PubMed Health⌕ Search

Biomedical subjects

R Leavitt

Publications and source records attributed to R Leavitt.

30 records · Page 2Linked to original sources
PubMed1983

Depression of natural killer cytotoxicity after in vivo administration of recombinant leukocyte interferon.

One hundred thirty-four patients with a variety of malignancies were treated in two phase I clinical trials of recombinant leukocyte A interferon (IFL-rA) produced by recombinant DNA methodology. IFL-rA was given by intra-muscular injection either twice daily or three times weekly for 28 days. Extensive monitoring of natural killer (NK) cell cytotoxicity was done on these patients with rigorously standardized assays and determination of the inherent variability of NK function for each individual. Interferon, as used in these two treatment regimens, failed to produce an appreciable increase in NK activity; in the majority of patients, there was no significant change in NK activity from the pretreatment baseline levels. An unexpected finding was the depression of NK activity in 30% of the patients. The data have been analyzed in terms of their possible relationship to dose and schedules of IFL-rA administration and to antitumor response.

Analysis of Variance↗
PubMed1981

The penetration of formulated Guthion spray through selected fabrics.

A technique for comparing pesticide penetration through fabric was devised. It involved passing fabric swatches through a controlled spray system and measuring the pesticide residue transferring on and through the tested fabric. Six variations in fabric were selected for testing: 100% cotton woven chambray, Scotch-guard treated chambray, Tyvek, Crowntex, and two variations of Gore Tex. Guthion (azinphos-methyl) was chosen as the insecticide for controlled use in this experiment because of its widespread use and relatively high toxicity. Gas chromatographic analysis of the amount of Guthion transferred through the outer fabric was made by the use of analysis of variance (ANOVA) and Duncan's multiple range test. The ANOVA for experiment replication showed no significant difference among the replications of each fabric. The treatment ANOVA was highly significant at the 0.01 level. Duncan's multiple range test further analyzed the differences in the treatment, and three groups were found to be significantly different from each other. The two types of Gore Tex, Tyvek and Crowntex comprised the group permitting the least penetration Scotch-guard treated chambray followed, and untreated chambray allowed the greatest penetration.

Azinphosmethyl↗
PubMed1978

Synthesis and infectivity of vesicular stomatitis virus containing nonglycosylated G protein.

The replication of vesicular stomatitis virus (VSV) is inhibited by tunicamycin (TM), an antibiotic that blocks the formation of N-acetylglucosaminelipid intermediates. We had shown previously that the viral glycoprotein (G) synthesized in cells treated with TM is not glycosylated and is not found on the outer surface of the cell plasma membrane. In this report, we shown that cells exposed to TM produce a low yield of infectious particles. The yield is increased when the temperature during infection is lowered from 37 to 30 degrees C. At 30 degrees C in the presence of TM, both wild-type VSV and the temperature-sensitive mutant ts045 produce particles that do not bind to concanavalin A Sepharose and contain only the nonglycosylated form of G. These particles have a specific infectivity (pfu/cpm) comparable to that of VSV containing glycosylated G.

Anti-Bacterial Agents↗
PubMed1977

Impaired intracellular migration and altered solubility of nonglycosylated glycoproteins of vesicular stomatitis virus and Sindbis virus.

Tunicamycin, an antibiotic which prevents the glycosylation of newly synthesized proteins, inhibits the replication of both vesicular stomatitis virus and Sindbis virus. In tunicamycin-treated infected cells, all of the viral proteins are synthesized but the glycoproteins are devoid of carbohydrate. The nonglycosylated glycoproteins could not be detected on the outside of the plasma membrane by lactoperoxidase labeling, indirect immunofluorescence staining, or chymotrypsin treatment of intact cells, whereas the glycosylated glycoproteins were readily detected by all three methods. These results indicate that the bulk of the nonglycosylated glycoproteins are unable to undergo the normal migration to the cell surface. In contrast to the normal glycosylated viral glycoproteins, the nonglycosylated glycoproteins were insoluble in nonionic detergents such as Triton X-100. The nonglycosylated glycoprotein of vesicular stomatitis virus could be solubilized using a combination of 6 M guanidine hydrochloride and 0.2% Triton X-100, but precipitated when the 6 M guanidine was removed by dialysis. These results suggest that the lack of carbohydrate alters the properties of the glycoproteins, which may explain their impaired mobility through the intracellular membranous system.

Anti-Bacterial Agents↗
PubMed1977

Tunicamycin inhibits glycosylation and multiplication of Sindbis and vesicular stomatitis viruses.

Tunicamycin (TM), an antibiotic that inhibits the formation of N-acetylglucosamine-lipid intermediates, thereby preventing the glycosylation of newly synthesized glycoproteins, inhibits the growth of Sindbis virus and vesicular stomatitis virus in BHK cells. At 0.5 mug of TM per ml, the replication of both viruses is inhibited 99.9%. Noninfectious particles were not detected. All the viral proteins were synthesized in the presence of TM, but the glycoproteins were selectively altered in that they migrated faster than normal viral glycoproteins when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting defective glycosylation. Within 1 h after TM addition, [14C]glucosamine incorporation into glycoproteins was inhibited 20%, whereas [35S]methionine incorporation was unaffected. By 2 to 3 h after TM addition, glucosamine incorporation had fallen to 15% of control value, with methionine incorporation being 60% of normal. TM did not affect the growth of the nomenveloped encephalomyocarditis virus in BHK cells, demonstrating that TM is not a general inhibitor of protein synthesis. These data demonstrate that TM specifically inhibits the glycosylation of viral glycoproteins and that glycosylation may be essential for the normal assembly of enveloped viral particles.

