Showing papers by "University of Calgary published in 2000"
TL;DR: This CT score is simple and reliable and identifies stroke patients unlikely to make an independent recovery despite thrombolytic treatment as well as primary outcomes, including symptomatic intracerebral haemorrhage and 3-month functional outcome.
2,044 citations
TL;DR: In both lakes and terrestrial systems, herbivores should have low growth efficiencies when consuming autotrophs with typical carbon-to-nutrient ratios and stoichiometric constraints on herbivore growth appear to be qualitatively similar and widespread in both environments.
Abstract: Biological and environmental contrasts between aquatic and terrestrial systems have hindered analyses of community and ecosystem structure across Earth's diverse habitats. Ecological stoichiometry1,2 provides an integrative approach for such analyses, as all organisms are composed of the same major elements (C, N, P) whose balance affects production, nutrient cycling, and food-web dynamics3,4. Here we show both similarities and differences in the C:N:P ratios of primary producers (autotrophs) and invertebrate primary consumers (herbivores) across habitats. Terrestrial food webs are built on an extremely nutrient-poor autotroph base with C:P and C:N ratios higher than in lake particulate matter, although the N:P ratios are nearly identical. Terrestrial herbivores (insects) and their freshwater counterparts (zooplankton) are nutrient-rich and indistinguishable in C:N:P stoichiometry. In both lakes and terrestrial systems, herbivores should have low growth efficiencies (10–30%) when consuming autotrophs with typical carbon-to-nutrient ratios. These stoichiometric constraints on herbivore growth appear to be qualitatively similar and widespread in both environments.
1,335 citations
TL;DR: The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables, and the allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters.
Abstract: Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.
1,152 citations
TL;DR: The various approaches to the validity problem are reviewed in the hope of turning this debate about what it means to do valid research in the field of qualitative inquiry into a dialogue.
Abstract: Designing and carrying out effective and valid research are the desired goals of all researchers, and demonstrating the trustworthiness of one's dissertation research is a requirement for all doctoral candidates. For qualitative researchers, reaching the desired goal and meeting the requirement of trustworthiness become particularly problematic due to the considerable debate about what it means to do valid research in the field of qualitative inquiry. This article reviews the various approaches to the validity problem in the hope of turning this debate into a dialogue. Validity is traced from its origins in the realist ontology and foundational epistemology of quantitative inquiry to its reformulations within the lifeworld ontology and non-foundationalism of interpretive human inquiry. Various recent qualitative approaches to validity are considered, and interpretive reconfigurations of validity are reviewed. Interpretive approaches to validity are synthesized as ethical and substantive procedures of validation.
1,151 citations
TL;DR: It is found that a large proportion of primary spinal afferent neurons also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2.
Abstract: Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.
915 citations
TL;DR: It is suggested that social capital's power as rhetoric and as a metaphor may be of value and that the coalescence of interests in context-level influences on health now invites a revitalisation of theories and interventions inspired by diverse fields, such as geography and ecological community psychology.
727 citations
TL;DR: Inhibition of both COX-1 andCOX-2 is required for NSAID-induced gastric injury in the rat, and the combination of SC-560 and celecoxib invariably caused hemorrhagic erosion formation, comparable to that seen with indomethacin.
712 citations
TL;DR: The results indicate that some areas of the brain activated by sound stimulation have a maturational time course that extends into adolescence and raises the possibility that the emergence of adult-like auditory processing skills may be governed by the same maturing neural processes that affect AEP latency and amplitude.
711 citations
TL;DR: In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotRexate maintains remission.
Abstract: Background Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. Methods We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. Results Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remissi...
655 citations
TL;DR: M Motors from different bacteria exhibited an identical steep input-output relation, suggesting that they actively contribute to signal amplification in chemotaxis, and can be extended to quantitative in vivo studies of other biochemical networks.
Abstract: Understanding biology at the single-cell level requires simultaneous measurements of biochemical parameters and behavioral characteristics in individual cells. Here, the output of individual flagellar motors in Escherichia coli was measured as a function of the intracellular concentration of the chemotactic signaling protein. The concentration of this molecule, fused to green fluorescent protein, was monitored with fluorescence correlation spectroscopy. Motors from different bacteria exhibited an identical steep input-output relation, suggesting that they actively contribute to signal amplification in chemotaxis. This experimental approach can be extended to quantitative in vivo studies of other biochemical networks.
