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)

Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain (ink4a/arf(-/-)), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single lig4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis.
Mol Cell 2001 Dec
PMID:Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions. 1177 95

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs, the pharmacokinetics of tacrolimus were investigated after 1-min intravenous administration of the drug (1 mg kg(-1)) to control rats and rats with uranyl nitrate-induced acute renal failure (rats with U-ARF). The impaired kidney and hepatic functions were observed in rats with U-ARF on the basis of physiological parameters and by microscopy of the tissues. After intravenous infusion of tacrolimus, the total area under the blood concentration-time curve from time zero to time infinity was significantly greater in rats with U-ARF than that in control rats (35.8 versus 29.2 microg min mL(-1)) due to significantly slower total body clearance of tacrolimus (27.9 versus 34.3 mL min(-1) kg(-1)), and this could be due to significantly slower nonrenal clearance (because of impaired hepatic function). The urinary excretion of unchanged tacrolimus was almost negligible for both groups of rats, therefore, effects of kidney impairment on the pharmacokinetics of tacrolimus seemed to be minor.
Res Commun Mol Pathol Pharmacol
PMID:Pharmacokinetic changes of intravenous tacrolimus in rats with uranyl nitrate-induced acute renal failure. 1195 89

BMP-7, a member of the bone morphogenetic protein subfamily of the TGFbeta-superfamily is highly expressed in the murine kidney. BMP-7 is involved in fetal nephron development and mesenchymal to epithelial cell differentiation. Constitutive BMP-7 expression is found in tubular and glomerular epithelial cells of the adult kidney. BMP-7 may play a role in physiology and pathophysiology of the adult kidney since BMP-7 gene expression in acute renal ischemia is diminished and injection of recombinant BMP-7 into rats with ischemic acute renal failure preserves renal function. In order to investigate the transcriptional regulation of BMP-7, this study was undertaken to clone and characterize the promoter of the murine BMP-7 gene. A 1394 bp sequence of the 5'-flanking region of the BMP-7 gene was isolated and subcloned. No TATA and CAAT box consensus motifs could be identified as shown for promoters of other BMPs. Using in vitro transfection assays, the 5'-flanking region revealed moderate to strong basal promoter activity. PMA increased basal BMP-7 promoter activity. Thus BMP-7 gene transcription might involve at least in part a PKC-dependent pathway. The cloning of a 5'-flanking region of the BMP-7 gene should provide a useful tool for future studies on the transcriptional regulation of BMP-7 gene expression.
Mol Cell Biochem 2002 Apr
PMID:Cloning of the 5'-flanking region of the murine bone morphogenetic protein-7 gene. 1208 77

Currently, pyogenic liver abscess is not frequent, but it is a severe infectious disease. However a strategy for the effective treatment of liver abscess is not established. We analyzed 75 cases of liver abscess over an eight year period and evaluated their prognosis, any associated underlying disease, or the effect of percutaneous transhepatic abscess drainage (PTAD). For all 75 cases, laboratory data were analyzed and imaging studies were performed. Next, PTAD and antibiotic administration were started on these cases as first choice treatments. These treatments were continued until the laboratory data of the patient were restored to within the normal range. Those cases that were PTAD non-effective or required operation for underlying diseases, underwent operations. Of the total 75 cases, 63 survived after treatment and 12 cases died. Bacteria were detected in 50 cases and Klebsiella pneumoniae was detected in 31 of these 50 cases, but 25 out of 75 cases were negative. The biliary system was the main route of infection. PTAD was effective, especially in cases that were complicated with disseminated intravascular coagulation (DIC) or acute renal failure (ARF). PTAD is an effective treatment for liver abscess, it is especially useful in the restoration of severe general conditions as indicated by this study.
Int J Mol Med 2002 Nov
PMID:Clinicopathological analysis of liver abscess in Japan. 1237 5

