Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes

Cytotoxic T lymphocyte (CTL) senescence may be an important mechanism of immune failure in HIV-1 infection. We find that senescence of HIV-1-specific CTL clones causes loss of killing activity, preventable by transduction with telomerase. Furthermore, senescence is associated with reduced expression of the effector molecules granzyme and perforin, suggesting CTL "exhaustion" can result in hypofunction. These results agree with other studies showing that HIV-1-specific CTL exhibit abnormal phenotypes in vivo, and suggest the possibility that chronic turnover is an important mechanism of antiviral failure in HIV-1 infection.     

Novel 2(3H)-Benzothiazolones as Highly Potent and Selective Sigma-1 Receptor Ligands

In an effort to produce a new pharmacological probe with high affinity and selectivity for the sigma-1 receptor, we have synthesized a series of original 2(3H)-benzothiazolones utilizing compound 4 [3-(1-piperidinoethyl)-6-propylbenzothiazolin-2-one] as a lead. Receptor binding affinities were determined at sigma-1 and sigma-2 receptors. The best ligand (9, sigma-1 K_i = 0.56 nM, selectivity ratio >1000) was obtained with an azepine side-chain. When tested on a wide battery of receptors, including 5HT_2A(h), 5HT₃(h), α₁, α ₂, β₁, β₂, H₁, H₂, opioids, D₁(h), D₂(h), 5HT uptake, and DOPA uptake, compound 9 showed submicromolar affinity only for α₂ (K_i = 205 nM) and H₁ (K_i = 311 nM).     

Inhibition of carcinogen-induced DNA damage in rat liver and colon by garlic powders with varying alliin content

The present study was designed to investigate the protective efficiency of three garlic powders, obtained from bulbs grown in soils with different levels of sulfur fertilization, against DNA damage. Increasing fertilization of soil resulted in an increased alliin content of the powders. Garlic powders were administered to rats for 2 weeks (5% of the diet) and their antigenotoxic effects were examined in the liver and the colon using the comet assay. Consumption of the different garlic powders induced a 35-60% reduction in DNA damage induced by N-nitrosodimethylamine (NDMA) in rat liver. Increased alliin content of the garlic powder was associated strongly with a proportional decrease in NDMA induced DNA alteration. DNA damage induced by aflatoxin B1 in the liver or by 1,2-dimethylhydrazine in the colon were also decreased strongly by the three garlic powders but these decreases were not correlated to the alliin content of the garlic powders. Feeding garlic powders did not modify the genotoxic activity of the direct-acting carcinogen methylnitrosourea in the colon. Part of our results supports evidence that fertilization can have an impact on the protective capacity of garlic bulbs.     

Migrations of fluid of pancreatic origin: Ultrasonic and CT study of 28 cases

Efficacious management of migratory collections of pancreatic origin requires precise topographic diagnosis. Such collections can be multiple, atypical and ubiquitous, extending from the mediastinum down to the pelvis, within peritoneal recesses and retroperitoneal spaces, and even within viscera such as the liver, spleen or kidney. Sonography and CT are complementary in the diagnosis and management of such collections.