Biomedical subjects

R C Boston

Publications and source records attributed to R C Boston.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of daily floor treatment with sodium bisulfate on the fly population of horse stalls.

OBJECTIVE: To determine application rate and effectiveness of sodium bisulfate to decrease the fly population in a horse barn environment. SAMPLE POPULATION: 12 privately owned farms in southeastern Pennsylvania. PROCEDURE: Application rates of sodium bisulfate were approximately 2.3 kg/stall, 1.1 kg/stall, and 0.5 kg/stall. Two or 3 stalls were treated, and 1 or 2 stalls were not treated (control stalls) at each farm. Farm personnel applied sodium bisulfate in treated stalls daily for 7 days. Fly tapes were hung from the same site in treated and control stalls. After 24 hours, the fly tape was removed, flies adhering to the sticky surface were counted and recorded, and a new fly tape was hung. This procedure was repeated daily during each of the testing periods. RESULTS: Following the application of 2.3 kg of sodium bisulfate/stall, the numbers of flies collected on the fly tape were significantly decreased in treated stalls, compared with control stalls during the same time periods on 9 of the 12 farms evaluated. Following the application of 1.1 kg of sodium bisulfate/stall, fly numbers were significantly decreased in treated stalls on 6 of the 9 farms evaluated. Following the application of 0.5 kg of sodium bisulfate/stall, fly numbers were significantly decreased in the treated stalls on 3 of the 4 farms evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that sodium bisulfate would be effective for fly control in horse barns.

Animals↗

PubMed1998

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction.

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.

Animals↗

PubMed1998

Distributing working versions of published mathematical models for biological systems via the Internet.

Mathematical models are useful tools for investigating complex systems. By representing physiological systems as models, theories can be tested quantitatively against data from the system. Models can be used to explore new theories prior to experimentation and to design studies to optimize experimental resources. They can also be used as teaching tools to illustrate physiochemical principles. In spite of their usefulness and the time invested in developing models, published models are often underused due to the difficulty in obtaining working versions of the model. To address this problem we have designed a library for mathematical models of biological systems on the Internet. The library contains published models of biological systems in formats compatible with several modeling packages, from the fields of physiology, metabolism, endocrinology, biochemistry, and chemistry. The models can be viewed graphically, model solutions can be viewed as plots against data, and models can be downloaded to be run with software on the user's own system. The address of the library is: http://biomodel.georgetown.edu/model/ Investigators are invited to submit working versions of published models to the library. Models can be submitted electronically at the time a manuscript is accepted for publication. As journals go online, articles containing models can be linked to working versions of the models in the library. By increasing access to working versions of models, more of the investment in kinetic studies and model development can be realized.

Computer Simulation↗

PubMed1997

The effect of norepinephrine on insulin secretion and glucose effectiveness in non-insulin-dependent diabetes.

It has previously been shown that in normal subjects, physiological elevation of norepinephrine (NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The aim of this study was to determine the effect of short-term physiological elevation of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. The IVGTTs were performed in random order after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate insulin secretion rate using the ISEC program. NE infusion produced approximately a threefold increase in plasma NE, associated with (1) a significant reduction in glucose disposal ([KG] SAL v NE, 0.73 +/- 0.06 v 0.61 +/- 0.06 x 10(-2).min-1, P < .05), (2) no reduction in Si (2.33 +/- 0.8 v 2.62 +/- 0.9 x 10(-4).min-1/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 +/- 0.19 v 1.01 +/- 0.16 x 10(-3) pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 +/- 0.08 v 1.63 +/- 0.2 x 10(-2).min-1, P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin ([GEZI] 0.55 +/- 0.13 v 1.30 +/- 0.33 x 10(-2).min-1, P < .05). These results show that in contrast to normal subjects, physiological elevation of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose disposal related to inhibition of insulin secretion that is only partially compensated for by increased Sg.

Adult↗

PubMed1997

A compartmental model depicting short-term kinetic changes in selenium metabolism in ewes fed hay containing normal or inadequate levels of selenium.

