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Biomedical subjects

E Henderson

Publications and source records attributed to E Henderson.

At least 37 records · Page 2Linked to original sources

A fast 3D look-locker method for volumetric T1 mapping.

We introduce a fast technique, based on the principles of the 2D Look-Locker T1 measurement scheme, to rapidly acquire the data for accurate maps of T1 in three dimensions. The acquisition time has been shortened considerably by segmenting the acquisition of the k(y) phase encode lines. Using this technique, the data for a 256 x 128 x 32 volumetric T1 measurement can be acquired in 7.6 min. T1 measurements made in phantoms with T1s between 200 and 1200 ms had an accuracy of 4% and a reproducibility of 3.5%. Measurements of T1 made in normal brain using the fast 3D sequence corresponded well with inversion-recovery fast spin-echo measurements.

Brain↗

A comparison of the reproducibility and the sensitivity to change of visual analogue scales, Borg scales, and Likert scales in normal subjects during submaximal exercise.

OBJECTIVE: To assess which subjective scale, the visual analogue scale (VAS), the Borg CR10 (Borg) scale, or the Likert scale (LS), if any, is decidedly more reproducible and sensitive to change in the assessment of symptoms. DESIGN: Prospective clinical study. SETTING: Exercise laboratory. PARTICIPANTS: Twenty-three physically active male subjects (mean +/- SD age of 30 +/- 4 years old) were recruited. INTERVENTION: Each subject attended the exercise laboratory on four occasions at intervals of 1 week. Three subjective scales were used: (1) the VAS (continuous scale); (2) the Borg scale (12 fixed points); and (3) the Likert scale (LS; 5 fixed points). Four identical submaximal tests were given (2 min at 60% maximum oxygen uptake [VO(2)max] and 6 min at 70% VO(2)max). Two tests were undertaken to assess the reproducibility of scores that were obtained with each subjective scale. Two other tests were undertaken to assess the sensitivity of each scale to a change in symptom perception: a double-blind treatment with propranolol, 80 mg, (ie, active therapy; to increase the sensation of breathlessness and general fatigue during exercise) or matching placebo. The subjective scale scores were measured at 1 min 30 s, 5 min 30 s, and 7 min 15 s of exercise. Reproducibility was defined as the proportion of total variance (ie, between-subject plus within-subject variance) explained by the between-subject variance given as a percentage. Sensitivity was defined as the effect of the active drug therapy over the variation within subjects. RESULTS: Overall, the VAS performed best in terms of reproducibility for breathlessness and general fatigue, with reproducibility coefficients as high as 78%. For sensitivity, the VAS was best for breathlessness (ratio, 2.7) and the Borg scale was most sensitive for general fatigue (ratio, 3.0). The relationships between the respective psychological and physiologic variables were reasonably stable throughout the testing procedure, with overall typical correlations of 0.73 to 0.82 CONCLUSION: This study suggests that subjective scales can reproducibly measure symptoms during steady-state exercise and can detect the effect of a drug intervention. The VAS and Borg scales appear to be the best subjective scales for this purpose.

Adrenergic beta-Antagonists↗

Alcohol dependence and conduct disorder among Navajo Indians.

OBJECTIVE: The purpose of this study is to examine the association between conduct disorder before age 15 and subsequent alcohol dependence, and to describe the lifetime prevalence of alcohol dependence among Navajo Indian women and men. METHOD: This was a case-control design which included both men (n = 735) and women (n = 351) and in which the Diagnostic Interview Schedule was used for the diagnosis of the lifetime history of alcohol dependence and conduct disorder. Alcohol dependent cases were selected from inpatient and outpatient treatment programs (204 men, 148 women). Whenever possible, controls were matched for age, sex and community of residence and were randomly selected and interviewed until a nonalcohol dependent individual was found. Among the men, there were 374 alcohol dependent controls and 157 nonalcohol dependent controls. Among the women, the figures were 60 and 143, respectively. When combined, the controls comprise samples of the adult male and female populations from which estimates of lifetime prevalence of alcohol dependence, and of the amount of alcohol dependence in the population attributable to conduct disorder, may be inferred. RESULTS: Conduct disorder is a risk factor for alcohol dependence among both men and women. Lifetime prevalence of alcohol dependence in this population is high (70.4% for men and 29.6% for women), but the amount of alcohol dependence in the population attributable to conduct disorder is low. On the other hand, among the alcohol dependent, those with conduct disorder had the most severe alcohol- and nonalcohol-related problems. CONCLUSIONS: The potential limitations of the study are those common to case-control designs, especially biased recall by cases. There are also potential sampling biases among the controls. It is shown that none of the potential biases invalidate the findings, which support the hypothesis that in this population conduct disorder is a risk for alcohol dependence. The implications for primary prevention of alcohol dependence are discussed.

