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Biomedical subjects

J K Brown

Publications and source records attributed to J K Brown.

At least 55 records · Page 3Linked to original sources

Nasal rather than rectal benzodiazepines in the management of acute childhood seizures?

Benzodiazepines are routinely used by the rectal route for the treatment of acute epileptic seizures: if a benzodiazepine was absorbed from nasal administration this could provide a more acceptable alternative to rectal administration. Nineteen children (age range 7 months to 14 years) with intractable epilepsy were chosen. The EEG's showed unequivocal epileptic activity persisting during the recording. The midazolam was dripped slowly into the anterior nares. Fifteen had a positive response, a dramatic improvement in their EEG or cessation of fits. Drug induced beta activity occurred in 14 children. The mean time to appearance of beta activity was 111.5 secs (SD = 95.3 secs). The reduction in spike count pre and post midazolam was statistically significant (p < 0.01). The improvement in EEG background was also statistically significant. Midazolam is absorbed via the i.n. route. With the dosages used it suppressed epileptic activity and produced an improvement in EEG background. The children and parents found the method acceptable. This is the first study to use the i.n. route for anti-convulsant drugs.

Acute Disease↗

The maturation of motor dexterity: or why Johnny can't go any faster.

The speed of alternating movements at the ankle, metacarpophalangeal and wrist joints in 11 healthy children and 13 adults doubled between age 3 and 11 years, despite a 32-fold increase in limb-segment inertia produced by the doubling in limb length over the same period. The data for the children showed little or no practice effect. The speeds for the adults, though faster than those for the children, were more widely dispersed, indicating the possibility that training might increase the speed of the slowest adult. The findings are consistent with a previous report demonstrating a parallel increase in the speed of calf muscles over the first 10 years of life and it is inferred that the increase in dexterity at the wrist and metacarpophalangeal joints also depends on an increase in muscle speed with age. Muscle maturation may impose a rate-limiting envelope for all motor tasks which is particularly evident in rapidly alternating movements. These findings have implications for training in sport and music and for the understanding of motor delay, clumsiness and speech difficulties.

Adult↗

Characterization and correction of pulse pile-up in simultaneous emission-transmission computed tomography.

We have developed an emission-transmission CT (ETCT) system capable of both single-photon emission computed tomography (SPECT) imaging and x-ray transmission CT imaging using a common photon counting detector. In principle, SPECT and x-ray CT projection data can be acquired simultaneously with the ETCT system; however, doing so results in contamination of the SPECT projection data due to pulse pile-up caused by the relatively high x-ray fluence rate. In this study, we characterize the effects of pulse pile-up for simultaneous ETCT imaging through computer simulation and experimental studies. We demonstrate that pulse pile-up in the SPECT energy window can be well approximated by a simple quadratic relationship between the pile-up rate and the x-ray fluence rate for sufficiently small x-ray fluence rates. Using this quadratic relationship, we developed a simple pile-up correction scheme that subtracts the pile-up counts from the emission data and also truncates the exterior regions of the emission projection data. Analysis of difference images and profiles indicate that this method permits us to reconstruct SPECT images with no apparent noise or resolution degradation in comparison to those obtained via sequential emission and transmission scans.

Biophysical Phenomena↗

A bound on the energy resolution required for quantitative SPECT.

Scattered radiation is one of several physical perturbations that limit the accuracy of quantitative measurements in single-photon emission computed tomography (SPECT). Improvement in detector energy resolution leads to a reduction of scatter counts and a corresponding improvement in the quantitative accuracy of the SPECT measurement. In this study, simulated SPECT projections of a simple myocardial perfusion phantom were used to investigate the effect of detector energy resolution on the data. The phantom consists of a spherical shell of radionuclide within a 15 cm radius water-filled cylinder. Each projection contains on the order of 3 x 10(5) counts. The results demonstrate that a full-width, half-maximum energy resolution of 3-4 keV is sufficient to render the error due to scatter insignificant compared to the uncertainty due to photon statistics in this case. Further simulations verify that because smaller objects produce less scatter, they can be imaged accurately with degraded energy resolution. These results are useful when designing prototype systems that utilize solid-state detectors and low-noise electronics to achieve improved energy resolution.

Biometry↗

QTL analysis of flowering time in Arabidopsis thaliana.