Changes in Se metabolism were studied in ewes fed hay containing normal or inadequate levels of Se. After intravenous injection of 75Se-sodium selenite, blood, feces and urine were collected at different times, and the concentrations of labeled and unlabeled Se were determined. Ewes were killed 1, 5, 9 or 14 d after tracer injection, and tissues were obtained for determination of radioactivity and Se concentration. The data were fitted to a compartmental model using the SAAM/CONSAM computer program, and kinetic parameters and steady-state transport rates were estimated. Daily Se intake (Vi) and fecal excretion (VF) were significantly (P < 0.001) higher in the ewes fed normal hay (6.06 +/- 1.09 and 3.36 +/- 0.88 mumol/d, respectively) than in those fed Se-deficient hay (0.64 +/- 0.18 and 0.26 +/- 0.15 mumol/d). The net absorption (Va) of Se was significantly higher in ewes fed normal hay [3.19 +/- 0.82 mumol/d by the balance method, Va = Vi-(VF -Vf) (Vf = endogenous fecal Se) and 1.05 +/- 0.38 mumol/d by using the model (plasma entry rate, U(1))] than in those fed hay deficient in Se [0.57 +/- 0.33 mumol/d (balance) and 0.28 +/- 0.08 mumol/d (model)]. The efficiency of absorption [alpha = U(1) divided by Vi] was significantly higher (0.46 +/- 0.19) in ewes fed Se-deficient hay than in those fed normal hay (0.18 +/- 0.09). Simultaneous fitting of the tracer data of both the groups showed that changes in hepatic extraction and urinary and fecal excretion were sufficient and necessary to account for the kinetic differences observed between treatments.

Animals↗

PubMed1996

A compartmental model predicts that dietary potassium affects lithium dynamics in rats.

Lithium is the treatment of choice for manic depression, but therapy often results in nephrogenic diabetes insipidus and lithium intoxication. To investigate the effects of dietary potassium on potential side effects of lithium therapy, a mathematical model was built using the modeling program SAAM (Simulation, Analysis, And Modeling). Experimental data modeled were from adult male Sprague-Dawley rats fed diets with or without lithium and one of three levels of potassium for 17 d. A five-compartment model of lithium dynamics was built that was consistent with data from rats fed a lithium-containing diet adequate in potassium. This model was then compared with data from rats fed the other two lithium-containing diets. The model predicts that both the fractional transfer coefficient and rate of transport of lithium to the serum compartment from the kidney compartment are lower in rats fed the potassium-adequate diet than in those fed the potassium-deficient diet, and even lower in those fed the potassium-supplemented diet. In addition, fractional transfer coefficients into the serum compartment from the sampled and simulated tissue compartments changed differently with time depending on the amount of dietary potassium. The model also predicts that there would be less accumulation of lithium in the kidney, sampled tissue and simulated tissue compartments with supplemental dietary potassium. The model suggests that potassium supplementation, after a 7-d delay, protects against nephrogenic diabetes insipidus and the potentially toxic accumulation of lithium by decreasing the reabsorption of lithium from the kidneys and increasing lithium efflux from the tissues.

Absorption↗

PubMed1994

A modelling procedure for the analysis of dynamic drug--DNA interactions probed during active transcription of the DNA.

A multicompartment simulation analysis (CONSAM) has been used to describe the in vitro inhibition of transcription of DNA by echinomycin. The model assumes that at all drug blockage sites the fractional amount of blocked RNA polymerase is defined by the relative drug occupancy at that site (and is released at a rate defined by the drug dissociation rate), with all remaining enzyme being rapidly transferred past that site. The solution to the 48 parameters (three per drug site, 16 sites), which fully described the echinomycin-DNA transcription data set, can readily be accomplished without manual intervention within an hour on a MS-DOS, 486D-based microcomputer, compared to several months for a similar solution by Monte-Carlo simulation (requiring repeated intervention). The adequacy of the parameters to describe the model was confirmed by four independent criteria. The approach is applicable to the analysis of any enzyme system where an inhibitor of any type (interacting in either a reversible or irreversible manner) prevents the processive movement of enzyme along the template.

Base Sequence↗

PubMed1993

Clearance from plasma of triacylglycerol and cholesteryl ester after intravenous injection of chylomicron-like lipid emulsions in rats and man.