Multiorgan dysfunction syndrome (MODS) is one of the most frequent conditions encountered in intensive-care medicine. MODS is defined as total or partial loss of two or more organs with vital functions. The development of acute renal failure (ARF) in MODS leads to an additional aggravation with considerably higher hospital mortality than in other ICU patients with MODS. Whereas dissolved substances involved in the regulation of regional blood flow, endothelial cell injury, microvascular permeability, oxygenation, and nutrition of cells are at the focus of interest in MODS, hardly any scientific attention is paid to their main solvent water. An impaired renal water excretion and an increased metabolic water volume requiring excretion interfere with diffusive and convective oxygen transport through the different fluid compartments. It will be shown first that the ratio of U(osm)/ P(osm) appears to be a reliable tool to assess overhydration in ARF. Secondly, the limits of urinary output in response to water intake will be considered. Furthermore, the metabolic water formation by an enhanced degradation of endogenous protein and fat will be discussed. Finally, the daily caloric intake is questioned with respect to energy expenditure and metabolic water formation.
J Cell Mol Med
PMID:Multiorgan dysfunction syndrome: how water might contribute to its progression. 1261 50

To determine the role of nitric oxide (NO) in acute renal failure (ARF), we have studied the time course change activities to activity of nitric oxide synthase (NOS) isoform activities, both calcium dependent and independent NOS, in experimental ischemic ARF. We have also analyzed change activities to activity of the NOS activities in both renal cortex and medulla. Male SD rats (n = 5) were inducted to ARF by ischemia-reperfusion injury and divided into the following groups; Control group (sham operation), Day 0 group, (measurement performed on that day of operation), Day 1 group, (measurement performed one day after induction of ARF), Day 3 group and Day 7 group. Measurement of NOS activity was based on the following principles; NO is synthesized from arginine by nitric oxide synthase (NOS) and NO is converted to NO2(-)/NO3(-)(NOx) by oxidation. Detection of the final metabolite of NO, NOx was done using flow injection method (Griess reaction). The results were, (1) calcium dependent NOS activity in the cortex and medulla decreased, however it increased in the recovery period in the renal cortex (Cortex; Control, 0.941 +/- 0.765, D0, 0.382 +/- 0.271, D1, 0.118 +/- 0.353, D3, 2.030 +/- 0.235, D7, 3.588 +/- 2.706, Medulla; Control, 1.469 +/- 0.531, D0, 0.766 +/- 0.156, D1, 0.828 +/- 0.187, D3, 2.078 +/- 0.094, D7, 1.289 +/- 0.313 micromol NOx produced/mg protein/30 min). (2) On the other hand, iNOS activity increased in the early phase of ARF, both in the cortex and medulla, but returned to control values during the recovery phase in cortex and was maintained at higher levels in the medulla (Cortex; Control, 0.333 +/- 0.250, D0, 0.583 +/- 0.428, D1, 1.167 +/- 0.262, D3, 0.250 +/- 0.077, D7, 0.452 +/- 0.292, Medulla; Control, 0.139 +/- 0.169, D0, 0.279 +/- 0.070, D1, 1.140 +/- 0.226, D3, 0.452 +/- 0.048, D7, 0.625 +/- 0.048 micromol NOx produced/mg protein/30 min). These findings suggest that the role of NOS in ARF are different for the different NOS isoforms and have anatomic heterogeneity.
Mol Cell Biochem 2003 Feb
PMID:Role of nitric oxide synthase activity in experimental ischemic acute renal failure in rats. 1270 21

