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Query: UNIPROT:P06889 (Mol)
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1. Human polymorphonuclear leucocyte elastase and cathepsin G were incubated with preparations of isolated human glomerular basement membrane at neutral pH and 37 degrees C. 2. The ability of these enzymes to degrade glomerular basement membrane was followed by the release of hydroxyproline. Both proteinases released considerable amounts of hydroxyproline. 3. By using Sephadex G-100 it was shown that the solubilized basement membrane fragments appeared as a single peak and had a molecular weight of over 100 000. These proteins after reduction were analysed by sodium dodecyl sulphate-gel electrophoresis to examine their subunit pattern and determine their molecular size. 4. The released basement membrane proteins gave at least four precipitin lines with a rabbit anti-(glomerular basement membrane) antiserum. 5. These results support the concept that polymorphonuclear leucocyte neutral proteinases play an important role in the pathogenesis of glomerulonephritis. 6. At acid pH values cathepsin B also released hydroxyproline from human glomerular basement membrane but the lysosomal carboxyl proteinase, cathepsin D, had no action.
Clin Sci Mol Med 1978 Mar
PMID:The degradation of human glomerular basement membrane with purified lysosomal proteinases: evidence for the pathogenic role of the polymorphonuclear leucocyte in glomerulonephritis. 63 Aug

1. The casual blood pressure is the sum of the relatively stable basal pressure taken under defined conditions of rest and the labile supplemental pressure (casual minus basal), which represents the response to the current degree of physical, mental and probably metabolic stimulation. 2. The basal and supplemental blood pressures behave differently and it seems likely that different factors are involved in their pathogenesis. 3. The 5 and 8 years follow-up mortality is closely related to the basal pressure but not to the supplemental pressure. 4. The rise with age in the basal blood pressure is greater in the relatives of substantial hypertensive patients than in population control subjects. 5. Above the age group 30-39 years there is an increase in the rate of rise of the mean basal blood pressure with age among the first-degree relatives of hypertensive patients. In a population control group an acceleration in the rate of rise of the mean basal blood pressure with age also occurs but a decade or more later than in the relatives of hypertensive patients. 6. In males the mean supplemental pressures (systolic and diastolic) do not rise appreciably with age and the mean supplemental pressures of first-degree relatives and control subjects do not differ appreciably. 7. In females the mean supplemental pressures rise with age but, except after age 60 years, the pressure rise in first-degree relatives is only a little greater than in control subjects. 8. When hypertensive patients with similar casual blood pressures are compared the basal blood pressures are higher in patients with glomerulonephritis than in essential hypertensive patients. 9. In the first-degree relatives of substantial hypertensive patients high-ranking basal blood pressures occur much more frequently than in general population control subjects. 10. The close resemblance of the blood pressures in like twins indicates that genetic or familial factors have an important influence on blood pressure, and on the occurrence of frank hypertension.
Clin Sci Mol Med Suppl 1976 Dec
PMID:Casual, basal and supplemental blood pressures in 519 first-degree relatives of substantial hypertensive patients and in 350 population controls. 107 88

Renal biopsies (n = 45) from patients with various forms of glomerulonephritis (GN), comprising mesangial IgA-GN (n = 25), focal glomerular sclerosis (n = 13) and acute GN (n = 7), were examined by double staining immunocytochemistry (APAAP, streptavidin-peroxidase) using unconjugated monoclonal antibodies (Ab) against--(i) the CD1b antigen expressed on dendritic cells (DCs), (ii) the invariant chain (Ii), and (iii) biotin-conjugated Ab against HLA-DR. In normal control kidneys (n = 7) without interstitial inflammation, CD1b-positive DCs were not detected. Glomerular endothelial cells and a few cells in mesangial areas showed double staining with the Ab against HLA-DR in Ii. In GN without active interstitial inflammation (n = 9), CD1b-positive DCs were not found. In biopsies with interstitial inflammation (n = 36) CD1b-positive DCs were found interspersed among other inflammatory cells. In seven of the biopsies showing IgA-GN DCs were seen in the vicinity of those glomeruli that exhibited either crescents or glomerular sclerosis with splitting of Bowman's capsule. In proximal tubular epithelial cells de novo expression of HLA-DR/Ii-chain was only seen when DCs were present. We conclude that in different forms of GN: (i) CD1b-positive DCs play an important role in the development of interstitial inflammation, and (ii) their presence may be related to the de novo coexpression of HLA-DR/Ii in tubular epithelial cells, possibly mediated through the production of interferon gamma and other cytokines.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Dendritic cells in glomerulonephritis. 128 Aug 85