Chylomicrons transport fat and cholesterol via lymphatic vessels from the intestine into the bloodstream. The understanding of the metabolism of chylomicrons in man has been slowed by the difficulty of obtaining lymph chylomicrons for experimental studies. Acceptable methods for the study of chylomicron clearance in man are required, because the metabolism of chylomicrons may be abnormal in diseases such as diabetes mellitus. Metabolism of chylomicrons may also play a role in the development of atherosclerosis. In the present work, lipid emulsions were used as a physical model of chylomicrons. Triacylglycerol-rich lipid emulsions labelled with tracer amounts of radioactive triolein and cholesteryl oleate were prepared by sonication and purified by density gradient ultracentrifugation, then injected into unanaesthetized rats and normal human subjects. Plasma radioactivities were measured for 30 min in rats and 90 min in human subjects. Rat lymph chylomicrons were also injected into rats for comparison with the clearance of the lipid emulsions. The plasma clearance data for triacylglycerols and cholesteryl esters were fitted with a kinetic model using the SAAM/CONSAM programs. Multiple studies analysis of the individual studies in each group was used to obtain estimates of the parameter average values and variabilities. The plasma residence times of the lipid labels were obtained from the fitted clearance data. Our results suggest that information about chylomicron metabolism in man can be obtained by analysis of the plasma clearance data following the injection of suitably labelled chylomicron-like lipid emulsions. Our data provide a baseline for comparisons with individuals having abnormalities of lipid metabolism or risk factors for arteriosclerosis.

Animals↗

PubMed1992

Application of models to determination of nutrient requirements: experimental techniques employing tracers.

This paper concerns some issues involved in the design of tracer experiments for the development of whole-body compartmental models of nutrient metabolism. It focuses on tracer administration protocol, use of multiple tracers, sampling strategy, measurement types and experiment duration in a pragmatic approach to obtaining data suitable for analysis and interpretation with use of models.

Animals↗

PubMed1991

A modified minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in insulin-dependent diabetes.

Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman et al can be applied to a frequently sampled intravenous glucose tolerance test (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (KG) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate SI and SG. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L; "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/- 0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4); SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X 10(2); P less than .05). This reduction in SG was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X 10(2)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

A new approach to the quantitative estimation of nitrogen metabolic pathways in the rumen.

Rumen nitrogen metabolism values were estimated by the use of a single injection of 15(NH4)2SO4 into the rumen of sheep and consecutive 15N enrichment measurements in the rumen ammonia pool, rumen non-NH3-N (NAN) pool, rumen purine pool and blood urea-N (BUN) pool for a period of 24 h. Synthesis and degradation of N compounds in the rumen and passage of N to and from the rumen were evaluated on a chemical rather than a microbial basis; microbial fractions were not separated. This model was examined in two experiments. In Expt 1 a ram (55 kg) was given a semi-synthetic diet (1067 g dry matter (DM), 22.8 g N) in which soya-bean meal provided over 90% of the N. In Expt 2, two rams (45 kg) were given in three consecutive periods a semi-synthetic basal diet containing: (1) roasted soya-bean meal (SBM, 725 g DM, 14.8 g N/d); or (2) fishmeal (FM, 728 g DM, 15.5 g N/d); or (3) raw soya-bean meal (RSBM, 724 g DM, 13.8 g N/d). In all these rations, the main protein source provided over 90% of the N. In Expt 1, 68.3% of N intake was degraded directly to NH3 in the rumen, 21.2% escaped rumen degradation and 10.5% was incorporated into stable N compounds in the rumen. Net NH3 transfer to the blood was 30.4%, NH3 flow from the rumen was 6.6% and rumen NAN output was 63% of N intake. In Expt 2, rumen NAN output was larger (7.67, 14.36 and 8.89 g N/d for diets containing SBM, FM and RSBM respectively; P less than 0.05) and net NH3 loss to the blood was smaller (6.1, 0.39 and 4.17 g N/d for diets SBM, FM and RSBM respectively; P less than 0.05) for diet FM as compared with the soya-bean diets. The percentage of rumen NAN that was synthesized from NH3 was larger for diet RSBM (36.4, 40.3 and 49.1 for diets SBM, FM and RSBM respectively; P less than 0.05) than for the other two rations. NH3 pool sizes (g N) were 0.463, 0.385 and 0.301 for diets SBM, FM and RSBM respectively (P less than 0.05), while their hourly turnover rates were 15.8, 26.1 and 5.12 for diets SBM, FM and RSBM respectively (P less than 0.01), indicating no correlation between pool size and its turnover rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Ammonia↗

PubMed1990

Fluorinated anthracyclines: interactions with DNA.

