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)

1. Human leucocytes were isolated from venous blood and resuspended in the subjects plasma. 2. Intracellular pH measurements were made in vitro by the dimethyloxazolidinedione technique in 13 healthy subjects and in 11 subjects with renal failure and metabolic acidosis. 3. The intracellular pH of the healthy subjects was found to be 7-07 (SD 0-04), significantly lower than that of the patients, which was 7-11 (SD 0-03). For all estimations plasma PCO2 was maintained at approximately 5-5 kPa. The methodological and possible metabolic reasons for this difference in intracellular pH are discussed.
Clin Sci Mol Med 1977 Mar
PMID:Leucocyte intracellular pH in patients with the metabolic acidosis of renal failure. 1 6

1. Plasma concentrations of human calcitonin were measured in groups of patients with chronic renal failure, treated either conservatively or by haemodialysis, and compared with a normal group of persons. 2. Plasma calcitonin was statistically significantly elevated in both groups with renal failure. 3. When the data from the three groups were pooled, plasma calcitonin was found to be inversely correlated with total calcium and directly correlated with plasma creatinine.
Clin Sci Mol Med 1977 Jun
PMID:Plasma calcitonin in chronic renal failure: relation to other factors of importance in bivalent ion metabolism. 32 18

1. In twenty-three uraemic patients on regular dialysis, plasma renin activity and blood volume were measured before and after a single dialysis. Three groups were identified; the first had a low or normal plasma renin activity and a high or normal blood volume, the second had a high plasma renin activity and a low blood volume and the third had both variables above normal. 2. In spite of these differences, diastolic blood pressure before and after dialysis was the same in the three groups and multiple regression analyses failed to demonstrate any dependence of blood pressure on plasma renin activity, blood volume or body weight taken separately or together. 3. We conclude that other factors besides plasma renin activity and blood volume are important in maintaining arterial hypertension in terminal renal failure.
Clin Sci Mol Med 1977 Jan
PMID:Blood pressure control in end-stage renal disease in man: indirect evidence of a complex pathogenic mechanism besides renin or blood volume. 60 60

1. A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [14C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. 2. Synthesis of 14C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. 3. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values obtained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. 4. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [14C]glycine incorporation into urinary uric acid.
Clin Sci Mol Med 1978 Jun
PMID:Purine biosynthesis de novo by lymphocytes in gout. 65 27

1. Acute renal failure was induced in female Sprague-Dawley rats by the subcutaneous injection of glycerol. 2. Four groups of rats were studied; all animals received a glycerol challenge. Group A (control) were sham-operated only, group B received an infusion of sodium chloride solution (150 mmol/l; saline) for 24 h, group C received an infusion containing prostaglandin E2 (PGE2, 1.7 micronmol/l) in saline and group D a solution containing PGE2 (3.4 micronmol/l) in saline. 3. All rats were killed 48 h after glycerol challenge. The degree of renal impairment was assessed by serum creatinine concentration, which did not differ in sham-operated animals and the group receiving saline alone. The group of rats receiving the lower dose dose of PGE2 has a significantly lower mean serum creatinine concentration than the saline-infused control rats (P less than 0.0025). Creatinine concentration was further lowered by the higher dose of PGE2 but there was not a significant difference in the number of rats showing severe tubular necrosis histologically. 4. The study demonstrates that intravenous infusion of prostaglandin E2 has a protective influence on glycerol-induced renal failure in the rat; the protection afforded may be due to the vasodilator effect of PGE2 and/or an effect on glomerular permeability.
Clin Sci Mol Med 1978 Nov
PMID:Protective effect of prostaglandin [PGE2] and in glycerol-induced acute renal failure in rats. 72 5

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous injections (3 mg day-1 kg-1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), tension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1-15 to 0-2 ng/ml, SEM 0-2; P less than 0-01) and plasma renin activity (20 to 3 ng h-1 ml-1, SEM 1, P less than 0-01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31-5 ng h-1 ml-1, SEM 3 and 4 respectively; P less than 0-01) and plasma prostaglandin E2 (1-2 to 3-4 ng/ml, SEM 0-2 and 0-4 respectively; P less than 0-05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7-6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, SEM 7-7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, SEM 4 and 6 respectively; P less than 0-01) and decreased renal function (plasma creatinine 0-9 +/- 0-04 to 3-5 +/- 1 mg/100 ml, SEM 0-04 and 1 respectively; P less than 0-01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
Clin Sci Mol Med Suppl 1976 Dec
PMID:Effects of indomethacin in rabbit renovascular hypertension. 107 20

