Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 is a recently discovered peptide mainly released from endothelial cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11, thrombin and transforming growth factor beta 1 stimulate the formation of the peptide. On the other hand the synthesis of endothelin is inhibited by nitric oxide and atrial natriuretic peptide via the formation of cyclic guanosine monophosphate. Released from endothelial cells endothelin-1 mediates transient vasodilation followed by a profound and longlasting vasoconstriction. Endothelin is also a mitogen for smooth muscle proliferation. Endothelins exert their biological effects via activation of specific receptors. Two different receptors have been cloned from mammalian tissues (ET(A) and ET(B) receptors). On vascular smooth muscle cells both receptors mediate contractions. Endothelial cells only express ET(B) receptors linked to the formation of nitric oxide and/or prostacyclin formation. Increased plasma concentrations of endothelin-1 have been described in a variety of diseases such as pulmonary hypertension, arteriosclerosis, renal failure, acute coronary syndromes, heart failure, migraine and vascular diseases. Recently an increasing number of endothelin receptor antagonists have been synthetized, which have been shown to inhibit endothelin-mediated vasoconstriction. Clinical studies are now ongoing to elucidate the pathophysiologic role of endothelin and the potential benefit of the blockade of the system in different disease states.
Mol Cell Biochem
PMID:Endothelin and endothelin antagonists: potential role in cardiovascular and renal disease. 873 56

The aim of this study was to study a possible new non-aluminum phosphate-binder to limit hyperphosphatemia in patients with renal failure. Zirconyl chloride octahydrate was evaluated as a dietary phosphate binder in rats. Aluminum chloride hexahydrate was used as a reference. Animals were divided into six groups (6 animals per group): One - control group (C), two - aluminum groups (Al1 and Al2) and three - zirconium groups (Zr1, Zr2 and Zr3) receiving different doses of zirconyl chloride octahydrate. Urines were collected during the experimental period. At the end of the treatment, the animals were sacrified and plasma and different organs were collected (liver, spleen, kidneys, brain and femur). Determination of phosphorus and calcium levels in plasma indicated that zirconyl chloride octahydrate yielded as good results as aluminum chloride hexahydrate did. Zirconyl chloride octahydrate significantly (p<0.01) reduced bone phosphorus burden. Urinary excretion of phosphorus indicated a severe phosphorus depletion in all treatments. Not even traces of zirconium could be determined in the different tissues, in urines or in plasma. Consequently, it is important to carry out experiments with zirconium compounds in order to develop non-aluminum-containing phosphate binders.
Res Commun Mol Pathol Pharmacol 1995 Dec
PMID:Reduction of dietary phosphorus absorption by oral phoshorus binders. 874 85

Until recently, the nature of the molecules involved in inherited cystic disease of the kidney remained unknown. These diseases are characterized by the development of multiple abnormal fluid-filled sacs or dilations in the kidney parenchyma, often leading to significant renal failure. The recent characterization of the PKD1 gene product and of other genes involved in murine polycystic models underscores the complexity of the pathways that lead to renal cystic disease.
Mol Med Today 1996 Feb
PMID:Advances in polycystic kidney disease. 879 59

Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene disorder resulting in renal failure. It is generally an adult onset disease, but rarely, cases of severe childhood polycystic disease arise in ADPKD families. The clear clinical anticipation in these pedigrees has led to the suggestion that the mutation may be an unstable trinucleotide repeat. We have now identified a nonsense mutation, Tyr3818Stop, in one such family (P117) within the major ADPKD gene, polycystic kidney disease 1 (PKD1). The mutation is shown to be a de novo change in the father, and of grandpaternal origin. PKD1 manifests as typical adult onset disease in the father, but is seen as severe disease, detected as enlarged polycystic kidneys in utero, in one of a pair of dizygotic twins; the other twin has the mutation but no evidence of cysts, consistent with an adult onset disease course. The finding of the same stable mutation associated with very different disease severity in this family indicates that phenotypic variation in PKD1 is not due to a dynamic mutation. It seems most likely that a small number of modifying factors may radically affect the course of disease in PKD1; identification of such factors will have important prognostic implications in this disorder.
Hum Mol Genet 1996 Apr
PMID:A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1). 884 49

