Advance in Genetic Mechanism of Primary Progressive Aphasia (review) / 中国康复理论与实践

Primary progressive aphasia (PPA) is a common neurodegenerative speech disease. Earlier studies on PPA merely observed preliminary pathogenic factors at the brain level. Based on genetic technology, almost 20% to 30% patients with autosomal dominant inheritance reveals that this deficit is closely relevant to gene mutation. C9 gene mutation is the primary factor related to amyotrophic lateral sclerosis and frontotemporal dementia, which is attributed to the main causes of PPA. Repeating expansion of C9 gene may influence the expression of C9 gene, block the combination of RNA and protein, and destroy RNA function.

HLA class I (ABC) upregulation on peripheral blood CD3+/CD8+ T lymphocyte surface is a potential predictor of acute rejection in renal transplantation.

BACKGROUND: Renal transplantation is currently the prevalent therapy for most patients with end-stage renal disease. No clinical markers for such rejection have been universally accepted. We aimed to investigate the possibility of use of human leukocyte antigen (HLA) class I (ABC) on peripheral blood CD3+/CD8+ T lymphocytes as a marker of acute rejection. METHODS: For recipients undergoing renal transplantation from September 2007 to November 2008, peripheral blood samples were obtained pretransplantation and at days 3 and 7 posttransplantation when the patients were still hospitalized and at weeks 2 and 3 and months 1, 2, 3, and 6 posttransplantation. For patients with fever, lumbodynia, gross hematuria, or oliguria after transplantation, blood samples were collected immediately before and at days 3 and 7 after the administration of anti-inflammatory regents. The level of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes was measured on flow cytometry. RESULTS: For the 79 transplant recipients, the level of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes was consistently elevated during the first 3 weeks after transplantation, declined gradually to pretransplantation levels, then tapered off and remained stable. Patients experiencing acute rejection (AR) or not after transplantation did not differ in level of HLA class I (ABC) up to 6-month follow-up, except at days 14 and 21 after transplantation, when the level was higher for patients experiencing AR (P<0.01). CONCLUSIONS: Upregulation of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes could be used as an accurate and reliable predictor of AR after renal transplantation.

Repressive effects of resveratrol on androgen receptor transcriptional activity.

BACKGROUND: The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity. METHODOLOGY: The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of AR-negative HeLa cells to generate the AR(+) cells. The constitutively expressed AR was characterized by monitoring hormone-stimulated nuclear translocation, DNA binding, and transcriptional activation, with the AR(-) cells serving as controls. AR(+) cells were treated with RSV, and both AR protein levels and AR transcriptional activity were measured simultaneously. Chromatin immunoprecipitation (ChIP) assays were used to detect the effects of RSV on the recruitment of AR to its cognate element (ARE). RESULTS: AR in the AR (+) stable cell line functions in a manner similar to that of endogenously expressed AR. Using this model system we clearly demonstrated that RSV represses AR transcriptional activity independently of any effects on AR protein levels. However, neither the hormone-mediated nucleus translocation nor the AR/ARE interaction was affected by RSV treatment. CONCLUSION: We demonstrated unambiguously that RSV regulates AR target gene expression, at least in part, by repressing AR transcriptional activity. Repressive effects of RSV on AR activity result from mechanisms other than the affects of AR nuclear translocation or DNA binding.