Anti-Bacterial Agents↗
PubMedDate not supplied

A unique metabolite of nimesulide.

Nimesulide is a nonsteroidal anti-inflammatory drug recently detected in equine blood and urine samples taken at the race track. The detection of the drug in a blood sample led to the identification of an unknown thin-layer chromatographic (TLC) spot in track urine samples as a metabolite of nimesulide. Characterization of the unknown TLC spot and comparison with the synthesized compound shows that the unknown TLC spot is a previously unreported equine metabolite of nimesulide. The metabolite was identified as resulting from the reduction of the nitro group on nimesulide to an amino group. This reduced nitro metabolite (4-amino-2-phenoxy-methanesulfonanilide) is a major metabolite of nimesulide in the equine.

Administration, Oral↗
PubMedDate not supplied

The urinary elimination profiles of diazepam and its metabolites, nordiazepam, temazepam, and oxazepam, in the equine after a 10-mg intramuscular dose.

A method for the extraction of diazepam and its metabolites (nordiazepam, temazepam, and oxazepam) from equine urine and serum and their quantitation and confirmation by liquid chromatography-tandem mass spectrometry is presented. Valium, a formulation of diazepam, was administered at a dose of 10 mg intramuscularly to four standard-bred mares. Diazepam is extensively metabolized in the horse to nordiazepam, temazepam, and oxazepam. Diazepam urinary concentrations were found to be less than 6 ng/mL. Nordiazepam was found to be mainly in its glucuronide-conjugated form and was measured out to a collection time of 53-55 h. Oxazepam and temazepam were entirely conjugated, and their urinary concentrations were measured out to collection times of 121 h and 77-79 h, respectively. Diazepam and nordiazepam were measured in equine postadministration serum out to collection times of 6 and 54 h, respectively. Oxazepam and temazepam were not detected in postadministration serum.

Animals↗
PubMedDate not supplied

The elimination profiles of tenoxicam and hydroxytenoxicam in equine urine and serum after a 200-mg oral dose.

Tenoxicam (Mobiflex) was administered orally to four standardbred mares at a dose of 200 mg. Elimination profiles of tenoxicam and hydroxytenoxicam were generated based on quantitation of these analytes in urine and serum by liquid chromatography (LC) with ultraviolet detection. Tenoxicam was confirmed by LC-tandem mass spectrometry daughter ion mass spectra in the last postadministration sample in which tenoxicam was detected. The tenoxicam and hydroxytenoxicam urinary elimination profiles had the same shape for the same horse; however, each horse was significantly different from the others. One horse (Horse 15) showed a much broader and flatter elimination profile than the other horses. Each horse had a peak in analyte concentration at different collection times. The latest detection for both tenoxicam and hydroxytenoxicam was 29-31 h for all horses. The urinary tenoxicam limit of detection (LOD) and limit of quantitation (LOQ) were 0.3 and 0.4 microg/mL, respectively. The urinary hydroxytenoxicam LOD and LOQ were 0.6 and 0.8 microg/mL, respectively. Hydroxytenoxicam was found to be completely conjugated and tenoxicam completely unconjugated in equine urine. Serum elimination profiles of tenoxicam were measured to 120 h postadministration. Hydroxytenoxicam was not detected in postadministration serum. The last serum tenoxicam detection was at the 24-h collection time for all horses. The peak average concentration was 434.5 ng/mL at 3 h. The serum tenoxicam LOD and LOQ were 5.7 and 7.3 ng/mL.

Administration, Oral↗
PubMedDate not supplied

The elimination profiles of oxaprozin in equine urine and serum after a 4.8-g dose.

A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented. Confirmation of oxaprozin in postadministration extracts was accomplished by gas chromatographic- mass spectrometric analysis of methylated extracts or liquid chromatography with tandem mass spectrometry daughter ion mass spectra of underivatized extracts. Daypro, a formulation of oxaprozin, was administered orally at a dose of 4.8 g to four standardbred mares. Urine and serum samples were collected to 120 h postadministration. Base hydrolysis of equine urine before extraction resulted in an increase in the amount of oxaprozin measured, an indication of conjugation by ester formation. The urinary elimination profiles of each horse were significantly different from each other with more than one peak in oxaprozin concentration before the 29-31-h collection time. After this collection time, the differences between the oxaprozin urinary concentrations of each horse follow each other more closely. The peak average urinary concentrations of oxaprozin were 25.1 and 17.0 microg/mL at collection times of 8-10 and 18-22 h, respectively. The latest detection of oxaprozin in urine was at the last collection time of 119-121 h postadministration at a concentration close to the detection limit of approximately 0.1 microg/mL. The serum elimination profiles do not vary between horses as much as the urinary elimination profiles. The peak average serum concentration was 49.0 microg/mL at a collection time of 6 h postadministration. The latest detection was at the last collection time of 120 h. Oxaprozin is metabolized in the horse by hydroxylation. Two major urinary metabolites were isolated and identified as hydroxylated oxaprozin. The two urinary metabolites were isolated from equine postadministration urine and analyzed by mass spectrometry and proton nuclear magnetic resonance spectroscopy, which showed that the hydroxylation had occurred at the para positions of the two aromatic rings.

Administration, Oral↗