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Biomedical subjects

D E Pearson

Publications and source records attributed to D E Pearson.

At least 19 recordsLinked to original sources

Subinhibitory concentrations of tetracycline alter fibrinogen binding by Bacteroides intermedius.

Previous studies from our laboratory have shown that a strain of Bacteroides intermedius, VPI 8944, an organism isolated originally from a patient with acute necrotizing ulcerative gingivitis, binds human fibrinogen rapidly, reversibly, specifically, saturably, and with high affinity (M.S. Lantz, L.M. Switalski, K.S. Kornman, and M. Höök, J. Bacteriol. 163:623-628, 1985). We examined the effect of growth in subinhibitory levels (sub-MICs) of tetracycline on fibrinogen binding by these bacteria and found concentration-dependent inhibition of fibrinogen binding by bacteria grown in the presence of tetracycline over the range of tetracycline concentrations from 1/64 to 1/8 the MIC. Analysis of the binding data suggests that bacteria grown in the presence of sub-MICs of tetracycline bind fewer fibrinogen molecules per cell than do bacteria grown in the absence of the drug. If fibrinogen-mediated adherence is important in the establishment B. intermedius in periodontal lesions and lesions of acute necrotizing ulcerative gingivitis, then tetracycline may be effective in disrupting establishment of these organisms at concentrations well below those required to achieve a bacteriostatic effect.

Bacteroides↗

Transmitting deaf sign language over the telecommunications network.

An experimental investigation is reported into the use of moving cartoon images for two-way communication by the deaf. The images are derived by special signal-processing operations on the output of a conventional television camera, according to a new theory of perceptually important human features. Calculations show that, using facsimile-type coding and digital modems, the images are capable of transmission over the Public Switched Telephone Network; in enhanced form (with more resolution and optional voice accompaniment) they could be carried on the emerging Integrated Services Digital Network or transmitted over teletext.

Communication Devices for People with Disabilities↗

Radial arm maze performance in rats following neonatal dopamine depletion.

Neonatal dopamine (DA) depletion produces learning impairments both during development and throughout adulthood in the rat. The present experiment further investigated the memory capabilities of the dopamine-depleted rat by assessing performance in the radial arm maze. Results showed that, following neonatal injection of 6-hydroxydopamine and desmethylimipramine, lesioned rats per-performed more accurately than controls. In this paradigm, DA-depleted rats tended to enter each arm to obtain a food pellet and not enter unbaited, incorrect arms. The difference in performance of control and treated rats could not be accounted for by differences in locomotor activity, body weights, or motivational factors. A computer analysis of the data revealed that DA-depleted animals adopted a strategy of choosing adjacent arms consecutively, which probably accounted for their superior performance. Results are discussed in terms using algorithms versus extra-maze cues to complete the maze following early brain injury.

Animals↗

The synthesis of deuterium-substituted, spin-labeled analogues of AMP and NAD+ and their use in ESR studies of lactate dehydrogenase.

Two spin-labeled analogues of AMP and NAD+ were synthesized, in which a perdeuterated nitroxide radical (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, TEMPAMINE) was attached to C-6 or C-8 position of the adenine ring. The ESR spectra of these derivatives exhibit a 4-fold increase in sensitivity and a concomitant decrease in line-width as compared to the corresponding protonated analogues. The improved resolution of composite spectra consisting of freely tumbling and immobilized components is demonstrated in ternary complexes of the spin-labeled NAD+ derivatives with lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) and oxalate.

Adenosine Monophosphate↗

Angiotensin I recovery from plasma incubated with organic reagents.

(1) In order to explore the possible mechanism that organic reagents used in the incubation step of the plasma renin activity (PRA) analysis act as a angiotensinase inhibitors we did angiotensin I (AI) recovery studies from plasma with such reagents. The organic acids and their mean difference in percent recovery of AI as compared to that for hydrochloric acid (HCI) are respectively as follows for one and a three hour incubation time: maleic (0.7%, 4.5%); and potassium hydrogen phthalate (KHphthalate) (7.2%, 9.6%). The tris(hydroxymethyl)aminomethane (Tris) organic acid salts and their mean difference in percent recovery of AI as compared to that for Tris-HCl are as follows for a one hour incubation: Tris-acetylsalicylate (3.6%), Tris-phenoxyacetate (3.6%), Tris-benzoate (2.6%), and Tris-salicylate (4.9%). (2) Of the reagents studied KHphthalate after a three hour incubation produced a statistically significant difference from the HCl reagent. The recovery data for all the organic reagents suggested that the primary mechanism of action was not that of an angiotensinase inhibitory one.

Angiotensin I↗

15N- and 2H-substituted maleimide spin labels: improved sensitivity and resolution for biological EPR studies.