Adolescent↗

Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays.

This paper combines the topographic imaging capability of the atomic force microscope (AFM) with a compositionally patterned array of immobilized antigenic rabbit IgG on gold as an approach to performing immunoassays. The substrates are composed of micrometer-sized domains of IgG that are covalently linked to a photolithographically patterned array of a monolayer-based coupling agent. The immobilized coupling agent, which is prepared by the chemisorption of dithiobis(succinimidyl undecanoate) on gold, is separated by micrometer-sized grids of a monolayer formed from octadecanethiol (ODT). The strong hydrophobicity of the ODT adlayer, combined with the addition of the surfactant Tween 80 to the buffer solution that is used in forming the antibody-antigen pairs, minimizes the nonspecific adsorption of proteinaceous materials to the grid regions. This minimization allows the grids to function as a reference plane for the AFM detection of the height increase when a complementary antibody-antigen pair is formed. The advantageous features of this strategy, which include ease of sample preparation, an internal reference plane for the detection of topographic changes, and the potential for regeneration and reuse, are demonstrated using rabbit IgG as an immobilized antigen and goat anti-rabbit IgG as the complementary antibody. The prospects for further miniaturization are discussed.

Animals↗

Purification, characterization and molecular cloning of TGP1, a novel G-DNA binding protein from Tetrahymena thermophila.

G-DNA, a polymorphic family of four-stranded DNA structures, has been proposed to play roles in a variety of biological processes including telomere function, meiotic recombination and gene regulation. Here we report the purification and cloning of TGP1, a G-DNA specific binding protein from Tetrahymena thermophila. TGP1 was purified by three-column chromatographies, including a G-DNA affinity column. Two major proteins (approximately 80 and approximately 40 kDa) were present in the most highly purified column fraction. Renaturation experiments showed that the approximately 80 kDa protein contains TGP1 activity. Biochemical characterization showed that TGP1 is a G-DNA specific binding protein with a preference for parallel G-DNAs. The TGP1/DNA complex has a dissociation constant (Kd) of approximately 2.2 x 10(-8) M and TGP1 can form supershift in gel mobility shift assays. The cDNA coding TGP1 was cloned and sequenced based upon an internal peptide sequence obtained from the approximately 80 kDa protein. Sequence analyses showed that TGP1 is a basic protein with a pI of 10.58, and contains two extensively hydrophilic and basic domains. Homology searches revealed that TGP1 is a novel protein sharing weak similarities with a number of proteins.

Amino Acid Sequence↗

A Tetrahymena thermophila G4-DNA binding protein with dihydrolipoamide dehydrogenase activity.

G4-DNA is a four-stranded structure that is formed by guanine-rich sequences. We report here the purification and characterization of a novel G4-DNA binding protein from Tetrahymena thermophila, designated TGP2. TGP2 was found to preferentially bind to G4-DNA oligonucleotides with adjacent single-stranded domains containing phosphorylated 5' ends and the sequence element, 5'-ACTG-3'. The amino acid sequence of TGP2 has high similarity to dihydrolipoamide dehydrogenase (DLDH) from a variety of species, and TGP2 was shown to have DLDH activity. Purified DLDH from porcine heart and bovine intestinal mucosa were shown to bind specifically to G4-DNA oligonucleotides. On the basis of these results we conclude that TGP2 is DLDH in T. thermophila and suggest that the G4-DNA binding capability of TGP2/DLDH may be biologically relevant.

Amino Acid Sequence↗

Temporal sampling requirements for the tracer kinetics modeling of breast disease.