1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested. 2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling. 3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14-C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high. 4. Creatinine, incubated at 38 degrees C for 24 h in Krebs bicarbonate solution (pH 7-38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur "non-enzymatically".
Clin Sci Mol Med 1975 May
PMID:Factors affecting the metabolic production of methylguanidine. 112 27

1. The clearance of isotopically labelled sodium diatrizoate by haemodialysis was measured in vitro, with simulated extracellular fluid, and in vivo in eleven patients, at varying rates of fluid or plasma flow. Clearance was also measured in five patients undergoing peritoneal dialysis. In all instances simultaneous measurements of urea clearance were made and the diatrizoate/urea clearance ratio was calculated. 2. In haemodialysis studies, diatrizoate and urea clearances showed a linear increase with increasing 'extracellular fluid' or plasma flow through the dialyser diatrizoate/urea clearance ratio fell. 3. The clearance of diatrizoate in vivo was slightly less than clearance in vitro at corresponding flow rates, but the diatrizoate/urea clearance ratio showed no significant difference. 4. Diatrizoate and urea clearances during peritoneal dialysis were very much lower than during haemodialysis but the diatrizoate/urea clearance ratios were within the same range. 5. The rapid removal of diatrizoate in patients with renal failure requires haemodialysis.
Clin Sci Mol Med 1976 Jan
PMID:A comparison of the clearance of urographic contrast medium (sodium diatrizoate) by peritoneal and haemodialysis. 124 4

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease which frequently results in renal failure. The major ADPKD gene, polycystic kidney disease 1 (PKD1), has recently been identified. In an attempt to understand better the aetiology of this disorder we have searched for mutations in the PKD1 gene. Analysis of three regions in the 3' part of the gene has revealed two mutations that occur by a novel mechanism. Both mutations are deletions (of 18 or 20 bp) within the same 75 bp intron and although these deletions do not disrupt the splice donor or acceptor sites at the boundary of the intron, they nevertheless result in aberrant splicing. Two different transcripts are produced in each case; one includes the deleted intron while the other has a 66 bp deletion due to activation of a cryptic 5' splice site. No normal product is generated from the deleted gene. Aberrant splicing probably occurs because the deleted intron is too small for spliceosome assembly using the authentic splice sites; this mechanism has previously only been described from in vitro studies of vertebrate genes. A 9 bp direct repeat has been identified within the intron, which probably facilitated deletion by promoting misalignment of sequence. The possible phenotypic implications of producing more than one aberrant PKD1 transcript in these cases are discussed.
Hum Mol Genet 1995 Apr
PMID:Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion. 763 5

Alport syndrome is a mainly X-linked hereditary disease of basement membranes characterized by progressive renal failure, deafness, and ocular lesions. The alpha 3(IV) and alpha 4(IV) collagen genes have been recently shown to be involved in the less frequent autosomal recessive form. When screening lymphocyte COL4A3 mRNAs from Alport patients, we found a mutant whose transcripts were disrupted by a 74 bp insertion at the junction of exons IV or V and VI. The insertion derives from an antisense Alu element in COL4A3 intron V, which has been spliced into the alpha 3(IV) mRNA due to a G to T transversion activating a cryptic acceptor splice site in this Alu element. There is complete segregation of this mutation with the disease in the family. Our findings provide the first evidence for the pathogenic role of abnormal splicing of COL4A3. Moreover, we demonstrate the superiority of mutation screening at the mRNA level to detect a hitherto poorly recognized mutation mechanism in humans, splice-mediated insertion of an Alu fragment into a coding sequence.
Hum Mol Genet 1995 Apr
PMID:Splice-mediated insertion of an Alu sequence in the COL4A3 mRNA causing autosomal recessive Alport syndrome. 763 17


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