Primary vesicoureteric reflux (VUR) is one of the more common genetic disorders. Little is yet known about the genetics of this potentially manageable childhood condition, which is characterised by regurgitation of urine from the bladder to the kidney. The VUR phenotype is associated with shortness of the submucosal segment of the ureter due to congenital lateral ectopia of the ureteric orifice. VUR is found in 30-50% of infants and young children with a urinary tract infection. A serious concern in families with an affected patient is that approximately one half of siblings or offspring will be affected, but up to a half of these affected siblings and offspring may be asymptomatic in childhood. If left untreated, these patients may present later in life with proteinuria, hypertension or renal failure. VUR is the commonest cause of end-stage renal failure in children, and an important cause in adults. As the kidney damage resulting from severe VUR is preventable, early detection is desirable. The techniques for clinical diagnosis are invasive and costly, reinforcing the importance of identification of a gene for VUR to facilitate genetic screening. Although family studies suggest a major dominant gene, the inheritance pattern is still a matter of debate. In rare instances, VUR occurs in association with other diseases, such as the coloboma-ureteric-renal syndrome, which is caused by a PAX2 gene mutation. In this review, we present evidence that this common disorder may be caused by mutations in the developmental pathway of which the PAX2 gene forms a part.
Hum Mol Genet 1996
PMID:Unravelling the genetics of vesicoureteric reflux: a common familial disorder. 887 47

Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.
Biochem Mol Biol Int 1996 Sep
PMID:Guanidino compounds generate reactive oxygen species. 888 79

Significantly higher levels of plasma urea creatinine and potassium were observed in patients with renal failure compared to normal controls. The RBC sodium concentration was raised whereas the RBC potassium concentration was decreased in chronic renal failure. These alterations in the RBC Na+ and K+ concentrations were associated with decrease in ouabain sensitive sodium efflux rate and ouabain sensitive sodium efflux rate constant. However, there was no significant impact of acute hemodialysis on the intracellular electrolytes levels, ouabain sensitive sodium efflux rate and ouabain sensitive sodium efflux rate constant. These findings suggest an intrinsic alteration in the transport capacity of Na(+)-K+ pump which could account for the rise in intracellular sodium and fall in intracellular potassium content in the RBCs of chronic renal failure patients.
Biochem Mol Biol Int 1996 Dec
PMID:Modulation of ouabain sensitive sodium potassium pump of erythrocytes from patients with chronic renal failure: role of acute hemodialysis. 898 20

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.
Res Commun Mol Pathol Pharmacol 1997 Feb
PMID:Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis. 909 Jul 49

The Wilms' tumor gene WT1 plays a key role in genitourinary development and subsequent normal function. Homozygous mutations of WT1 can be found in approximately 15% of Wilms' tumors. Furthermore, somatic heterozygous loss of WT1 is known to lead to cryptorchidism and hypospadias in males. A much more severe phenotype is seen in patients with Denys-Drash syndrome which results from heterozygous dominant-negative mutations of the gene. Characteristic features are mesangial sclerosis with early kidney failure, varying degrees of gonadal dysgenesis and high risk of Wilms' tumors. Here we show that a related disease, Frasier syndrome, characterized by focal glomerular sclerosis, delayed kidney failure and complete gonadal dysgenesis, is probably caused by specific intronic point mutations of WT1 that preferentially affect a CpG dinucleotide. Disruption of alternative splicing at the exon 9 splice donor site prevents synthesis of the usually more abundant WT1 +KTS isoform from the mutant allele. In contrast to Denys-Drash syndrome, no mutant protein is produced. The splice mutation leads to an imbalance of WT1 isoforms in vivo , as detected by RT-PCR on streak gonadal tissue. Thus, WT1 isoforms must have quite different functions, and the pathology of Frasier syndrome suggests that especially gonadal development may be particularly sensitive to imbalance or relative underrepresentation of the WT1 +KTS isoform.
Hum Mol Genet 1998 Apr
PMID:Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. 949 25

We measured the concentration of serum glycosaminoglycans (GAGs) in patients with glomerulonephritis, renal failure and on hemodialysis using the dye binding method. In glomerulonephritis, concentration of serum GAGs did not increase, and there was no correlation between serum and urinary GAGs. In patients with renal failure and hemodialysis, concentration of serum GAGs was significantly lower than in controls. Concentration of serum GAGs was correlated with concentration of serum albumin, which is an indicator of malnutrition in patients on hemodialysis. One month of hemodialysis did not affect the concentration of serum GAGs in patients with renal failure, but six months of hemodialysis increased the concentration of serum GAGs. These results suggest that matrix production is suppressed in renal failure with malnutrition.
Res Commun Mol Pathol Pharmacol 1998 Feb
PMID:Levels of serum glycosaminoglycans in renal failure. 958 96


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