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Biomedical subjects

W H Prusoff

Publications and source records attributed to W H Prusoff.

At least 109 records · Page 6Linked to original sources
PubMed1976

Successful therapy of herpes hominis keratitis in rabbits by 5-iodo-5'-amino-2'5'-dideoxyuridine (AIU): a novel analog of thymidine.

The efficiency of 5-iodo-5'-amino-2'5'-dideoxyuridine (AIU) in the therapy of experimental herpes keratitis in rabbits has been examined. Virus infections were established bilaterally in 40 animals using herpes simplex, type 1 (NIH strain 11124). Twenty-four hours after infection the rabbits were divided into five matched groups of eight and each group was treated, double-blind, with topical drugs at four-hour intervals for a total of 72 hours. The solutions instilled were: (1) saline; (2) IdUrd, 1 mg. per milliliter; (3) AIU, 1 mg. per milliliter; (4) AIU, 4 mg. per milliter; and (5) AIU, 8 mg. per milliliter. Each eye was examined daily for 12 days and graded independently by two ophthalmologists. Although IdUrd and AIU (8 mg. per milliliter) were effective therapeutically, IdUrd had a greater effect. The AIU at 1 and 4 mg. per milliliter were less active, but showed more rapid healing than the saline control. Viral recovery studies are consistent with the clinical observations. A second independent experiment, similar to that described above, gave essentially identical results. Although less potent than IdUrd, AIU does provide effective therapy for herpes keratitis.

Administration, Topical↗
PubMed1975

Deoxyribonucleotide metabolism in Herpes simplex virus infected HeLa cells.

The effect of Rolly No. 11 strain herpes simplex virus infection of HeLa cells in culture on deoxynucleotide metabolism and the level of various enzymes concerned with the biosynthesis of DNA has been investigated. Of 18 enzyme activities studied, thymidine kinase, DNA polymerase and deoxyribonuclease were markedly augmented, a finding in agreement with previous reports. Deoxycytidine kinase, ribonucleotide reductase, thymidylate kinase and deoxycytidylate deaminase activities, in contrast with previous reports, did not increase; the activities of the other enzymes studied, also did not increase. Whereas most of the radioactivity derived from [14-C] thymidine in the acid-soluble fraction of the uninfected cells was present as deoxythymidine triphosphate, that present in the infected cells was primarily in the form of deoxythymidine monophosphate. Thus, in the infected cell deoxythymidylate kinase is a rate-limiting enzyme in the biosynthesis of deoxythymidine triphosphate. A marked increase in the pools of the four naturally occurring deoxynucleoside triphosphates (dTTP, dCTP, dATP, dGTP) was found. The rate of formation of the virus-induced enzymes was determined, as were the various nucleoside triphosphate pools and the other phosphorylated derivatives of thymidine; a maximum was reached for all these csmponents between 6 to 8 h post infection. Although an apparent greater synthesis of DNA occurred in the uninefected cells, when the specific activity of the radioactive deoxythymidine triphosphate was taken into account, there was actually a greater rate of DNA synthesis in the infected cells, with the peak at 8 h post infection.

Biological Transport↗
PubMed1975

Multiplicity reactivation of 5-iodouracil-substituted, nonviable bacteriophage T4td8.

Nonviable, 5-iodouracil (IUra)-substituted bacteriophage T4td8 can be multiplicity reactivated. The data indicate that two nonviable, IUra-substituted T4td8 phage can complement each other intracellularly to produce viable progeny. Phage particles in lysates of T4td8-infected Escherichia coli BT(-), prepared in the presence of varying mole fractions of IUra plus thymine, were examined by infecting with low and high dilutions of lysate. The yields of multiplicity reactivable particles were identical, regardless of the mole fractions of IUra present in the growth media. However, the yields of viable phage, measured at low multiplicities of infection, decreased with increasing mole fraction of IUra. The results are consistent with the hypothesis that the lethal effect of IUra is a consequence of its incorporation into DNA. Further, the IUra-induced lesion cannot involve genetic damage that shuts off expression at a single region of the genome.

Coliphages↗
PubMed1975

Selective inhibition of herpes simplex virus by 5-amino-2,5-dideoxy-5-iodouridine.

5-Amino-2,5-dideoxy-5-iodouridine, a nel thymidine analogue, is a potent inhibitor of herpes simplex virus type 1 replication. In contrast to most other nucleoside analogues which possess antiviral activity, 5-amino-2,5-dideoxy-5-iodouridine exhibits little, if any, cellular toxicity. Preliminary evidence suggests that 5-amino-2,5-dideoxy-5-iodouridine selectively inhibits viral-specific DNA synthesis.

Amines↗