An experimental nephritis accompanied by transient proteinuria can be produced by an intravenous injection of the monoclonal antibody, 1-22-3, raised against isolated rat glomeruli. The present study deals with the ultrastructural changes in the glomeruli in rats after the injection of this antibody. At 2 h after injection, all the mesangial cells had completely degenerated and neutrophils invaded most mesangial areas. Monocytes occupied the vacant mesangial areas at 24 h and gradually increased in number over the next 4 days. At 4 and 6 days, macrophage-like cells, possibly derived from monocytes, underwent frequent mitosis, resulting in a remarkable proliferation of these cells. The interpretation of these cells as macrophages was strongly supported by the fact that they contained previously injected latex particles in large numbers. From 2 to 4 weeks after injection, the macrophage-like cells gradually transformed into cells indistinguishable from normal mesangial cells. In the present experimental nephritis where all mesangial cells were initially destroyed, cells of the monocyte-macrophage system appear to play a leading role in the pathogenesis of the ensuing proliferative glomerulonephritis, and represent the source of the replacing mesangial cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:An ultrastructural study of proliferative nephritis induced experimentally by a monoclonal antibody against mesangial cells: replacement of mesangial cells by cells of the monocyte-macrophage system. 134 79

To clarify the mechanisms of glomerular pericapillary fibronectin deposition in human membranous nephropathy and mesangial proliferative glomerulonephritis, intraglomerular fibronectin distribution was examined by light and electron microscopy using the experimental rat models of Heymann and nephrotoxic serum nephritis. As previously demonstrated by immunofluorescence microscopy (Pettersson and Colvin 1978; Ikeya et al. 1985, 1986), fibronectin was distributed in the mesangial areas and occasionally on percicapillary walls of normal glomeruli, while in nephrotoxic serum nephritis and Heymann nephritis, fibronectin was diffusely located along glomerular capillary walls as well as in the mesangium. By immunoelectron microscopy using the immunogold technique, fibronectin was also noted in the mesangial areas and the lamina densa of the glomerular basement membrane (GBM) in normal glomeruli. In nephrotoxic serum nephritis, fibronectin was seen around mesangial cells situated between endothelial cells and the GBM, suggesting that pericapillary fibronectin in nephrotoxic serum nephritis reflects mesangial extension. However, in Heymann nephritis, it was found uniformly in the lamina rara interna, lamina densa and lamina rara externa of the GBM, indicating no specific relation to glomerular cells. When sections of normal and both experimental nephritis kidneys were incubated with fluorescein isothiocyanate conjugated with rat plasma fibronectin, a linear pattern of fluorescein staining along the glomerular capillary walls was observed in Heymann nephritis but not in normal or nephrotoxic serum nephritic rats. The GBM in Heymann nephritis would thus appear to have an affinity for plasma fibronectin. Based on the above findings, fibronectin in the GBM of rats with Heymann nephritis may reasonably be concluded to originate from the plasma.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Intraglomerular fibronectin in rat experimental glomerulonephritis. 135 19

The presence of the measles (rubeola) virus genome was searched for in the lymphocytes from the peripheral blood of patients suffering from the acute (16 persons) or chronic (164 persons) glomerulonephritis. Dot hybridization technique with the plasmid borne probes to the measles viral genes NP, P and H have been used for the search. The measles viral genome has been detected in 58% of lymphocytes from the patients with the chronic glomerulonephritis and in 50% of lymphocytes from the patients suffering from the acute form of the disease. The genome was not found in the material from the control group including donors and traumatology ward patients. 25 samples of lymphocytes from the patients with the chronic glomerulonephritis contained the RNA that was not hybridizable with the viral genes probes by dot hybridization technique, thus containing no genes homologous to parotitis viral genes. The average titer of anti-measles antibodies in the serum from patients with chronic glomerulonephritis the lymphocytes of which contained the measles viral genome was 1:304, while it was 1:154 for patients with the negative probes. The average anti-measles antibodies titers are the same (1:166 and 1:142) for analogical groups of patients with acute form of disease.
Mol Gen Mikrobiol Virusol 1990 Oct
PMID:[Detection of the measles virus genome in the peripheral blood lymphocytes of patients with chronic and acute glomerulonephritis]. 170 85

The nephritogenic antigen that induces antiglomerular basement membrane antibody-induced glomerulonephritis (anti-GBM nephritis) in rats was isolated from collagenase-solubilized bovine renal basement membranes. Purification was achieved using antibody-coupled affinity columns which were originally used for the purification of trypsin-solubilized nephritogenic antigen (Sado et al. 1984a). The nephritogenic antigen was a heteropolymer composed of P2 (Mr 28 kDa) and P3 (Mr 30 kDa) polypeptides as monomers and their dimers in sodium-dodecyl-sulfate (SDS) polyacrylamide gel electrophoresis. The P3 polypeptide was considered to be the nephritogenic epitope, since a fraction composed of the P2 polypeptide alone was not nephritogenic. The properties of the nephritogenic epitope were the same as those of the Goodpasture epitope (M2*), which is a noncollagenous domain of the alpha 3 chain of type IV collagen (Butkowski et al. 1985; Saus et al. 1988), indicating that the nephritogenic antigen is the same as the Goodpasture antigen.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Properties of bovine nephritogenic antigen that induces anti-GBM nephritis in rats and its similarity to the Goodpasture antigen. 172 95

