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Biomedical subjects

R J Brown

Publications and source records attributed to R J Brown.

At least 55 records · Page 3Linked to original sources
PubMed1996

A robust method for calculating geometric mean times from multiexponential relaxation data, using only a few data points and only a few elementary operations.

A method is presented to compute values of geometric mean time Tg that uses only a few data points equispaced in the logarithm of time (or equispaced in time and weighted by 1/t) and a few elementary operations for the computation. The method has been tested on a large number of synthetic relaxation data and on actual NMR relaxation measurements in porous samples, using as few as four points (including the two points needed to normalize the relaxation for decay from 1.0 to 0) on each relaxation curve. This computation of the geometric-mean rate very adequately matches the synthetic data and the results of multiexponential inversion of many (or only a few) data points from NMR measurements. When many computations are needed in short times, as for voxel-by-voxel computations in magnetic resonance imaging (MRI) or for depth-by-depth computation in nuclear magnetism logging (NML) of oilwells, a very quickly computed estimate of Tg should be useful.

Algorithms↗
PubMed1996

What happens to binocularity in primate strabismus?

Normal humans for whom the positions and movements of the two eyes are constrained to be yoked together are able to extract rich binocular sensory information from the environment. Humans with strabismus are deficient in extracting some of this information. Studies of strabismus in non-human primates can augment what has been learned from humans about relationships between strabismus and sensory binocular function. For example, speculation about the role of binocular vision in primate evolution can help us understand why it is that the advantages of sensory binocular function outweigh the disadvantages of having the positions of the two eyes yoked together. Physiological optics assessments of fixation patterns and accommodative responses in monkeys provide information about how the brain accomplishes and coordinates motor and sensory binocular functions, and sets the stage for determining underlying neural mechanisms responsible for this coordination. Finally, a developmental perspective, concerned with events that occur during an early sensitive period in the life span of an infant primate, can help us understand how nature and nurture interact to set up this complex neural system in normal individuals, and how this process is disrupted in conditions such as strabismus.

Accommodation, Ocular↗
PubMed1996

Expression of de novo designed alpha-helical bundles.

The successful design of proteins requires careful consideration of the multiplicity of forces that stabilize their three-dimensional structures including hydrophobic interactions, hydrogen-bonding, electrostatics and weakly polar interactions. Early attempts to design proteins relied too heavily on hydrophobic interactions to provide stability, resulting in structures with dynamic properties. Addition of more specific interactions to these initial designs gives rise to proteins with more native-like properties. This manuscript describes the design of native-like three- and four-helix bundles, and their cloning and expression of these proteins.

Amino Acid Sequence↗
PubMed1995

Diurnal variation in tardive dyskinesia.

Tardive dyskinesia (TD) is a common movement disorder that is associated with chronic neuroleptic exposure. To better characterize the clinical aspects of TD, we investigated the diurnal pattern of involuntary movements by blindly rating videotaped examinations of patients from the morning shortly after awakening and later in the same afternoon. In 10 patients, average TD ratings were worse in the afternoon than in the morning, especially in the case of limb-trunk dyskinesias. These findings suggest that it is important to rate patients at the same time of day in TD studies. Moreover, patients should be evaluated at least several hours after awakening.

Adult↗
PubMed1995

Structure-activity relationships of new heterocycle-containing bisphosphonates as inhibitors of bone resorption and as inhibitors of growth of Dictyostelium discoideum amoebae.

