Biomedical subjects
L Smith
Publications and source records attributed to L Smith.
Estimation of variance components for censored data with applications to blood pressure variability.
Ideally, the basis for estimation of variance components is large random samples selected from a well-defined reference population. Some large biomedical studies, however, consist of a random sample (S) of individuals ascertained at an initial visit, with a selected subsample from S seen on one or more follow-up visits. In this setting, the usual formulae for estimation of variance components are problematic since they do not take into account the censored nature of the data. For this purpose, we consider both maximum likelihood and moments estimation methods that take the censoring into account, and we compare their performance, in terms of bias and mean squared error, with that of the usual variance components estimators that ignore censoring. We find the maximum likelihood estimators somewhat more efficient than method of moments estimators, provided that the assumption of multivariate normality is met; furthermore, these estimators are substantially more efficient than those that ignore the censoring. It is important to record data on all individuals, even those who do not meet screening criteria; one can estimate between- and within-person variance more accurately with use of all available data. The resulting estimates are crucial in calculation of power for the design of future studies.
Intrachromosomal location of the telomeric repeat (TTAGGG)n.
Eukaryotic telomeres are specialized DNA-protein structures that are thought to ensure chromosomal stability and complete replication of the chromosome ends. All telomeres which have been studied consist of a tandem array of G-rich repeats which seem to be sufficient for telomere function. Originally, the human telomeric repeat (TTAGGG)n was assumed to be exclusively located at the very end of all human chromosomes. More recent evidence, however, suggests an extension into proterminal regions. Very little is known about the interstitial distribution of telomeric repeats. Here we present evidence for the presence of (TTAGGG)n repeats in internal loci on the long and short arms of different human chromosomes. In addition, we studied the genomic organization of these repeats in more detail and discuss possible functions of interstitial telomeric repeats in the human genome.
The reactions of the oxidase and reductases of Paracoccus denitrificans with cytochromes c.
Electron transport in the Paracoccus denitrificans respiratory chain system is considerably more rapid when it includes the membrane-bound cytochrome c552 than with either soluble Paracoccus c550 or bovine cytochrome c; a pool function for cytochrome c is not necessary. Low concentrations of Paracoccus or bovine cytochrome c stimulate the oxidase activity. This observation could explain the multiphasic Scatchard plots which are obtained. A negatively charged area on the "back side" of Paracoccus c which is not present in mitochondrial c could be a control mechanism for Paracoccus reactions. Paracoccus oxidase and reductase reactions with bovine c show the same properties as mammalian systems; and this is true of Paracoccus oxidase reactions with its own soluble cytochrome c if added polycation masks the negatively charged area. Evidence for different oxidase and reductase reaction sites on cytochrome c include: (1) stimulation of the oxidase but not reductase by a polycation; (2) differences in the inhibition of the oxidase and reductases by monoclonal antibodies to Paracoccus cytochrome c; and (3) reaction of another bacterial cytochrome c with Paracoccus reductases but not oxidase. Rapid electron transport occurs in cytochrome c-less mutants of Paracoccus, suggesting that the reactions result from collision of diffusing complexes.
Sodium-calcium exchange in renal epithelial cells: dependence on cell sodium and competitive inhibition by magnesium.
