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Biomedical subjects

D R McMillan

Publications and source records attributed to D R McMillan.

At least 19 recordsLinked to original sources
PubMed2001

Development and implementation of an information management and information technology strategy for improving healthcare services: a case study.

PeaceHealth is a multistate, not-for-profit integrated delivery network that owns and operates five acute care hospitals, one critical access hospital, and twenty-five outpatient clinics. PeaceHealth employs approximately two hundred physicians and seventy allied health professionals; it has relationships with one thousand affiliated physicians. In 1990, PeaceHealth developed a set of strategic priorities for delivering seamless care across the continuum, and creating partnerships between caregivers and patient-consumers. A major component of these strategies was development and implementation of the technology, knowledge, organizational, and community infrastructures that would support delivering and using high-quality, timely information when and where it is needed for effective clinical, operational, and financial decision making. Executing this strategy has resulted in implementation of standard enterprisewide information systems, including a computer-based patient record system in inpatient and outpatient settings, tactical and strategic decision support systems, a well-developed intranet and access to the Internet, and a knowledgeable workforce that have enabled PeaceHealth to support and improve its services and business by bringing interactive information directly to patients, caregivers, managers, directors, and executives. This case study discusses the drivers behind the development of this strategy, specific components of the information management and information technology infrastructure, examples of the impact they have had on patients, caregivers, and the organization, and lessons learned.

Computer Communication Networks↗
PubMed2000

Sequence similarities between a novel putative G protein-coupled receptor and Na+/Ca2+ exchangers define a cation binding domain.

cDNA clones encoding a novel putative G protein-coupled receptor have been characterized. The receptor is widely expressed in normal solid tissues. Consisting of 1967 amino acid residues, this receptor is one of the largest known and is therefore referred to as a very large G protein-coupled receptor, or VLGR1. It is most closely related to the secretin family of G protein-coupled receptors based on similarity of the sequences of its transmembrane segments. As demonstrated by cell surface labeling with a biotin derivative, the recombinant protein is expressed on the surface of transfected mammalian cells. Whereas several other recently described receptors in this family also have large extracellular domains, the large extracellular domain of VLGR1 has a unique structure. It has nine imperfectly repeated units that are rich in acidic residues and are spaced at intervals of approximately 120 amino acid residues. These repeats resemble the regulatory domains of Na+/Ca2+ exchangers as well as a component of an extracellular aggregation factor of marine sponges. Bacterial fusion proteins containing two or four repeats specifically bind 45Ca in overlay experiments; binding is competed poorly by Mg2+ but competed well by neomycin, Al3+, and Gd3+. These results define a consensus cation binding motif employed in several widely divergent types of proteins. The ligand for VLGR1, its function, and the signaling pathway(s) it employs remain to be defined.

Adrenal Glands↗
PubMed1999

HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice.

HSF1 is the major heat shock transcriptional factor that binds heat shock element (HSE) in the promoter of heat shock proteins (Hsps) and controls rapid Hsp induction in cells subjected to various environmental stresses. Although at least four members of the vertebrate HSF family have been described, details of their individual physiological roles remain relatively obscure. To assess whether HSF1 exhibited redundant or unique in vivo functions, we created Hsf1(-/-) deficient mice. We demonstrate that homozygous Hsf1(-/-) mice can survive to adulthood but exhibit multiple phenotypes including: defects of the chorioallantoic placenta and prenatal lethality; growth retardation; female infertility; elimination of the 'classical' heat shock response; and exaggerated tumor necrosis factor alpha production resulting in increased mortality after endotoxin challenge. Because basal Hsp expression is not altered appreciably by the HSF1 null mutation, our findings suggest that this factor, like Drosophila Hsf protein, might be involved in regulating other important genes or signaling pathways. Our results establish direct causal effects for the HSF1 transactivator in regulating critical physiological events during extra-embryonic development and under pathological conditions such as sepsis to modulate pro-inflammatory responses, indicating that these pathways have clinical importance as therapeutic targets in humans.

Animals↗
PubMed1998

Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease.

How a cell responds to stress is a central problem in cardiovascular biology. Diverse physiological stresses (eg, heat, hemodynamics, mutant proteins, and oxidative injury) produce multiple changes in a cell that ultimately affect protein structures and function. Cells from different phyla initiate a cascade of events that engage essential proteins, the molecular chaperones, in decisions to repair or degrade damaged proteins as a defense strategy to ensure survival. Accumulative evidence indicates that molecular chaperones such as the heat shock family of stress proteins (HSPs) actively participate in an array of cellular processes, including cytoprotection. The versatility of the ubiquitous HSP family is further enhanced by stress-inducible regulatory networks, both at the transcriptional and posttranscriptional levels. In the present review, we discuss the regulation and function of HSP chaperones and their clinical significance in conditions such as cardiac hypertrophy, vascular wall injury, cardiac surgery, ischemic preconditioning, aging, and, conceivably, mutations in genes encoding contractile proteins and ion channels.

