Chromosome 21 does not code for an interferon receptor.
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Biomedical subjects
Publications and source records attributed to V G Edy.
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One patient with hepatitis-B surface antigen (HBsAg)-positive chronic aggressive hepatitis, and two chimpanzee carriers of HBsAg, were each given seven doses of 10(7) I.U. of human fibroblast interferon over two weeks. The main differnce observed after treatment was a depression of the nucleocapsid hepatitis-0 core antigen in the liver, indicating that hepatitis-B virus infection is sensitive to interferon. Except for a short febrile reaction, no undesirable effects were seen after the administration of human fibroblast interferon which has not been previously given to man.
Double-stranded RNAs from Penicillium chrysogenum virus have been treated with RNAse III, pancreatic RNAse A and RNAse T1 and the degradation of the RNAs has been studied under different conditions. It was found that only the two former enzymes cut across both strands, RNase T1 cannot cleave double strands. RNase III was shown to digest double-stranded RNA by a two step process: an initial phase of specific cleavage is followed by random degradation. In the first phase the enzyme exhibited a definite preference for some specific base pattern. Partial or complete degradation with pancreatic RNase A could also be achieved in media with high salt concentration provided that the enzyme: substrate ratio was increased together with the salt concentration. By combining different assay techniques, the process of degradation was followed from the early stages to complete digestion and the breakdown products were characterised. It is suggested that a structural change in the enzyme molecules enables them to act on double-stranded RNA. RNAse T1, being unable to cleave double strands, provides a useful tool for studying the secondary structure of RNA molecules. Treatment with different nucleases yielded some new information on the structure of different RNA species in Penicillium stoloniferum virus.
In view of the lower physical stability of human fibroblast interferon than of human leukocyte interferon, the rates of clearance of the two types of interferon were compared in vivo. Both types were injected intravenously and intramuscularly into rabbits, and serum titers were determined at various times after injection. The rates of clearance of the two types of interferon were very similar after both intravenous and intramuscular injection, a finding which indicated that, at least in the circulatory system of rabbits, human fibroblast interferon is not less stable than human leukocyte interferon. After intravenous injection of either type, very little interferon was found in soluble extracts of the rabbit liver. This result implies that heterologous interferon is broken down rapidly in the liver, that it is bound to some particulate fraction, or that it does not accumulate in the liver.
Preparations of human fibroblast and leukocyte interferons of similar potency show markedly different dose-response curves in an assay which measures the degree of protection of tissue cultures against virus c.p.e. The effect is observed with both vesicular stomatitis virus (VSV) and Mengovirus, and is not altered by purification of the interferons.
Human fibroblast and mouse L929 cell interferons can be purified by adsoprtion to and subsequent elution from Controlled Pore Glass. Purification of 40 to 90-fold to specific activities of 1 to 5 times 10(6) units/mg of protein can be achieved in a single step, with good recovery of activity. Human leukocyte interferon does not bind to the glass and cannot be purified in this way.
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The effect of interferon on the synthesis and release of A-, B- and C-type viruses by oncornavirus carrier lines was studied. Murine cell lines were selected which carry either of these viruses and are sensitive to the antiviral effect of interferon, as measured by inhibition of vesicular stomatitis virus. Release of C-type virus was found to be highly sensitive. Release of B-type virus, on the contrary, was only marginally inhibited. Synthesis of intracisternal A-type particles was finally not inhibited by interferon pretreatment. These differences between infectious C-type and non-infectious A- and B-type viruses may reflect fundamental differences in the synthesis of these viruses.
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Human fibroblast interferon preparations were completely stabilized to 100 degrees C by sodium dodecyl sulphate (SDS) in the presence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS without mercaptoethanol. On the contarary, human leukocyte interferon preparations were completely stabilized to 100 degrees C by SDS in the absence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS in the presence of mercaptoethanol. Furthermore, human fibroblast interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS under reducing conditions, but only a minor part of their activities were restored by SDS in the absence of reduction. On the contrary, human leukocyte interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS in the absence of reduction, but only a minor part of their activities were restored by SDS under reducing conditions. These data suggest that there are distinct molecular species of human interferons.
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Priming with interferon prior to poly(I).poly(C) treatment of a mouse cell line, MO 57/2, followed by sequential administration of metabolic inhibitors, resulted in the production of high yields of mouse interferon.
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