Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 36 patients with incipient and advanced renal failure (CCr 80--30 ml/min X 1.73 m2), serum chemistry including ionized Ca, serum PTH and fractional intestinal absorption of Ca (whole body counter; two-dose-technique; 47Ca p.o. and i.v. to correct for urinary and endogenous fecal loss were measured. Quantitative bone histology after in vivo tetracycline double labeling was evaluated from undecalcified sections before and 18 months after therapy with vitamin D3 or 5,6-trans-25-OH-CC in a dose sufficient to raise intestinal absorption and/or urinary excretion of Ca. Intestinal absorption of Ca was impaired in some patients at a GFR of 60 ml/min/1.73 m2. After up to 10000 U/d 5,6-trans-25-OH-CC and 8000 IU/d vitamin D3, respectively, fractional intestinal absorption of Ca rose and was normalized in all patients. There was a concomitant rise in urinary Ca. Serum PTH fell, but did not always return into the normal range. Ionized Ca rose in all patients. Bone histology was evaluated in 17 of these 36 patients after informed consent was obtained. The mass of mineralized bone (Vv) rose in 7/17 patients, pointing to a positive calcium balance. Volumetric density of osteoid (Vvos) and surface density of osteoid (Svos) fell in 10/17 patients concomitant with an increase in the fraction of mineralizing seams and a decrease in the number of lamellae in osteoid seams. Osteoclastic resorption (OCl) fell as did the fraction of woven osteoid seams. However, woven osteoid failed to disappear completely and osteoclastic resorption stayed elevated in some patients. 5,6-trans-25-OH-CC and vitamin D3, in doses that normalized intestinal absorption of Ca, failed to restore completely bone histology to normal although mineralization and collagen texture of osteoid were consistently improved. The dose response characteristics to vitamin D of different abnormalities of Ca metabolism appear to be non-uniform.
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PMID:Long-term administration of vitamin D steroles in incipient and advanced renal failure: effect on bone histology. 21 65

Dogs were dialyzed with collagen and cuprophane membranes, human renal failure patients were dialyzed with cuprophane membranes, and samples of the membranes were observed by scanning electron microscopy at different time periods. Fixation was done in glutaraldehyde and cacodylate buffer, and samples were dried at the critical point. All cellular elements were well preserved and appeared viable. Cuprophane adsorbed platelets almost selectively in dog dialyses, whereas collagen adsorbed a smaller number and more heterogeneous group of cells. In contrast to these findings, when cuprophane was used in clinical dialyses, the cell population was predominantly polymorphonuclear leukocytes.
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PMID:Deposition of blood cells on collagen and cuprophane membranes. 117 20

Infection with Listeria monocytogenes is known to occur more frequently in immunosuppressed patients, including those receiving high-dose prednisone or cytotoxic therapy for collagen vascular disease. We reviewed three cases of listeriosis and systemic lupus erythematosus (SLE) seen at our institution, in addition to five cases reported in the English literature. Seven of the eight patients had non-CNS listerial infections. All patients but one had associated risk factors of either renal failure or pregnancy. From our review, we found that listeriosis is uncommon in SLE, and patients without renal failure or pregnancy do not seem to be at increased risk for listeriosis. Although most patients were treated with high-dose prednisone, with or without cytotoxic drugs, the role of immunosuppression by these drugs as a risk factor for listeriosis remained unclear.
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PMID:Listerial infections in patients with systemic lupus erythematosus. 141 34

Fibrin deposits are frequent in experimental and human glomerulonephritides. In rapidly progressive glomerulonephritis (RPGN), fibrin deposits are considered as a factor generating glomerular sclerosis leading to renal failure. In RPGN, proliferation of epithelial cells associated with macrophages and fibrin deposits is observed in Bowman's space. It is known that 1) thrombin may be locally generated by tissue factor from glomerular cells and macrophages, 2) active thrombin may be adsorbed into the plug. Using immortalized human glomerular epithelial cells, we have tested the hypothesis that active thrombin may be a potential mediator of cellular proliferation, fibrin deposits persistency and collagen IV synthesis. The results clearly demonstrate that epithelial cells bind specifically iodinated alpha-thrombin. Thereafter, these cells synthesize specific inhibitors of plasminogen activators, converting their fibrinolytic activity into antifibrinolytic activity. Moreover, they synthesize soluble form of type IV collagen. A new therapeutical approach of RPGN may be taken into account based on the ability of new drugs inhibiting the binding of thrombin on its specific receptors, and/or inhibiting the extrinsic pathway of the fibrin formation.
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PMID:[Extracapillary glomerulonephritis with fibrin deposits. Role of thrombin]. 146 28

Mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen have been found in linkage with X-chromosomal Alport syndrome (AS). To identify COL4A5 mutations in patients from Germany with clinically defined AS, DNA from 20 unrelated patients was analyzed by conventional Southern blotting. By using full length alpha 5(IV) cDNA probes, large COL4A5 deletions could be detected in two patients. In one case, a 34 kb deletion affecting the 14 most 3' exons of the gene was observed. The second patient harbored a complete COL4A5 deletion. In both cases, functional alpha 5(IV) mRNA was unlikely to be present. Clinically, both patients developed end-stage renal failure before age 30. Furthermore, they had characteristic retinal flecks, and sensorineural hearing loss with typical changes on the audiogram. The patient with the complete deletion of COL4A5 lost the renal allograft due to an anti-GBM mediated glomerulonephritis.
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PMID:Deletions of the COL4A5 gene in patients with Alport syndrome. 147 65