The mechanisms by which bisphosphonate drugs inhibit osteoclast-mediated bone resorption are unclear. Effects of bisphosphonates on cellular enzymes, metabolic pathways, and osteoclast morphology have previously been described and could culminate in a generalized cytotoxic effect or a decreased capacity of osteoclasts to resorb bone. Recent studies of the structure-activity relationship for the bisphosphonate side chain indicate, however, that at least the newer generations of nitrogen-containing bisphosphonates probably act by binding to a specific target at a site that is complementary in structure to the bisphosphonate side chain. We have previously proposed that such a target for bisphosphonates is also present in amoebae of the cellular slime mold Dictyostelium discoideum, because growth of this microorganism is inhibited by a wide range of bisphosphonates in a manner that closely reflects the antiresorptive potencies of the bisphosphonates in vivo. We have added support for this view by examining the potency towards Dictyostelium of bisphosphonates in which slight changes in the structure of the side chain or conformational restrictions to the side chain have marked effects on antiresorptive potency. The changes in the side chain that affected the in vivo antiresorptive potency of the bisphosphonates consistently affected in a similar manner the potency of the bisphosphonates as inhibitors of the growth of Dictyostelium amoebae. These observations confirm that bisphosphonate drugs have a molecular target that is common to both Dictyostelium amoebae and osteoclasts.

Animals↗
PubMed1994

Chromatographic purification of immunoglobulin G from bovine milk whey.

We used thiophilic chromatography on T-gel, a resin of the structure agarose-O-CH2CH2SO2CH2 CH2SCH2CH2OH, to purify immunoglobulin G from "sweet" cheese whey. The purity of immunoglobulin G, as indicated by radial immunodiffusion, was 74% after a single chromatography on T-gel. Preparation of samples for adsorption onto thiophilic gels requires only the addition of salt (sodium/potassium sulfate) to the samples. Thus, this method may be suitable for large-scale whey IgG isolation.

Adsorption↗
PubMed1994

Taking, processing, and interpreting spin-echo data in porous media and tissues.

Measurements of T2 by the Carr-Purcell-Meiboom-Gill (CPMG) method without externally applied field gradients for fluids in porous media are affected by locally inhomogeneous fields from susceptibility differences. Diffusion leads to a substantial range of correlation times tau c for change of local field. Wide distributions often lead to the dependence of 1/T2 on tau (half pulse spacing) of the form 1/T2 approximately R1 + R2 tan-1 (R3 tau), while narrow distributions require the extra term (R2R3/R4)exp(-R4 tau). To determine tau-dependence, the effects of different ranges of data coverage can be minimized by using only data within the time range common to all measurements and by adding a virtual n = 0 point to each data set, where n is echo number and this point is determined by extrapolating echo amplitudes for the small tau values.

Animals↗
PubMed1994

Water-air saturation changes in restricted geometries studied by proton relaxation.

The results are reported of a systemic T1 and T2 investigation of natural (sandstones) and artificial (microporous porcelain) porous media, after each step of a water desaturation process by centrifugation in air. The analysis of the relaxation curves permitted distinguishing well the different behaviour of the natural samples as compared to the artificial ones, which can be explained by the different pore structures. In both kinds of samples the evolution of the relaxation time distributions yielded a clear picture of the changes of the water distribution in the pore framework following the displacement process, until irreducible water saturation was attained. The results are compatible with the assumption of a fixed amount of surface area contributing to the relaxation of decreasing amounts of fluid as SW is reduced.

Air↗
PubMed1994

A comparison among different inversion methods for multi-exponential NMR relaxation data.

The inversion of data to be represented by sums or continuous distributions of exponentials is done by different algorithms and compared. The published CONTIN program presents a chosen solution with an appropriate amount of detail. An in-house program EXDISTR allows operative choice of various constraints in order to show the consequences in quality of fit of allowing various features such as extra maxima or minima. Another in-house program based on the system theory approach, IDENT, treats the data as the output samples of a linear, time-invariant, autonomous dynamic system.

Algorithms↗
PubMed1993

Some contrast agents in oil well logging and in medical MRI.

Magnetite particles and paramagnetic ion chelates are used as contrast agents in both nuclear magnetism logging of oil wells and in medical MRI. An analytic expression for reduction of T2 for free precession signal decay (or gradient echoes) by magnetite particles does not depend on diffusion and agrees with published Monte Carlo computations.

Contrast Media↗
PubMed1993

An audit of the activities of the paediatric oncology unit in Edinburgh, 1982-1991.

