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Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 523 records · Page 29Linked to original sources

Crystallization and preliminary X-ray diffraction analysis of nuclear transport factor 2.

We have cloned and expressed in Escherichia coli cDNA for rat nuclear transport factor 2 (NTF2), a key cytoplasmic factor that facilitates the import of proteins into the nucleus through nuclear pores. We have used this bacterially expressed material to produce orthorhombic crystals suitable for high-resolution X-ray diffraction structure determination. The crystals have P212121 symmetry with a = 55.9 A; b = 56.7 A; c = 88.3 A and diffract past 2 A on laboratory X-ray sources. The asymmetric unit of these crystals contains two NTF2 polypeptide chains, consistent with the reported dimeric structure of the molecule.

Amino Acid Sequence↗

New crystal forms of the motile major sperm protein (MSP) of Ascaris suum.

We have obtained two new crystal forms of the Ascaris major sperm protein (MSP) that mediates amoeboid cell motility in nematode sperm. We obtained crystals with C2 symmetry from bacterially expressed alpha-MSP with a = 216.5 A, b = 38.6 A, c = 32.5 A, gamma = 93.1 degrees and also crystals with P2(1) symmetry from native beta-MSP with a = 63.1 A, b = 91.7 A, c = 72.5 A, gamma = 91.3 degrees. A full native data set has been collected for each crystal form using synchrotron radiation. Both crystal forms diffract to 2 A and are suitable for high-resolution structural investigation.

Amino Acid Sequence↗

A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex.

The effects of different orientations of a Cadwell round magnetic coil (MC) were compared with each other and with surface electrical stimulation of motor cortex in monkeys anesthetized with pentobarbital or urethane. Recordings were made from within the lateral corticospinal tract, either from axonal populations or with a microelectrode from individual axons. A lateral-sagittally orientated MC directly excited corticospinal neurons at lower stimulus intensity than was required for indirect, i.e., transsynaptic excitation via inputs to corticospinal neurons. By contrast, in 2 out of 3 macaques tested, a vertex-tangential orientation could excite corticospinal neurons indirectly at lower intensities than were required for direct excitation; at higher intensities, direct excitation also occurred. The site of direct corticospinal excitation by a lateral-sagittally orientated MC was inferred by comparing the response variability and latency to MC and surface electrical stimuli. Cathodal stimuli elicited more variable corticospinal population responses and later individual axonal responses than were obtained with anodal stimuli. The variability in response is attributed to interaction between nearby, on-going synaptic bombardment and the stimulus, implying that surface cathodal stimuli directly activate corticospinal neurons at the spike trigger zone (presumably the initial segment). By contrast, the consistency and reduced latency of the corticospinal responses to surface anodal stimuli are attributed to the direct excitation of corticospinal fibers within the white matter. When the stimulus intensity is clearly above threshold, surface anodal and cathodal stimuli can activate corticospinal neurons both directly and indirectly. Direct corticospinal excitation by the MC can resemble the effects of either surface anodal or surface cathodal stimuli. We conclude that the MC can activate corticospinal neurons at the spike trigger zone or their fibers deeper in white matter. The findings in the monkey are used to interpret the effects of different MC orientations in the human.

Action Potentials↗

Telephone support for Canadian nurses in HIV/AIDS care.

An assessment study was conducted with Canadian nurses (N = 177) in HIV/AIDS care to determine how social support influences the relationship between job stress and health (job satisfaction and burnout). The assessment study revealed that social support and coping both moderate the effects of these stressors on nurses' health and functioning outcomes (i.e., job satisfaction and burnout). Accordingly, the follow-up study tested the effectiveness of an intervention designed to enhance social support, promote the use of certain coping strategies for managing occupational stress, and prevent burnout in nurses. Telephone support groups, co-led by an expert facilitator and an expert AIDS nurse, were tested in a demonstration project for nurses in HIV/AIDS care (n = 30). The nurse participants reported that the intervention enhanced their coping, confidence, relationships, client care, and connections to the HIV/AIDS nursing community.

Acquired Immunodeficiency Syndrome↗

Electron microscopy of frozen-hydrated biological material.