620 citations
TL;DR: This mechanistic proposal is supported by a kinetic isotope effect of 1.4(5) for the hydrosilation of acetophenone, the observation that B(C(6)F(5))(3) catalyzes H/D and H/H scrambling in silanes in the absence of substrate, computational investigations, the synthesis of models for proposed intermediates, and other isotope labeling and crossover experiments.
Abstract: The strong organoborane Lewis acid B(C6F5)3 catalyzes the hydrosilation (using R3SiH) of aromatic and aliphatic carbonyl functions at convenient rates with loadings of 1−4%. For aldehydes and ketones, the product silyl ethers are isolated in 75−96% yield; for esters, the aldehydes produced upon workup of the silyl acetal products can be obtained in 45−70% yield. Extensive mechanistic studies point to an unusual silane activation mechanism rather than one involving borane activation of the carbonyl function. Quantitative kinetic studies show that the least basic substrates are hydrosilated at the fastest rates; furthermore, increased concentrations of substrate have an inhibitory effect on the observed reaction rate. Paradoxically, the most basic substrates are reduced selectively, albeit at a slower rate, in competition experiments. The borane thus must dissociate from the carbonyl to activate the silane via hydride abstraction; the incipient silylium species then coordinates the most basic function, whic...
TL;DR: In this article, the authors examined goals pertaining to start-up, operations, the family, and ultimate disposition of the enterprise by family and owner-operated businesses in the rural tourism and hospitality sectors.
TL;DR: In this article, the authors investigated the circumstances under which environmental supply chain dynamics (ESCD) emerge, a phenomenon where environmental innovations diffuse from a customer firm to a supplier firm, and showed that ESCD emerges if there is a channel leader with sufficient channel power over their suppliers, technical competencies, and are themselves under specific environmental pressure.
TL;DR: This paper examined how the influence of minority directors on corporate boards is contingent on the prior experience of board members and the larger social structural context and found that minority directors' influence is dependent on their prior experience and social structure.
Abstract: This study examines how the influence of directors who are demographic minorities on corporate boards is contingent on the prior experience of board members and the larger social structural context...
TL;DR: Olanzapine has some superior cognitive benefits relative to haloperidol and risperidone, and a larger sample replication study is necessary to confirm and generalize the observations of this study.
Abstract: Background The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia. Methods Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment. Results The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test. Conclusions These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.
TL;DR: The use of methylprednisolone administration in the treatment of acute SCI is not proven as a standard of care, nor can it be considered a recommended treatment, and evidence of the drug's efficacy and impact is weak and may only represent random events.
Abstract: Object. Since publication in 1990, results from the National Acute Spinal Cord Injury Study II (NASCIS II) trial have changed the way patients suffering an acute spinal cord injury (SCI) are treated. More recently, recommendations from NASCIS III are being adopted by institutions around the world. The purpose of this paper is to reevaluate carefully the results and conclusions of these studies to determine the role they should play in influencing decisions about care of the acutely spinal cord—injured patient. Methods. Published results from NASCIS II and III were reviewed in the context of the original study design, including primary outcomes compared with post-hoc comparisons. Data were retroconverted from tabular form back to raw form to allow direct inspection of changes in treatment groups. These findings were further analyzed with respect to justification of practice standards. Although well-designed and well-executed, both NASCIS II and III failed to demonstrate improvement in primary outcome measu...
TL;DR: A growing number of sociologists, political scientists, development economists, and organizational theorists have invoked the concept of social capital in their search for answers to a broadening range of questions confronting their own fields.
Abstract: A growing number of sociologists, political scientists, development economists, and organizational theorists have invoked the concept of social capital in their search for answers to a broadening range of questions confronting their own fields Seeking to clarify the utility of the concept for organizational theory, this paper synthesizes the theoretical research undertaken in these various disciplines and develops a common conceptual framework that identifies the sources, benefits, and risks of social capital
TL;DR: Significant variation in NICU practices and outcomes was observed despite Canada's universal health insurance system and is provided for planning research, allocating resources, designing health and public policy, and serving as a basis for longitudinal studies of NICU care in Canada.
