Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A positive association between hyperuricemia and cardiovascular disease has been reported, but no study has evidenced yet the precise role of serum uric acid in the development of cardiovascular disease. In addition, no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia, even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage. The present prospective cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population. The subjects were 49,413 Japanese male railroad workers, aged 25-60 years at enrollment. Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982. The vital status of the subjects was traced until the end of 1985 for those who remained alive. During an average 5.4-year study period, 984 deaths were recorded. Those with serum uric acid over 8.5 mg/dl showed elevated relative risks (RRs) of death in all causes (RR 1.62, p<0.01), coronary heart disease ( RR 1.52), stroke (RR 2.33, p<0.01), hepatic disease (RR 3.58, p<0.01), and renal failure ( RR 8.52, p<0.01), as compared with those with serum uric acid levels of 5.0-6.4mg/dl. The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol (2.00, p<0.01), age and alcohol intake (1.85, p<0.001), age and smoking (1.69, p<0.001), age and gout treatment (1.61, p<0.05), and also age and BMI (1.50, p< 0.05). On the other hand, the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose (1.62), age and systolic blood pressure (1.32), age and GOT (1.23), and also age and history of cardiovascular disease (1.17). These results showed that hyperuricemia has a strong association with the RRs of death in all causes, coronary heart disease, stroke, hepatic disease and renal failure, and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy.
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PMID:Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. 1121 Jan 10

Celastrus paniculatus L. (Celastraceae) (CP), Picrorhiza kurroa L. (Scrophulariaceae) (PK) and Withania somnifera L. (Solanaceae) (WS) are Indian medicinal plants having a remarkable reputation, as a factor of health care, among the indigenous medical practitioners. The plants exhibit varying degrees of therapeutic value some of which useful in the treatment of cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, dyspepsia. In this work, we have investigated the free radical scavenging capacity of methanolic extracts from CP, PK, WS and the effect on DNA cleavage induced by H2O2 UV-photholysis. In addition, we investigated whether these plant extracts are capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. These extracts showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage; methanolic extracts from PK was more active than extracts from CP and WS. These results were confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA damage in human non-immortalized fibroblasts. These antioxidant effects of active principle of CP, PK and WS may explain, at least in part, the reported anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory and antiaging effects produced by them in experimental animal and in clinical situations and may justify the further investigation of their other beneficial biological properties.
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PMID:Indian medicinal plants as antiradicals and DNA cleavage protectors. 1131 55

Sedanolide is a natural compound occurring in edible umbelliferous plants. Celery seed oil, a significant source of sedanolide, is used as an herbal remedy to treat inflammatory-associated conditions such as gout and rheumatism. The objective of this study was to assess the potential protective properties of sedanolide against hydrogen peroxide (H(2)O(2))- and tert-butyl hydroperoxide (tBOOH)-induced toxicity in HepG2 and CaCo-2 cells. Viability of HepG2 and CaCo-2 cells was unaffected by a 24-h exposure to sedanolide (7-500 microM), however, when the cells were cultured in sedanolide-free medium for a further two cell cycles (72 h), a decrease in cell viability was observed for HepG2 cells previously exposed to 500 microM of the compound. Cells pretreated with sedanolide (100 microM for 24 h) and exposed to either H(2)O(2) or tBOOH did not exhibit statistically significant difference in viability from controls. A significant increase (p < 0.05) in DNA strand breaks, as measured by the comet assay, was observed in HepG2 but not CaCo-2 cells following a 24-h incubation with 500 microM sedanolide. Sedanolide did not modulate H(2)O(2)- and tBOOH-induced DNA damage. Sedanolide is relatively nontoxic to cells in culture, however, the protection it afforded against H(2)O(2)- and tBOOH-induced toxicity was not statistically significant.
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PMID:Sedanolide, a natural phthalide from celery seed oil: effect on hydrogen peroxide and tert-butyl hydroperoxide-induced toxicity in HepG2 and CaCo-2 human cell lines. 1184 95

