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Biomedical subjects

D L Robertson

Publications and source records attributed to D L Robertson.

65 records · Page 4Linked to original sources

Identification of degradation products in a phenylbutazone tablet formulation.

Two previously reported but unidentified phenylburazone degradation products were isolated from a tablet that was stored at 60 degrees for 203 days. The compounds, alpha-(N-phenylcarbamoyl)-N-caproylhydrazobenzene and alpha-hydroxy-alpha-(N-phenylcarbamoyl)-N-caproylhydrazobenzene, were isolated by chromatography, identified by mass and NMR spectrometry, and synthesized by the reaction of aniline with phenylbutazone or its hydroxy analog, respectively.

Chemical Phenomena↗

Family pharmacy and family medicine: a viable private practice alliance.

The association of the new roles of the family physician and the family pharmacist in a model private practice is described. The pharmacist works closely with the family physician to offer personalized patient education and follow-up for therapeutic effectiveness. He also serves as a consultant to the physician for up-to-date drug information and assists in solving difficult therapeutic problems. Reimbursement for pharmacy services occurs for consultative time as well as by traditional methods. Initial response by the professionals themselves as well as the patients and staff has been very positive. An appropriate physical plant and ongoing communication between physician and pharmacist are mandatory for the success of this model. Some specifics of this practice at its present stage of development are included.

Family Practice↗

Stability-indicating high-performance liquid chromatographic determination of chlorpropamide, tolbutamide, and their respective sulfonamide degradates.

A quantitative high-performance liquid chromatographic method for the determination of chlorpropamide, tolbutamide, and their respective hydrolysis products, p-chlorobenzenesulfonamide and p-toluenesulfonamide, in solid dosage forms was developed. The method is stability indicating and can be used to determine the sulfonamide hydrolysis product and the intact drug in the presence of minor degradates. Method reproducibility, demonstrated by repeated injections of a calibration standard, was 1.21%. The lower limit of quantitation of the hydrolysis products, p-chlorobenzenesulfonamide and p-toluenesulfonamide, was 0.2 microgram/5-microliter injection. The accuracy of the method for intact drugs was determined by comparison of the HPLC results to those obtained by the appropriate USP or BP assays. The mean of the results obtained by the two methods differed by 0.7% for chlorpropamide and 0.3% for tolbutamide. Pure drug samples were spiked with amounts of the hydrolysis products ranging from 20 to 120% of the intact content. The mean percent recovery for p-chlorobenzenesulfonamide was 98.6%; for p-toluenesulfonamide, it was 100.6%. A qualitative TLC procedure for the detection of chlorpropamide, p-chlorobenzenesulfonamide, dipropylurea, propylurea, n-propylamine, tolbutamide, p-toluenesulfonamide, dibutylurea, butylurea, and n-butylamine is also described.

Chlorpropamide↗

Structural analysis of the intracellular RNAs of murine mammary tumor virus.

We have characterized murine mammary tumor virus (MuMTV)-specific RNA in several types of cells in which viral DNA is transcribed into RNA: cultured GR mouse mammary tumor cells, S49 lymphoma cells from BALB/c mice, lactating mammary glands from C57BL/6 mice, and mink lung cells infected in vitro with MuMTV. In all cell types studied, there are three distinct species of intracellular viral RNA, with sedimentation coefficients of 35S, 24S, and 13S (or molecular weights of 3.1 X 10(6), 1.5 X 10(6), and 0.37 X 10(6), as determined by rate-zonal sedimentation in sucrose gradients and by electrophoresis in agarose gels under denaturing conditions. These three viral RNA species appear to be present regardless of viral RNA concentration, responsiveness to glucocorticoid hormones, production of extracellular virus, and use of either endogenous or acquired MuMTV proviral DNA as template. The three viral RNAs display characteristics of mRNAs in that they are polyadenylated, associated with polyribosomes, and released from polyribosomes by treatment with EDTA; hence all three species presumably direct the synthesis of virus-coded proteins. The two larger species of viral RNA are probably responsible for synthesis of the structural proteins of the virion, but the function of the 13S RNA is not known. Both of the subgenomic RNAs contain sequences found at the 3' terminus of 35S (or genomic) RNA. However, only the 24S RNA (not the 13S RNA) contains sequences which are located at the 5' terminus of 35S RNA and are apparently transposed during RNA synthesis of maturation, as described for subgenomic mRNA's of other retroviruses.

Base Sequence↗

Characterization of the proteins of intracisternal type A and extracellular oncornavirus-like particles produced by MOPC-460 myeloma cells.