Abstract: Background. Previous reports of variations in outcomes among neonatal intensive care units (NICUs) examined only specific subpopulations of interest (eg, very low birth weight [VLBW] infants Objectives. We report on current practice and outcomes variations in a population-based national study of Canadian NICUs from January 8, 1996 to October 31, 1997. Method. Information on 20 488 admissions to 17 tertiary level NICUs across Canada was prospectively collected by trained abstractors using a standard manual of operations and definitions. Data were verified and analyzed in concert with a steering committee comprising experienced researchers and neonatologists. Patient information included demographic information, antenatal history, mode of delivery, problems at delivery, status of infant and problems at birth, illness severity (Clinical Risk Index for Babies, Score for Neonatal Acute Physiology, Score for Neonatal Acute Physiology-Version II), therapeutic intensity (Neonatal Therapeutic Intensity Scoring System [NTISS]), selected NICU practices and procedures, use of technology and resources, and selected patient outcomes. Patients were tracked until death or discharge home. Results. The mean number of annual admissions to an NICU was 657, with 26% outborn infants. Fifty-three percent were Conclusion. This study provides population-based information about NICU outcomes. Significant variation in NICU practices and outcomes was observed despite Canada9s universal health insurance system. This national database provides valuable information for planning research, allocating resources, designing health and public policy, and serving as a basis for longitudinal studies of NICU care in Canada.
Book•
31 Aug 2000TL;DR: This book discusses how to represent Knowledge Representation in Agent-Based Concurrent Design and Manufacturing Systems and some of the approaches taken to achieve this goal.
Abstract: Part One: Introduction Chapter 1: General Introduction. 1.1 Motivation. 1.2 Book Organization. 1.3 How To Use This Book. Chapter 2: Collaborative Design and Manufacturing. 2.1 Introduction. 2.2 Engineering Design. 2.3 Advanced Manufacturing Systems. 2.4 Next Generation Collaborative Design and Manufacturing Systems. Chapter 3: DAI and Agents. 3.1 Classic AI and DAI. 3.2 Research Themes in DAI. 3.3 Models of DAI Systems. 3.4 Objects vs. Agents. 3.5 Different Types of Agents. 3.6. Why Agents for Collaborative Design and Manufacturing. Part Two: Important Issues Chapter 4: Knowledge Representation in Agent-Based Concurrent Design and Manufacturing Systems. 4.1 Introduction 4.2 What needs to be Represented. 4.3 How to Represent Knowledge in Agent-Based Systems. 4.4 Research Literature and Further References. Chapter 5: Learning in Agent-Based Concurrent Design and Manufacturing Systems. 5.1 Introdution. 5.2 Why to Learn. 5.3 Single-Agent Learning or Multi-Agent Learning. 5.4 When to Learn. 5.5 Where to Learn. 5.6 What is to be Learned. 5.7 How to Learn. 5.8 Examples. 5.9 Research Literature and Additional References. Chapter 6: Agent Structures. 6.1 Introduction. 6.2 Desirable characteristics of an agent. 6.3 Essential Modules (Components) for agents. 6.4 Different Approaches. 6.5 Comparison of Different Approaches. 6.6 Research Literature and further References. Chapter 7: Multi-Agent System Architectures. 7.1 Introduction. 7.2 Organization and System Architectures. 7.3 Different Approaches. 7.4 Select a suitable system architecture for a specific application. 7.5 Research Literature and Additional Readings. Chapter 8: Communication, Cooperation and Coordination. 8.1 Introduction. 8.2 Communication. 8.3 Coordination. 8.4 Cooperation. 8.5 Coordination, Cooperation and Communication. 8.6 Research Literature and Further References. Chapter 9: Collaboration, Task Decompsition and Allocation. 9.1 Introduction. 9.2 Different Approaches for Task Decomposition and Allocation. 9.3 Coordinated Task Allocation by Mediation. 9.4 Distributed Task Allocation. 9.5 Task Decomposition in MetaMorph: an Example. 9.6 Research Literature and Additional References. Chapter 10: Negotiation and Conflict Resolution. 