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Biomedical subjects

P McConnell

Publications and source records attributed to P McConnell.

At least 19 recordsLinked to original sources
PubMed2002

A framework for integrating the songbird brain.

Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors.

Animals↗
PubMed2001

Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion.

Acetaminophen is a phenol with antioxidant properties, but little is known about its actions on the mammalian myocardium and coronary circulation. We studied isolated, perfused guinea pig hearts, and tested the hypothesis that acetaminophen-treated hearts would be protected during ischemia-reperfusion. Acetaminophen concentrations in the range of 0.3-0.6 mmol/l caused modest but significant (P < 0.05) coronary vasoconstriction and positive inotropy. The effects were more brisk during constant pressure perfusion than during constant flow. During 20 min of low-flow, global myocardial ischemia and 40 min of reperfusion, hearts treated with acetaminophen retained or recovered a greater percentage of left ventricular function than hearts treated with vehicle. Myofibrillar ultrastructure appeared to be preserved in the reperfused myocardium with acetaminophen. By using chemiluminescence and spin-trap methodologies, we investigated acetaminophen-mediated antioxidant mechanisms to help explain the cardioprotection. The burst of hydroxyl radicals seen between 0 and 10 min of reperfusion was significantly attenuated (P < 0.05) by acetaminophen but not by vehicle. The 3-morpholinosydnominine (SIN-1) generation of peroxynitrite and its oxidative interaction with luminol to produce blue light during ischemia-reperfusion was also blocked by acetaminophen. Our results show that acetaminophen provides significant functional and structural protection to the ischemic-reperfused myocardium, and the mechanism of cardioprotection seems to involve attenuation of the production of both hydroxyl radicals and peroxynitrite.

Acetaminophen↗
PubMed2000

Variations in the normal anatomy of the collateral ligaments of the human elbow joint.

The variations which occur in the medial and lateral ligament complexes of the elbow were investigated. These occurred frequently with the standard appearances occurring in no more than half the specimens on the medial side and one quarter of those on the lateral side. Surgeons who regularly perform elbow arthroplasty must be aware of these considerations, especially with the introduction of unconstrained prostheses which rely upon the ligament complex for their postoperative stability.

Aged↗
PubMed1998

Application of electrospray ionization mass spectrometry for studying human immunodeficiency virus protein complexes.

Mass spectrometry (MS) with electrospray ionization (ESI) has shown utility for studying noncovalent protein complexes, as it offers advantages in sensitivity, speed, and mass accuracy. The stoichiometry of the binding partners can be easily deduced from the molecular weight measurement. In many examples of protein complexes, the gas phase-based measurement is consistent with the expected solution phase binding characteristics. This quality suggests the utility of ESI-MS for investigating solution phase molecular interactions. Complexes composed of proteins from the human immunodeficiency virus (HIV) have been studied using ESI-MS. Multiply charged protein dimers from HIV integrase catalytic core (F185K) and HIV protease have been observed. Furthermore, the ternary complex between HIV protease dimer and inhibitor pepstatin A was studied as a function of solution pH. Zinc binding to zinc finger-containing nucleocapsid protein (NCp7) and the NCp7-psi RNA 1:1 stoichiometry complex was also studied by ESI-MS. No protein-RNA complex was observed in the absence of zinc, consistent with the role of the zinc finger motifs for RNA binding.

Amino Acid Sequence↗
PubMed1998

Blood supply of the Achilles tendon.

The Achilles tendon is one of the most common sites of injury and rupture as a result of overuse. Evidence suggests that the pathogenesis of rupture could involve the pattern of its blood supply. With use of angiographic and histological techniques, the blood supply of the Achilles tendon was investigated in 12 human cadaveric specimens. Angiography confirmed Mayer's 1916 finding that the blood supply to the tendon is from three areas: the musculotendinous and osseotendinous junctions and the paratenon, with the posterior tibial artery providing the major contribution. However, qualitative and quantitative histological analyses in this study showed that the Achilles tendon has a poor blood supply throughout its length, as determined by the small number of blood vessels per cross-sectional area, which do not in general vary significantly along its length. In light of these findings, it is suggested that poor vascularity may prevent adequate tissue repair following trauma, leading to further weakening of the tendon.

Achilles Tendon↗
PubMed1997

Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand.