Adaptation, Physiological↗
PubMed1998

Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis.

Heat shock transcription factor 1 (HSF1) is a member of the vertebrate HSF family that regulates stress-inducible synthesis of heat shock proteins (HSPs). Although the synthesis of the constitutively expressed and inducible members of the heat shock family of stress proteins correlates with increased cellular protection, their relative contributions in acquired cellular resistance or "thermotolerance" in mammalian cells is presently unknown. We report here that constitutive expression of multiple HSPs in cultured embryonic cells was unaffected by disruption of the murine HSF1 gene. In contrast, thermotolerance was not attainable in hsf1(-/-) cells, and this response was required for protection against heat-induced apoptosis. We conclude that 1) constitutive and inducibly expressed HSPs exhibit distinct physiological functions for cellular maintenance and adaptation, respectively, and 2) other mammalian HSFs or distinct evolutionarily conserved stress response pathways do not compensate for HSF1 in the physiological response to heat shock.

Alleles↗
PubMed1994

The cellular response to unfolded proteins: intercompartmental signaling.

Both prokaryotic and eukaryotic cells respond to the accumulation of unfolded proteins by increasing the transcription of genes encoding molecular chaperones and other stress-responsive proteins. Different sets of genes are activated when particular cellular compartments are burdened with unfolded proteins. Cells thus maintain mechanisms to monitor changes in the concentration of unfolded proteins not only in the cytosol, but also in membrane-bound extracytoplasmic compartments. During the past year, work in yeast has identified a transmembrane receptor that appears to play a pivotal role in the regulation of protein folding. This receptor monitors the concentration of available chaperone molecules in the endoplasmic reticulum and transmits a signal to the cytosol to activate the transcription of nuclear genes encoding chaperones that are localized in the endoplasmic reticulum. Work using Escherichia coli suggests that prokaryotes also contain an intercompartmental 'unfolded protein' signaling pathway, in this case from the periplasmic space or outer membrane to the cytoplasm.

Animals↗
PubMed1992

The expression and characterization of rat IgE produced by construction of the epsilon-heavy chain gene from exon modules.

A system of exon "modules" was produced from the functionally rearranged epsilon-heavy gene isolated from the rat IgE-secreting immunocytoma IR162. The five individual exons, encoding the variable and constant region domains, were isolated and subcloned into the multiple cloning site of a pair of plasmid vectors with opposed orientation multiple cloning sites. The use of opposed orientation multiple cloning sites and the flanking restriction enzyme sites contained therein allows for the modular manipulation of the gene. These exon modules were initially used to reconstruct the epsilon-heavy chain gene into the native configuration to demonstrate the efficacy of the modular system for synthesis of IgE. Upon transfection into the rat myeloma cell line Y3, the reconstructed gene produced a polypeptide that associated with the endogenous light chain polypeptide and was secreted from the cell as tetrameric IgE. All physical and functional characterizations indicate that the IgE molecule produced is indistinguishable from native IR162 IgE. This modular system of exons will facilitate the manipulation of IgE structure through the systematic assembly of different epsilon-heavy chain mutant constructions. The resulting novel IgE proteins will be very useful to study the molecular nature of the interaction of IgE with its Fc receptor.

Animals↗
PubMed1989

Centers of rotation during jaw movements.

Anatomists consider the articulation of movable joints to be complex, involving movable instantaneous centers of rotation (ICR). However, prosthodontists often treat the temporomandibular joint (TMJ) as a model of a simple hinge. The aim of this study was to examine the case for a movable ICR during habitual opening and closing jaw movements. Young, dentate subjects were examined with a kinesiograph. Jaw movements were performed and recorded. The center of rotation of each movement pattern was identified, and its location related to the position of the TMJ. The results showed that opening and closing jaw movements were predominantly non-coincident, with a movable ICR located at a variable distance and direction from the TMJ. There was no evidence to suggest that the TMJ functioned as a simple hinge during jaw movements.

Adult↗
PubMed1987

The position and branching pattern of the facial nerve and their effect on transcutaneous electrical stimulation in the orofacial region.

A significant proportion (31%) of southern (Hong Kong) Chinese patients who received therapeutic transcutaneous electrical stimulation with the Myo-Monitor experienced uncomfortable twitching of the muscles of facial expression of the upper and middle portions of the face. This can be attributed, at least in part, to anatomic variation in the position and branching pattern of the upper (temporofacial) division of the facial nerve in the sample population. Our observations of living patients support the contention that muscular contraction resulting from Myo-Monitor stimulation is neurally mediated.

Aged↗
PubMed1986

A comparison of habitual jaw movements and articulator function.

Inherent in adjustable articulators are errors related either to recordings from the patient or to adjustments to the instrument, or both. Furthermore, the validity of the geometric concepts on which the design of these instruments is based, stressing the dominant role of the temporomandibular joints in mandibular movements, is open to question. Microchip technology now makes it possible to view jaw movements in three dimensions while impeding physiological activity minimally. Using a kinesiograph, young dentate Swedish and Chinese adults were examined on two occasions, and the magnitude and direction of some jaw movements were recorded. The results showed that voluntary opening and closing excursions of the mandible frequently followed disparate paths and that closure from the rest position to occlusion was three-dimensional, a lateral component of movement being usual. Retruded contact position was both uncomfortable and unstable. These findings suggest that current procedures for designing and refining occlusal schemes on articulators are invalid.