10.1 Introduction. 10.2 Classification of Negotiation Categories. 103. Negotiation Protocols. 10.4 Negotiation Strategies. 10.5 Negotiation for Conflict Resolution. 10.6 Examples in Concurrent Design and Manufacturing. 10.7 Research Literature and Additional Information. Chapter 11: Ontology Problems. 11.1 Introduction. 11.2 What is Ontology? 11.3 Ontology and Knowledge Sharing. 11.4 Ontology Problems in Concurrent Design and Manufacturing. 11.5 Related concepts, Theories and Methods. 11.6 Ontolingua: A System for Managing Portable Ontologies. 11.7 Research Literature and Additional References. Chapter 12: Other Important Issues. 12.1 Introduction. 12.2 Agent Encapsulation. 12.3 Human machine integration (human participation). 12.4 System dynamics. 12.5. Design and manufacturability assessments. 12.6 Integration of manufacturing Planning, Scheduling and Execution. 12.7 Distributed Dynamic Scheduling. 12.8 Enterprise Integration and Supply Chain Management. 12.9 Legacy problem. 12.10 External interfaces. Part Three: Agent-Based Systems for Engineering Design & Manufacturing Chapter 13: Agent-Based Engineering Design Systems. 13.1 Introduction. 13.2 PACT (PACE) 13.3 SHARE (DSC) 13.4 First-Link, Next-Link and Process Link. 13.5 DIDE. 13.6 SiFAs. 13.7 RAPPID. 13.8 Other projects. 13.9 Summary. Chapter 14: Agent-Based manufacturing Planning, Scheduling and Control. 14.1 Introduction. 14.2 MetaMorph. 14.3 AARIA. 14.4 ADDYMS. 14.5 Other Projects. 14.6 Summary. Chapter 15: Enterprise Integration and Supply Chain Management. 15.1 Introduction. 15.2 ISCM. 15.3 CIIMPLEX. 15.4 MetaMorph II. 15.5 AIMS. 15.6 Other Projects. 15.7 Summary. Part Five: Developing Agent-Based Design and Manufacturing Systems Chapter 16: Methodology, Standards, Tools, Languages, and Frameworks. 16.1 Introduction. 16.2 Tools and Framework. 16.3 Methodology, Languages, and Standards. 16.4 Further references. Chapter 17: Building Agent-Based Design and Manufacturing Systems. 17.1 Introduction. 17.2 Selecting or developing an agent architecture. 17.3 Selecting an approach for agent organization. 17.4 Selecting or developing protocols for inter-agent communication. 17.5 Developing mechanisms for cooperation, coordination and negotiation. 17.6 Selecting platforms, tools and languages. 17.7 Agent-Oriented Design and Analysis. 17.8 Simulation and Implementation. 17.9 Testing, Debugging and Evaluation. Chapter 2: Collaborative Design and Manufacturing, Chapter 3: DAI and Agents. Part Two: Important Issues Chapter 4: Knowledge Representation in Agent-Based Concurrent Design and Manufacturing Systems. Chapter 5: Learning in Agent-Based Concurrent Design and Manufacturing Systems. Chapter 6: Agent Structures. Chapter 7: Multi-Agent System Architectures. Chapter 8: Communication, Cooperation and Coordination. Chapter 9: Collaboration, Task Decomposition and Allocation. Chapter 10: Negotiation and Conflict Resolution. Chapter 11: Ontology Problems. Chapter 12: Other Important Issues. Part Three: Agent-Based Systems for Engineering Design and Manufacturing Chapter 13: Agent-Based Engineering Design Systems. Chapter 14: Agent-Based manufacturing Planning, Scheduling and Control. Chapter 15: Enterprise Integration and Supply Chain Management. Part Four: Developing Agent-Based Design and Manufacturing Systems Chapter 16: Methodlogy, Standards, Tools, Languages, and Frameworks
TL;DR: In this article, a recombinant adeno-associated virus (rAAV) was used to produce a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels.
Abstract: A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy1. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells2,3,4,5,6. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells7. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.
TL;DR: The Olympic bid for the 2004 Olympics by Cape Town, South Africa represented the first bid from Africa, and the most successful bid to date from a developing country as discussed by the authors, and the unique theme of the Cape Town bid was human/urban development, and yet a direct response to problems created by the apartheid city.