The resolution and sensitivity of electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) for biological applications are greatly improved by deuteration and substitution of (15)N for (14)N in the spin-labeled probe N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide (MSL). The EPR and ST-EPR spectra of the deuterated analogue [(2)H]MSL and the (15)N-substituted and deuterated derivative [(15)N, (2)H]MSL were compared with those of the parent MSL. The [(15)N, (2)H]MSL showed the greatest gain in sensitivity and the most marked sharpening of spectral features. These improvements were due to (i) a reduction in the spectral linewidths resulting from the relatively weak hyperfine interactions of the unpaired electron with deuterium and (ii) spectral simplification due to a reduction in the number of nuclear manifolds from three to two in replacing (14)N with (15)N. In the freely tumbling state, the spectra of [(15)N, (2)H]MSL and [(2)H]MSL showed 10-fold and 5-fold increases, respectively, in signal heights compared to MSL. To study the slow tumbling frequencies characteristic of biological molecules, the MSL and its derivatives were covalently bound to the enzyme glyceraldehyde-3-phosphate dehydrogenase [GAPDHaase; D-glyceraldehyde-3-phosphate:NAD(+) oxidoreductase (phosphorylating), EC 1.2.1.12] on cysteine-149 of the catalytic site. The EPR and ST-EPR spectra of [(15)N, (2)H]MSL and [(2)H]MSL adducts showed 3- and 1.5-fold gains in sensitivity, respectively. More important, there were striking increases in resolution, particularly for [(15)N, (2)H]MSL over MSL. These improvements were observed throughout the correlation time range from 0.1 musec to 1 msec. The EPR spectrum of [(15)N, (2)H]MSL-GAPDHase at X-band showed no overlap of the two nuclear manifolds; therefore, all the elements of the A and g tensors could be measured directly from the spectrum. The increase in sensitivity and resolution of the (15)N- and deuterium-substituted spin labels permitted quantitative simulation of the EPR and ST-EPR spectra of a labeled protein. Computation time was reduced 90% by (15)N substitution. Use of (15)N-substituted and deuterated spin probes substantially improved characterization of the motional properties of a protein.

Computers↗

Structural and motional changes in glyceraldehyde-3-phosphate dehydrogenase upon binding to the band-3 protein of the erythrocyte membrane examined with [15N,2H]maleimide spin label and electron paramagnetic resonance.

Binding of the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase [GAPDHase; D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating EC 1.2.1.12], to the cytoplasmic segment of band-3 protein in the erythrocyte (RBC) membrane has been examined by electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) spectroscopies. GAPDHase, which was isolated from rabbit muscle and labeled with the resolution-enhancing deuterated N-(15N-1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide spin label ([15N,2H]MSL), showed the same binding specificity for the transmembrane band-3 protein of human erythrocyte membranes as reported for unlabeled GAPDHase from human RBC. Experimental EPR lineshapes from soluble and membrane-bound enzymes were analyzed by direct stimulation of spectra and indicated a structural alteration of the bound GAPDHase in the vicinity of the spin label, which was attached covalently to the active-site cysteine-149 residue. A rigorous theoretical analysis of the ST-EPR spectra of soluble and membrane-bound enzyme is presented and utilized in conjunction with model system analysis to demonstrate that the motion of membrane-bound GAPDHase could be characterized by an effective isotropic rotational correlation time of 20 microseconds. This indicated that the GAPDHase--band-4 complex exhibits motional freedom relative to the membrane-spanning segment of the band-3 protein or the RBC. The double substituted spin label [15N,2H]MSL affords gains in sensitivity and resolution that permit studies of membrane-bound enzymes at physiological levels and quantitative simulations of the EPR and ST-EPR lineshapes with reasonable computation times.

Anion Exchange Protein 1, Erythrocyte↗

Environmental influences on body weight and behavior in developing rats after neonatal 6-hydroxydopamine.

There is less hyperactive motor activity and better avoidance performance in rat pups treated with 6-hydroxydopamine as neonates and reared with vehicle-treated littermates than in pups reared in litters composed solely of other 6-hydroxydopamine-treated animals. Thus, in this experimental model of hyperactivity, an environmental manipulation provides an alternative to pharmacologic agents in reducing activity and improving learning performance.

Animals↗

Effect of some organic acid salts of tris(hydroxymethyl)aminomethane in the incubation step on plasma renin activity.

The tris(hydroxymethyl)aminomethane salts of the organic acids acetylsalicylic, phenoxyacetic, salicylic, benzoic, acetic, and maleic were used to buffer the pH of plasma between 7.4 and 7.7 in a 1 h incubation step of the procedure for the determination of plasma renin activity. When compared to the plasma renin activity determined with tris(hydroxymethyl)aminomethane hydrochloride or with no buffer, it was found that all of the tris(hydroxymethyl)aminomethane salts of the organic acids studied produced a statistically significant increase in plasma renin activity except the salt of acetic acid when compared to tris(hydroxymethyl)aminomethane hydrochloride. In comparison to tris(hydroxymethyl)aminomethane hydrochloride and unbuffered plasma the organic acid salts and their mean percent difference in plasma renin activity are as follows: tris(hydroxymethyl)aminomethane phenoxyacetate (101%, 105%); tris(hydroxymethyl)aminomethane acetylsalicylate (79%, 115%); tris(hydroxymethyl)aminomethane benzoate (70%, 107%); tris(hydroxymethyl)aminomethane salicylate (64%, 70%); tris(hydroxymethyl)aminomethane maleate (32%, 60%); and tris(hydroxymethyl)aminomethane acetate (--1.6%, 43%).

Acetates↗

Subcutaneously implanted alginate as a continuous-release source of fluoride.

The fluoride concentrations of seven brands of alginate ranged from 8600 to 30,500 ppm. In acute and chronic in vivo studies, fluoride was continuously released from subcutaneously implanted alginate cylinders for up to three weeks. This technique is a simple and economical method for elevating soft and hard tissue fluoride levels.

Alginates↗