Many renal diseases progress to end-stage renal failure with glomerulosclerosis, irrespective of the cause of the disease. Glomerulosclerosis is characterized by an accumulation of extracellular matrices (ECM) due to increased synthesis of the ECM and/or decreased degradation of the ECM. Sclerotic lesions represent an accumulation of normal constituents of the ECM, including type IV collagen, laminin, proteoglycans, as well as, abnormal constituents such as type I and III collagens. The cDNAs for various ECM constituents have been obtained and it has become possible to study the status of their synthesis, in the transcriptional level, in various glomerular diseases. Studies suggest that hemodynamic factors and growth factors, such as, TGF-beta and PDGF are responsible for the development of glomerulosclerosis. Inappropriate expression of intrinsic mesangial cell metalloproteinases and tissue inhibitors of metalloproteinases also lead to glomerulosclerosis.
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PMID:[Glomerular extracellular matrix in glomerulosclerosis by molecular biology]. 149 57

Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5 or 7 mg paraquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, GOT, GPT and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary hemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electromicroscopic examination on the surviving animals revealed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts.
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PMID:Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections. 150 67

Patients infected with human immunodeficiency virus type 1 (HIV-1) develop a renal syndrome characterized by proteinuria, renal failure, and focal segmental glomerulosclerosis. By using a noninfectious HIV-1 DNA construct lacking the gag and pol genes, three transgenic mouse lines have been generated that develop a syndrome remarkably similar to the human disease. In the present study, we have characterized in detail one of these lines, Tg26. In Tg26 mice, proteinuria was detectable at approximately 24 days of age, followed by severe nephrotic syndrome and rapid progression to end-stage renal failure. Renal histology showed focal segmental glomerulosclerosis and microcystic tubular dilatation. Indirect immunofluorescence studies demonstrated increased accumulation of the basement membrane components laminin, collagen type IV, and heparan sulfate proteoglycan. The viral protein Rev was present in sclerotic glomeruli. Northern blot analysis of total renal RNA showed expression of viral genes prior to the appearance of histologic renal disease, with greatly diminished viral gene expression late in the disease course. Kidneys from transgenic mice expressed increased steady-state levels of collagen alpha 1(IV) mRNA when glomerulosclerosis was present. We conclude that the presence of HIV-1 genes is associated with progressive renal dysfunction and glomerulosclerosis in transgenic mice.
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PMID:Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. 154 49

Polycystic kidney disease is an inherited disorder of parenchymal structure that leads to renal failure. Cysts begin as focal dilations in proximal tubules and collecting ducts, giving rise to cyst walls lined by a phenotypically disturbed epithelium that expresses dysfunctional transport and matrix proteins. We used an mRNA search protocol to probe efficiently for tissue-specific disturbances that might underlie the formation of cysts. This search assessed the relative abundance of transcripts encoding a variety of growth factors (transforming growth factor-beta 1, interleukin-6, tumor necrosis factor, and endothelin-1), structural proteins (collagen IV, nidogen, fibronectin, and laminins A and B1), and cell adhesion molecules (CAMs; E-cadherin, N-CAM, laminin receptor, and fibronectin receptor) in the cystic kidneys of cpk/cpk mice and uncovered a previously unrecognized early reduction in mRNA encoding N-CAM (54%) and E-cadherin (56%) (n = 5; P less than 0.001). Levels of transcripts for growth factors, structural proteins, and for fibronectin and laminin receptors in normal and cystic kidneys were generally similar. The reduction in transcripts for N-CAM and E-cadherin in kidneys from cystic mice was not observed in autologous liver. The immunofluorescent staining of cystic kidneys confirmed that the decrease in N-CAM and E-cadherin was generally confined to regions abundant in developing cystic epithelium. The presence of both N-CAM and E-cadherin appears to guide the sequential differentiation and polarization of normal renal epithelium, and their attenuated expression in the kidney of cpk/cpk mice may be a material factor contributing to the pathogenesis of cyst formation.
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PMID:Attenuated expression of epithelial cell adhesion molecules in murine polycystic kidney disease. 156 81

A single base mutation was identified in the type IV collagen alpha 5 chain gene (COL4A5) of a Danish kindred with Alport syndrome. The 27-year-old male proband developed hematuria in childhood and terminal renal failure at the age of 25 years. He has no hearing loss or ocular lesions. Electron microscopy demonstrated splitting of the lamina densa of the glomerular basement membrane. The proband's mother has had persistent microscopic hematuria since the age of 40 years, but no other manifestations. Southern analysis of MspI-digested genomic DNA from the proband showed the absence of 1.3-kb and 0.9-kb fragments present in control DNA but the presence of a 2.2-kb variant fragment, indicating the loss of an MspI restriction site in the 3' end of the gene. The mother had all three fragments, indicating heterozygosity. PCR amplification of exon 14 (counted from the 3' end) and subsequent denaturing gradient gel electrophoresis analysis suggested a sequence variant in the proband and his mother. This was confirmed by sequencing of the PCR-amplified exon 14 region of the hemizygous proband, which demonstrated the base change G----A abolishing an MspI restriction site. Hybridization analysis with allele-specific probes confirmed the inheritance of the mutation with the phenotype. The mutation changed the GGC codon for glycine-1143 to GAC for aspartate. Substitution of glycine-1143, located in the collagenous domain of the alpha 5(IV) chain, for any other amino acid can be expected to interfere with the maintenance of the triple-helical conformation of the collagen molecule. This could, in turn, weaken the glomerular-basement-membrane framework and lead to increased permeability.
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PMID:Mutation in the alpha 5(IV) collagen chain in juvenile-onset Alport syndrome without hearing loss or ocular lesions: detection by denaturing gradient gel electrophoresis of a PCR product. 159 9


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