Abstract: Mega-events are short-term high-profile events like Olympics and World Fairs that always have a significant urban impact. They re-prioritize urban agendas, create post-event usage debates, often stimulate urban redevelopment, and are instruments of boosterist ideologies promoting economic growth. While mega-events have normally been the preserve of industrial/postindustrial cities, the bid for the 2004 Olympics by Cape Town, South Africa represented the first bid from Africa, and the most successful bid to date from a developing country. The unique theme of the Cape Town bid was human/urban development — a contradiction given the elitist and commercial nature of mega-events — and yet a direct response to problems created by the apartheid city. The developmental aspects of the Cape Town bid are assessed in their South African context in order to ascertain whether development was only a legitimation for business interests (or growth machines) or whether and how the mega-event would contribute to urban restructuring. It is concluded that the bid represented a form of urban/national boosterism that repositioned Cape Town and South African interests in the global economy — particularly relevant given its previous apartheid pariah status. As a pro-growth strategy advocated by political and economic elites, the Olympic bid was less important as a sporting event at the grassroots than as a symbol of expectations of economic betterment. Whether mega-events like the Olympics can carry such far-reaching objectives within their more specific mandates is a matter for further reflection.
Les mega-evenements sont des evenements a court terme tres en vue comme les jeux Olympiques et les foires mondiales qui ont toujours un impact urbain considerable. Ils changent les priorites des programmes urbains, ils creent des debats d'usage apres l'evenement, encouragent souvent le redeveloppement urbain, et sont les instruments des ideologies de relance qui supportent la croissance economique. Les mega-evenements prennent place habituellement dans les villes industrialisees/post-industrialisees, mais la tentative du Cap en Afrique du Sud pour obtenir les jeux Olympiques de 2004 represente la premiere offre de l'Afrique. C'est la tentative venant d'un pays en voie de developpement qui a ce jour a ete la plus couronnee de succes. Le theme unique de la tentative du Cap etait le developpement humain/urbain — une contradiction, en vue de la nature commerciale et elitiste des mega-evenements — et cependant une reponse directe aux problemes crees par la ville apartheid. Les aspects du developpement de l'enchere du Cap sont evalues dans leur contexte sud-africain afin d'etablir si le developpement etait simplement une justification des interAts commerciaux (ou machines de croissance) ou si le mega-evenement pouvait contribuer a la restructuration urbaine, et comment. Je conclus que l'enchere representait une forme de relance urbaine/nationale qui a replace le Cap et l'Afrique du Sud dans l'economie globale — particulierement pertinente en vue de son statut precedent d'apartheid paria. En tant que strategie preconisee par les elites politiques et economiques pour stimuler la croissance, la tentative des jeux Olympiques etait moins importante comme evenement sportif populaire que comme le symbole d'une attente d'amelioration economique. Il reste a savoir si les mega-evenements comme les jeux Olympiques peuvent atteindre de tels objectifs de grande envergure dans leurs mandats specifiques.
TL;DR: HIV-1 VCT is highly cost-effective in urban east African settings, but slightly less so than interventions such as improvement of sexually transmitted disease services and universal provision of nevirapine to pregnant women in high-prevalence settings.
TL;DR: Although potentiation and fatigue have opposing effects on force production in skeletal muscle, these two presumed mechanisms can coexist and be associated with a Ca2+-related mechanism.
Abstract: Twitch potentiation and fatigue in skeletal muscle are two conditions in which force production is affected by the stimulation history. Twitch potentiation is the increase in the twitch active force observed after a tetanic contraction or during and following low-frequency stimulation. There is evidence that the mechanism responsible for potentiation is phosphorylation of the regulatory light chains of myosin, a Ca2+-dependent process. Fatigue is the force decrease observed after a period of repeated muscle stimulation. Fatigue has also been associated with a Ca2+-related mechanism: decreased peak Ca2+ concentration in the myoplasm is observed during fatigue. This decrease is probably due to an inhibition of Ca2+ release from the sarcoplasmic reticulum. Although potentiation and fatigue have opposing effects on force production in skeletal muscle, these two presumed mechanisms can coexist. When peak myoplasmic Ca2+ concentration is depressed, but myosin light chains are relatively phosphorylated, the force response can be attenuated, not different, or enhanced, relative to previous values. In circumstances where there is interaction between potentiation and fatigue, care must be taken in interpreting the contractile responses.