Four fluorine containing derivatives of anthracyclines (daunomycin and adriamycin) were synthesised, and comprised C-13, 1,1,1-trifluoroethyl-hydrazones of each anthracycline, and C-14 4-F and 4-CF3-benzoate esters of adriamycin. All four derivatives intercalated into DNA in a manner similar to their parent anthracycline. The ester derivatives exhibited 3-4-fold higher binding affinity to DNA, and slower DNA dissociation kinetics than adriamycin. This stabilisation derives from additional contacts of the C-14 side chain to the DNA minor groove. The hydrazone derivatives showed lower binding affinity to DNA, and dissociated from DNA 3-4 times faster than the parent compound. The 19F resonance of the bound drug was broadened to 120 Hz and shifted 60 Hz downfield (0.32 ppm) relative to the sharp (7.5 Hz) peak of the free drug. These values imply a rapid exchange between the free and DNA bound forms (DNA lifetime greater than 5 ms), with the fluorine group residing in a hydrophobic region in close contact with the DNA minor groove. The 4-8 fold lesser specific potency of the ester derivatives supports the concept that DNA binding is an important factor, but not sole determinant of biological activity of these analogues.

Animals↗

PubMed1990

Application of the SAAM modeling program to minimal model analysis of intravenous glucose tolerance test data.

The minimal model approach to analysis of intravenous glucose tolerance tests (IVGTT) yields estimates of parameters representing insulin sensitivity, glucose-mediated glucose disposal and pancreatic responsiveness. The precision of these estimates can deteriorate if the glucose and insulin data lack well-defined structure or freedom from data noise (random error). The precision of parameter estimates can be enhanced if data sets from two or more IVGTTs, obtained under different experimental conditions in the same subject, are analysed together in one data file. Following initial fitting using CONSAM, the conversational version of the modeling program SAAM, those parameters whose estimates remain at the same value under the different experimental conditions are constrained. This effectively reduces the number of adjustable parameters, and their estimates can then be fine-tuned with enhanced precision using the batch version of SAAM.

Animals↗

PubMed1989

A resource facility for kinetic analysis: modeling using the SAAM computer programs.

Kinetic analysis and integrated system modeling have contributed significantly to understanding the physiology and pathophysiology of metabolic systems in humans and animals. Many experimental biologists are aware of the usefulness of these techniques and recognize that kinetic modeling requires special expertise. The Resource Facility for Kinetic Analysis (RFKA) provides this expertise through: (1) development and application of modeling technology for biomedical problems, and (2) development of computer-based kinetic modeling methodologies concentrating on the computer program Simulation, Analysis, and Modeling (SAAM) and its conversational version, CONversational SAAM (CONSAM). The RFKA offers consultation to the biomedical community in the use of modeling to analyze kinetic data and trains individuals in using this technology for biomedical research. Early versions of SAAM were widely applied in solving dosimetry problems; many users, however, are not familiar with recent improvements to the software. The purpose of this paper is to acquaint biomedical researchers in the dosimetry field with RFKA, which, together with the joint National Cancer Institute-National Heart, Lung and Blood Institute project, is overseeing SAAM development and applications. In addition, RFKA provides many service activities to the SAAM user community that are relevant to solving dosimetry problems.

Animals↗

PubMed1989

Alternative method for minimal model analysis of intravenous glucose tolerance data.

The minimal models of glucose-insulin kinetics were used to analyze sets of data obtained from human subjects and dogs during frequently sampled intravenous glucose tolerance tests (FSIGTs). Analysis of some data sets from both species resulted in poor identification of parameters. To improve the parameter resolution, the information base on which the parameters are estimated was enlarged. This was accomplished by incorporating into the analysis 1) glucose data obtained between 0 and 8 min of the FSIGT and some of the insulin data obtained prior to the insulin peak and 2) a second set of FSIGT data for each individual obtained during a physiological perturbation. As a result, data analysis was considerably enhanced, with parameter fractional standard deviation being routinely reduced to less than 0.5. Analysis of stimulated data with noise levels for glucose and insulin set between 0.05 and 0.15 confirmed the improvement in parameter estimates. This modified approach to analysis of FSIGTs therefore consistently leads to well-defined kinetic descriptions of experimental data in various situations and supports the usefulness of the minimal model in examining the complex interplay between the parameters that influence overall glucose tolerance.

Adult↗

PubMed1988

Hormonal effects of norepinephrine on acute glucose disposal in humans: a minimal model analysis.