The noncollagenous domain hexamer of collagen IV from bovine alveolar basement membrane was excised with bacterial collagenase, purified under nondenaturing conditions, and characterized. The hexamer is comprised of four distinct subunits [alpha 1(IV)NC1, alpha 2(IV)NC1, alpha 3(IV)NC1, and alpha 4(IV)NC1]. Each subunit exists in both monomeric and dimeric (disulfide-crosslinked) form, and both monomers and dimers have charge isoforms. Certain dimers also contain nonreducible crosslinks. The alpha 3(IV)NC1 subunit, in both the monomeric and dimeric form, reacts with Goodpasture (GP) antibodies. The GP epitope is sequestered within the hexamer and becomes reactive with antibody upon exposure with protein denaturants. These results reveal that the alveolar basement membrane hexamer is identical to the hexamer from glomerular basement membrane with respect to subunit composition, identity of subunits reacting with GP antibodies, and sequestration of the GP epitope but differs greatly in the relative amount of the GP-reactive subunit and the degree of disulfide and nondisulfide crosslinking of subunits. This study leads to the conclusion that pulmonary hemorrhage associated with GP syndrome is mediated by the same autoantibody that mediates the glomerulonephritis, namely anti-collagen [alpha 3(IV)] antibody.
Am J Respir Cell Mol Biol 1991 Aug
PMID:Alveolar basement membrane: molecular properties of the noncollagenous domain (hexamer) of collagen IV and its reactivity with Goodpasture autoantibodies. 171 46

Morphologic studies were performed in a passive model of in situ immune complex glomerulonephritis in rats. The formation and fate of subepithelial immune complexes as well as the role of glomerular polyanion in the induction of disease were examined. Unilateral in situ immune complex glomerulonephritis was induced in rats by perfusion of cationised horse spleen ferritin (pI greater than 9.5) (400 micrograms/rat) into the left kidney followed by systemic injection of 0.2 ml (= 400 micrograms precipitating antibody) of sheep anti-ferritin antiserum 2 h later. This schedule induced glomerulonephritis with proteinuria (mean maximum 100 mg/24 h between the 5th and the 12th day). Rats were sacrificed at intervals between 1 h and 42 days after induction of glomerulonephritis, samples of renal tissue were examined by light, immunofluorescence and electron microscopy (including staining of anionic sites by polyethyleneimine). The lesion induced closely resembled that of membranous glomerulonephritis in man as massive subepithelial deposits were seen with very little cellular infiltration or proliferation. The antigen (ferritin) deposits were initially located subepithelially; from 2 weeks onwards intramembranous deposits in the thickened basement membrane were present, the apparent translocation being due to excessive newly synthesised basement membrane material which encloses the deposits. A loss of anionic sites in the lamina rara interna, lamina rara externa and on the epithelial cell surface coat preceded the development of proteinuria.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Ultrastructural studies in passive in situ immune complex glomerulonephritis. A rat model for membranous glomerulonephritis. 248 73

Immune complexes occur spontaneously in the testis of Brown-Norway (BN) inbred rats between the basal lamina of the seminiferous tubules and the outer lamina of the myoid testicular cells. The deposits can be detected immunohistologically (IgG; C3) and by electron microscopy. The immune complexes appear between the 8th and 12th weeks of life, increase in amount up to the 30th week and decrease thereafter. After about the 20th week, of life, 15% of the animals show destruction of the germinal epithelium accompanied by an infiltration of lymphocytes and plasma cells. The final stage of this disease, which initially shows no signs of inflammation, is characterized by diffuse tubular atrophy. However, up to the 70th week of life, 85% of the animals with immune complexes show no pathological alterations. Antibodies eluated from the testes react with spermatocytes I and structures close to the lumen of the seminiferous tubules, but not with mature sperms. Serum antibodies to sperms occur in about 25% of the BN rats, but the presence of these antibodies shows no correlation with the immunohistological findings. This newly described spontaneous immune complex orchitis is regarded as a further example of an in-situ-induced immune complex disease. The observations made here can be compared with those in (peri-) membraneous glomerulonephritis, another example of a disorder resulting from in-situ-formation of immune deposits.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Spontaneous immune complex orchitis in brown Norway rats. 256 48


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