The electron microscopy of frozen-hydrated specimens has the potential to allow biological material to be examined in conditions very similar to the native state, and so has excited considerable interest. Although not all of the problems associated with the method have been solved, the technique has already provided important insights into macromolecular structure and assembly and promises to be a powerful tool for investigating the structure of cellular components and their interactions.

Crystallography↗

Promoting positive affect and diminishing loneliness of widowed seniors through a support intervention.

Seniors are most vulnerable to conjugal bereavement. Although social support buffers the effects of bereavement, widows and widowers have lower levels of social support than married individuals. Self-help/support groups can supplement support from their depleted natural networks. Accordingly, the aim of this demonstration project was to examine the impact of support groups on widowed seniors' loneliness, affect, and perceived support. Four face-to-face support groups for widowed seniors were conducted weekly for a maximum of 20 weeks. Participants completed pretest, posttest, and delayed posttest measures of support need and support satisfaction, positive and negative affect, and loneliness/isolation. The statistically significant impacts of the intervention were enhanced support satisfaction, diminished support needs, and increased positive affect. There was a trend toward decreased social isolation and emotional loneliness. In postintervention semistructured interviews, bereaved seniors reported increased hope, improved skills in developing social relationships, enhanced coping, new role identities, and less loneliness. Community health nurse researchers could conduct randomized controlled trials of face-to-face and telephone support groups for bereaved people of all ages. Community health nurse practitioners could benefit from lessons learned about timing, duration, and selection of sensitive outcomes.

Aged↗

Inheritance of a new bleeding disease in a herd of swine with Willebrand's disease.

A herd of swine affected by Willebrand's disease was begun in 1967 at the Mayo Clinic in order to study the inherited hemostatic abnormality in swine as a model for the human disease. Affected individuals have bleeding times in excess of 15 minutes, extremely low levels of Willebrand factor (less than or equal to 0.25 percent of normal), and decreased levels of VIII coagulant activity. Individuals with long bleeding times, higher levels of Willebrand factor and normal levels of VIII coagulant activity began to appear in the colony. It is hypothesized that this new (N) condition is inherited as a simple autosomal recessive (N/n) at a locus separate and independent of the similarly autosomal recessive (A/a) von Willebrand locus. In addition, the Willebrand locus is epistatic to the N locus, i.e., individuals will only express the new condition provided there is at least one normal allele at the von Willebrand locus. Therefore, individuals with genotype aa--are all von Willebrand phenotypically, and A-nn individuals have the new disease.

Animals↗

Alcohol withdrawal syndromes: clinical management with lofexidine.

Sixty-three mainly male alcoholics were randomly assigned to placebo or lofexidine treatment for 48 hr shortly after admission to the hospital. Their starting points were similar regarding their semiquantitative estimates of alcohol withdrawal symptoms (AWS). Their demographics, histories of past alcohol use, physical findings, and laboratory abnormalities usually associated with alcoholism were similar. Starting 3 hr after 0.4 mg of oral lofexidine, which was given every 6 hr as eight doses, the AWS scores were significantly lower than those of the placebo group. Hypotension was the strongest finding. Six placebo recipients had to be prematurely interrupted due to increasing or intolerable alcohol withdrawal symptoms and switched to a benzodiazepine. Only one lofexidine recipient was prematurely interrupted, due to transient hallucinations. The study has a large placebo effect, as both groups of patients rated the treatment process very highly. Lofexidine, an alpha 2-adrenergic agonist, was superior to placebo in alcohol withdrawal. This drug, as with its analogue clonidine, may represent a new and important pharmacological treatment for alcohol withdrawal symptoms.

Adult↗

Alcohol versus natural drying for newborn cord care.

