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

1. A patient with polyuria in whom diabetes insipidus had been diagnosed was treated with Pitressin. Resistance to this therapy developed after 18 months and a circulating antibody to vasopressin was then demonstrated. Withdrawal of therapy led to a fall in titre of the antibody and an increase in maximal urinary concentration. 2. The antibody to vasopressin was associated with the IgA fraction of the serum immunoglobulins and its characteristics are described.
Clin Sci Mol Med 1976 Apr
PMID:Polyuria associated with an antibody to vasopressin. 126 Dec 9

Several aspects of tryptophan distribution and metabolism in chronic renal insufficiency (CRI) were investigated in a rat model prepared by partial nephrectomy. Partially nephrectomized (pNx) rats with a moderate degree of CRI demonstrated a 40% decrease in plasma total tryptophan concentration between 5 and 11 weeks after the acute reduction of renal functional mass. This decrease was accompanied by hypoalbuminemia, polyuria, albuminuria, and tryptophanuria. After 5 weeks of sustained plasma total tryptophan deficiency (from Week 6 to Week 11), the plasma free tryptophan concentration, the plasma concentrations of large neutral amino acids, and the tryptophan levels in red cells, liver, and kidney of the pNx rats were similar to those of the controls. However, evidence for abnormal brain tryptophan metabolism in pNx rats after 11 weeks of CRI included 16% reductions of tryptophan levels in the midbrain and pons and 65% increases in the serotonin contents of the hypothalamus and medulla. Monoamine oxidase activities in hypothalamus and cerebellum of pNx rats were the same as those of the controls. These studies indicate that tryptophanuria is an important factor in the development of the plasma tryptophan deficiency in the pNx model. In addition, the results support the hypothesis that regional abnormalities in tryptophan metabolism contribute to the neurological and neuroendocrine dysfunction of CRI.
Exp Mol Pathol 1987 Feb
PMID:Tryptophan distribution and metabolism in experimental chronic renal insufficiency. 243 52

Cis-diamminedichloroplatinum (II) (cisplatin), an inorganic platinum salt used in cancer chemotherapy, is characterized by a renal toxicity recognized both in experimental animals and in patients treated with the compound. The purpose of the present study was to explore by both light and electron microscopy the morphological alterations induced in the rat kidney by cisplatin administration and, in particular, to analyse the tissue repair reaction following nephrotoxic injury. Experimental animals (four rats per group) were treated i.p. with 2, 4 or 8 mg/kg cisplatin administered in four consecutive daily injections. The rats were sacrificed 4 days after the last injection. In addition, the persistence of renal lesions and the duration of the repair reaction were determined in rats given 8 mg/kg cisplatin and killed 4, 7, 14 or 21 days after the last injection. The cell proliferation associated with tissue repair was estimated both quantitatively (rate of DNA synthesis) and qualitatively (histoautoradiography and electron microscopy examination) 1 h after in vivo exposure to [3H] thymidine. Renal tissue alterations and the repair reaction were minimal after the administration of 2 or 4 mg/kg cisplatin. In contrast, 8 mg/kg cisplatin caused a spectrum of morphological abnormalities affecting proximal, distal and collecting tubules, and ranging from sublethal cell alterations to tubular necrosis and cystic dilatation. The latter degenerative change primarily involved the straight portion of proximal tubules and seemed to develop over the weeks following cisplatin administration. Concomitantly with the tissue lesions, a burst of cell proliferation, associated with stimulation of DNA synthesis, was apparent in the renal cortex and outer medulla. Whereas a very high incidence of S-phase cells was encountered in seemingly undifferentiated tubules, they also appeared in differentiated proximal, distal and collecting tubules, but were infrequent in cystic tubules. Proliferation of fibroblasts was also stimulated in the renal interstitium. The proliferative response persisted for the whole duration of the experiment, indicating incomplete tissue repair. The long-lasting tubular injury and the slowness of repair are consistent with the chronic renal dysfunction (polyuria and hypomagnesemia) that cisplatin is known to induce in both man and experimental animals.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Tissue injury and proliferative response induced in rat kidney by cis-diamminedichloroplatinum (II). 289 21