The purpose of this study was to examine whether interleukin-1 beta (IL-1beta) promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical manifestations in Taiwanese patients with gout. The study included 196 patients in addition to 103 unrelated healthy control subjects living in central Taiwan. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta exon 5 were typed. Allelic frequencies were compared between the two groups, and the relationship between allelic frequencies and clinical manifestations of gout was evaluated. No significant differences were observed in the allelic frequencies of the IL-1beta promoter between patients with gout and healthy control subjects. Additionally, we did not detect any association of the IL-1beta promoter genotype with the clinical and laboratory profiles of gout patients. However, there was a significant difference between the two groups in terms of hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There was also a significant difference in the genotype of IL-1beta exon 5 polymorphism between patients with and without hypertriglyceridemia. Results of the present study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are not related to gout patients in central Taiwan.
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PMID:Interleukin-1beta gene polymorphisms in Taiwanese patients with gout. 1466 Nov 13

Human embryonic stem (ES) cells are pluripotent cells derived from blastocyst-stage embryos. It has been suggested that these cells should play a major role in transplantation medicine and be able to advance our knowledge in human embryology. We propose that these cells should also play a vital role in the creation of models of human disorders. This aspect would be most valuable where animal models failed to faithfully recapitulate the human phenotype. Lesch-Nyhan disease is caused by a mutation in the HPRT1 gene that triggers an overproduction of uric acid, causing gout-like symptoms and urinary stones, in addition to neurological disorders. Due to biochemical differences between humans and rodents, a mouse lacking the HPRT expression will fail to accumulate uric acid. In this research we demonstrate a model for Lesch-Nyhan disease by mutating the HPRT1 gene in human ES cells using homologous recombination. We have verified the mutation in the HPRT1 allele at the DNA and RNA levels. By using selection media, we show that HPRT1 activity is abolished in the mutant cells, and the HPRT1-cells show a higher rate of uric acid accumulation than the wild-type cells. Therefore, these cells recapitulate to some extent the characteristics of Lesch-Nyhan syndrome and can help researchers further investigate this genetic disease and analyze drugs that will prevent the onset of its symptoms. We therefore suggest that human diseases may be modeled using human ES cells.
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PMID:Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells. 1527 9

Chemokine production has been associated with leukocyte infiltration into the joint during gouty arthritis, and monosodium urate (MSU) crystals, the causative agent of this arthropathy, have been shown to modulate their expression. In the present study, we investigated the transductional mechanisms underlying this cellular regulation in the murine macrophage cell line B10R. We report that MSU crystals rapidly and transiently increase mRNA levels of various chemokines in a concentration-dependent manner. Examination of second messenger activation revealed that macrophage exposure to MSU crystals led to MEK1/2, ERK1/2, and inhibitory protein kappaBalpha phosphorylation as well as to NF-kappaB and AP-1 nuclear translocation. Of interest, specific blockage of the ERK1/2 pathway drastically reduced up-modulation of MSU crystal-mediated chemokine production and activation of nuclear factors. Similarly, selective inhibition of NF-kappaB suppressed NF-kappaB DNA binding activity and the induction of all chemokine transcripts. These findings indicate that ERK1/2-dependent signals seem to be required for AP-1 and NF-kappaB activation and subsequent mRNA expression of the various macrophage chemokines. In addition, transcription and stability assays performed in presence of actinomycin D showed that MSU crystal-mediated MIP-1beta mRNA up-regulation resulted solely from transcriptional control, whereas that of MIP-1alpha, MIP-2, and MCP-1 was due to both gene transcription activation and mRNA posttranscriptional stabilization. Overall, the results of this study help to define the molecular events that govern macrophage chemokine regulation in response to MSU crystals, which is of paramount importance to better understand, and eventually to tame, the inflammatory response during acute gout.
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PMID:Signaling events involved in macrophage chemokine expression in response to monosodium urate crystals. 1547 69