TL;DR: Findings strongly support a causative role of impaired metabolism in the cardiomyopathy observed in db/db diabetic hearts.
Abstract: Contractile function and substrate metabolism were characterized in perfused hearts from genetically diabetic C57BL/KsJ-leprdb /leprdb (db/db) mice and their non-diabetic lean littermates. Contract...
TL;DR: The history behind the discovery and initial characterization of SRC and the regulatory mechanisms of Src activation, in particular, regulation by modification of the carboxy-terminal regulatory tyrosine by phosphatases and kinases are discussed.
Abstract: Since the discovery of the v-src and c-src genes and their products, much progress has been made in the elucidation of the structure, regulation, localization, and function of the Src protein. Src is a non-receptor protein tyrosine kinase that transduces signals that are involved in the control of a variety of cellular processes such as proliferation, differentiation, motility, and adhesion. Src is normally maintained in an inactive state, but can be activated transiently during cellular events such as mitosis, or constitutively by abnormal events such as mutation (i.e. v-Src and some human cancers). Activation of Src occurs as a result of disruption of the negative regulatory processes that normally suppress Src activity, and understanding the various mechanisms behind Src activation has been a target of intense study. Src associates with cellular membranes, in particular the plasma membrane, and endosomal membranes. Studies indicate that the different subcellular localizations of Src could be important for the regulation of specific cellular processes such as mitogenesis, cytoskeletal organization, and/or membrane trafficking. This review will discuss the history behind the discovery and initial characterization of Src and the regulatory mechanisms of Src activation, in particular, regulation by modification of the carboxy-terminal regulatory tyrosine by phosphatases and kinases. Its focus will then turn to the different subcellular localizations of Src and the possible roles of nuclear and perinuclear targets of Src. Finally, a brief section will review some of our present knowledge regarding Src involvement in human cancers.
TL;DR: The legitimacy of an interest in illness narratives that is therapeutic, emancipatory, and pre-occupied with ethics is defended and how qualitative methods can inform changing relationships between illness, health, medicine, and culture is considered.
Abstract: The legitimacy of an interest in illness narratives that is therapeutic, emancipatory, and pre-occupied with ethics is defended in response to Atkinson's critique of this interest as a blind alley. The value of storytelling as complementary to story analysis is argued, and the importance of recognizing one's own standpoint is emphasized. The conclusion considers how qualitative methods can inform changing relationships between illness, health, medicine, and culture.
TL;DR: The contribution made by NO to the ability of the gastrointestinal mucosa to resist injury induced by luminal toxins and to defend against microbial invasion is summarized.
TL;DR: Only quinapril was associated with significant improvement in FMD, and this response was related to the presence of the insertion allele of the ACE genotype.
TL;DR: It is predicted that recently developed ELISA and flow cytometry techniques using purified HLA antigen will increase the clinical relevance of posttransplantation HLA antibody monitoring by allowing the detection of low levels of donor antibody and easily distinguishing the isotype and target (HLA class I or class II) of the antibodies.
Abstract: We have cited more than 23 studies showing that de novo development of anti-HLA antibodies is associated with increased acute and chronic rejection and decreased graft survival in kidney, heart, lung, liver, and corneal transplants. Antibodies to both HLA class I and class II antigens seem to be detrimental. Antibodies of the IgG isotype and possibly the IgM isotype were clinically relevant. Most studies showed that donor-specific antibodies were associated with rejection and graft loss. Therefore, HLA antibodies provide a clinical readout for patient alloreactivity that may have the ability to distinguish graft dysfunction due to immunologic and nonimmunologic causes. Antibody may act as a critical trigger for rejection of allografts and may serve as an early indicator of a slowly smoldering chronic rejection that is not manifested at a given time by biochemical measures such as serum creatinine levels. The effectiveness of various drugs on chronic rejection should be evaluable by their effects on HLA antibody production. We predict that recently developed ELISA and flow cytometry techniques using purified HLA antigen will increase the clinical relevance of posttransplantation HLA antibody monitoring by (1) allowing the detection of low levels of donor antibody; (2) easily distinguishing the isotype and target (HLA class I or class II) of the antibodies; and (3) correlating the antibody with specific graft pathology.