We measured 2',5'-oligoadenylate synthetase activities in serum and peripheral blood mononuclear cells from 10 patients with chronic hepatitis B who were being treated with interferon so as to determine whether 2',5'-oligoadenylate synthetase activity in serum reflected 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells, and whether it could be used to monitor interferon treatment. Pretreatment values of 2',5'-oligoadenylate synthetase activity in patients' serum and peripheral blood mononuclear cells were not statistically different from values from control subjects. When interferon was administered, serum levels of 2',5'-oligoadenylate synthetase began to rise within 3 hr, reached peak values at 12 hr and then declined. The levels of 2',5'-oligoadenylate synthetase activity both in serum and peripheral blood mononuclear cells increased substantially during interferon treatment, ranging 2- to 50-fold greater than initial levels. The levels of 2',5'-oligoadenylate synthetase in serum correlated closely with levels in peripheral blood mononuclear cells. In addition, when the levels of 2',5'-oligoadenylate synthetase rose during interferon administration, serum hepatitis B virus DNA polymerase values fell, and, in some cases, DNA polymerase rose again when 2',5'-oligoadenylate synthetase fell after discontinuation of interferon. These findings suggest that 2',5'-oligoadenylate synthetase activity in serum accurately reflects the antiviral effect of interferon and could be used to monitor interferon treatment.
The distribution of serotonin-containing nerve fibers in the substantia nigra of the rat, cat and monkey was studied with a highly sensitive peroxidase-antiperoxidase immunohistochemical method. Serotonin fibers in the substantia nigra of all species consisted of fine varicose fibers and formed a fine network. In the zona compacta of all species, serotonin fibers were sparsely distributed. In the zona reticularis of the rat and cat, these fibers were densely distributed and their distributional pattern was almost uniform, while in the monkey such fibers were unevenly distributed and high and low dense areas were intermingled. In the pars lateralis of all species, serotonin fibers were diffusely distributed, and the distributional density was much higher in the cat and monkey than in the rat. Immunoelectron-microscopic studies further revealed that a majority of the labeled varicosities in the rat substantia nigra were in close apposition to peridendritic axon terminals and were also free in the neuropil; occasionally they exhibited symmetrical synapses of "en passant" type with non-immunoreactive dendrites or somata. Our results support a functional significance of serotonergic regulation of the substantia nigra in mammals.
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