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Siddharth K. Prakash 《American journal of medical genetics. Part C, Seminars in medical genetics》2019,181(1):110-115
Somatic mosaicism is a major modifier of turner syndrome (TS) features and may be more prevalent than once thought, as new molecular techniques enable detection of tissue‐specific mosaicism. This review explores the causes of mosaicism, discusses how mosaicism may impact congenital aortic defects in TS, and summarizes molecular methods to detect mosaicism in different contexts. 相似文献
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The RAD6 gene of Saccharomyces cerevisiae is required for post-replication repair of UV-damaged DNA, UV mutagenesis, and sporulation. Here, we show that the radiation sensitivity of a MAT
a
rad6 strain can be suppressed by the MAT2 gene carried on a multicopy plasmid. The a1-2 suppression is specific to the RAD6 pathway, as mutations in genes required for nucleotide excision repair or for recombinational repair do not show such mating-type suppression. The a1-2 suppression of the rad6 mutation requires the activity of the RAD52 group of genes, suggesting that suppression occurs by channelling of post-replication gaps present in the rad6 mutant into the RAD52 recombinational repair pathway. The a1-2 repressor could mediate this suppression via an enhancement in the expression, or the activity, of recombination genes. 相似文献
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Fas Ligand-dependent and -independent mechanisms of toxicity induced by T cell lymphomas in lymphoid organs and in the liver 总被引:15,自引:0,他引:15
Lombard C McKallip RJ Hylemon PB Nagarkatti PS Nagarkatti M 《Clinical immunology (Orlando, Fla.)》2003,109(2):144-153
In the current study, we investigated the effect of growth of FasL+ tumors in vivo on the functions of peripheral lymphoid organs and the liver. Injection of FasL+ LSA tumor cells into syngeneic C57BL/6 wild-type mice but not C57BL/6 lpr/lpr (Fas-deficient) mice caused apoptosis in splenocytes. Spleen cells expressing CD3, CD4, CD8, CD19, Mac-3, and CD44 were all susceptible to tumor-induced apoptosis. Also, activated T cells were more sensitive to apoptosis induced by LSA tumor cell lysate when compared to naïve T cells. In contrast, anti-Fas Abs (Jo2) induced apoptosis in only activated but not naïve T cells. When the LSA tumor-bearing mice were injected with a superantigen (SEA), these mice showed a significant decrease in the expansion of SEA-reactive Vβ3+ and Vβ11+ T cells. When injected into syngeneic mice, the FasL+ LSA tumor cells caused hepatotoxicity, as indicated by an increase in serum aspartate aminotransferase (AST) levels. Interestingly, Fas-deficient C57BL/6 lpr/lpr mice also showed significant AST levels in the serum following LSA tumor growth. Moreover, hepatocytes isolated from C57BL/6 wild-type and C57BL/6 lpr/lpr mice were equally susceptible to apoptosis induced by LSA tumor cell lysate in vitro. Using cDNA array, LSA tumor cells were found to express several cytokine genes including IL-2, IL-7, IL-11, IL-13, IL-16, lymphotoxin β, and tumor necrosis factor β. Together, these data suggested that, in mice bearing FasL+ LSA tumor, the immunotoxicity is FasL-based, whereas the hepatotoxicity, at least in part, may be FasL-independent. 相似文献
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Aneja R Dass SK Prakash S Chandra R 《Artificial cells, blood substitutes, and immobilization biotechnology》2004,32(1):159-172
Gossypol prevents the liberation of oxygen from oxyhemoglobin and exerts a hemolytic effect on erythrocytes. In excessive dosages of gossypol, an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Chromium protoporphyrin (CrPP) has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occurring or experimentally induced forms of jaundice in animals and man. In this communication, a novel tissue dependent response to gossypol (50 micromol/kg bw) and gossypol in association with CrPP (50 micromol/kg bw) is described. Our results revealed that gossypol stimulated the hepatic, splenic, and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. In consonance with the increased hepatic and renal HMOX activity, a marked increase was observed in total serum bilirubin concentration in gossypol treated rats. When rats were given CrPP simultaneously with gossypol, the gossypol mediated increase in hepatic and renal HMOX activity was effectively blocked. Furthermore, the increase in enzymatic activity was accomplished by a decline in the total microsomal protein content on gossypol administration. These findings emphasize the toxic effect of gossypol in eliciting increased heme degradation by stimulating HMOX activity in the liver and the kidney and the potential usefulness of CrPP in experimental and perhaps clinical conditions in which hyperbilirubinemia occurs. 相似文献
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Adenosine Deaminase (ADA) levels were estimated in cord blood of 30 neonates born with birth weight less than or equal to 2.5 kg and 30 neonates born with birth weight greater than 2.5 kg. The mean ADA levels in low birth weight (LBW) group was found to be 6.94 U/L and in normal birth weight group the mean ADA levels were 14.37 U/L which was statistically significant. Therefore ADA may be useful in assessing CMI status in low birth weight infants. 相似文献