The physiological parameters measured in the tracer kinetics modeling of data from a dynamic contrast-enhanced magnetic resonance (MR) breast exam (blood flow-extraction fraction product [FE], volume of the extracellular extravascular space [Ve], and blood volume [Vb]) may enable non-invasive diagnosis of breast cancer. One of the factors that compromises the accuracy and precision of the parameter estimates, and therefore their diagnostic potential, is the temporal resolution of the MR scans used to measure contrast agent (gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]) concentration in an artery (arterial input function [AIF]) and in the tissue (tissue residue function [TRF]). Using computer simulations, we have examined, for several AIF widths, the errors introduced into estimates of tracer kinetic parameters in breast tissue due to insufficient temporal sampling. Temporal sampling errors can be viewed as uncertainties and biases in the parameter estimates introduced by the uncertainty in the relative alignments of the AIF, TRF, and sampling grid. These effects arise from the model's inherent sensitivity to error in either the AIF or TRF, which is dependent on the values of the tracer kinetic parameters and increases with AIF width. Based on the results of the simulations, to ensure that the error in FE and Ve will be under 10% of their true values, we recommend a rapid bolus injection of contrast agent (approximately 10 s), that the AIF be sampled every second, and that the TRF be sampled every 16 s or less. An accurate measurement of Vb requires that the TRF be sampled at least every 4 s. The results of these investigations can be used to set minimum dynamic imaging rates for tracer kinetics modeling of the breast.

Breast↗

Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B.

BACKGROUND: The purpose of this study was to compare the long-term psychosocial adaptation of Hodgkin's disease and adult acute leukemia survivors. PATIENTS AND METHODS: Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute leukemia (AL) survivors were interviewed by telephone concerning their psychosocial adjustment and problems they attributed to having been treated for cancer, using identical research procedures and a common set of instruments. The following measures were used: Psychosocial Adjustment to Illness Scale (PAIS); Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index (NSI). All participants had been treated on one of nine Hodgkin's disease or 13 acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966-1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL = 5.6). RESULTS: HD survivors' risk of having a high distress score on the BSI was almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs. 14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations above the norm, suggestive of a possible psychiatric disorder. HD survivors reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001), greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning (PAIS Sexual Relationships, P = 0.0001), than AL survivors. CONCLUSIONS: Treatment-related issues may have placed HD survivors at a greater risk for problems in long-term adaptation than AL survivors.

Adaptation, Psychological↗

Tetrahymena mutants with short telomeres.

Telomere length is dynamic in many organisms. Genetic screens that identify mutants with altered telomere lengths are essential if we are to understand how telomere length is regulated in vivo. In Tetrahymena thermophila, telomeres become long at 30 degrees, and growth rate slows. A slow-growing culture with long telomeres is often overgrown by a variant cell type with short telomeres and a rapid-doubling rate. Here we show that this variant cell type with short telomeres is in fact a mutant with a genetic defect in telomere length regulation. One of these telomere growth inhibited forever (tgi) mutants was heterozygous for a telomerase RNA mutation, and this mutant telomerase RNA caused telomere shortening when overexpressed in wild-type cells. Several other tgi mutants were also likely to be heterozygous at their mutant loci, since they reverted to wild type when selective pressure for short telomeres was removed. These results illustrate that telomere length can regulate growth rate in Tetrahymena and that this phenomenon can be exploited to identify genes involved in telomere length regulation.

Animals↗

Boarding and public schools: Navajo educational attainment, conduct disorder, and alcohol dependency.

Many critics of United States government operated boarding schools for American Indians have asserted that the boarding school experience has lasting deleterious effects on personality development. Specifically, it has been suggested that a boarding school education is likely to lead to problems with alcohol in adulthood. To examine that assertion, data from interviews with over 1000 Navajos are analyzed concerning schooling, conduct disorder and the history of alcohol use. Consistent with data on the U.S. population generally, Navajo high school dropouts reported greater problems with alcohol than did graduates. Contrary to expectations, Navajos with a history of alcohol dependency were no more likely to have attended boarding schools than those who did not report patterns of alcohol dependency.

Achievement↗

Mapping elasticity of rehydrated metaphase chromosomes by scanning force microscopy.

