Biomedical subjects

R Henderson

Publications and source records attributed to R Henderson.

At least 55 records · Page 3Linked to original sources

PubMed2000

Effects of HIV/AIDS education and training on patient care and provider practices: a cross-cutting evaluation.

Initial and continuing training in HIV/AIDS service provision is a critical way to enable the nation's health providers to use state-of-the-art developments and perspectives. Typically, the efficacy of HIV/AIDS training programs is evaluated using assessments administered to trainees immediately following the training. This study reports cross-cutting findings from telephone interviews conducted with 218 trainees an average of 8 months after training. Long-term training effects are examined in three domains: (a) general perspectives on HIV/AIDS; (b) health care provider service provision; and (c) changes in procedures and operations at the health care system level. The findings show the different ways that the training experience had long-term positive and observable effects in these three domains. In some cases, background characteristics and job positions predicted the specific type of reported training effects. The pattern of results suggests ways in which training methods can be targeted to specific audiences.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Do characteristics of HIV/AIDS education and training affect perceived training quality? Lessons from the evaluation of seven projects.

Initial and continuing HIV/AIDS education and training has been a critical way to bring the nation's health providers up to date on emerging developments and approaches. This study reports cross-cutting findings from seven HIV/AIDS education and training projects. Trainers described over 600 training sessions from these projects in terms of their structural characteristics and design elements, while trainees described these sessions on several dimensions related to training quality. Training characteristics were compared to trainee assessments of training quality. Using a decision-tree analytic approach for major training attributes, considerable support emerged for links between training characteristics and perceived quality of the HIV/AIDS training experience. More favorable quality ratings were associated with certain projects, the training setting, the types of trainees served by the training, the intended training impact, discussion of special populations, and training methods involving interactive learning. With increased knowledge regarding how these educational experiences relate to the ways they are perceived and processed, more targeted approaches to training design on HIV/AIDS can be developed.

Adult↗

PubMed1999

Electron crystallography of bacteriorhodopsin with millisecond time resolution.

The goal of time-resolved crystallographic experiments is to capture dynamic "snapshots" of molecules at different stages of a reaction pathway. In recent work, we have developed approaches to determine determined light-induced conformational changes in the proton pump bacteriorhodopsin by electron crystallographic analysis of two-dimensional protein crystals. For this purpose, crystals of bacteriorhodopsin were deposited on an electron microscopic grid and were plunge-frozen in liquid ethane at a variety of times after illumination. Electron diffraction patterns were recorded either from unilluminated crystals or from crystals frozen as early as 1 ms after illumination and used to construct projection difference Fourier maps at 3.5-A resolution to define light-driven changes in protein conformation. As demonstrated here, the data are of a sufficiently high quality that structure factors obtained from a single electron diffraction pattern of a plunge-frozen bacteriorhodopsin crystal are adequate to obtain an interpretable difference Fourier map. These difference maps report on the nature and extent of light-induced conformational changes in the photocycle and have provided incisive tools for understanding the molecular mechanism of proton transport by bacteriorhodopsin.

Bacteriorhodopsins↗

PubMed1999

Protein conformational changes in the bacteriorhodopsin photocycle.