Kinetic properties of Na(+)-Ca2+ exchange in a renal epithelial cell line (LLC-MK2) were assessed by measuring cytosolic free Ca2+ with fura-2 and 45Ca2+ influx. Replacing external Na+ with K+ produced relatively small increases in free Ca2+ and 45Ca2+ uptake unless the cells were incubated with ouabain. Ouabain markedly increased cell Na+ and strongly potentiated the effect of replacing external Na+ with K+ on free Ca2+ and 45Ca2+ uptake. 45Ca2+ influx in 140 mM K+ or N-methyl-D-glucamine minus influx in 140 mM Na+ was used to quantify Na(+)-Ca2+ exchange activity of Na(+)-loaded cells. The dependence of exchange on cell Na+ was sigmoidal; the K0.5 was 26 +/- 3 mmol/liter cell water space, and the Hill coefficient was 3.1 +/- 0.2. The kinetic features of the dependence of exchange on cell Na+ partly account for the small increase in Ca2+ influx when all external Na+ is replaced by K+. Besides raising cell Na+ ouabain appears to activate the exchanger. Magnesium competitively inhibited exchange activity. The potency of Mg2+ was 8.2-fold lower with potassium instead of N-methyl-D-glucamine or choline as the replacement for external Na+. Potassium also increased the Vmax of exchange by 86% and had no effect on the Km for Ca2+. The exchanger does not cause detectable 22Na(+)-Mg2+ exchange and does not appear to require K+ or transport 86Rb+. Although exchange activity was plentiful in the epithelial cells from monkey kidney, others from amphibian, canine, opossum, and porcine kidney had no detectable exchange activity. All of the measured kinetic properties of Na(+)-Ca2+ exchange in the renal epithelial cells are very similar to those of the exchanger in rat aortic myocytes.
Epithelial differentiation in the absence of extracellular matrix.
To investigate the regulation of epithelial differentiation, normal human epidermal keratinocytes were cultured floating on the surface of culture medium without attachment to a solid substrate. Keratinocytes spread out on the surface of the medium, proliferated and differentiated either into several flat lacy sheets 1 to 3 cells thick (on medium containing 0.15 mM calcium) or formed one single aggregate of cells from 5 to 15 cells in thickness on medium containing 1.15 mM calcium. The cell aggregates demonstrated a pattern of ordered epithelial differentiation. Levels of progressive differentiation resembling the structure of normal human epidermis were identified by light microscopy, immunohistochemistry, and electron microscopy. Differentiation proceeded from cells at the air side toward cells at the medium side with basal appearing cells on the air side and keratinocytes expressing filaggrin and involucrin on the side toward the medium. These results demonstrate that organized epithelial differentiation can occur in the absence of extracellular matrix. In contrast with other air-liquid interface cultures, epithelial differentiation in the absence of extracellular matrix progresses from air towards medium.
Controlling system uncertainty in sport and work.
An applied psychological framework for coping with performance uncertainty in sport and work systems is presented. The theme of personal control serves to integrate ideas prevalent in industrial and organisational psychology, the stress literature and labour process theory. These commonly focus on the promotion of tacit knowledge and learned resourcefulness in individual performers. Finally, data from an empirical evaluation of a development training programme to facilitate self-regulation skills in professional athletes are briefly highlighted.
A tool for measuring the asthma self-management competency of families.
A tool for measuring a family's asthma self-management behaviour has been developed for a study examining the relationships of asthma self-management behaviour, knowledge, and psychosocial factors with various indices of morbidity in children with asthma. The tool involves a structured interview which includes three typical situations of asthma self-management (scenarios). Each of the scenarios is divided into graded challenges. A scoring schedule was developed according to the critical incidents of self-management inherent in each situation. This schedule was then applied to the verbatim transcripts of the subjects' responses. These were presented to 380 asthmatic children aged 5-11 yr and their primary caregivers. Inter-rater reliability, inter-rater agreement and test-retest reliability coefficients indicate that the scores obtained are stable across raters and time. Correlations between scores on different scenarios suggest there is a common factor of self-management competency across all scenarios, but families are better at some aspects of self-management than others. The distribution of scores for each scenario is presented. The place of this tool as a means of assessing self-management behaviour is discussed.
Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1.
Fibrillin (FBN), a large extracellular matrix glycoprotein, is an important component of structures called microfibrils. Because fibrillin microfibrils appear to be abnormal in patients with the Marfan syndrome, fibrillin is a candidate for the gene defect in the Marfan syndrome. Derived clones from fibrillin cDNA were used as probes in isotopic and nonisotopic in situ hybridization studies to map the chromosomal location of the fibrillin gene. Fluorescent signals were found on chromosome 15 band q21.1; an excess of silver grains was noted over a similar region of chromosome 15 following in situ hybridization with a tritium-labeled probe. These results are consistent with linkage studies that localize the Marfan gene to chromosome 15.
Vowel and consonant recognition with the aid of a multichannel cochlear implant.
