Biomedical subjects
Publications and source records attributed to J R Brown.
The degradation of malathion, undiluted and diluted with No. 2 fuel oil, in thermally generated aerosol clouds was examined at selected temperatures ranging from 121 to 566 degrees C. Undiluted malathion residues decreased from 1.76 to 0.21 micrograms/ml over this range of temperatures. Malathion diluted with fuel oil decreased from 0.14 to 0.02 microgram/ml as the temperature was increased 288 to 510 degrees C.
A two-part crossover study assessed the efficacy of nonprescription support pantyhose by evaluating the relative performance of sheer- versus firm-support types in 30 women with lower extremity complaints. In this clinical trial, 23 women wore nonprescription firm-support pantyhose and seven wore sheer-support pantyhose during the initial 4-week treatment period. Next, treatment was discontinued for 2 weeks, after which a 4-week crossover trial was started. During the crossover, the 23 women who had worn the firm-support hose during the initial trial wore the sheer-support hose, and the seven who had worn the sheer-support hose switched to wearing the firm-support hose. The 2-week washout period did not prove sufficient to allow measured values to return to baseline, thus invalidating the crossover comparisons between the sheer- and firm-support pantyhose. However, the direct comparison of results showed that patients generally experienced an improvement in venous circulation by using either firm- or sheer-support hose as evaluated by venous index measurements and a corresponding decrease in subjective complaints. One year after this study was completed, the patients were recalled. Of the 25 who were seen at this follow-up, 91% continued to use support hose, either when they had symptoms or on a regular daily basis. Venous circulation, as evaluated by noninvasive Doppler ultrasound and photoplethysmography, remained improved.
Sulfite has been identified as an essential metabolite by means of growth studies using a chemically-defined, protein-free medium for culture of human peripheral lymphocytes. Sulfite reduced the amount of cysteine required for optimum growth by at least four-fold. In some subjects, sulfite stimulated growth even in the presence of optimal amounts of cysteine indicating that lymphocytes of some individuals are unable to convert cysteine to sulfite in adequate amounts.
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The DNA-binding properties of the 2-substituted-1,4-dihydroxyanthraquinones 5-12 were examined. Compounds 5 and 6 were synthesized in this study, 7-12 were already available. Spectral studies were consistent with intercalation of 5, 6 and 8 into DNA. Affinity constants were in the range of 3 x 10(4)M-1. Compounds 7 and 10-12 showed no DNA binding, presumably being sterically excluded from binding. The kinetics of the DNA interaction of 5, 6 and 8 were studied. There is a biphasic process. This may reflect an initial reaction, with drug from this first mode of binding moving into the second binding mode (a sequential process) or independent binding of drug in two sets of sites (a parallel process). The methods used in this study do not allow us to discriminate between these models. However, if the parallel binding model is correct, the compounds show sequence selectivity of binding, and provide a lead for further development of neutral DNA-binding ligands with sequence selectivity.
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Extensive length polymorphism and heteroplasmy (multiple forms within an individual) of the D-loop region are observed in mitochondrial DNA of the white sturgeon (Acipenser transmontanus). The nucleotide sequence of this region, for both a short and a long form, shows that the differences are due to variable numbers of a perfect 82-bp direct repeat. We propose a model for the replicative origin of length differences, involving a competitive equilibrium between the heavy strand and the D-loop strand. This model suggests that frequent misalignment in the repeat region prior to elongation, facilitated by a stable secondary structure in the displaced strand, can explain both the polymorphism and heteroplasmy in this species.