We report a comprehensive electron crystallographic analysis of conformational changes in the photocycle of wild-type bacteriorhodopsin and in a variety of mutant proteins with kinetic defects in the photocycle. Specific intermediates that accumulate in the late stages of the photocycle of wild-type bacteriorhodopsin, the single mutants D38R, D96N, D96G, T46V, L93A and F219L, and the triple mutant D96G/F171C/F219L were trapped by freezing two-dimensional crystals in liquid ethane at varying times after illumination with a light flash. Electron diffraction patterns recorded from these crystals were used to construct projection difference Fourier maps at 3.5 A resolution to define light-driven changes in protein conformation. Our experiments demonstrate that in wild-type bacteriorhodopsin, a large protein conformational change occurs within approximately 1 ms after illumination. Analysis of structural changes in wild-type and mutant bacteriorhodopsins under conditions when either the M or the N intermediate is preferentially accumulated reveals that there are only small differences in structure between M and N intermediates trapped in the same protein. However, a considerably larger variation is observed when the same optical intermediate is trapped in different mutants. In some of the mutants, a partial conformational change is present even prior to illumination, with additional changes occurring upon illumination. Selected mutations, such as those in the D96G/F171C/F219L triple mutant, can sufficiently destabilize the wild-type structure to generate almost the full extent of the conformational change in the dark, with minimal additional light-induced changes. We conclude that the differences in structural changes observed in mutants that display long-lived M, N or O intermediates are best described as variations of one fundamental type of conformational change, rather than representing structural changes that are unique to the optical intermediate that is accumulated. Our observations thus support a simplified view of the photocycle of wild-type bacteriorhodopsin in which the structures of the initial state and the early intermediates (K, L and M1) are well approximated by one protein conformation, while the structures of the later intermediates (M2, N and O) are well approximated by the other protein conformation. We propose that in wild-type bacteriorhodopsin and in most mutants, this conformational change between the M1 and M2 states is likely to make an important contribution towards efficiently switching proton accessibility of the Schiff base from the extracellular side to the cytoplasmic side of the membrane.

Bacteriorhodopsins↗

PubMed1999

The projection structure of the low temperature K intermediate of the bacteriorhodopsin photocycle determined by electron diffraction.

Bacteriorhodopsin (bR) is an integral membrane protein which absorbs visible light and pumps protons across the cell membrane of Halobacterium salinarium. bR is one of the few membrane-bound pumps whose structure is known at atomic resolution. Changes in the protein structure of bR are a crucial element in the mechanism of proton pumping and can be followed by a variety of spectroscopic, and diffraction methods. A number of intermediates in the photocycle have been identified spectroscopically and a number of laboratories have been successful in reporting the structural changes taking place in the later stages of the photocycle over the millisecond time-scale using diffraction techniques. These studies have revealed significant changes in the protein structure, possibly involving changes in flexibility and/or movement of helices. Earlier intermediates which arise and decay on the picosecond to microsecond time-scale have proven more difficult to trap. Here, we report for the first time the successful trapping and diffraction analysis of bR in a low temperature state resembling the very early intermediate, K. We have calculated a projection difference map to 3.5 A resolution. The map reveals no significant structural changes in the molecule, despite having a very low background noise level. This does not rule out the possibility of movements in a direction perpendicular to the plane of the membrane. However, the data are consistent with other evidence that significant structural changes do not occur in the protein itself.

Bacteriorhodopsins↗

PubMed1999

Systems change resulting from HIV/AIDS education and training. A cross-cutting evaluation of nine innovative projects.

An evaluation of nine diverse HIV/AIDS training programs assessed the degree to which the programs produced changes in the ways that health care systems deliver HIV/AIDS care. Participants were interviewed an average of 8 months following completion of training and asked for specific examples of a resulting change in their health care system. More than half of the trainees gave at least one example of a systems change. The examples included the way patient referrals are made, the manner in which agency collaborations are organized, and the way care is delivered.

Adolescent↗

PubMed1999

The effect of a copay increase on pharmaceutical utilization, expenditures, and treatment continuation.

OBJECTIVE: No research has evaluated the impact of an increase to a copay that is reflective of today's healthcare market. This study examined the effect of an increase from a $10 to $15 copay for brand drugs on key pharmaceutical utilization measures, including participation rates, treatment continuation, and expenditures, in an adult population. STUDY DESIGN: A quasi-experimental, pre-post design with control group was used. PATIENTS AND METHODS: Two different employer plans implemented an increase from $10 to $15 for brand copays in January of 1997. The utilization and expenditures of these plans were compared with those of a control group with a constant brand copay of $10 for 6 months preceding and 6 months following the copay increase. RESULTS: When other predictor variables were controlled for, the copay increase was not associated with a statistically significant difference in overall utilization compared with the control group, although brand utilization was significantly lower in the copay group. Savings to the payer were substantial, and resulted primarily from cost-shifting, reduction in brand utilization, and an increase in the generic fill rate. The rates of continuation with chronic medications in the 6 months following the copay increase were not reduced in the copay group compared with the control group. CONCLUSION: A copay increase can provide substantial savings to a payer without being a major deterrent to overall utilization or resulting in discontinuation of chronic medications.