Metallothionein (MT) is induced by various types of oxidative stress. However, whether or not MT is induced in renal ischemia/reperfusion injury, in which oxidative stress is believed to play a major role, remains unknown. The present study investigated MT expression in the kidneys of rats with ischmic acute renal failure (IARF). Rats were subjected to 60 min of bilateral renal ischemia followed by reperfusion. Renal MT mRNA expression was then analyzed by Northern blotting. MT expression in ischemic kidney was also localized by in situ hybridization and immunohistochemistry. Renal MT mRNA expression, which was barely detectable in the sham-operated control kidney, increased significantly at 3 h afer reperfsion, continued to increase to a maximal level at 24 h that was maintained for 48 h. The level of MT mRNA expression returned to that of the control by day 4. A morphological study revealed that MT was expressed exclusively in the renal tubular epithelial cells, which are the targets of ischemia/reperfusion injury, and that MT predominated in the outer medulla in the IARF rat kidney at transcriptional and translational levels. These results suggest that MT induced in the IARF rat kidney plays an important role in protecting renal cells against oxidative stress induced by ischemia/reperfusion.
Res Commun Mol Pathol Pharmacol 2001
PMID:Induction of renal metallothionein in rats with ischemic renal failure. 1276 Apr 85

Acute renal failure (ARF) represents a common and serious problem in clinical medicine. Renal ischemia-reperfusion injury (IRI) is the major cause of ARF in the native and transplanted kidney. Several decades of research have provided successful therapeutic approaches in animal models, but translational efforts in humans have yielded disappointing results. The major reasons for this include a lack of early markers for ARF (and hence a delay in initiating therapy), and the multi-factorial nature of the disease. This review focuses on the use of cDNA microarrays to elucidate the molecular genetic mechanisms underlying tubule cell apoptosis, and to identify novel biomarkers for early renal IRI. Also presented is a comparative temporal analysis of cDNA microarray results from mature kidneys following IRI and during normal nephrogenesis. Molecular genetic evidence for the notion that regeneration recapitulates development in the kidney, and that injured tubule cells possess the capacity to de-differentiate to the earliest stages of development, is presented. The implications of these findings to the ability of the kidney to repair itself and potential strategies for accelerating recovery are briefly discussed.
Mol Genet Metab 2003 Dec
PMID:Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. 1465 49

Despite advances in medical technology, acute renal failure (ARF) still represents a major challenge in clinical medicine, as morbidity and mortality have remained unchanged over the past two decades. The pathophysiology of ARF is highly complex and only poorly understood; new insights into the pathophysiology of ARF are therefore of utmost importance to develop better understanding and therapies. Acute tubular necrosis (ATN) is the predominant cause of ARF and often arises as a consequence of septic, toxic, or ischemic insults. The recruitment of leukocytes into the kidney has recently emerged as a key event in the development of experimental ischemic and septic ARF. A few descriptive clinical studies support this idea. However, the clinical relevance of various animal models remains unclear, as does the importance of different leukocyte subsets, and even methodological aspects as how to quantify renal leukocyte recruitment. This review summarizes and critically evaluates experimental findings that provide insight into the role of leukocytes and their recruitment during ARF. We aim to provide a valid description of ARF, illustrate animal models of ARF, review qualitative and quantitative methods to assess renal leukocyte recruitment, and discuss the components of the leukocyte recruitment cascade and their role in ARF.
J Mol Med (Berl) 2004 Feb
PMID:Leukocyte recruitment and acute renal failure. 1466 1

Shiga toxin-producing Escherichia coli (STEC), especially of serotype O157:H7, cause a zoonotic food or waterborne enteric illness that is often associated with large epidemic outbreaks as well as the hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in children. After ingestion, STEC colonize enterocytes of the large bowel with a characteristic attaching and effacing pathology, which is mediated by components of a type III secretion apparatus encoded by the LEE pathogenicity island. Shiga toxins are translocated from the bowel to the circularoty system and transported by leukocytes to capillary endothelial cells in renal glomeruli and other organs. After binding to the receptor globotriaosylceramide on target cells, the toxin is internalized by receptor-mediated endocytosis and interacts with the subcellular machinery to inhibit protein synthesis. This leads to pathophysiological changes that result in HUS. Specific therapeutic or preventive strategies are presently not available. The recent sequencing of genomes of two epidemic E. coli O157 strains has revealed novel pathogenicity islands which will likely provide new insights into the virulence of these bacteria.
Mol Biotechnol 2004 Feb
PMID:Infection by Shiga toxin-producing Escherichia coli: an overview. 1476 37


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