Scanning force microscopy was used for mapping the viscoelastic properties of metaphase chromosomes. These properties were probed by scanning with various imaging forces and subsequent calculation of the difference image. The procedure allows a mapping of the viscoelastic behavior expressed as force-dependent indentation of the local surface feature and results in an image with material contrast. The approach is demonstrated on rehydrated metaphase chromosomes, which were spread and air-dried before rehydration in aqueous buffer. The rehydration resulted in a swelling of the chromosome structure and was accompanied by drastic changes in the viscoelastic properties. For comparisons, force-distance curves on metaphase chromosomes were accumulated; these curves were also used for the calculation of the stiffness curve. The demonstrated approach of mapping viscoelasticity by differential scanning force microscopy allows the detection of domains with varying mechanical properties in biomolecules such as chromosomes.

Chromosomes↗

Scanning Force Microscopy Study of Methanol-Induced Changes in the Distribution of Silver Particles in Colloidal Metal Films

Colloidal silver particles were attached to a solid surface for use as a substrate for surface-enhanced Raman scattering and surface enhanced fluorescence spectroscopies. The enhancement of Raman scattering is dramatically increased after exposure of the substrates to methanol solution. Scanning force microscopy was used to visualize the substrate before and after the methanol treatment, and a statistical evaluation of the particle distribution revealed some differences. The nearest-neighbor distance was decreased after the exposure to methanol. This effect suggests that an aggregation of the particles occurred. This aggregation is probably based on increased attractive interactions and lateral mobility of the particles in methanol.

Journal Article↗

Effect of fetal movement on the amniotic fluid index in diamniotic twin gestations.

Fetal movement changes the size and location of amniotic fluid pockets during measurement of the amniotic fluid index. In singleton gestations, the effect of redistributing the fixed intrauterine fluid volume on the amniotic fluid index is clinically insignificant. In this study, we tested the hypothesis that the index in twin pregnancies is unaffected by fetal movement. A single examiner prospectively determined the amniotic fluid index before and after three discrete episodes of movement by both fetuses of 82 diamniotic twin pregnancies referred for obstetric sonograms between 20 and 38 weeks' menstrual age. A reliable blinded examiner provided a second post-movement measurement as a control. Data were analyzed by the paired t-test. The mean change in the amniotic fluid index after fetal movement was 2.1 +/- 0.2 cm and 3.7 +/- 0.3 cm for post-movement determinations by the same and blinded examiners, respectively (p < .001). Interobserver variation was 3.5 cm. Intraobserver variation was 1.8 cm for the first examiner and 2.2 cm for the second examiner. Therefore, interobserver and intraobserver variation can account for the observed change in the amniotic fluid index following movement of both diamniotic twins.

Amniotic Fluid↗

Chicken erythrocyte nucleosomes have a defined orientation along the linker DNA--a scanning force microscopy study.

The orientation of nucleosomes was investigated using scanning force microscopy (SFM) of hypotonically spread chicken chromatin. A virtual cross section parallel to the substrate at half maximum height of the nucleosomal structure revealed an elliptical shape. The orientation of the major axis of this ellipse was investigated in reference to the direction of the axis of the nucleosomal chain. An alignment of the nucleosomes along the nucleosomal chain was observed, with more than 50% of the nucleosomes aligned with the long axis of the chain within < or = 30 degrees deviation. The alignment distribution peaked at 10-20 degrees. The application of SFM-based image processing for the structural investigation of a protein-DNA complex demonstrates the potential for this approach in structural molecular biology.

Algorithms↗

Catecholamines contribute to exertional dyspnoea and to the ventilatory response to exercise in normal humans.

BACKGROUND: Exogenous catecholamine administration in humans stimulates ventilation. The present study was designed to investigate whether increased endogenous catecholamine release influences objective measures of ventilation and subjective measures of breathlessness in normal subjects. METHODS: Yohimbine, a pre-synaptic alpha 2 adrenoceptor antagonist, or placebo was administered to 10 normal male subjects in a double-blind cross-over fashion. Ventilation and metabolic gas exchange were measured during steady state exercise at 60% of previously determined maximal oxygen consumption. Venous lactate and noradrenaline were measured during exercise. Subjects' sensation of breathlessness and fatigue were recorded using visual analogue scales. RESULTS: Plasma noradrenaline was higher following yohimbine administration (at 6 min exercise; 4.58 +/- 0.56 nmol.l-1 vs 8.74 +/- 1.53; P < 0.05). Oxygen consumption was unchanged, but ventilation was greater throughout exercise following yohimbine. The sensation of exertion was greater following yohimbine, and at any given level of ventilation, the sensation of exertion was greater. CONCLUSIONS: Yohimbine administration causes increased noradrenaline release. This is associated with an increased ventilatory response and an increase in the sensation of exertion during steady state exercise. An increase in circulating noradrenaline might be a mechanism for both increased ventilation and pathological conditions of breathlessness such as chronic heart failure.