Adult↗

PubMed1998

Magnetic field conditioned taste aversion in rats.

Conditioned taste aversion is a common classic conditioning procedure used to identify noxious stimuli. When a rat is given a taste solution, the conditioned stimulus (CS), followed by an unpleasant experience, the unconditioned stimulus (US), the rat will avoid consumption of the CS in future presentations. These experiments use the taste aversion procedure to examine the effect of exposure to a high magnetic field. A solution consisting of 3.0 g glucose and 1.25 g saccharin per 1 L of solution (G+S) was used as the CS and a 9.4-T magnet served as the US. In Experiment 1, all rats received a 10 min presentation of the G+S solution followed by either a 30 min exposure to the magnetic field (Magnet, n = 8), a 30-min exposure in a container with similar conditions but lacking the magnetic field (Sham, n = 8), or no exposure (Control, n = 8). The Magnet Group showed a taste aversion on the first day of preference testing (p < 0.05). Experiment 2 employed the same US-CS protocol for 3 consecutive days of conditioning. The Magnet Group demonstrated a taste aversion for the postexposure Days 1-8 (p < 0.01). There was no difference between the Sham and Control Groups in either experiment. The results of this study clearly demonstrate that the rats associated the G+S solution with the experience of being exposed to the high magnetic field and avoided the solution in subsequent presentations.

Animals↗

PubMed1998

False negative factor V Leiden assay following allogeneic stem cell transplant.

We report a case where a phenotypic test (an activity assay for activated protein C resistance) correctly indicated that the patient had an abnormality, whereas the initial genetic test (a PCR-based DNA assay used to detect the mutation in the FV gene) incorrectly indicated that the patient did not. The apparent false negative result of the DNA-based test was due to the use of peripheral blood leucocytes for DNA analysis. The patient had undergone a stem cell transplant several months before, and the leucocytes in her blood were derived from the stem cell donor, which lacked the FV defect.

Blood Protein Disorders↗

PubMed1998

The anticarcinogenic conjugated fatty acid, 9c, 11t-18:2, in human milk: confirmation of its presence.

The concentration of the anticarcinogenic fatty acid, 9c, 11t-18:2, in human milk was determined by gas-liquid chromatography (GLC). The mean concentration of 20 samples from 5 women taken at 1, 7, 14, and 21 days was: 0.18% +/- 0.02; range, 0.14-0.28%. Identity was confirmed by GLC-mass spectrometry (MS). Conjugated isomers other than 9c, 11t-18:2 were not detected. The amounts were not changed by supplementation of the maternal diet with fish oil beginning on day 1 after the milk sample was taken.

Anticarcinogenic Agents↗

PubMed1998

Macromolecular structure and self-assembly.

