The purpose of this study is to obtain the clinicopathological characteristics of replication error-positive (RER ) gastric adenocarcinoma in Korean, and to identify the significance of RER in adenoma stage of gastric carcinogenesis. Microsatellite instability was examined at D2S71, D2S119, D3S1067, D6S87, D11S905, DM, AR, VWF, HPRT, and BAT-26 loci. Frameshift mutation of BAX gene was analyzed in RER tumors. Normal and tumor DNA of 76 cases of gastric carcinoma and 25 cases of adenoma were examined. RER was found in 8 of 76 cases (10.5%), and it was more frequently found in adenocarcinoma of female (17.7%) than those of male (4.8%). The frequency of RER was not different between the histologic types, age of the patient, anatomical location of the carcinoma, and the stage. The RER found in adenoma suggests that RER contributes to the malignant transformation early in the adenoma stage of the gastric carcinogenesis. None of the RER tumors revealed frameshift mutation of the BAX gene.
Adenocarcinoma* ; Adenoma ; Carcinogenesis ; DNA ; Female ; Frameshift Mutation ; Humans ; Hypoxanthine Phosphoribosyltransferase ; Male ; Microsatellite Instability

PURPOSE: Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients. MATERIALS AND METHODS: LMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients were profiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs with higher weighting factors in discriminating CRT responses were selected using principal components analysis and discriminant analysis. Selected LMIs were identified using the Human Metabolome Database. The concentrations of identified LMIs were determined by colorimetric enzyme assay, and compared according to post-CRT pathological stage (ypStage) or Dworak's tumor regression grade (TRG). RESULTS: The nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and 169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP), respectively. Higher HX concentration was observed in patients with ypStage 0-1 compared to ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observed between TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 muM showed significant association with ypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. In contrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared with TRG 2-1 (p=0.012). CONCLUSION: Findings of this study demonstrated that serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC patients before treatment.
Biological Markers* ; Chemoradiotherapy* ; Enzyme Assays ; Humans ; Hypoxanthine* ; Ions ; Mass Spectrometry ; Metabolome ; Phosphoenolpyruvate ; Rectal Neoplasms*

In order to examine the neurotoxic mechanism of oxygen radicals on cultured bovine oligodendrocytes, cytoxic effect of oxygen radicals was examined when cultures were treated with various concentrations of xanthine oxidase (XO) and hypoxanthine (HX) in culture medium. In addition, the neuroprotective effect of iron-chelators against the neurotoxicity induced by oxygen radicals was evaluated by MTT assay. Cell viability was remarkably decreased in a time-dependent manner after exposure of cultured bovine oligodendrocytes to 20mU/ml XO and 0.1mM HX for 4 hours. In the neuroprotective effect of iron-chelators on oxidant-induced neurotoxicity, tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) blocked the neurotoxicity induced by oxygen radicals, while DFX was not effective in blocking oxidant-induced neurotoxicity in these cultures. These results suggest that oxygen radicals are toxic in cultured bovine oligodendrocytes, and also selective iron-chelators such as TPEN are effective in blocking the neurotoxicity induced by oxygen radicals.
Allopurinol* ; Cell Survival ; Hypoxanthine ; Neuroprotective Agents ; Oligodendroglia ; Reactive Oxygen Species ; Xanthine Oxidase

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a Chinese pedigree with Lesch-Nyhan syndrome (LNS) but no specimen from the affected probands. METHODS: All affected individuals in this pedigrees were male and had deceased during childhood, with no biological specimen left. Based on their typical neurological dysfunction and tendency for self-mutilation, the diagnosis of LNS was suspected. Sanger sequencing was carried out to detect potential variant of the HPRT1 gene among female members from the pedigree. Following the identification of the pathogenic variant, prenatal diagnosis was provided for a high-risk fetus. RESULTS: The proband's mother and three other females were found to harbor heterozygous c.500_501delGGinsC (p.Arg167fs*23) variant of the HPRT1 gene, which was unreported previously. Prenatal diagnosis showed that the fetus was a male and had inherited the same pathogenic variant. CONCLUSION The c.500_501delGGinsC variant of the HPRT1 gene probably underlay the LNS in this pedigree. Above finding has provided a basis for prenatal diagnosis and genetic counseling for this pedigree.
Male ; Female ; Humans ; Pregnancy ; Lesch-Nyhan Syndrome/genetics* ; Pedigree ; Hypoxanthine Phosphoribosyltransferase/genetics* ; Prenatal Diagnosis ; China ; Mutation