Adrenergic alpha-Antagonists↗

Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene.

The mammalian homeobox gene pdx-1 is expressed in pluripotent precursor cells in the dorsal and ventral pancreatic bud and duodenal endoderm, which will produce the pancreas and the rostral duodenum. In the adult, pdr-1 is expressed principally within insulin-secreting pancreatic islet beta cells and cells of the duodenal epithelium. Our objective in this study was to localize sequences within the mouse pdx-1 gene mediating selective expression within the islet. Studies of transgenic mice in which a genomic fragment of the mouse pdx-1 gene from kb -4.5 to +8.2 was used to drive a beta-galactosidase reporter showed that the control sequences sufficient for appropriate developmental and adult specific expression were contained within this region. Three nuclease-hypersensitive sites, located between bp -2560 and -1880 (site 1), bp -1330 and -800 (site 2), and bp -260 and +180 (site 3), were identified within the 5'-flanking region of the endogenous pdx-1 gene. Pancreatic beta-cell-specific expression was shown to be controlled by sequences within site 1 from an analysis of the expression pattern of various pdr-1-herpes simplex virus thymidine kinase promoter expression constructs in transfected beta-cell and non-beta-cell lines. Furthermore, we also established that this region was important in vivo by demonstrating that expression from a site 1-driven beta-galactosidase reporter construct was directed to islet beta-cells in transgenic mice. The activity of the site 1-driven constructs was reduced substantially in beta-cell lines by mutating a hepatocyte nuclear factor 3 (HNF3)-like site located between nucleotides -2007 and -1996. Gel shift analysis indicated that HNF3beta present in islet beta cells binds to this element. Immunohistochemical studies revealed that HNF3beta was present within the nuclei of almost all islet beta cells and subsets of pancreatic acinar cells. Together, these results suggest that HNF3beta, a key regulator of endodermal cell lineage development, plays an essential role in the cell-type-specific transcription of the pdx-1 gene in the pancreas.

Animals↗

Functional characterization of the transactivation properties of the PDX-1 homeodomain protein.

Pancreas formation is prevented in mice carrying a null mutation in the PDX-1 homeoprotein, demonstrating a key role for this factor in development. PDX-1 can also bind to and activate transcription from cis-acting regulatory sequences in the insulin and somatostatin genes, which are expressed in pancreatic islet beta and delta cells, respectively. In this study, we compared the functional properties of PDX-1 with those of the closely related Xenopus homeoprotein XIHbox8. Analysis of chimeras between PDX-1, XIHbox8, and the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that their transactivation domain was contained within the N-terminal region (amino acids 1 to 79). Detailed mutagenesis of this region indicated that transactivation is mediated by three highly conserved sequences, spanning amino acids 13 to 22 (subdomain A), 32 to 38 (subdomain B), and 60 to 73 (subdomain C). These sequences were also required by PDX-1 to synergistically activate insulin enhancer-mediated transcription with another key insulin gene activator, the E2A-encoded basic helix-loop-helix E2-5 and E47 proteins. These results indicated that N-terminal sequences conserved between the mammalian PDX-1 and Xenopus XIHbox8 proteins are important in transcriptional activation. Stable expression of the PDX-1 deltaABC mutant in the insulin- and PDX-1-expressing betaTC3 cell line resulted in a threefold reduction in the rate of endogenous insulin gene transcription. Strikingly, the level of the endogenous PDX-1 protein was reduced to very low levels in these cells. These results suggest that PDX-1 is not absolutely essential for insulin gene expression in betaTC3 cells. We discuss the possible significance of these findings for insulin gene transcription in islet beta cells.

Amino Acid Sequence↗