Adult↗
PubMed1981

Comparison of DNA damage by methylmelamines and formaldehyde.

The cytoxicity and DNA damaging activity of S9-activated hexamethylmelamine (HMM) and pentamethylmelamine (PMM) were compared with suspected active metabolites in mouse leukemia L1210 cells. The presence of semicarbazide hydrochloride did not alter the cytotoxicity of S9-activated HMM and PMM or that of their hydroxylated analogs monomethylolpentamethylmelamine (MPM) and trimethyloltrimethylmelamine (TTM), which have been suggested as active metabolites. Following treatment of L1210 cells with high concentrations of activated HMM and PMM, there were no DNA single-strand breaks or interstrand cross-links observed by DNA alkaline elution and only a low frequency of DNA-protein cross-links. Formaldehyde (FA) at nonlethal concentrations caused far greater DNA-protein cross-linking. In contrast, the polyfunctional TTM produced both DNA-protein cross-linking and DNA interstrand cross-linking. The cytotoxicities of HMM and PMM were found unlikely to be related to extracellular or intracellular release of FA.

Altretamine↗
PubMed1978

Age changes in the perception of comfortable mandibular occlusal positions.

It has been shown that a zone of comfort in maxillo-mandibular relationships in edentulous subjects can be identified with some precision. Whilst the neurophysiological mechanism involved has not been explained fully, the phenomenon is influenced by starting position and by fatigue. This experiment was set up to test the hypothesis that age is another significant factor in perception of the comfortable zone. A group of seventeen subjects with a mean age of 62 years and an equivalent younger group, the mean age of which was 28 years, were tested with Timmer screw jacks applied using the central approach to record the upper and lower limits of the zone fifteen times in succession for each subject. A linear statistical model was used to analyse the data from upper and lower borders separately. The results showed that the effect of making successive adjustments, whilst not significant statistically in the young group, was significant in the more elderly. Regression lines from the young group data were horizontal signifying the high degree of accuracy with which their perceptual mechanisms worked: the upwards inclination of those from the more elderly was interpreted as showing that initial appreciations were subjected to constant correction.

Adolescent↗
PubMed1977

A new intra-oral screw jack.

A new pattern of screwjack for assessing the vertical dimension for occlusion utilizing an edentulous patient's proprioceptive sensation is described. It provides a greater range of movement than other, giving infinitely variable heights between 9 and 21 mm. The elements being captive, it cannot come to pieces in use. Laboratory experiments were contrived to define the magnitude of reading errors and the play in the screw threads. It was found that, only in instances where a graduation related closely to the datum mark, did errors of interpretation arise. These were found to exceed the height set for test purposes by 0-1 mm consistently. An error of this order is of no practical significance clinically and is no impediment to such an application of the device. Mean play in the new pattern jacks was 0-01 mm compared to 0-05 mm in the Timmer versions. In a clinical experiment the performance of the screw was compared to that of Timmer. Statistical evidence was found which suggested a functional difference between the two, the new pattern being significantly more accurate.

Aged↗
PubMed1977

A comparative study of three different approaches to the comfortable zone.

By means of a screw jack device, applied to thirteen edentulous subjects, the comfortable zone was approached in three different ways, by the central, the internal and the external approaches. Correspondingly, the zonal borders behaved differently. Applying the central approach it was found that the initial height of the screw jack had a lingering effect upon subsequent adjustments of the screw. Moreover, lower border data collected by the external approach distinguished themselves from other zonal border data by showing a significantly lower susceptibility to successive adjustments. The study suggests that muscle activity is a factor on which the perceptual mechanism relies, when a zonal border is assessed subjectively by a patient.

Aged↗
PubMed1976

The fallacy of facial measurements of occlusal height in edentulous subjects.

A controlled trial was made using fifteen subjects and making 120 measurements with a caliper gauge between marks disposed on the upper lip and the point of the chin when maxillo-mandibular relationships were altered vertically by known amounts within a range of 6 mm. It was found that mean facial measurements could account for only half of the skeletal movement involved. The variability of soft tissue translation in relation to skeletal movement led to the conclusion that such facial measurements are inappropriate to clinical practice.

Adult↗
PubMed1976

The linear model: a statistical tool applied to psychophysical research in dental prosthetics.

The construction of a linear model is described, and its function in analysing variations in the perception of comfortable mandibular occlusal positions is explained. In principle, the model combines analyses of variance and regression in a number of simple computer operations. Data from a clinical study were used to demonstrate the analytical capacity of a specific model, designed to estimate the effect of factors, which were supposed to influence the perception of comfortable mandibular positions.

Adult↗