1 We investigated the ability of N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide (AC-5216), a novel mitochondrial benzodiazepine receptor (MBR) ligand, to produce anti-anxiety and antidepressant-like effects in various animal models. 2 AC-5216 showed high affinity for MBRs prepared from rat whole brain (K i 0.297 nM), rat glioma cells (IC 50 3.04 nM) and human glioma cells (IC 50 2.73 nM), but only negligible affinity for the other main receptors including central benzodiazepine receptors. 3 AC-5216 produced anti-anxiety effects in the Vogel-type conflict test in rats, and in the light/dark box and social interaction tests in mice at 0.1-3, 0.003-0.01 and 0.01-0.3 mg kg À1 , p.o., respectively. These effects of AC-5216 were antagonized by PK11195, an MBR antagonist. In the forced swimming test in rats, AC-5216 (3-30 mg kg À1 , p.o.) reduced the immobility time, and this effect was blocked by PK11195. 4 AC-5216 had no myorelaxant effects, did not affect the memory or prolong hexobarbitoneinduced sleep in mice, even at doses as high as 1000 mg kg À1 , p.o. Although it did slightly prolong the ethanol-induced sleep time at 1000 mg kg À1 , AC-5216 (1-100 mg kg À1 , p.o.) produced no distinct change in the rat electroencephalogram. 5 These results indicate that AC-5216 produces anti-anxiety and antidepressant-like effects that are mediated by MBR, but does not cause the side effects normally associated with conventional benzodiazepines. Hence, AC-5216 shows potential for the treatment of stress-related disorders including anxiety and depression.

The gene frequencies and haplotypic associations within the HLA region have been investigated in 916 unrelated Japanese individuals. HLA class I and class II antigens were studied by conventional serology, and class II alleles, DRB1, DRB3, DQA1, DQB1 and DPB1 were typed by using polymerase-chain reaction amplification and sequence-specific oligonucleotide probe (PCR-SSOP) method. Thirty DRB1, 3 DRB3, 8 DQA1, 15 DQB1 and 13 DPB1 alleles were found in our population. DR-NJ25, a characteristic antigen in the native American and Asian populations, was observed at 3.0%. This antigen was observed mainly with the DRB1*1403 and 1406 alleles. Twenty-seven out of 30 DRB1 alleles found in this study had a high positive linkage disequilibrium with DQB1 alleles and 20 of them had an exclusive association with one specific DQA1-DQB1 combination. The strong association between DRB1 alleles and HLA-B antigens was the most striking finding in this study. Twenty-eight out of 30 DRB1 alleles had a positive linkage disequilibrium with 24 HLA-B antigens (p < 0.01). The other two alleles, DRB1*0404 and 1402, were very rare, and their frequencies were 0.2% and 0.1%, respectively. The data presented in this population study should be useful for the studies on anthropology, organ transplantation and disease susceptibility.

The reason for the decreased fluorescence in diseased tissues appears to be a decrease in collagen fluorescence due to the screening effect of mucosal thickening or replacement of submucosa by cancer cells.

No abstract

Mucosal thickening as a result of cancer cell invasion had a large impact on the detection rate of the LIFE-GI system. As a result, this method may not be useful for the detection of undifferentiated cancer, which may invade in a more dispersed manner, without altering the mucosal thickness.