Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Lesch-Nyhan syndrome is commonly regarded as a metabolic disorder of the purine metabolism without specific morphological changes. In the present paper a report is given on a 13-year-old boy. The neuropathological investigation revealed PAS positive deposits in the ganglion cells of the nucleus olivaris. In HE preparations, the storage material appears as light foamy accumulations displacing nuclei to the cell border. The deposits are sudan-III-negative and there is no UV fluorescence. Electron microscopically the primarily formol fixed tissue of the nucleus olivaris shows circumscribed accumulations of a relatively homogeneous substance with medium density in the dilated smooth endoplasmic reticulum. The diameter ranges from 476 to 850 nm. In this connection, it seems to be possible that the lack of cGMP might lead to disturbances of the protein metabolism of postsynaptic structures, the significance of which is discussed. It is suggested that further investigations of the CNS in Lesch-Nyhan patients should be focussed on the nucleus olivaris.
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PMID:[Neuropathological findings in Lesch-Nyhan syndrome (author's transl)]. 709 Jun 6

Ground glass hepatocytes (GGHs) are the historic hallmarks for the hepatocytes in the late and non-replicative stages of hepatitis B virus (HBV) infection. We have identified type I and type II GGHs that contain two mutant types of large HBV surface antigens (HBsAg) with deletions over the pre-S1 and pre-S2 regions, respectively. These pre-S mutant HBVsAg accumulate in endoplasmic reticulum (ER), resulting in strong ER stress. Type II GGHs often appear in hepatic nodules in the late phases of HBV infection and proliferate in clusters, suggesting that these mutant pre-S1/S2 HBsAg may be involved in HBV-related hepatocarcinogenesis, associated with ER stress. In this study, we investigated the potential genomic instability imposed by pre-S mutant HBsAg. Based on the analysis of comet assays, we found that the pre-S1 and pre-S2 mutant HBsAg caused oxidative stress and DNA damage. The DNA repair gene ogg1 was greatly induced by over-expression of pre-S mutant HBsAg. Induction of the DNA repair gene ogg1 was also detected in the pre-S2 HBsAg transgenic mice, as well as the type II GGHs from patients with hepatocellular carcinoma, strongly suggesting that the pre-S mutant HBsAg contributes to the oxidative DNA damage to hepatocytes. In addition, the mutation rates in the X-linked hprt gene were enhanced in mouse hepatoma ML1-4a cells, which constitutively expressed the pre-S1/S2 HBsAg. These results indicate that pre-S1/S2 mutant HBsAg, which make up GGHs, induce oxidative DNA damage and mutations in hepatocytes in the late stages of HBV infection.
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PMID:Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. 1518 Sep 47