Four 9,10-anthraquinones (AQ) mono- or bis-substituted with the -NH(CH2)2NH(CH2)2OH group were studied. 1-AQ, 1,5-AQ and 1,8-AQ but not 1,4-AQ (100 microM) generated pBR322 plasmid DNA single strand breaks in the presence of purified NADPH dependent cytochrome P450 reductase. 1-AQ, 1,5-AQ and 1,8-AQ (at 100 microM) stimulated hydroxyl radical formation in MCF-7 S9 cell fraction (as measured by dimethyl pyrolline N-oxide spin trapping) and MCF-7 DNA strand breaks as measured by alkaline filter elution. In contrast 1,4-AQ did not stimulate hydroxyl radical formation and produced considerably less strand breaks in MCF-7 cells compared to the other AQ's. It would appear that the position of the -NH(CH2)2NH(CH2)2OH groups on the chromophore is an important determinant in the metabolic activation of cytotoxic anthraquinones. This may contribute to the cytotoxicity (ID50 values) of 1-AQ (0.06 microM), 1-8-AQ (0.5 microM) and 1,5-AQ (12.3 microM) but not the 1,4-AQ (1.2 microM).
Three distances (1.2, 3.0 and 7.6 m) and 4 methods (complete diagonal swing, impinger, top diagonal swing and vertical swing) were compared in analyzing the droplet spectra of electrically generated ULV aerosol clouds. There were no significant differences among the 4 methods and no interaction between method and distance. However, when compared over distance, the percent variability indicated the complete diagonal swing provided the most consistent results. Two additional methods (pendulum and settling chamber) were compared with the original 4 methods at 1.2 m only. At this distance, there was no significant difference among the 6 methods.
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In a series of hydroxyethylaminoalkylaminoanthraquinones (AQ's) based on mitozantrone, 1-AQ (340%) and 1,8-AQ (137%) stimulated basal rate NADPH oxidation (72 + 18 pmol min-1 mg S9 protein-1) whilst 1,4-AQ, 1,5-AQ and mitozantrone had no effect. A similar trend was observed for O2.- generation (measured as nmol acet. cyt c reduction min-1 mg protein-1) by these compounds in MCF-7 S9 fraction: 1-AQ (9.5) and 1,8-AQ (7.9), whilst 1,5-AQ, 1,4-AQ and mitozantrone showed no significant effect. All the AQ's including mitozantrone were cytotoxic to MCF-7 cells in a dose dependent manner with EC50 values as follows: 1-AQ (0.01 micron) greater than doxorubicin (0.4 microM) greater than mitozantrone (0.6 microM) greater than 1,8-AQ (2.0 microM) greater than 1,5-AQ (4.0 microM) greater than 1,4-AQ (8.0 microM). Thus the redox active AQ's were also the most cytotoxic. Mitozantrone however was not redox active but was more cytotoxic than all but 1-AQ hence it would appear that factors other than free radical generation contribute to the antitumor activity of this group of compounds.
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Activities of a range of macromolecular conjugates of daunorubicin against Trypanosoma brucei rhodesiense in vitro and in vivo are described and compared to those of free daunorubicin. Conjugates tested were daunorubicin attached to bovine serum albumin by (i) a labile 'glutaraldehyde' linkage (D-BSAG), and (ii) a stable succinyl linkage (D-BSAS), daunorubicin covalently linked to agarose beads (D-AG), and daunorubicin adsorbed onto polyisobutylcyanoacrylate nanoparticles (D-PICA). Trypanocidal activity in vitro was retained in all except D-BSAS, whereas in vivo only D-BSAG had any activity. The results indicate that daunorubicin must be released from the conjugate before it can exert its activity.
The psychosexual sequelae of diagnosis and treatment of pre-invasive cervical atypia were assessed in three groups of women. The first group included 30 women referred to a colposcopy clinic with an abnormal cervical smear indicating cervical intraepithelial neoplasia (CIN), the second comprised 50 women who were traced as sexual partners of men with penile human papillomavirus (HPV) infection; 26 of them had histologically proven cervical atypia and 24 had no such evidence. The third group included 25 women traced as partners of men with non-specific urethritis and who did not have cervical disease. Before and after questionnaires assessed six aspects of sexual behaviour and responses before diagnosis and 6 months after treatment in women with cervical atypia. These were compared with answers given by women investigated and treated, if necessary, as partners of men with sexually transmitted disease (control group). There were statistically significant adverse psychosexual sequelae associated with diagnosis and treatment of pre-invasive cervical epithelial disease.