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Biomedical subjects

M Barnes

Publications and source records attributed to M Barnes.

At least 37 records · Page 2Linked to original sources
PubMed1997

Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain.

We have recently shown that collagen activates platelets through a pathway dependent on the Fc receptor gamma-chain and the tyrosine kinase Syk. We report here that the Fc receptor gamma-chain and the candidate collagen receptor glycoprotein VI (GPVI) co-associate. Furthermore, cross-linking GPVI stimulates a similar pattern of tyrosine phosphorylation to that stimulated by collagen, including tyrosine phosphorylation of Fc receptor gamma-chain. These results support a model where GPVI couples collagen-stimulation of platelets to phosphorylation of the Fc receptor gamma-chain leading to activation of Syk and phospholipase Cgamma2.

Blood Platelets↗
PubMed1997

A modulator of rho family G proteins, rhoGDI, binds these G proteins via an immunoglobulin-like domain and a flexible N-terminal arm.

BACKGROUND: The rho family of small G proteins, including rho, rac and cdc42, are involved in many cellular processes, including cell transformation by ras and the organization of the actin cytoskeleton. Additionally, rac has a role in the regulation of phagocyte NADPH oxidase. Guanine nucleotide dissociation inhibitors (GDIs) of the rhoGDI family bind to these G proteins and regulate their activity by preventing nucleotide dissociation and by controlling their interaction with membranes. RESULTS: We report the structure of rhoGDI, determined by a combination of X-ray crystallography and NMR spectroscopy. NMR spectroscopy and selective proteolysis show that the N-terminal 50-60 residues of rhoGDI are flexible and unstructured in solution. The 2.5 A crystal structure of the folded core of rhoGDI, comprising residues 59-204, shows it to have an immunoglobulin-like fold, with an unprecedented insertion of two short beta strands and a 310 helix. There is an unusual pocket between the beta sheets of the immunoglobulin fold which may bind the C-terminal isoprenyl group of rac. NMR spectroscopy shows that the N-terminal arm is necessary for binding rac, although it remains largely flexible even in the complex. CONCLUSIONS: The rhoGDI structure is notable for the existence of both a structured and a highly flexible domain, both of which appear to be required for the interaction with rac. The immunoglobulin-like fold of the structured domain is unusual for a cytoplasmic protein. The presence of equivalent cleavage sites in rhoGDI and the closely related D4/Ly-GDI (rhoGDI-2) suggest that proteolytic cleavage between the flexible and structured regions of rhoGDI may have a role in the regulation of the activity of members of this family. There is no detectable similarity between the structure of rhoGDI and the recently reported structure of rabGDI, which performs the same function as rhoGDI for the rab family of small G proteins.

Amino Acid Sequence↗
PubMed1997

The Electronic Spectrum of Gaseous CoO in the Visible Region

Laser excitation spectra of gaseous CoO have been recorded using Doppler-limited intracavity spectroscopy and supersonic jet-cooled molecular beam methods. As seen in the molecular beam spectra there are nearly 100 bands arising from the X4Delta7/2 spin component of the ground state in the wavelength region 430-720 nm. All of them are very strongly red-degraded and most of them are perturbed. 59Co hyperfine broadenings or splittings have been observed in many. The bands can be arranged into five electronic transitions, together with a considerable number of "extra" bands induced by perturbations; two of the excited electronic states are 4Phi, while the other three, which lie within 1700 cm-1, are 4Delta. Semi-empirical calculations have been carried out for the 4Delta excited states, using exchange integrals transferred from the TiO and VO spectra; the predicted energies, spin-orbit structures, and relative intensities in absorption are consistent with the assignment of all three 4Delta states to the same electron configuration, (4ssigma)1(3ddelta)3(3dpi)2(3dsigma)1. It seems that there are extensive interactions between the excited 4Delta states, because only one of them gives rise to a recognizable, though irregular, long vibrational progression in absorption. The other two progressions die out abruptly and unexpectedly after three or four members, presumably as a result of interference effects; however, wavelength-resolved fluorescence studies, together with calculations of the Franck-Condon overlap integrals to the various vibrational levels of the ground state, show that the upper state progressions reappear following a region of confused absorption. All of the excited states show highly irregular variations of their vibrational intervals and rotational constants with the vibrational quantum number, v. The wavelength-resolved fluorescence spectra give evidence for new low-lying electronic states of CoO at 3038, 5989, and 9105 cm-1; based on its vibrational frequency the 3038 cm-1 state is possibly the sigmadelta4pi2 B4Sigma- state. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Application of the fuzzy ART/MAP and MINMAX/MAP neural network models to radiographic image classification.

This paper concerns the classification analysis of exercise-induced lower leg pain by applying competitive neural network clustering and mapping techniques to type 1 and type 2 fuzzy descriptions of bone scan images of the tibia. The clusters are described and compared with each other and with the experts known classes that would be expected from medical findings. The discovered clusters provide training sets for supervised learning by an ARTMAP and similar neural network. These were used to classify the previously unclassified images and hence improve the classification process. The overall conclusion is that the use of the neural clustering methods has improved the classification process of the shin images despite the paucity of data and its inherent uncertainty.