The activities of the paediatric oncology unit at the Royal Hospital for Sick Children, Edinburgh during 1982-1991 were audited. There were 254 new patients of whom 240 had a malignancy, seven had Langerhans cell histiocytosis and seven had non malignant tumours. Of the 254,131 (52%), 78 (31%), 14 (65), were normally resident within the Lothian, Fife and Borders regions respectively. Therefore, although the unit is a part of the Lothian Health Board, it is in practice, the referral centre for S.E. Scotland. A majority (92%) of patients were treated according to national or international protocols during the last five years and of the 240 children diagnosed to have cancer, 158 (66%) are at present in clinical remission. These figures compare favourably with national averages for protocol compliance and survival. During these ten years, an additional 69 children with cancer from S.E. Scotland were treated at other centres. Therefore, while the unit justifies its existence it has yet to realise its full potential.

Adolescent↗
PubMed1993

Inhibition of plasmin by beta-lactoglobulin using casein and a synthetic substrate.

Bovine plasmin (EC 3.4.21.7) activity was measured on H-D-valyl-L-leucyl-L-lysyl-4-nitroanilide and acid casein in the presence of native and heat-denatured beta-lactoglobulin (denatured at 100 degrees C for 15 min before being mixed with plasmin solutions). Native or denatured beta-lactoglobulin was then heated with plasmin at 60 degrees C for 15 min. Enzyme activity again was estimated after this mild heat treatment. Native and denatured beta-lactoglobulin inhibited the action of plasmin on H-D-valyl-L-leucyl-L-lysyl-4-nitroanilide and casein. The mild heat treatment (60 degrees C for 15 min) caused stronger inhibition of the activity of plasmin against casein and the synthetic substrate. For H-D-valyl-L-leucyl-L-lysyl-4-nitroanilide, inhibition was competitive in unheated mixtures, but heating beta-lactoglobulin with plasmin changed inhibition type to mixed. This change suggests a heat-dependent interaction between plasmin and beta-lactoglobulin. Native beta-lactoglobulin was more inhibitory of plasmin's action against casein than was denatured beta-lactoglobulin. The converse was observed when plasmin activity was measured with the synthetic substrate.

Animals↗
PubMed1993

Preattentive and cognitive effects on perceptual completion at the blind spot.

Our findings indicate that preattentive processes, such as the filling in of homogeneously colored areas, discrete dots, or bars across the blind spot, take into account both the color and the form that stimulate the retina around the optic disk. Perceptual completion of the "junction" of two opposite colors facing each other on opposite sides of the blind spot was resolved by simultaneous segregation of the two colors at the location of a filled-in perpendicular line that suggested a boundary separating the two colors. Orientation preference and relative salience of one color versus the other determined which color was perceptually completed in a forced-choice situation that involved perceptual completion at the intersection of a cross formed by bars of opposite colors. A 1-min exposure to these stimuli presented an ambiguous situation for perceptual completion of either color within the blind spot, and resulted in a perceptual "flip-flop" from one color to the other, much like the phenomenon that occurs in figure reversal. Instructions to speed up this reversal process led to a fivefold reduction in latency to first reversal.

Adult↗
PubMed1992

Proteolytic activity of proteinases on macropeptide isolated from kappa-casein.

Proteolytic activities of chymosin, bovine pepsin, Mucor miehei rennet, Cryphonectria parasitica (formerly Endothia parasitica) rennet, trypsin, and chymotrypsin on kappa-casein macropeptide were measured. Macropeptide solutions (10 mg/ml of .05 M, pH 6.6 phosphate buffer) were incubated with the enzymes at 37 degrees C for various times, and their reactions were stopped by adding .025 ml of pepstatin (1 mg/ml of methanol). Peptides released from kappa-casein macropeptide were then fractionated using reverse-phase HPLC. At the pH of milk (pH 6.6), kappa-casein macropeptide was resistant to enzymic action by chymosin, bovine pepsin, and M. miehei and C. parasitica rennets. Bovine pepsin hydrolyzed kappa-casein macropeptide at pH 3. kappa-Casein macropeptide was readily hydrolyzed at pH 6.6 by trypsin and chymotrypsin. Possible physiological functions of the kappa-casein macropeptide are discussed in light of these findings.

Carbohydrate Sequence↗