The output from the molecular biology revolution has grown steadily and logarithmically from the first protein sequence, insulin (Ryle AP et al 1955 Biochem J 60:541-556), the first three-dimensional atomic structure of a macromolecule, myoglobin (Kendrew JC et al 1960 Nature 185:422-427), the first DNA gene sequence, phi X174 gene J (Sanger F et al 1977 Nature 265:687-695) and the first genome sequence for a free-living organism, Haemophilus influenzae (Fleischmann RD et al 1995 Science 269:496-512) to the current situation where the output rate is close to one new gene sequence every few minutes, several new three-dimensional structures a day and a new (bacterial) genome completed every few months. Those working in this field must readjust their horizons to this changing situation every year or two. In the area of three-dimensional structure of macromolecules and macromolecular assemblies, the methods of X-ray crystallography, nuclear magnetic resonance and electron microscopy have combined to produce powerful insights into how these molecular machines work. In this paper, I present three examples of molecular machines whose structure tells us a lot about how they work. These are the light-driven proton pump bacteriorhodopsin, the ATP synthetase molecule which contains a tiny motor and generator, and the flagellar rotary motor which provides the thrust to power physical movement of the bacterial cell. The structure itself in three-dimensional detail is thus often seen to provide the most important single insight into how things work, reducing biology to chemistry and physics. The reductionist approach in this field seems to be limited only by the accuracy by which it is possible to describe inter- and intra-molecular interactions in terms of hydrogen bonds, van der Waals interactions and electrostatic forces. At present, there is no fundamental limit in sight.

Animals↗

PubMed1997

Electron diffraction studies of light-induced conformational changes in the Leu-93 --> Ala bacteriorhodopsin mutant.

We previously have presented evidence for prominent structural changes in helices F and G of bacteriorhodopsin during the photocycle. These changes were determined by carrying out electron diffraction analysis of illuminated two-dimensional crystals of wild-type bacteriorhodopsin or the Asp-96 --> Gly mutant that were trapped at a stage in the photocycle after light-driven proton release, but preceding proton uptake from the aqueous medium. Here, we report structural analysis of the long-lived O intermediate observed in the photocycle of the Leu-93 --> Ala mutant, which accumulates after the release and uptake of protons, but before the reisomerization of retinal to its initial all-trans state. Projection Fourier difference maps show that upon illumination of the Leu-93 --> Ala mutant, significant structural changes occur in the vicinity of helices C, B, and G, and to a lesser extent near helix F. Our results suggest that (i) all four helices that line the proton channel (B, C, F, and G) participate in structural changes during the late stages of the photocycle, and (ii) completion of the photocycle involves significant conformational changes in addition to those that are associated with steps in proton transport.

Bacteriorhodopsins↗

PubMed1997

Maternal vitamin A deficiency and child growth failure during human immunodeficiency virus infection.

Although vitamin A is thought to influence growth, the relationship between maternal vitamin A deficiency during pregnancy and child growth is unknown. A longitudinal cohort study of 467 HIV-infected women and their children was conducted in Blantyre, Malawi. The children's weight and height were measured every 3 months until they were 24 months old. Maternal vitamin A deficiency was independently related to both linear and ponderal growth after adjustment for effects of body mass index, child gender, and child HIV status. By 12 months of age, infants born to mothers who were vitamin A-deficient during pregnancy weighed approximately 8% less (p < 0.001) and were approximately 2% shorter (p < 0.001) than infants born to mothers who were not deficient. This study suggests children born to HIV-infected women who are vitamin A-deficient during pregnancy are more likely to have growth failure.

Age Factors↗

PubMed1997

A controlled trial of fluoxetine in nondepressed patients with Huntington's disease.

To examine the antidepressant specificity of fluoxetine in Huntington's disease (HD), we carried out a randomized, double-blind, placebo-controlled trial of this medication in nondepressed HD patients. Thirty patients with early HD who were depressed (Hamilton Depression Inventory < 16) were randomized to placebo (N = 13) or fluoxetine 20 mg/day (N = 17) and were followed up for 4 months. Outcome measures included changes in total functional capacity (TFC) and in standardized neurological, cognitive, and behavioral ratings. After adjustment for the higher education level found in the placebo group at baseline, no differences between the treatment groups were found in TFC, neurological, or cognitive ratings. Fluoxetine-treated patients did show a slight reduction in agitation and in the need for routine. Although fluoxetine may be a useful antidepressant in depressed HD patients, it failed to exert substantial clinical benefits in nondepressed HD patients.

Adult↗

PubMed1997

Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis.