A 29-year-old woman was referred to our department because of gout. Routine laboratory data showed hyperuricemia, a high level of plasma oxypurines, increased urinary uric acid excretion, and increased urinary oxypurine excretion, with decreased hypoxanthine phosphoribosyl transferase (HPRT) activity in the erythrocytes. From these findings, the patient was diagnosed with a partial deficiency of HPRT. To determine its properties, a cDNA sequence encoding HPRT and the androgen receptor AR XIST minimal promoter gene, as well as methylation of the AR gene were investigated. The HPRT cDNA sequence revealed a point mutation of G to A in nucleotide 40, which changed codon 14 from GAA (Glu) to AAA (Lys) in the mutant gene. In addition, the HPRT genomic DNA sequence, including the mutation site, revealed the same point mutation, indicating that the patient was heterozygote. Further analysis of the AR gene on the X chromosome suggested nonrandom X-chromosome inactivation, whereas the AR XIST minimal promoter gene was normal. Such results have not been previously reported in a female with partial HPRT deficiency.
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PMID:Identification of a new point mutation in hypoxanthine phosphoribosyl transferase responsible for hyperuricemia in a female patient. 1553 9

Inherited mutation of hypoxanthine guanine phosphoribosyltransferase, (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified 34 mutations in 28 Japanese, 7 Korean, and 1 Indian families with the patients manifesting different clinical phenotypes, including two rare cases in female subjects, by the analysis of all nine exons of HPRT from the genomic DNA and reverse transcribed mRNA using PCR technique coupled with direct sequencing.
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PMID:Mutations in the hypoxanthine guanine phosphoribosyltransferase gene (HPRT1) in Asian HPRT deficient families. 1557 Dec 23

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency always causing hyperuricemia presents various degrees of neurological manifestations, the most severe which is Lesch-Nyhan syndrome. The HPRT gene is situated in the region Xq26-q27.2 and consists of 9 exons. At least 300 different mutations at different sites in the HPRT coding region from exon 1 to exon 9 have been identified. A new mutation in the HPRT gene has been determined in one patient with complete deficiency of erythrocyte activity, with hyperuricemia and gout but without Lesch-Nyhan disease. Analysis of cultured fibroblasts revealed minimal residual HPRT activity mainly when guanine was the substrate. Genomic DNA sequencing demonstrated patient's mother heterozygosity for the mutation and no mutation in her brother. The mutation consists in a C-->T transversion at cDNA base 463 (C463T) in exon 6, resulting in proline to serine substitution at codon 155 (P155S). This mutation had not been reported previously and has been designated HPRT(Sardinia). The mutation identified in this patient allows some expression of functional enzyme in nucleated cells such as fibroblasts, indicating that such cell type may add further information to conventional blood analysis. A multicentre survey gathering patients with variant neurological forms could contribute to understand the pathophysiology of the neurobehavioral symptoms of HPRT deficiency.
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PMID:HPRTSardinia: a new point mutation causing HPRT deficiency without Lesch-Nyhan disease. 1621 73

Inherited mutations of a purine salvage enzyme, hypoxanthine guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8), give rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified a number of HPRT mutations in Asian patients manifesting different clinical phenotypes, by analyzing all nine exons of the HPRT gene (HPRT1) from genomic DNA and reverse-transcribed mRNA using the PCR technique coupled with direct sequencing. In this study, we update the spectrum of mutations with nine novel mutations. Two missense mutations (T124P and D185G) were detected in patients with HRH (HPRT-related hyperuricemia). In a patient having a severe partial deficiency of HPRT with neurological dysfunction (HRND: HPRT-related neurological dysfunction), a single nucleotide substitution (27+5G > A) causing a splicing error was found in intron 1. The mutation resulted in a remarkably decreased level of normal mRNA, and production of an abnormal mRNA with a 49-bp insert at the 5'-end of intron 1, which caused the frame-shift of an amino acid codon (10fs27X). In six typical Lesch-Nyhan families, we found two 3-bp deletions responsible for single amino acid deletions (V8del and Y28del), two 1-bp deletions (440delA and 635delG) generating a frame-shift, an insertion of two amino acids (159insKV), and a 4,131-bp deletion from introns 4 to 6 resulting in two types of abnormal mRNA. Including these nine mutations, 42 HPRT1 mutations have been identified among 47 Asian families with deficiency of HPRT.
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PMID:Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian mutations with novel mutations. 1702 11


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