It is not known whether circulating norepinephrine (NE) has a direct hormonal influence on glucose disposal. This study examines whether moderate elevation of NE alters the disposal of an acute intravenous (IV) glucose load, as analysed by the minimal model of Bergman. Eight healthy normal subjects were infused with either 25 ng/kg/min NE (plasma NE 1,284 +/- 259 pg/mL) or normal saline (plasma NE 314 +/- 86 pg/mL), 30 minutes prior to and during an IV glucose tolerance test (GTT). There was a small but significant rise (P less than .05) in basal blood glucose levels during the initial 30-minute NE infusion which was accompanied by a 40% increase (0.39 +/- .02 to 0.59 +/- .07 nmol/L, P less than .01) in nonesterified fatty acid levels (NEFA). Insulin, C-peptide, and glucagon levels did not change. NE impaired the rate of acute glucose disposal (Kg 1.74 +/- 0.24 v 2.10 +/- 0.23 (min-1, P less than .05). Minimal model analysis revealed a corresponding 35% decrease in insulin sensitivity (SI 4.85 +/- 1.51 v 7.28 +/- 1.16 min-1 microU-1 mL-1 x 10(4), P less than .05) but no significant differences between glucose-mediated glucose disposal or pancreatic B-cell responsiveness. The glucose disposition index (si* phi2), a direct measure of an individual's overall insulin- mediated glucose disposal, was reduced by 70% in the NE-infussed subjects (si* phi2 69 +/-22 v 223 +/- 76 mg-1 ml-1 min-3 x 10(2), p< .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Effects of epinephrine infusion on determinants of intravenous glucose tolerance in dogs.

Effects of four- to fivefold elevations of epinephrine (EPI) on glucose (Glc) metabolism were assessed in eight dogs before and after an intravenous Glc tolerance test, performed 30 min (short EPI) and 72 h (long EPI) after start of EPI infusion. Short EPI increased plasma nonesterified fatty acids (NEFA; 0.46 +/- 0.08 to 0.78 +/- 0.12 mmol/l, P less than 0.05), but Glc and insulin were unchanged. After long EPI, NEFA returned to control but Glc increased from 5.1 +/- 0.1 to 5.7 +/- 0.2 mmol/l (P less than 0.05). EPI reduced overall Glc tolerance (KG) from 3.5 +/- 0.7 to 2.5 +/- 0.2 (short EPI, P less than 0.05) and 2.3 +/- 0.3%/min (long EPI, P less than 0.02). Minimal model analysis showed that short EPI decreased insulin sensitivity (SI) from 7.9 +/- 1.1 to 4.2 +/- 1.2 min-1 per mU/l X 10(-4) (P less than 0.005) and increased pancreatic responsiveness (phi 1 from 3.7 +/- 0.3 to 7.4 +/- 2.9 mU/l.min-1 per mg/dl, P less than 0.025; phi 2 from 2.6 +/- 0.7 to 4.9 +/- 1.2 mU/l.min-2 per mg/dl). After long EPI SI, phi 1, and phi 2 returned to control. In contrast, Glc-mediated Glc disposal (SG) was decreased from 3.5 +/- 0.5 X 10(-2) to 2.8 +/- 0.6 X 10(-2) (short EPI) and 1.3 +/- 0.6 X 10(-2) min-1 (long EPI, P less than 0.02). We conclude that prolonged infusion of EPI leads to adaptation to its acute effects on NEFA, SI, phi 1, and phi 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Daunomycin-DNA dissociation kinetics.

The dissociation of daunomycin from DNA was examined using a sodium dodecyl sulfate-sequestered stopped flow procedure. Two dissociation processes were observed with calf thymus and bacterial DNA, with approximately 45% of the amplitude associated with the faster process. Both processes were largely independent of DNA sequence for bacterial DNA, comprising 30-70% (G + C) content. The rate of both processes increased by a similar amount with increasing ionic strength. The faster process decreased with decreasing drug loading, whereas the slower process was independent of drug loading. Only one dissociation event was observed for the dissociation of daunomycin from four different synthetic polydeoxynucleotides. All observations are consistent with a parallel model of sodium dodecyl sulfate-induced dissociation of daunomycin from DNA, where the two processes observed reflect two resolvable processes that may be comprised of a series of rate constants for the dissociation of drug from differing environments. The slower process observed with bacterial DNA (0.5-0.7 sec-1) is related to dissociation from preferential 5'-CA DNA-binding sites, whereas the faster process reflects dissociation of drug from lower affinity sites on heterogenous DNA (3.2-4.1 sec-1). Dissociation of daunomycin from four different synthetic polydeoxynucleotides (which did not contain the 5'-CA preferential daunomycin-binding site) exhibited dissociation rates characteristic of low affinity sites (3.3-4.8 sec-1).

Base Composition↗