Quantitative trait loci (QTL) analyses based on restriction fragment length polymorphism maps have been used to resolve the genetic control of flowering time in a cross between two Arabidopsis thaliana ecotypes H51 and Landsberg erecta, differing widely in flowering time. Five quantitative trait loci affecting flowering time were identified in this cross (RLN1-5), four of which are located in regions containing mutations or loci previously identified as conferring a late-flowering phenotype. One of these loci is coincident with the FRI locus identified as the major determinant for late flowering and vernalization responsiveness in the Arabidopsis ecotype Stockholm. RLN5, which maps to the lower half of chromosome five (between markers mi69 and m233), only affected flowering time significantly under short day conditions following a vernalization period. The late-flowering phenotype of H51 compared to Landsberg erecta was due to alleles conferring late flowering at only two of the five loci. At the three other loci, H51 possessed alleles conferring early flowering in comparison to those of Landsberg erecta. Combinations of alleles conferring early and late flowering from both parents accounted for the transgressive segregation of flowering time observed within the F2 population. Three QTL, RLN1, RLN2 and RLN3 displayed significant genotype-by-environment interactions for flowering time. A significant interaction between alleles at RLN3 and RLN4 was detected.

Alleles↗

Ten measurement commandments that often should be broken.

Many of the measurement aspects of nursing research have been governed by rules regarding the minimum values of certain summary indexes (such as Cronbach's coefficient alpha and Cohen's kappa), the required numbers of subjects per item for factor analyses, and the like. In this article a case is made for violating these rules whenever the circumstances warrant such violations.

Nursing Research↗

Characterization and distribution of esterase electromorphs in the whitefly, Bemisia tabaci (Genn.) (Homoptera: Aleyrodidae).

Esterase profiles were examined for over 40 populations of the whitefly, Bemisia tabaci, obtained from native and cultivated plant hosts worldwide. Twelve unique electromorphs were identified from distinct populations concentrated largely in Central America, Africa, and India. One electromorph, type B, has recently been proposed as a separated species, Bemisia argentifolii, and has recently spread throughout much of the world. When considered with evidence from mating studies and the ability to induce phytotoxic disorders (squash silverleaf disorder), our data suggest that the single taxon Bemisia tabaci may actually represent a species complex.

Alleles↗

Tryptase, the dominant secretory granular protein in human mast cells, is a potent mitogen for cultured dog tracheal smooth muscle cells.

Hyperplasia of airway smooth muscle cells is present in the airways of asthmatic patients and may contribute to the development of the bronchial hyperresponsiveness that occurs in these patients. Because tryptase is an abundant component of mast cell granules and has demonstrated growth-stimulatory effects in other mesenchymal cells (J. Clin. Invest. 1991; 88:493-499), the goal of our study was to determine whether tryptase is a mitogen for airway smooth muscle cells. The mitogenic effects of tryptase were tested in passages 1 through 5 of dog tracheal smooth muscle cells, either by counting smooth muscle cells or by monitoring uptake of bromodeoxyuridine (BrdU) into cellular DNA during S-phase. With respect to its efficacy, at a near maximal concentration (4 nM), tryptase increased cell numbers 2.1 +/- 0.2- or 2.8 +/- 0.6-fold above controls after 2 or 4 days, respectively, and these increases were approximately the same as those induced by platelet-derived growth factor (50 ng/ml) or 10% calf serum. With respect to potency, tryptase caused concentration-dependent increases in BrdU uptake, as detected in an enzyme-linked immunosorbent assay or by counting BrdU-labeled nuclei, with an EC50 of 2 nM. Pretreatment of tryptase with diisopropylfluorophosphate, to reduce markedly its catalytic as a activity as a proteinase, attenuated its growth-stimulated effects by 58 +/- 16%. Tryptase-induced mitogenesis was not a nonspecific effect of all serine proteinases, because thrombin, another proteinase with mitogenicity for fibroblasts, stimulated neither increases in cell counts nor BrdU uptake in our cells. We conclude that tryptase is a potent mitogen for airway smooth muscle cells in culture.

Animals↗

Bootstrap hypothesis tests for evolutionary trees and other dendrograms.

The bootstrap computer-intensive statistical technique is frequently applied to statistical analyses of phylogenetic trees. The widely used rule that a group is supported significantly if it appears in at least 95% of bootstrap trees is conservative in most situations. This paper describes three ways of using the bootstrap to carry out statistical inference on phylogenies. The first method tests whether there is nonrandom support for a single group or tree. The second method compares the support for two groups or trees. The third method tests whether a single group or tree has better support than the set of all possible alternatives; this may be a replacement for the "95% rule." These tests generally require fewer bootstrap trees to be estimated than do other methods of bootstrapping phylogenies. A simple, sequential statistical method can be used to increase the efficiency further. These methods can be applied to tests of multiple hypotheses about a single phylogeny. Parsimony analyses of 5S rRNA sequences of plants and cluster analyses of randomly amplified polymorphic DNA bands in three pathotypes of the cereal eyespot fungus are used as illustrative examples. The tests can be used to analyze dendrograms in subjects other than taxonomy.

Base Sequence↗

Physiological maturation of muscles in childhood.