Isoproterenol-induced myocardial necrosis was examined in male mice with alloxan-induced and genetically transmitted diabetes. Ten days after alloxan treatment, mice exhibited an elevation in blood glucose concentrations, weight loss, polyuria and decreased heart rates (510 +/- 15 v. 675 +/- 11 beats/min) compared with matched control mice. Similarly, genetically diabetic mice exhibited lower heart rates than the corresponding age-matched controls (383 +/- 30 v. 603 +/- 30 beats/min). In comparison to matched controls, both groups of diabetic mice had a significant decrease in the severity of the cardiac necrosis which was induced by the administration of isoproterenol. The reduction in isoproterenol-induced cardiac lesions was similar in mice with chemically induced diabetics and mice with genetically transmitted diabetes. Biochemical studies of ventricular slices revealed no change in basal cAMP levels and no differences in isoproterenol-induced changes in cAMP levels in mouse hearts from both models of diabetes. Insulin treatment corrected the chemically induced diabetic state and restored the cardiotoxic potential of isoproterenol.
J Mol Cell Cardiol 1985 Apr
PMID:Influence of the diabetic state on isoproterenol-induced cardiac necrosis. 299 38

Experimental work in our laboratory has confirmed the protective activity of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, diabetic cataract has also been partially prevented. Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and vanadate, with the purpose of eliciting the best possible antidiabetic protection. More recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against brain injury and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100 times more effectively than vitamin E. This investigation has introduced a combination of the vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer, U-83836E, in order to improve the insufficient protection when vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces, glycosuria and proteinuria were determined on biological samples obtained in metabolic cages; body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled and registered. At the end of the experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by vanadate alone. At subsequent steps, U-83836E significantly improved the protective effect of vanadate alone on polydipsia and polyuria, but especially on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.
Res Commun Mol Pathol Pharmacol 1994 Sep
PMID:Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin treated rats. 782 6

The purpose of the present study was to compare the time required to develop each of the following diabetic symptoms after the streptozocin administration (60 mg/kg, iv) in rats: hyperglycaemia, glycosuria, polyuria, polydipsia, polyphagia, and body weight reduction. The data showed that hyperglycaemia, glycosuria, polyuria and polydipsia were significantly increased in 24 hours after the streptozocin administration; however, there was a delay of 3 days before a significant reduction of body weight was detected, and the food intake was not significantly increased until 7 days after the streptozocin administration.
Biochem Mol Biol Int 1993 Aug
PMID:Appearance of different diabetic symptoms after streptozocin administration: a comparison study. 822 Feb 50

a fpreviously produced angiotensinogen-deficient mice, i.e. mice with deleted renin-angiotensin system (RAS), with a genetic background on C57BL/6J - C57BL/6J-agt (-/-) -, but no C57BL/6J-agt (-/-) which survived long enough to be weaned. In the present study, we attempted to prevent neonatal death and analyzed pathological development in C57BL/6J-agt (-/-). We indicate that mortality in C57BL/6J-agt (-/-) derived from C57BL/6J-agt (+/-) can be reduced by hypodermic saline injection in the 7 days following birth, that hydronephrosis developed by day 14 in association with polydiplasia and polyuria by day 30, and that chronic hypotension occurs. Hydronephrosis is less damaging to electrolyte resorption in younger mice, but not in adults. We also observed that C57BL/6J-agt (-/-) derived from C57BL/6J-agt (-/-) frequently develop fetal hydronephrosis and die of respiratory failure at birth. These results suggest that maternal RAS is associated with structural maturation of kidney and lung in late fetus and that postnatal RAS plays important roles in structural and functional maintenance of the kidneys.
Int J Mol Med 1998 Mar
PMID:Pathologic characterization of hypotensive C57BL/6J-agt: angiotensinogen-deficient C57BL/6J mice. 985 67