In this report we review the vowel and consonant recognition ability of patients who use a multichannel cochlear implant and who achieve relatively good word identification scores. The results suggest that vowel recognition is accomplished by good resolution of the frequency of the first formant (F1) combined with poor resolution of the frequency of the second formant (F2). The results also suggest that consonant recognition is accomplished (1) by using information from the amplitude envelope, including periodicity/aperiodicity, as cues to manner and voicing, (2) by using F1 as an aid to the identification of manner and voicing, and (3) by using information from cochlear place of stimulation to provide a very crude indication of the shape of the frequency spectrum above 1 kHz.
Interdisciplinary monitoring of medication errors in a nursing quality assurance program.
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A study of role negotiation between nurses and the parents of hospitalized children.
The role of the parent of a hospitalized child has changed considerably over the past 30 years. Where parents were previously expected to had responsibility for care over to their child's nurses, there is now an expectation that parents will be extensively involved in the care of their hospitalized children. The negotiation of roles between nurses and parents has been advocated by workers concerned about conflicts between nurses and parents. However, it is not known whether such negotiation takes place between nurses and parents. It is clear that power is not evenly distributed between nurses and parents: issues of territory, stress, anxiety, uncertainty, control and conflicts arising from parental competence all place the parent in a weaker position. It is argued that the nurse holds the initiative in the decision about whether negotiation takes place. A small study is described in which nurses were invited to describes their response to their perception that a parent wanted to increase or decrease her or his involvement in her or his child's care. The critical incident technique (Flanagan 1954) was used to collect data. Nurses' responses were categorized into categories of 'encouragement', 'explanation/advice' and 'negotiation'. Responses were then placed in more specific subcategories. The inter-rater reliability of the categorization was measured. Owing to the limitations of the study, the results can only be regarded as suggestive. Nevertheless, significant association was found between the category of response and the grade of staff, with a stratified pattern of category of response demonstrated. The implications of the study for future research are discussed.
Oxygen radicals and lung injury.
This article describes the formation of oxygen radicals and their biological effects, especially in relation to lung injury. Various recent experimental data are reviewed. The relationships between hydrostatic effects and permeability effects in producing injury and edema are stressed. Means of prevention and problems related to extrapolation to clinical situations are focused.
Sodium-calcium exchange in aortic myocytes and renal epithelial cells. Dependence on metabolic energy and intracellular sodium.
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Influence of age on neutrophil function in foals.
Functional activities (phagocytosis and killing) of neutrophil leucocytes (NL) and immunoglobulin G concentrations were evaluated in six healthy foals from birth to 6 months of age. Peripheral blood NL were reacted with Streptococcus equisimilis in 20 per cent pooled equine serum for 30, 60 and 90 mins and functional activities of NL were determined using a fluorochrome microassay. Values for foal NL function were compared with those of healthy adult horses (n = 28). Foal neutrophil function was influenced by age. Killing capacity of NL decreased, whereas phagocytic capacity increased, until 113 days of age, after which a reversal in trends became apparent. Immunoglobulin G concentrations changed significantly over time and were lowest at 29 to 56 days of age. All foal values for NL function fell within the range of normal values established for healthy adult horses.
Improved detection of in situ hybridization by laser scanning confocal microscopy.
Laser scanning confocal microscopy (LSCM) offers a significant improvement over conventional bright-field and dark-field light microscopy for producing images of silver grains in autoradiograms of specimens prepared by in situ hybridization. The out-of-focus image of the background silver grains present in the emulsion is eliminated from the in-focus image of the radioactive probe associated with the cells by optical sectioning with the LSCM operated in a reflected light mode. The improved images produced by the LSCM provide a significant increase in the sensitivity of detecting positively labeled cells and tissues prepared by in situ hybridization. The power of this detection method is demonstrated using samples of HIV-infected human peripheral blood cells, tissue sections of human placenta and human skin. It is anticipated that the method can be universally applied to samples prepared by in situ hybridization techniques.
Arthroscopic anterior and posterior cruciate ligament reconstruction technique.
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Relation of depression and mortality after myocardial infarction in women.
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