The specific association of an SH2 domain with a phosphotyrosine (pTyr)-containing sequence of another protein precipitates a cascade of intracellular molecular interactions (signals) which effect a wide range of intracellular processes. The nonreceptor tyrosine kinase Src, which has been associated with breast cancer and osteoporosis, contains an SH2 domain. Inhibition of Src SH2-phosphoprotein interactions by small molecules will aid biological proof-of-concept studies which may lead to the development of novel therapeutic agents. Structure-based design efforts have focused on reducing the size and charge of Src SH2 ligands while increasing their ability to penetrate cells and reach the intracellular Src SH2 domain target. In this report we describe the synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.

Binding Sites↗
PubMed1996

Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain.

A family of NMR solution structures of the growth factor receptor-bound protein 2 (Grb2) SH2 domain has been determined by heteronuclear multidimensional NMR. Proton, nitrogen, and carbon chemical shift assignments have been made for the SH2 domain of Grb2. Assignments were made from a combination of homonuclear two-dimensional and 15N- and 13C-edited three-dimensional spectra at pH 6.2 and 298 K. Structure-induced proton and carbon secondary shifts were calculated and used to facilitate the spectral assignment process. NOE, scalar coupling, secondary chemical shift, and amide proton exchange data were used to characterize the secondary structural elements and hydrogen-bonding network in the Grb2 SH2 domain. The three-dimensional structure of the Grb2 SH2 domain was calculated using 1112 restraints obtained from NOE, coupling constant, and amide proton exchange data. The rmsd for the 24 calculated structures to the mean structure of the Grb2 SH2 domain was 0.75 A for backbone and 1.28 A for all heavy atoms. The three-dimensional fold of the Grb2 SH2 domain is similar to that observed for other SH2 domains and consists of two alpha-helical segments and eight beta-strands, six strands that make up two contiguous antiparallel beta-sheets, and two strands that form two short parallel beta-sheets. The structure of the phosphotyrosine binding pocket of Grb2 is similar to that observed for other SH2 domains. The hydrophobic binding pocket of Grb2 is similar to that observed for Src with the exception that tryptophan 121 of Grb2 occupies part of the pY+3 binding pocket. Structural implications for the Grb2 SH2 domain selectivity at the pY+2 and pY+3 sites are discussed.

Amino Acid Sequence↗
PubMed1996

Development and validation of two solid-phase enzyme immunoassays (ELISA) for quantitation of human epidermal growth factors (hEGFs).

PURPOSE: The purpose of the present investigation was to develop and validate two separate enzyme-linked immunosorbent assays (ELISA) for quantitation of exogenous human epidermal growth factor (hEGF1-53) and its truncated fragment (hEGF1-48) in rat plasma. METHODS: The present assay systems were based on the sandwiching of the antigen between a monoclonal mouse anti-hEGF1-53 antibody, pre-coated on a 96-well polystyrene plate, and a polyclonal rabbit anti-hEGF1-48 antibody, which is then detected with a peroxidase-labeled goat anti-rabbit antibody. RESULTS: The calibration curves for hEGF1-48 and hEGF1-53 in plasma were validated over a concentration range of 7.8-250 and 62.5-1000 pg/ml, respectively. Determined from replicate assays of hEGF1-48 quality control samples, the intra-assay precision and accuracy were < or = 8.8% RSD and within +/- 9.8%; and the inter-assay precision and accuracy were < or = 14.8% RSD and within +/- 9.7% RE, respectively. Determined from replicate assays of hEGF1-53 quality control samples, the intra-assay precision and accuracy were < or = 10.0% RSD and within +/- 8.5%; and the inter-assay precision and accuracy were < or = 10.0% RSD and within +/- 5.7% RE, respectively. The limit of quantitation of the hEGF1-48 and hEGF1-53 assay using 200 microliters plasma per well is 7.8 and 62.5 pg/ml, respectively. These two ELISA methods are specific to hEGFs and do not cross-react with mouse EGF or other growth factors (TGF alpha, TGF beta, PDGF, and FGF) or lymphokines (IL1 beta and TNF alpha). These validated methods have been routinely applied to assay of plasma samples from various pharmacokinetic studies in rats receiving intravenous hEGFs. Both assay methods were also adapted to assay endogenous hEGFs in biological fluids of different animal species. CONCLUSIONS: Two sensitive ELISA methods have been validated for quantitation of hEGF1-53 and hEGF1-48 in rat plasma. Their utility has been demonstrated in the application of assaying immunoreactive concentration of exogenous and endogenous epidermal growth factors.

Animals↗
PubMed1996

Nurses' compliance with universal precautions before and after implementation of OSHA regulations.