Branching morphogenesis of the embryonic lung requires interactions between the epithelium and the mesenchyme. Previously, we reported that Sonic hedgehog (Shh) transcripts are present in the epithelium of the developing mouse lung, with highest levels in the terminal buds. Here, we report that transcripts of mouse patched (Ptc), the homologue of a Drosophila gene encoding a putative transmembrane protein required for hedgehog signaling, are expressed at high levels in the mesenchyme adjacent to the end buds. To investigate the function of SHH in lung development, Shh was overexpressed throughout the distal epithelium, using the surfactant protein-C (SP-C)-enhancer/promoter. Beginning around 16.5 dpc, when Shh and Ptc RNA levels are normally both declining, this treatment caused an increase in the ratio of interstitial mesenchyme to epithelial tubules in transgenic compared to normal lungs. Transgenic newborn mice die soon after birth. Histological analysis of the lungs at the light and electron microscope level shows an abundance of mesenchyme and the absence of typical alveoli. In vivo BrdU labeling indicates that Shh overexpression results in increased mesenchymal and epithelial cell proliferation at 16.5 and 17.5 dpc. However, analysis of CC-10 and SP-C expression reveals no significant inhibition in the differentiation of proximal and distal epithelial cells. The expression of genes potentially regulated by SHH was also examined. No difference could be observed between transgenic and control lungs in either the level or distribution of Bmp4, Wnt2 and Fgf7 RNA. By contrast, Ptc is clearly upregulated in the transgenic lung. These results thus establish a role for SHH in lung morphogenesis, and suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo.

Animals↗

PubMed1997

Profiles of hope.

Explore the source record for details and available documents.

Attitude to Death↗

PubMed1997

Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed.

The incidence of gastric, colonic, and rectal cancers was determined in a cohort of 73,076 men and women chronically immunosuppressed after heart or renal transplantation, to test the hypothesis that there would be a reduced incidence of gastric cancer by dampening chronic gastritis secondary to infection caused by Helicobacter pylori. Follow-up was from 1-13 years. No change in the incidence of gastric cancer was found (32 cases observed, 32.86 expected). An increase in colon cancer was found (75 cases observed, 62.27 expected). A significant reduction in the incidence of rectal cancer was found (15 cases observed, 41.5 expected). This led to a chi2 of 16.92 with 1 degree of freedom, significant at the 0.1% level. The effect was greater in men than women and more marked in heart recipients than in those receiving renal transplants. This unexpected finding led to a review of experiments in mice and rats that present evidence for immune promotion of large-bowel cancers induced by carcinogens by gut-associated lymphoid tissue. We conclude that an analysis of immune function in gut-associated lymphoid tissue in the stomach, colon, and rectum in healthy and immunosuppressed patients may lead to a better understanding of immunosurveillance in the colon and immune promotion of rectal cancers.

Animals↗

PubMed1996

Association of the APOE epsilon 4 allele with clinical subtypes of late life depression.

The APOE genotypes of 45 elderly inpatients with major depression were determined to investigate the relationship of this disorder to irreversible dementia in late life. We specifically tested the hypothesis that the frequency of the APOE epsilon 4 allele is elevated in depressed elders with cognitive impairment or psychotic features, subtypes that have been reported to be at increased risk of developing Alzheimer's disease (AD). The frequency of epsilon 4 allele was not elevated in the overall group of 45 inpatients and, contrary to our expectation, was not associated with cognitive impairment in this group. In contrast, the epsilon 4 allele frequency for the patients with psychotic features was nearly four times that for the patients without psychotic features and nearly double that of elderly controls. These data suggest that elderly depressed inpatients with cognitive impairment are at risk for developing AD by an epsilon 4-independent pathway, while those with psychotic features are at risk for developing AD by an epsilon 4-dependent pathway. These findings suggest that subtypes of idiopathic major depression in late life may serve as landmarks that distinguish separable pathogenetic pathways to AD.

Age of Onset↗