The glucocorticoid metabolising enzymes, 11beta-hydroxysteroid dehydrogenases (11beta-HSD), play a critical role in determining the availability of glucocorticoids to activate their receptors and hence modulate target gene transcription. There are two isozymes, 11beta-HSD-1 and -2, which act in opposing directions. 11beta-HSD-2 acts as a dehydrogenase, converting active corticosterone (cortisol in humans) to its inactive 11-keto derivative (11-dehydrocorticosterone in rodents and cortisone in humans), whereas 11beta-HSD-1 acts as a reductase, regenerating active glucocorticoids in a tissue-specific manner. Owing to the lack of specific inhibitors of these enzymes, it has been difficult to confirm the roles and determine the importance of these enzymes in vivo. Hence, to address this, we produced transgenic mice with null-mutations in the genes encoding the 11beta-HSD-1 or 11beta-HSD-2 enzymes. 11beta-HSD-2 -/- mice show signs of hypertension, hypotonic polyuria, hypokalemia and hypochloremia. These symptoms arise from illicit activation of mineralocorticoid receptors by glucocorticoids, in the absence of the protective action of 11beta-HSD-2. The phenotype is directly comparable to the Syndrome of Apparent Mineralocorticoid Excess, seen in humans with mutations in the 11beta-HSD-2 gene. Mice lacking 11beta-HSD-1, however, show a more subtle phenotype with reduced activation of glucocorticoid-induced processes. They were unable to convert 11-dehydrocorticosterone to corticosterone in vivo, confirming 11beta-HSD-1 as the sole 11-reductase in the mouse. They have elevated circulating levels of plasma corticosterone levels and adrenal hyperplasia, but they also have attenuated glucocorticoid-induced activation of gluconeogenic enzymes in response to fasting, and lower glucose levels in response to obesity or stress. Overall, these transgenic models have proved very useful for elucidating the roles of 11beta-HSDs in vivo and will be a unique resource for investigating the importance of each enzyme in the diverse actions of glucocorticoids.
Mol Cell Endocrinol 2001 Jan 22
PMID:Phenotypic analysis of mice bearing targeted deletions of 11beta-hydroxysteroid dehydrogenases 1 and 2 genes. 1116 6

Hepatocyte nuclear factor 1 alpha (HNF1alpha) is a transcription factor that is expressed in liver, pancreas, kidney and intestine. Mice lacking HNF1alpha are born normally but suffer from several defects including hyperphenylalaninemia, defective bile acid and cholesterol metabolism, an insulin secretion defect and renal Fanconi syndrome. The renal phenotype involves a defect in renal proximal tubule reabsorption, leading to polyuria, glucosuria, aminoaciduria and phosphaturia. We investigated the expression of genes encoding members of the sodium/phosphate cotransporter (Na(+)/Pi) family (namely Npt1, Npt2, Npt4 and Ram1). We show that Npt1 and Npt4 genes were expressed at reduced levels in the kidneys of HNF1alpha -/- mice, whereas the expression of Npt2, the major renal phosphate transporter, was not affected. Analysis of the Npt1 genomic sequence revealed the existence of several alternative promoters activated in liver and/or in kidney. All of these were down-regulated in the kidneys of HNF1alpha -/- animals. Several HNF1alpha binding sites (BS) play an important role in the transcriptional control of this locus, including low-affinity HNF1 BSs localised in a DNase I hypersensitivity site (HSS3). Transient transfection experiments confirmed that HNF1alpha directly transactivates the Npt1 promoter and that the HSS3 region contributes to this activation.
J Mol Biol 2002 Oct 04
PMID:Hepatocyte nuclear factor 1 alpha controls renal expression of the Npt1-Npt4 anionic transporter locus. 1236 19

The sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins that are encoded by a single gene in tandem within a large precursor protein (prosaposin) and are required for in vivo degradation of some sphingolipids with relatively short carbohydrate chains. Human patients with prosaposin or specific saposin B or C deficiency are known, and prosaposin- and saposin A-deficient mouse lines have been generated. Experimental evidence suggests that saposin D may be a lysosomal acid ceramidase activator. However, no specific saposin D deficiency state is known in any mammalian species. We have generated a specific saposin D(-/-) mouse by introducing a mutation (C509S) into the saposin D domain of the mouse prosaposin gene. Saposin D(-/-) mice developed progressive polyuria at around 2 months and ataxia at around 4 months. Pathologically, the kidney of saposin D(-/-) mice showed renal tubular degeneration and eventual hydronephrosis. In the nervous system, progressive and selective loss of the cerebellar Purkinje cells in a striped pattern was conspicuous, and almost all Purkinje cells disappeared by 12 months. Biochemically, ceramides, particularly those containing hydroxy fatty acids accumulated in the kidney and the brain, most prominently in the cerebellum. These results not only indicate the role of saposin D in in vivo ceramide metabolism, but also suggest possible cytotoxicity of ceramide underlying the cerebellar Purkinje cell and renal tubular cell degeneration.
Hum Mol Genet 2004 Nov 01
PMID:Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse. 1534 7


1 2 3 Next >>