Athletic Injuries↗
PubMed1997

Re-engineering surgical services in a community teaching hospital.

The Grace Hospital Surgical Services redesign project began in December 1995 and concluded in November 1996. It was led by the Chief of Surgery, the Surgical/Anesthesia Services Director, and the Associate Director of Critical Care/Trauma. The project was undertaken in order to radically redesign the delivery of surgical services in the Detroit Medical Center (DMC) Northwest Region. It encompassed the Grace Hospital Main Operating Room (10 operating theatres) and Post-Anesthesia Recovery Unit, and a satellite Ambulatory Surgery Center in Southfield, Michigan. The four areas of focus were materials management, case scheduling, patient flow/staffing, and business planning. The guiding objectives of the project were to improve upon the quality of surgical services for patients and physicians, to substantially reduce costs, and to increase case volume. Because the Grace Surgical Services redesign project was conducted in a markedly open communicative, and inclusive fashion and drew participation from a broad range of medical professionals, support staff, and management, it created positive ripple effects across the institution by raising staff cost-consciousness, satisfaction, and morale. Other important accomplishments of the project included: Introduction of block scheduling in the ORs, which improved room utilization and turnaround efficiencies, and greatly smoothed the boarding process for physicians. Centralization of all surgical boarding, upgrading of computer equipment to implement "one call" surgery scheduling, and enlarging the capacity for archiving, managing and retrieving OR data. Installation of a 23-hour, overnight recovery unit and provision of physician assistants at the Ambulatory Surgery Center, opening the doors to an expanded number of surgical procedures, and enabling higher quality care for patients. Reduction of FTE positions by 27 percent at the Ambulatory Surgery Center. This yielded a total cost reduction of +1.5 million per annum in the annual budget of +10.3 million; Recruited 10 new podiatrists and increased the volume of cases brought to Northwest Region facilities by surgical specialists. This added 100 cases in 1996, and is projected to add 500 cases in 1997. A 14.5 percent reduction in the cost of operating the Surgical Services was achieved. This was accompanied by enhanced staff morale, physician satisfaction and a higher quality of patient care.

Ambulatory Surgical Procedures↗
PubMed1997

Design of access control methods for protecting the confidentiality of patient information in networked systems.

Public awareness of the potential for violation of personal privacy in clinical information systems is increasing. Much of this increase can be attributed to the popularity and publicity of the World Wide Web. Nightly news reports of intruder break-ins and flaws in Internet software security have stimulated public interest in the security of clinical information systems available over the web. As part of the development of systems designed to provide clinical narratives to physicians over the Internet, we are exploring designs that provide additional protection and security to these systems. Specifically, we are developing and testing automated access control measures based on provider-patient relationships for controlling access to personally identifiable patient information.

Computer Communication Networks↗
PubMed1996

Tyrosine phosphorylation of the Fc receptor gamma-chain in collagen-stimulated platelets.

Stimulation of platelets by the extracellular matrix protein collagen leads to activation of a tyrosine kinase-dependent mechanism resulting in secretion and aggregation. Tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase Cgamma2 are early events in collagen-induced activation. We recently proposed that collagen-signaling in platelets involves a receptor or a receptor-associated protein containing an immunoreceptor tyrosine-based activation motif (ITAM) enabling interaction with Syk. In this report we show that collagen stimulation of platelets causes rapid tyrosine phosphorylation of the ITAM containing Fc receptor gamma-chain and that this is precipitated by the tandem Src homology 2 (SH2) domains of Syk expressed as a fusion protein. In addition we demonstrate an association between the Fc receptor gamma-chain with endogenous Syk in collagen-stimulated platelets. The Fc receptor gamma-chain undergoes tyrosine phosphorylation in platelets stimulated by a collagen-related peptide which does not bind the integrin alpha2beta1 and by the lectin wheat germ agglutinin. In contrast, cross-linking of the platelet low affinity receptor for immune complexes, FcgammaRIIA, or stimulation by thrombin does not induce phosphorylation of the Fc receptor gamma-chain. The present results provide a molecular basis for collagen activation of platelets which is independent of the integrin alpha2beta1 and involves phosphorylation of the Fc receptor gamma-chain, its association with Syk and subsequent phosphorylation of phospholipase Cgamma2. Collagen is the first example of a nonimmune receptor stimulus to signal through a pathway closely related to signaling by immune receptors.

Blood Platelets↗
PubMed1996

Tumors in dogs exposed to experimental intraoperative radiotherapy.

PURPOSE: The frequency of radiation-induced neoplasms was determined in dogs enrolled in the National Cancer Institute canine trials of intraoperative radiotherapy (IORT). METHODS AND MATERIALS: Twelve protocols assessing normal tissue response to IORT involved 238 dogs in a 15-year trial. Eighty-one dogs were followed for > 24 months postoperatively and were assessed for tumor development; 59 of these animals received IORT. RESULTS: Twelve tumors occurred in the 59 dogs receiving IORT. Nine were in the IORT portals and were considered to be radiation induced. No tumors occurred in 13 sham animals or in 9 animals treated with external beam radiotherapy alone. The frequency of radiation-induced malignancies in dogs receiving IORT was 15%, and was 25% in animals receiving > or = 25 Gy IORT. Frequency of all tumors, including spontaneous lesions, was 20%. CONCLUSIONS: Intraoperative radiotherapy contributed to a high frequency of sarcoma induction in these dogs. Unknown to date in humans involved in clinical trials of IORT, this potential complication should be looked for as long-term survivors are followed.