The principal objective of this study was to investigate whether or not nurses' compliance with universal precautions procedures improved after the mandatory Occupational Safety and Health Administration regulations were implemented in 1992. Two random samples of registered nurses and licensed practical nurses registered in Tennessee responded to survey questionnaires measuring universal precautions compliance and practice barriers to compliance in 1991 and 1993 (n = 306). The 1993 sample of nurses reported significantly greater compliance with universal precautions (p < 0.001) than the 1991 sample. The most noteworthy improvement between the 1991 and the 1993 groups was a significant increase in compliance for patients described as HIV/HBV-status unknown and HIV/HBV-negative (p < 0.001). Practice barriers hindering compliance with universal precautions decreased significantly (p < 0.001) in the 1991-1993 time frame. Problematic practice barriers identified in both groups were needle recapping, preference for isolation door signs, and concerns about offending patients and visitors.

Adult↗
PubMed1995

Applying TQM/CQI principles to information system selection.

Faced with the challenge of selecting a new information system, senior management at North Valley Hospital in Whitefish, Montana, decided to employ principles of total quality management and continuous quality improvement to help ensure an efficient process that involved and empowered those who would use the new system. Senior managers set a vision for the process, then assigned responsibility for system selection to a task force representing departments and disciplines that would be most affected by the system. The task force established a systematic process for identifying information system needs, evaluating existing products, and selecting among those products.

Decision Making, Organizational↗
PubMed1992

Dietitians view the horizon.

In honor of the American Dietetic Association's landmark 75th anniversary, FM asked ADA members representing six market sectors to share their perspectives on the opportunities & challenges for dietitians in the '90s. An exciting era lies ahead.

Administrative Personnel↗
PubMed1990

Regeneration of nerve fibres in the anterior medullary velum of neonatal and weanling rats.

The responses to injury of myelinated central axons in neonatal (5-day) and weanling (30-day) rats were compared, using the trochlear nerve fibres in the anterior medullary velum (AMV) as an experimental system. In intact animals, fibres of the trochlear nerve decussate completely in the AMV, to enter the contralateral nerve. Sprouting from proximal axon stumps was seen within 36 h after injury in silver-stained, whole mounts of mid-sagittally lesioned AMVs from weanlings. Subsequent growth produced a tangled axon mass which persisted until 15-20 days post-lesion (d.p.l.) but then began to degenerate. By 50 d.p.l., the majority of surviving axons looped within the AMV to enter the ipsilateral trochlear nerve; few axons remained growing randomly within the AMV. Axonal debris persisted within the velum 50 d.p.l. In neonatal rats, lesioned trochlear axons initially developed axon sprouts, but then degenerated with rapid clearance of debris, leaving the AMV devoid of both axons and degeneration products by 6 d.p.l. From 8 d.p.l., the velum became repopulated by axons which either grew randomly or looped to enter the ipsilateral peripheral nerve. Both patterns of axon growth were still observed 50 d.p.l. In both experimental groups, horseradish peroxidase injection to the right superior oblique muscle 40 d.p.l. indicated that at least some of the looping fibres observed within the lesioned AMVs originated in the ipsilateral trochlear nucleus. The origin of those axons growing randomly within the AMVs of neonatally-lesioned animals is unknown. The results are discussed with reference to current ideas concerning regeneration-inhibiting elements in the CNS, and regeneration-promoting factors in the PNS.

Aging↗
PubMed1984

The injury response of nerve fibres in the anterior medullary velum of the adult rat.

The injury response of myelinated central nervous system (CNS) axons was documented in the anterior medullary velum (AMV) of the adult rat. Study of silver-stained AMV whole-mounts revealed sprouting of injured axons as early as 14 h post-lesion (hpl), with a complex network of fibres formed by 48 hpl. Signs of fibre degeneration were also apparent from 48 hpl, increasing in extent until 15 days post-lesion (dpl). Fragmentation was largely confined to specific fibre bundles, constituted by the distal portions of severed axons. Although some degeneration of regenerated axons was evident from 15-20 dpl, many remained intact beyond this time, particularly in the area adjacent to the exit of the trochlear nerve, where most regenerated fibres penetrated the ipsilateral trochlear nerve. Counts of HRP filled neurons in the trochlear nucleus after injection of the superior oblique muscle showed that axons entering the IVth nerve rootlet were exclusively ipsilateral trochlear fibres. Less than 50% regenerated; most other severed axons degenerated. The few axons remaining in the AMV may have been fibres, undamaged by the original lesion, which normally course longitudinally through the ipsilateral AMV. These results show that IVth nerve fibres preferentially enter IVth nerve rootlets and, in so doing, survive the effects of injury. Most other CNS axons in the AMV which do not enter the trochlear root probably degenerate.

Animals↗