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Biomedical subjects

J R Brown

Publications and source records attributed to J R Brown.

At least 19 recordsLinked to original sources

Mitochondrial DNA length variation and heteroplasmy in populations of white sturgeon (Acipenser transmontanus).

Southern blot analysis was used to quantify the extent of mtDNA D-loop length variation in two populations of white sturgeon, Acipenser transmontanus. Over 42% of individuals were heteroplasmic for up to six different mtDNA length variants attributable to varying copy numbers of an 82-bp repeat sequence. Chi-square analyses revealed that the frequencies of length genotypes and the incidence of heteroplasmy were significantly different between Fraser and Columbia River sturgeon populations but not between restriction site haplotypes. Heteroplasmic fish have, on average, higher copy number than homoplasmic fish. Forty-five of 101 homoplasmic individuals carry only a single copy of the repeat, while none of the 73 heteroplasmic fish has the single repeat as the predominant variant. On the basis of differences in frequency distributions of copy number within and between fish, we suggest that (1) heteroplasmy is maintained by high recurrent mutation of multiple copy genomes, favoring increased copy number and (2) the mutation pressure toward higher copy number heteroplasmy is partially offset by selection to reduced genome size and segregation to the homoplasmic condition.

Animals

Talk with your mother or your sibling? Developmental changes in early family conversations about feelings.

Developmental changes in the pattern of family conversations and talk about feelings were examined in a longitudinal study of 50 families observed at home when the second-born children were 33 and 47 months old. Significant increases were noted in the total amount of talk and the frequency of talk about feelings between sibling pairs as well as decreases in the amount of mother-child conversation and references to feelings. Differences in whose feelings were discussed and in the context of references to feelings were found for mother-child and sibling-child dyads. Developmental changes in the children's use of feeling state language co-occurred with the increase in interaction between children and their siblings. The findings contrast the "complementary" nature of mother-child interaction and the "reciprocal" nature of child-sibling interaction and support the argument that the quality of particular relationships influences the use children make of their communicative competence.

Child Development

Method for analysis, and distribution profile, of covalently-linked ferritin-daunorubicin conjugate in the blood of trypanosome-infected mice.

Daunorubicin is a highly potent trypanocide in-vitro but is inactive in-vivo. When daunorubicin is conjugated to bovine serum albumin or horse spleen ferritin using Schiffs base linkages, the complex is trypanocidal in-vitro and in-vivo. We have developed novel analytical methods, using HPLC with fluorimetric detection, for the quantitation of daunorubicin and doxorubicin in biological samples, either as unconjugated drug, or when covalently linked to macromolecules or particles. Ferritin-daunorubicin conjugate (25 mg kg-1) was administered intraperitoneally to mice infected with monomorphic Trypanosoma brucei rhodesiense; peak plasma levels occurred after 1.5 h, and were 5 times higher than those resulting from administration of an equivalent amount of unconjugated daunorubicin. Plasma levels then declined rapidly (t1/2 for 1-6 h period was 0.58 and 0.86 h respectively for conjugated and unconjugated daunorubicin). However, higher plasma levels were seen 24 h after treatment, suggesting the distribution profile of daunorubicin when conjugated to ferritin is multiphasic with resultant high levels of daunorubicin obtained for a prolonged time period.

Animals

Passive exposure to cocaine in medical personnel and its effect on urine drug screening tests.

This report studies the importance of passive exposure of medical personnel to cocaine hydrochloride and its impact on urine screening testing. Eleven medical staff members were exposed to cocaine hydrochloride by means of aerosol and cutaneous application, similar to that which may occur in medical practice. Urine drug screening tests were negative for everyone tested. This finding is supported by known drug kinetics. It is unlikely that a single passive exposure of medical staff to cocaine hydrochloride will produce a positive urine screening test. In all cases of positive urine tests, contaminants should be tested for which may indicate a source of the drug. The routine use of gloves and masks--which is recommended to prevent HIV infection--should further decrease medical personnel's passive exposure to cocaine hydrochloride.

Administration, Cutaneous

Feeding wash water solids to sows during gestation and lactation: sow productivity, pig performance, and tissue compositions.