Animals↗
PubMed1996

NMR studies of the mode of binding of corepressors and inducers to Escherichia coli trp repressor.

The binding of the corepressors tryptophan and 5-methyltryptophan and of the inducers 3-indolepropionate, 3-indoleacrylate and 5-methylindole to the Escherichia coli trp repressor have been studied by 1H-NMR spectroscopy. Identification of the resonances of the protons of bound ligands and their NOEs to protons of the protein (measured as transferred NOE) was greatly facilitated by the use of samples of the protein in which the hydrogens of all residues except alanine, isoleucine and threonine was replaced by deuterium. Chemical-shift changes of protein-backbone resonances and side-chain-amide resonances on ligand binding were measured with generally or selectively 15N-labelled protein. The patterns of changes in the chemical shifts of protein resonances and, particularly, ligand resonances distinguish the corepressors from the inducers, indicating, in agreement with earlier work, that corepressors and inducers bind to the protein in different ways. The NOEs observed for the bond ligands have been used to determine the position of the ligands in the crystallographically determined binding site, by means of a simulated-annealing molecular-dynamics protocol. The structures obtained show that the orientation in the binding site of the indole rings of tryptophan and 5-methyltryptophan and of 3-indolepropionate and 3-indoleacrylate differ by approximately 180 degrees in solution (in agreement with the crystallographic data for complexes of the trp repressor with tryptophan or with 3-indolepropionate). The value and limitations of calculating ligand positions based on transferred NOE are discussed.

Bacterial Proteins↗
PubMed1996

Acute Myocardial Infarction in Canada: New Epidemiologic Insights on Incidence, Therapy, and Risk.

Objective: To define the changing incidence, risk, and therapy of acute myocardial infarction (A311). Data sources: Review of contemporary AMI data from the University of Alberta Hospitals, six other sites of the Clinical Quality Improvement Network (CQIN), and other Canadian and international centers. Data synthesis: Ischemic heart disease is age-related and the Canadian population is rapidly aging. At the University of Alberta Hospitals, the incidence of Q wave AMI (per 100,000 population) in 1985 was 113 and has remained unchanged (NS) since that time (129 in 1994). In contrast, the combined incidence of non.Q-wave AMI and unstable angina has increased markedly, from 74 in 1985 to 226 in 1994 (p < 0.05). The use of proven efficacious therapies for AMI has greatly increased in recent years, with thrombolytic drugs being given to approximately 35;percnt; of all patients by 1993; and beta-blockers and aspirin to 75;percnt; and 98;percnt; of patients, respectively. However, females and patients older than 70 years' despite their greater risk, received significantly less efficacious medication than males and younger AMI patients. The use of calcium antagonists decreased from a peak utilization rate of 60;percnt; for all AMI patients in 1989 to less than 10;percnt; by 1993. In-hospital AMI mortality risk has also decreased in the last several years, particularly among higher risk older patients (35;percnt;, 1987 vs. 19;percnt;,1993). In a population of 3896 consecutive AMI patients, recruited largely in 1992 and 1993 from seven CQIN sites, logistic regression analyses revealed aspirin was associated with the greatest relative risk reduction (61%); beta-blocker and thrombolytic therapy were related to risk reductions of 55;percnt; and 16;percnt;, respectively. Incremental age was the most important factor associated with increased relative risk in AMI, overall and in both sexes; sex was not an independent risk predictor. Qualitatively very similar AMI incidence, risk, and treatment data have also been recently observed in other centers in Canada, the United States, and elsewhere. Conclusions: Although widespread primary or secondary prevention is possibly contributory, the recent static incidence of Q-wave AMI and the marked increase in unstable angina and non-Q-wave AMI are more likely due to enhanced health awareness and diagnosis-seeking behavior in the population at risk. The decline in AMI mortality, at least for high-risk acute care patients, is compatible with a clinically relevant secondary prevention effect. There are still, however, windows of opportunity to further improve AMI outcomes by increasing the utilization of proven efficacious therapy, especially among women and older patients. Another particularly attractive epidemiologic benefit in the immediate future would accrue from the further development and effective use of efficacious therapies directed against unstable angina and n-Q-wave AMI.

Journal Article↗
PubMed1996

Euthanasia: Buddhist principles.

Religions provide various forms of motivation for moral action. This chapter takes Buddhism as an example from within the Indian "family' of religions and seeks to identify the doctrinal and cultural principles on which ethical decisions are taken. Although beginning from very different religious premises, it is argued that the conclusions to which Buddhism tends are broadly similar to those found within mainstream Christianity.

Buddhism↗