Adenine-induced selective apoptosis toward HIV chronically infected cells in vitro

A novel strategy for anti-HIV therapy is the clearance of the residual infected cells from the body. Here, we show that 6-aminopurine, adenine, induced selective apoptosis toward HIV-1 producing chronically infected MOLT4 cells (MOLT4/HIV) without augmentation of virus production, whereas the growth of uninfected MOLT4 was stimulated. This selective apoptosis did not occur with other adenine nucleotides or with other bases. The purine ring and the amino residue of adenine were responsible for the apoptosis induction and selectivity, respectively. In addition, adenine slightly but consistently reduced viable cell numbers and the production of virus in a fraction of HIV-1 chronically infected human peripheral blood mononuclear cells (PBMCs/HIV) at day 7. On the other hand, blastogenic response of normal PBMCs to PHA, PWM and Candida albicans were potentiated in the presence of adenine. These results indicated that the effect of adenine may be attributable to activation-induced selective apoptosis toward virus-infected cells.     

Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice.

Pancreatic islets from DBA/2 mice infected with the D variant of encephalomyocarditis (EMC-D) virus revealed lymphocytic infiltration with moderate to severe destruction of pancreatic beta cells. Our previous studies showed that the major population of infiltrating cells at the early stages of infection is macrophages. The inactivation of macrophages prior to viral infection resulted in the prevention of diabetes, whereas activation of macrophages prior to viral infection resulted in the enhancement of beta-cell destruction. This investigation was initiated to determine whether macrophage-produced soluble mediators play a role in the destruction of pancreatic beta cells in mice infected with a low dose of EMC-D virus. When we examined the expression of the soluble mediators interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in the pancreatic islets, we found that these mediators were clearly expressed at an early stage of insulitis and that this expression was evident until the development of diabetes. We confirmed the expression of these mediators by in situ hybridization with digoxigenin-labelled RNA probes or immunohistochemistry in the pancreatic islets. Mice treated with antibody against IL-1beta or TNF-alpha or with the iNOS inhibitor aminoguanidine exhibited a significant decrease in the incidence of diabetes. Mice treated with a combination of anti-IL-1beta antibody, anti-TNF-alpha antibody, and aminoguanidine exhibited a greater decrease in the incidence of disease than did mice treated with one of the antibodies or aminoguanidine. On the basis of these observations, we conclude that macrophage-produced soluble mediators play an important role in the destruction of pancreatic beta cells, resulting in the development of diabetes in mice infected with a low dose of EMC-D virus.     

Lycoparins A-C, new alkaloids from Lycopodium casuarinoides inhibiting acetylcholinesterase

Three new Lycopodium alkaloids, lycoparins A-C (1-3), have been isolated from the club moss Lycopodium casuarinoides. Structures and stereochemistry of 1-3 were elucidated on the basis of 2D NMR correlations. Lycoparins C (3) exhibited an inhibitory activity against acetylcholinesterase, while lycoparins A (1) and B (2) did not show activity.     

Purification and properties of diamine oxidase from pea epicotyls

Diamine oxidase (DAO) (EC 1.4.3.6) was purified from pea epicotyls to homogeneity by the criterion of polyacrylamide gel electrophoresis (PAGE). The pu     

The Lipid Phase of Thylakoid and Cytoplasmic Membranes from the Blue-Green Algae (Cyanobacteria), Anacystis nidulans and Anabaena variabilis

The lipid phases of the thylakoid and cytoplasmic membranesfrom the blue-green alga, Anacystis nidulans, were studied bya spin-probe method using 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxyl.The thylakoid and cytoplasmic membranes of this alga were bothin the liquid crystalline state at growth temperature, and inthe phase separation state at about 0?C. The thylakoid membranesentered the phase separation state at a temperature higher thanthe cytoplasmic membranes. The lipid phase of the thylakoidmembranes from Anabaena variabilis was studied in a similarway, and these membranes were found also to undergo the phasetransition. The temperature for the onset of the phase separationand the fluidity of the membrane lipids of both algae dependedon the growth temperature of the culture. (Received April 9, 1984; Accepted June 1, 1984)     

Evaluation of support materials for the immobilization of sulfate-reducing bacteria and methanogenic archaea

This paper reports on the adhesion of sulfate-reducing bacteria (SRB) and methanogenic archaea on polyurethane foam (PU), vegetal carbon (VC), low-density polyethylene (PE) and alumina-based ceramics (CE). Anaerobic differential reactors fed with a sulfate-rich synthetic wastewater were used to evaluate the formation of a biofilm. The PU presented the highest specific biomass concentration throughout the experiment, achieving 872 mg TVS/g support, while 84 mg TVS/g support was the maximum value obtained for the other materials. FISH results showed that bacterial cells rather than archaeal cells were predominant on the biofilms. These cells, detected with EUB338 probe, accounted for 76.2% (+/-1.6%), 79.7% (+/-1.3%), 84.4% (+/-1.4%) and 60.2% (+/-1.0%) in PU, VC, PE and CE, respectively, of the 4'6-diamidino-2-phenylindole (DAPI)-stained cells. From these percentages, 44.8% (+/-2.1%), 55.4% (+/-1.2%), 32.7% (+/-1.4%) and 18.1% (+/-1.1%), respectively, represented the SRB group. Archaeal cells, detected with ARC915 probe, accounted for 33.1% (+/-1.6%), 25.4% (+/-1.3%), 22.6% (+/-1.1%) and 41.9% (+/-1.0%) in PU, VC, PE and CE, respectively, of the DAPI-stained cells. Sulfate reduction efficiencies of 39% and 45% and mean chemical oxygen demand (COD) removal efficiencies of 86% and 90% were achieved for PU and VC, respectively. The other two supports, PE and CE, provided mean COD removal efficiencies of 84% and 86%, respectively. However, no sulfate reduction was observed with these supports.     

Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling.

Pulmonary fibrosis is a progressive disorder whose molecular pathology is poorly understood. Here we developed an in-house cDNA microarray ("lung chip") originating from a lung-normalized cDNA library. By using this lung chip, we analyzed global gene expression in a murine model of bleomycin-induced fibrosis and selected 82 genes that differed by more than twofold intensity in at least one pairwise comparison with controls. Cluster analysis of these selected genes showed that the expression of genes associated with inflammation reached maximum levels at 5 days after bleomycin administration, while genes involved in the development of fibrosis increased gradually up to 14 days after bleomycin treatment. These changes in gene expression signature were well correlated with observed histopathological changes. The results show that microarray analysis of animal disease models is a powerful approach to understanding the gene expression programs that underlie these disorders.