The prevalence of gout is increasing worldwide, and control of serum uric acid level has been regarded as one of the therapeutic methods for gout. Inhibition of xanthine oxidase (XO) activity which can oxidize hypoxanthine to uric acid has been commonly proposed to decrease serum uric acid level. The aim of this study was to demonstrate the hypouricemic effect of ethanol extract of Aster glehni leaves (EAG) by in vitro and in vivo study in potassium oxonate (PO)-induced hyperuricemic rats. EAG possessed 132.5 ± 6.8 mg QE/g of total flavonoid and showed antioxidant activity. EAG showed in vitro and in vivo inhibitory activity against XO and significantly decreased serum uric acid level in PO-induced hyperuricemic rats without liver toxicity. These results show that EAG significantly attenuates hyperuricemia by inhibiting XO activity, which resulted in the decrease of serum uric acid level. Therefore, EAG might possess a potential therapeutic ability for improving gout.
Animals ; Ethanol* ; Gout ; Hyperuricemia ; Hypoxanthine ; In Vitro Techniques ; Liver ; Potassium* ; Prevalence ; Rats* ; Uric Acid ; Xanthine Oxidase

Deficiency of hypoxanthine-guanine phosphoribosyltransferase is a purine nucleotide disorder and is the most common genetic cause of uric acid overproduction. This disease has a wide range of spectrum with regard to neurological features depending on the extent of the enzymatic deficiency. Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, called Lesch-Nyhan syndrome, is presented with hyperuricemia and characteristic neurological manifestation and self-mutilation. Partial hypoxanthine-guanine phosphoribosyltransferase--deficient patients are presented with a various intensities of the aforementioned symptoms, from almost normal neurologic manifestation to a severe form along with hyperuricemia. We report a twenty-year-old man with complete hypoxanthine-guanine phosphoribosyltransferase mutation and Lesch-Nyhan sydrome, who manifested gouty arthritis without neurologic symptom.
Arthritis, Gouty* ; Humans ; Hyperuricemia ; Hypoxanthine Phosphoribosyltransferase ; Lesch-Nyhan Syndrome* ; Neurologic Manifestations* ; Uric Acid

Animals ; Genes, T-Cell Receptor ; genetics ; Humans ; Hypoxanthine Phosphoribosyltransferase ; genetics ; Mice ; Mutation

OBJECTIVE: It has been known that the enzyme deficiency associated with uric acid production is the minor cause of gout. The purpose of this study is to evaluate the role of hypoxanthine- guanine phosphoribosyltransferase (HGPRT) activity deficiency in the development of gout. METHODS: Assay of HGPRT activity was performed on 38 gout patients and 107 controls compromising 82 men and 25 women. In the patients with gout, age of onset, sex, family history of gout, duration of disease, serum uric acid level, and uric acid concentration of 24-hour urine were analyzed. RESULTS: In gout patients and control male group, the HGPRT activity was lowest in the age of forties. But, in female, there was no decreasing tendency with aging. In 4 gout patients, HGPRT activities were severely deficient and their ages of onset were less than 30 years old, and all have a family history of gout. CONCLUSION: In men, the lowest HGPRT activity in the age of forties could be one of the factors that make the onset of gout is highest in the fifth decade of age. The deficiency of HGPRT enzyme and family history of gout are the important factors in the pathogenesis of early onset gout.
Adult ; Age of Onset ; Aging ; Female ; Gout* ; Humans ; Hypoxanthine Phosphoribosyltransferase* ; Male ; Uric Acid

Allopurinol(4-hydroxypyrazolo[3, 4-d]pyrimidine) is an analog of hypoxanthine, widely used in the treatment of gout and in some patients develop the allopurinol hypersensitivity syndrome. Allopurinol hypersensitivity syndrome is characterized by multiple symptoms and signs such as fever, rash, decreased renal function, hepatocellular injury, leukocytosis, and eosinophilia. Herein reported is a 44 year-old male patient who developed generalized erythematous skin eruption with severe hepatotoxicity 3 weeks after taking allopurinol medication. The patient improved by dropping the allopurinol medication, which was consistent with the allopurinol hypersensitivity syndrome.
Adult ; Allopurinol* ; Eosinophilia ; Exanthema ; Fever ; Gout ; Humans ; Hypersensitivity* ; Hypoxanthine ; Leukocytosis ; Male ; Skin

OBJECTIVETo examine the quality of Whitmania pigra from the different populations to provide the basis for new species selection.

METHODThe contents of the moisture, alcohol extractive, total ash, acid-insoluble ash, and the activity of antiplatelet aggregation enzyme of wild and the breeding W. pigra were determined by the methods were determined in Chinese Pharmacopoeia (2005 edition). The contents xanthine and hypoxanthine by HPLC.

RESULTIt showed that the contents of the alcohol extractive, total ash, acid-insoluble ash, antiplatelet aggregation enzyme, and xanthine and hypoxanthine content of the breeding population in Nanjing are lations. Many quality indexes of the breeding in Zhejiang Tongxiang base were beffer than the wild.

CONCLUSIONThe breeding W. pigra are good in quality, It suggested large-scale promotion of aquaculture.

Animals ; Breeding ; Female ; Hypoxanthine ; analysis ; Leeches ; chemistry ; physiology ; Male ; Xanthine ; analysis