Diets containing 0, 10, or 20% dried wash water solids (WWS) from a milk processing plant were fed to 54 Yorkshire gilts (160 to 270 kg) for five parities. Feed intake, weight changes, and morbidity of sows were measured; number of pigs per litter, birth weight, and weight gain of pigs were also determined. Blood, tissue, and milk samples were taken from sows for hematological and mineral analyses, and tissue samples were taken from newborn pigs from each treatment per parity. Overall, initial sow weight, sow weight at weaning, and weight losses were not affected (P greater than .05) by treatment. At 107 d of gestation, overall weights decreased (P less than .05) linearly with level of WWS in the diet. The number of pigs per litter and weight of pigs were not affected (P greater than .10) by diet. Concentrations of NA (P less than .10) and Cd (P less than .05) were lower in kidney of sows fed 20% WWS, and concentrations of Zn were lower in bone and in kidney of sows fed the 20% WWS diet. The Sr and Ba concentrations increased (P less than .05, P less than .10) linearly in bone from sows with level of WWS in the diet. In pigs, concentrations of Mn in kidney and Zn in liver were lower for the 20% WWS treatment. In conclusion, feeding WWS to sows over five parities had minimal adverse effects on sow productivity and pig performance; the reduction in Zn concentrations in tissues of sows and pigs seemed to be related to the Ca content of WWS.

Animal Feed

Degradation of malathion in thermally generated aerosols.

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.

Aerosols

Office diagnosis of lower extremity venous insufficiency and treatment with the use of nonprescription support hose.

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.

Adult

Evidence for sulfite as an essential metabolite for human peripheral lymphocytes.

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.

Cell Division

Kinetics of the DNA binding of 2-substituted anthraquinones.

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.

Anthraquinones

Length heteroplasmy of sturgeon mitochondrial DNA: an illegitimate elongation model.

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.

Animals

Involvement of hydroxyl radical formation and DNA strand breakage in the cytotoxicity of anthraquinone antitumour agents.

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).

Anthraquinones

ULV droplet spectra: comparative analysis of six droplet collection methods.

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.

Aerosols

The interaction of adriamycin and adriamycin analogues with nucleic acids in the B and A conformations.

The reinforced intercalative binding to DNA typical of adriamycin and daunomycin can still occur if there is epimerisation at C4' or if the O-methyl group is lost or if the 9-substituents are deleted or if the 4'-hydroxyl group is lost. In the latter two cases however, there is a reduction in affinity for the DNA, supporting the suggested role of the 9-hydroxyl and 4'-hydroxyl groups in secondary stabilization of the complex. Epimerisation at C-1' or at C-3' alters but does not abolish the intercalative mode of binding to DNA whereas epimerisation at C-7 precludes intercalation of the chromophore into the helix of DNA. In contrast to the interaction with the B-form found in DNA, the parent drugs do not intercalate into nucleic acids possessing the A-conformation and none of the above-mentioned structural changes will allow intercalation into A-form nucleic acids.

DNA

Adjuvant effects of low doses of a nuclease-resistant derivative of polyinosinic acid . polycytidylic acid on antibody responses of monkeys to inactivated Venezuelan equine encephalomyelitis virus vaccine.

Polyriboinosinic.polyribocytidylic acid [poly(I).poly(C)] stabilized with poly-l-lysine and carboxymethylcellulose [poly(ICLC)] has been previously shown to be a compound with marked adjuvant activity when given in high doses with inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine. This study investigated the effects of much lower doses of poly(ICLC) on the magnitude and kinetics of the primary and secondary humoral antibody responses of rhesus monkeys to inactivated VEE virus vaccine. Monkeys given a single injection of vaccine developed very low neutralizing antibody titers, whereas those given adjuvant plus vaccine had 30- to 100-fold-higher titers which remained elevated for longer than 6 months. Low doses of poly(ICLC) given with VEE virus vaccine resulted in a profound but transient increase in priming of secondary antibody responses to the antigen. In contrast, the administration of poly-l-lysine and carboxymethylcellulose alone without the poly(I).poly(C) component of the complex had no adjuvant effect on antibody responses of monkeys to VEE virus vaccine. The temporal development of antibody by class (immunoglobulin M-immunoglobulin G) in monkeys given two injections of adjuvant-vaccine was not different from that with vaccine alone. Serial hematological and clinical chemistry determinations on monkeys given single or multiple doses of poly(ICLC) with vaccine were not different from values in monkeys given vaccine alone.

Adjuvants, Immunologic