The mouse plasmacytoma cell line, MOPC-460, produces both intracisternal and intracytoplasmic A-type particles when grown as a solid tumor. When these cells are grown either as an ascites tumor or in tissue culture, a third type of particle is produced extracellularly. This particle, the "myeloma-associated virus," is closely related to, and probably an alternate form of, the intracisternal A-type particle. The proteins present in these two types of particles were compared by tryptic peptide mapping. Both types of particles were found to contain essentially the same major proteins of 76,000 (p76), 68,000 to 70,000 (p68-70), and 45,000 (p45) daltons, in addition to varying amounts of smaller proteins. The relative proportions of all these proteins varied from preparation to preparation in an unpredictable way. The p45, p68, and p70 proteins all contained sequences found in p76, suggesting precursor-product relationships of p76 leads to p70 leads to p45 for solid tumor A-type particles and p76 leads to p68 leads to p45 for extracellular myeloma-associated virus. In addition, immune precipitation experiments have established that p76 contains at least some of the antigenic determinants characteristic of murine leukemia virus p30. This confirms earlier nucleic acid hybridization studies which indicated a moderate degree of relatedness between MOPC-460 A-type particles and several standard murine leukemia and sarcoma viruses. Taken together, our results provide evidence supporting the concept that MOPC-460 A-type particles may represent aberrant forms of C-type murine viruses.

Animals↗

Relationships between intracisternal type A and extracellular oncornavirus-like particles produced in murine MOPC-460 myeloma cells.

Oncornavirus-like particles of the "A" (both intracisternal and intracytoplasmic) and "B" or "C" (extracellular) types are produced by murine MOPC-460 myeloma cells. This communication describes a comparative study on tracisternal A and extracellular particles. Both types of particles contain an RNA-dependent DNA polymerase activity, traces of 35S and 70 S RNA in addition to larger amounts of degraded RNA, and proteins of approximately 76,000 and 45, 000 daltons. The 76,000-dalton proteins from intracisternal A and extracellular particles have the same cyanogen bromide peptides. Hybridization kinetic analysis indicates that the RNAs in the two particles are identical or very closely related and share partial homology with Moloney leukemia virus RNA. In contrast, the particles appear to have little or no relationship to murine mammary tumor virus as judged by several different criteria. Electron microscope studies indicate that the extracellular particles arise from the budding of core components through the plasma membrane. These results suggest that the intracisternal A and extracellular oncornavirus-like particles produced by MOPC-460 cells are closely related.

Animals↗

Reverse transcriptase associated with A-type particles from murine myeloma cells.

Our findings may be summarized as follows: (a) a DNA polymerase is associated with murine type A particles, which is very similar to the reverse transcriptases found in true RNA tumor viruses; (b) the majority of the RNA isolated from A particles is of low molecular weight (probably due to degradation), byt appears to contain an amount of unique sequence information comparable to that found in other oncornavirus particles. These results suggest that A-type particles may be very similar, and perhaps related, to the two other classes (B and C) of oncornaviruses.

Base Sequence↗

Characterization of DNA polymerase and RNA associated with A-type particles from murine myeloma cells.

The RNA-dependent DNA polymerase present in intracisternal A-type particles from mouse myeloma tumor cells has been studied. This polymerase can use either endogenous A particle RNA or an exogenous synthetic polynucleotide [poly (rA)] as a template. The DNA reaction product is small (4S-10S) and over 90% of it hybridizes to A particle RNA, whereas up to 50% of it hybridizes to murine sarcoma-leukemia virus RNAs. The RNA isolated from purified A particles is generally of low molecular weight (5S-15S) but contains small amount of 70S and 35S components. These results suggest that A-type particles may be related to C-type oncornaviruses.

Animals↗

Drug inhibition and cellular regulation of prostaglandin G/H synthase isoenzyme 2.

Prostaglandin G/H synthase isoenzyme 2 (PGHS-2) was identified as an immediate-early gene product induced by Rous sarcoma virus, serum, phorbol ester and a wide variety of other mitogens. Induction of PGHS-2 occurs through an increase in PGHS-2 gene transcription. Dexamethasone inhibits both the basal and induced levels of PGHS-2 mRNA. In contrast, PGHS-1 gene transcription rate, mRNA, and protein levels are unaffected by mitogens and dexamethasone. Post-transcriptional down-regulation of PGHS-2 mRNA plays a significant role in causing dexamethasone's effect. Specific cell systems have been identified which allow selective analysis of PGHS-1 and PGHS-2 at the nucleic acid and protein levels. These cell systems indicate that PGHS-1 and PGHS-2 may have different sensitivities to non-steroidal anti-inflammatory drugs. Furthermore, inhibition of PGHS activity correlates well with suppression of the transformed phenotype in an in vitro cell model.

Animals↗