Little is known about the motor muscle physiology of growing children and it has been assumed that increasing motor dexterity and speed correspond solely to brain maturation, although there is evidence that muscles mature from studies of other mammalian species. Such a finding in children would throw light on the possible mechanics of motor delays in speech, hand function, athletic, and musical skills as well as helping towards a better understanding of pathological motor disorders such as the cerebral palsies. Our non-invasive observations of soleus-muscle relaxation times in healthy children suggest that a child's muscles are initially slow to relax but relaxation doubles in speed up to adult rates by early adolescence. Half-relaxation times halved from about 90 ms at age 3 to about 40 ms at age 10. On the basis of these studies, we suggest that muscle maturation rate-limits motor tasks; which should be borne in mind when considering motor development in muscles and when attempting to determine the effects of early brain or spinal cord damage. Such methods of measuring the dynamics of muscle open up new areas of research and offer the possibility of developing operationally-defined in-vivo measurements for use in motor assessment and for following up the effects on muscle or treatments such as physiotherapy, orthotics, surgery, and drugs.

Adolescent↗

The spatial localization of homologous chromosomes in human fibroblasts at mitosis.

Chromosomes from ten human male fibroblast metaphases were completely reconstructed from electron micrographs of serially sectioned material. Chromosome centromere positions were determined by finding the three-dimensional coordinates of the centromere midpoint. The data set showed the identity of nine chromosome types (chromosomes 1, 2, 3, 6, 9, 16, 17, 18 and the Y chromosome) preserved as they are positioned in vivo. The results indicate that there is (1) no significant association of the homologous chromosomes examined, (2) a significant tendency for a central location of the Y chromosome and of chromosome 18, (3) a significant tendency for a peripheral location of chromosome 6, (4) no significant tendency for homologous chromosomes to reorganize as metaphase advances and (5) no significant differential condensation across the metaphase plate. Therefore, the only organization pattern observed for the centromeres of the homologous chromosomes studied is some sorting by size across the metaphase plate. These results may be typical of dividing cell types. Different chromosome arrangements are found in some non-dividing cell types (e.g. mammalian brain cells). The different distributions of chromosomes in different cell types can be considered as forms of "nuclear differentiation". It is postulated that nuclear differentiation may be related to cell differentiation.

Cell Differentiation↗

Genetic analysis of DNA fingerprints and virulences in Erysiphe graminis f.sp. hordei.

A DNA probe, E9, which has been used extensively in population genetic studies of the barley powdery mildew pathogen, Erysiphe graminis f.sp. hordei, was shown to be homologous to dispersed sequences in the genome of this fungus. In a cross of the isolates CC52 and DH14, fragments with homology to E9 mapped to six clusters of loci. Avirulences matching five resistance genes in barley were controlled by single genes, in accordance with the gene-for-gene hypothesis, while avirulence matching a sixth resistance gene, Mla13, was controlled by two genes. A gene which controls the response to a fungicide, ethirimol, was not linked to any other gene. In all, seven linkage groups, comprising 22 loci, were detected. The results indicate that E9 can be used to identify members of a clone of E.g. f.sp. hordei, but should not be used for quantitative population genetic analysis.

Ascomycota↗

Chance and selection in the evolution of barley mildew.

Populations of the barley powdery mildew fungus are genetically very diverse. However, when a new resistance gene is introduced into barley to control mildew, the population of the pathogen may respond by rapid growth of a few virulent clones. These phases of rapid clonal evolution cause radical changes in the frequencies of mildew genotypes.

Biological Evolution↗

Iterative concurrent reconstruction algorithms for emission computed tomography.

Direct reconstruction techniques, such as those based on filtered backprojection, are typically used for emission computed tomography (ECT), even though it has been argued that iterative reconstruction methods may produce better clinical images. The major disadvantage of iterative reconstruction algorithms, and a significant reason for their lack of clinical acceptance, is their computational burden. We outline a new class of 'concurrent' iterative reconstruction techniques for ECT in which the reconstruction process is reorganized such that a significant fraction of the computational processing occurs concurrently with the acquisition of ECT projection data. These new algorithms use the 10-30 min required for acquisition of a typical SPECT scan to iteratively process the available projection data, significantly reducing the requirements for post-acquisition processing. These algorithms are tested on SPECT projection data from a Hoffman brain phantom acquired with a 2 x 10(5) counts in 64 views each having 64 projections. The SPECT images are reconstructed as 64 x 64 tomograms, starting with six angular views. Other angular views are added to the reconstruction process sequentially, in a manner that reflects their availability for a typical acquisition protocol. The results suggest that if T s of concurrent processing are used, the reconstruction processing time required after completion of the data acquisition can be reduced by at least 1/3T s.

Algorithms↗