomerular levels of mRNAs for lymphotactin and MCP-1, but not MIP-1beta, were higher in IgA nephropathy than controls. By immunohistochemical analysis, lymphotactin was detected in tryptase-positive cells (putative mast cells) in the interstitial space. These results suggest that lymphotactin, as well as MCP-1, may contribute to leukocyte infiltration and disease progression in IgA nephropathy.
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PMID:Enhanced expression of C chemokine lymphotactin in IgA nephropathy. 1205 63

An increasing body of evidence suggests that proteases may play a key role in the pathogenesis of tissue fibrosis. Protease-activated receptor-2 (PAR-2) is cleaved and activated by trypsin-like proteolytic enzymes, including tryptase and activated coagulation factor X (FXa). Both these soluble mediators have been demonstrated, directly or indirectly, at the interstitial level in progressive renal diseases, including IgA nephropathy (IgAN). PAR-2 mRNA and protein levels were investigated by RT-PCR and immunohistochemistry, respectively, in 17 biopsies from IgAN patients and 10 normal kidneys. PAR-2 expression was also evaluated, by RT-PCR and western blotting, in cultured human mesangial and proximal tubular cells. Finally, gene expression of plasminogen activator inhibitor-1 (PAI-1) and TGF-beta, two powerful fibrogenic factors, was evaluated in FXa-, trypsin-, and PAR-2 activating peptide-stimulated human proximal tubular cells by Northern blot. In normal kidneys, PAR-2 gene expression was barely detectable, whereas in IgAN biopsies the mRNA levels for this protease receptor were strikingly increased and directly correlated with the extent of interstitial fibrosis. Immunohistochemical staining demonstrated that PAR-2 protein expression in IgAN biopsies was mainly localized in the proximal tubuli and within the interstitial infiltrate. Proximal tubular cells in culture expressed PAR-2. Activation of this receptor by FXa in tubular cells induced a striking increase in intracellular calcium concentration. In addition, incubation of both cell lines with trypsin, FXa, or PAR-2 activating peptide caused a marked upregulation of PAI-1 gene expression that was not counterbalanced by an increased expression of plasminogen activators. Finally, PAR-2 activation induced a significant upregulation of TGF-beta gene and protein expression in both mesangial and tubular cells. On the basis of our data, we can suggest that PAR-2 expressed by renal resident cells and activated by either mast cell tryptase or FXa may induce extracellular matrix deposition modifying the PAI-1/PA balance and inducing TGF-beta expression. These molecular mechanisms may underlie interstitial fibrosis in IgAN.
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PMID:Protease-activated receptor-2 expression in IgA nephropathy: a potential role in the pathogenesis of interstitial fibrosis. 1287 61


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