Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms

BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. RESULTS: The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. CONCLUSION: These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone

Subcutaneous Single Injection Digital Block with Epinephrine

The aim of this study was to investigate the anesthetic effect and risk of epinephrine for subcutaneous single injection digital block. Either 3.0 mL 1.0% Lidocaine or a 3.0 mL 1.0% Lidocaine with (1 : 100,000) epinephrine was injected into the subcutaneous space at the middle point of the palmar digital crease of the 18 middle fingers of 9 healthy volunteers. The SpO2 of the fingers decreased to a maximum of 97. No subjects showed any symptoms of ischemic injury. The time to anesthesia for the fingers was significantly shorter (P < 0.05), and the duration of anesthesia was significantly longer (P < 0.01) for the fingers in the epinephrine group. In conclusion, a subcutaneous single injection digital blocks with 3.0 mL of 1.0% Lidocaine and (1 : 100,000) epinephrine were safe, reducing the time to the onset of anesthesia, while also markedly prolonging the anesthesia