Studies on the defectiveness of adeno-associated virus (AAV). I. Effects of phosphonoacetic acid and 2-deoxy-D-glucose on the replication of AAV.
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Biomedical subjects
Publications and source records attributed to J F Young.
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The genetic variation of the new pandemic H1N1 influenza A viruses isolated in 1977 was analyzed by two-dimensional oligonucleotide fingerprinting and RNA sequencing. Differences were observed in the fingerprints of the RNAs of these viruses, and analysis of the changes suggested that sequential mutations occurred in their genomes. Based on these data, a scheme is presented which proposes divergent evolution of strains from a common ancestry. Furthermore, it was found that mutations were not restricted to the genes coding for the hemagglutinin and the neuraminidase, but were scattered throughout the genome, suggesting that selective antibody pressure is not solely responsible for the emergence of genetic variants. Our data also strengthen the hypothesis that the new H1N1 influenza virus strains are derived from strains circulating in 1950.
In June of 1977, a new influenza A pandemic was started by strains of the H1N1 serotype. Oligonucleotide fingerprint analysis of the RNA from viruses isolated during the early stage of this pandemic demonstrated that genetic variation among these 1977 strains could be attributed to sequential mutation [Young, J.F., Desselberger, U. & Palese, P. (1979) Cell, 18, 73-83]. Examination of more recent strains revealed that the H1N1 variants that were isolated in the winter of 1978-1979 differed considerably from the H1N1 viruses isolated the previous year. Oligonucleotide and peptide map analysis of the new prototype strain (A/Cal/10/78) suggested that it arose by recombination. It appears that only the HA, NA, M, and NS genes of this virus are derived from the earlier H1N1 viruses and that the P1, P2, P3, and NP genes most likely originate from an H3N2 parent. These data suggest that genetic variation in influenza virus strains of the same serotype is not restricted to mutation alone, but can also involve recombination (reassortment).
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In this 54 year old woman with celiac disease, osteomalacia developed while she was on a gluten-free diet which had caused regression of her steatorrhea. She was not responsive to large doses of parenterally administered dihydrotachysterol and calcium, but she was responsive to the oral administration of 25-hydroxyvitamin D3 (25-OHD3). The data suggest that 25-OHD3 is the treatment of choice for patients with vitamin D deficiency due to intestinal malabsorption.
A pharmacokinetic study of an intentional pentachlorophenol ingestion by an elderly human has been undertaken. Information on the presence or absence of forced diuresis either continuously or for a short restricted period indicates that such treatment would materially reduce the body burden of pentachlorophenol. It is suggested that forced diuresis is the treatment of preference for such intoxication at this time.
Rats were anesthetized with pentobarbital, pentobarbital and atropine, inactin [5-ethyl-5-(1'-methyl-propyl)-2-thiobarbiturate], ether and inactin, or urethane. Cardiovascular and arterial acid-base parameters were monitored over a 3-hour period of anesthesia. Heart rate, arterial pressures, and pH progressively decreased with duration of pentobarbital anesthesia. Changes observed in rats anesthetized with the thiobarbiturate, inactin, were similar although generally less severe. Most subjects treated with the barbiturates were markedly hypercapnic. Urethane anesthesia was characterized by a higher and more stable heart rate and greater pulse pressure. Arterial carbon dioxide and bicarbonate levels in the urethane group were substantially lower at all sampling times than the values obtained in the barbiturate groups.
A simultaneous pharmacokinetic study of two chemicals has been conducted on a clinically stabilized human who had intentionally ingested a mixture of 2,4-D and Dicamba. The information developed can be useful to the clinical toxicilogist in the management of similar cases.
Chemical methods were developed for the trace analysis of the herbicide 2,4,5-trichlorophenoxyacetic acid, its glycineamide, and their alkaline hydrolyzable conjugates in mouse blood, urine, and feces. The salient elements of the methods are extraction of the free acids with benzene, methylation, cleanup on a silica gel column, and quantification via electron-capture GLC. Any unextracted conjugates remaining in the substrates are then subjected to alklaline hydrolysis, and the liberated 2,4,5-trichlorophenoxyacetic acid is assayed. Data are presented concerning recoveries of the compounds from the three spiked substrates. The utility of the procedures is illustrated by a preliminary pharmacolinetic study employing parallel electron-capture GLC and radioassays of the three substrates from mice injected with a single intravenous dose of 14C-2,4,5-trichlorophenoxyacetic acid. GLC characteristics and partition values of the the compounds and hydrolysis of the glycineamide under various conditions also are discussed.
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The use of pharmacokinetics can improve the extrapolation of animal teratology data for human risk evaluation. Before one can extrapolate between species, however, the pharmacokinetic model must be predictable within the species for which it was developed. This article summarizes an approach being used for correlating pharmacokinetics and teratology endpoints in the same animal and predicting the teratogenic outcome for other animals of the same species. With the aid of micro-sampling procedures, and sensitive and rapid analytical techniques, blood, urine and feces samples are obtained from individual animals following dosing and the data are simulated using a hybrid computer to develop a pharmacokinetic model. The model is validated in other animals by measuring the parent compound and metabolites in various "compartments" predicted by the model. Then the pharmacokinetic model is tested by predicting the teratogenic outcome in single ani-analyses indicated the most predictive pharmacokinetic parameters to be two maternal blood concentration values. Prediction of the teratogenic outcome based on these parameters was accurate for 74% of the litters in the 95% confidence interval. This approach is discussed as it relates to its utility for other exposure routes and for extrapolation to other species.