OBJECTIVE: To compare alcohol cleaning and natural drying of newborn umbilical cords. DESIGN: Prospective, randomized controlled trial. SETTING: Tertiary-level university teaching hospital and level II community hospital. PARTICIPANTS: Of 1,876 singleton full-term newborns enrolled, 1,811 completed the study. INTERVENTIONS: Newborns, from birth until separation of the cord, were randomized to either (a) umbilical cleansing with 70% isopropyl alcohol at each diaper change or (b) natural drying of the umbilical site without special treatment. MAIN OUTCOME MEASURES: Umbilical infection, cord separation time, maternal comfort, and cost. RESULTS: No newborn in either group developed a cord infection. Primary care providers obtained cultures for cord concerns in 32 newborns (1.8%), with colonization for normal flora, Staphylococcus aureus, and Group B streptococcus proportionately equal in alcohol and air dry groups. Cord separation time was statistically significantly different (alcohol group, 9.8 days; natural drying group, 8.16 days; t = 8.9, p = < .001). Mothers described similar comfort with cord care and relief with cord separation. Costs of alcohol drying while in the hospital were greater than those of natural drying. CONCLUSIONS: (a) Evidence does not support continued use of alcohol for newborn cord care; (b) health care providers should explain the normal process of cord separation, including appearance and possible odor; and (c) health care providers should continue to develop evidence to support or eliminate historic practices.

2-Propanol↗

Three-dimensional optical tomographic brain imaging in small animals, part 1: hypercapnia.

In this study, we explore the potential of diffuse optical tomography for brain oximetry. While several groups have already reported on the sensitivity of optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood volume, these studies were often limited to single source-detector geometries or topographic maps, where signals obtained from within the brain are projected onto 2-D surface maps. In this two-part study, we report on our efforts toward developing a volumetric optical imaging system that allows one to spatially resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the instrumentation, optical probe design, and the model-based iterative image reconstruction algorithm employed in this work. Consideration of how a priori anatomical knowledge can be incorporated in the reconstruction process is presented. This system is then used to monitor global hemodynamic changes that occur in the brain under various degrees of hypercapnia. The physiologic cerebral response to hypercapnia is well known and therefore allows an initial performance assessment of the imaging system. As expected, we observe global changes in blood volume and oxygenation, which vary linearly as a function of the concentration of the inspired carbon dioxide. Furthermore, experiments are designed to determine the sensitivity of the reconstructions of only 1 mm to inaccurate probe positioning. We determine that shifts can significantly influence the reconstructions. In part 2 we focus on more local hemodynamic changes that occur during unilateral carotid occlusion performed at lower-than-normal systemic blood pressure. In this case, the occlusion leads to a predominantly monohemispherically localized effect, which is well described in the literature. Having explored the system with a well-characterized physiologic effect, we investigate and discuss the complex compensatory cerebrovascular hemodynamics that occur at normotensive blood pressure. Overall, these studies demonstrate the potential and limitations of our diffuse optical imager for visualizing global and focal hemodynamic phenomenon three dimensionally in the brains of small animals.

Algorithms↗

Three-dimensional optical tomographic brain imaging in small animals, part 2: unilateral carotid occlusion.

This is the second part of a two-part study that explores the feasibility of 3-D, volumetric brain imaging in small animals by optical tomographic techniques. In part 1, we demonstrated the ability to visualize global hemodynamic changes in the rat head in response to elevated levels of CO(2) using a continuous-wave instrument and model-based iterative image reconstruction (MOBIIR) algorithm. Now we focus on lateralized, monohemispherically localized hemodynamic effects generated by unilateral common carotid artery (CCA) occlusion. This illustrates the capability of our optical tomographic system to localize and distinguish hemodynamic responses in different parts of the brain. Unilateral carotid occlusions are performed in ten rodents under two experimental conditions. In the first set of experiments the normal systemic blood pressure is lowered to 50 mmHg, and on unilateral carotid occlusion, we observe an ipsilateral monohemispheric global decrease in blood volume and oxygenation. This finding is consistent with the known physiologic response to cerebral ischemia. In a second set of experiments designed to observe the spatial-temporal dynamics of CCA occlusion at normotensive blood pressure, more complex phenomena are observed. We find three different types of responses, which can be categorized as compensation, overcompensation, and noncompensation.

Algorithms↗

Rebound hypertension during initiation of transdermal clonidine.

Rebound hypertension with a neurological complication occurred during an attempt to substitute transdermal for oral clonidine in a patient with severe hypertension. Published studies have not established an unequivocal correlation between previous oral clonidine dose and the dose of transdermal clonidine required for equally effective antihypertensive therapy. Close observation of blood pressure may be advisable for at least one week following substitution of transdermal for oral clonidine, especially in patients with severe hypertension.

Administration, Cutaneous↗