scispace - formally typeset
Search or ask a question

Showing papers by "University of Calgary published in 1994"


Journal ArticleDOI
01 Nov 1994-Neuron
TL;DR: In vitro formation of clonally derived spheres of cells that exhibit stem cell properties such as self-maintenance and the generation of a large number of progeny comprising the major cell types found in the central nervous system suggest that a relatively quiescent subependymal cell is the in vivo source of neural stem cells.

1,482 citations


Journal ArticleDOI
TL;DR: The pathophysiological significance of the microvascular responses to inflammation are discussed in terms of adhesion‐directed strategies for the treatment of different cardiovascular diseases and circulatory disorders.
Abstract: The accumulation of leukocytes in inflamed tissue results from adhesive interactions between leukocytes and endothelial cells within the microcirculation. These adhesive interactions and the excessive filtration of fluid and protein that accompanies an inflammatory response are largely confined to one region of the microvasculature: postcapillary venules. The nature and magnitude of the leukocyte-endothelial cell adhesive interactions that take place within postcapillary venules are determined by a variety of factors, including expression of adhesion molecules on leukocytes and/or endothelial cells, products of leukocyte (superoxide) and endothelial cell (nitric oxide) activation, and the physical forces generated by the movement of blood along the vessel wall. The contribution of different adhesion molecules to leukocyte rolling, adherence, and emigration in venules is discussed. Emerging views on potential endogenous antiadhesion molecules produced by endothelial cells as well as the influence of alterations in shear rate on leukocyte adhesion are addressed. Finally, the pathophysiological significance of the microvascular responses to inflammation are discussed in terms of adhesion-directed strategies for the treatment of different cardiovascular diseases and circulatory disorders.

845 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examined the effect of education and experience using U.S. census data and concluded that a general education has a strong positive influence on entrepreneurship in terms of becoming self-employed and success.

763 citations


Journal ArticleDOI
26 May 1994-Nature
TL;DR: It is suggested that visual attention is not a high-speed switching mecha-nism, but a sustained state during which relevant objects become available to influence behaviour, consistent with recent physiological results in the monkey.
Abstract: In vision, attentional limitations are reflected in interference or reduced accuracy when two objects must be identified at once in a brief display. In our experiments a brief temporal separation was introduced between the two objects to be identified. We measured how long the object continued to interfere with the second, and hence the time course of the first object's attentional demand. According to conventional serial models, attention is assigned rapidly to one object after another, with a dwell time of only a few dozen milliseconds per item. But we report here that interference lasts for several hundred milliseconds--an order of magnitude more than the prediction of conventional models. We suggest that visual attention is not a high-speed switching mechanism, but a sustained state during which relevant objects become available to influence behaviour. This conclusion is consistent with recent physiological results in the monkey.

630 citations


Journal ArticleDOI
11 Oct 1994-Gene
TL;DR: The nucleotide sequence of the 1.9-kb PstI fragment from pRO1614, that allows stable maintenance of pMB1 (ColE1)-based cloning vectors in Pseudomonas, was determined and encodes a putative origin of replication, a replication-controlling protein, and the C terminus of the Tn3 beta-lactamase-encoding gene.

584 citations


Journal ArticleDOI
29 Sep 1994-Nature
TL;DR: A full-length complementary DNA clone showed that p25 is a truncated form of a larger protein precursor, p35, which seems to be the predominant form of the protein in crude brain extract, and is the first example of a Cdc2-like kinase with neuronal function.
Abstract: Phosphorylation of the neurofilament proteins of high and medium relative molecular mass, as well as of the Alzheimer's tau protein, is thought to be catalysed by a protein kinase with Cdc2-like substrate specificity. We have purified a novel Cdc2-like kinase from bovine brain capable of phosphorylating both the neurofilament proteins and tau. The purified enzyme is a heterodimer of cyclin-dependent kinase 5 (Cdk5) and a novel regulatory subunit, p25 (ref. 8). When overexpressed and purified from Escherichia coli, p25 can activate Cdk5 in vitro. Unlike Cdk5, which is ubiquitously expressed in human tissue, the p25 transcript is expressed only in brain. A full-length complementary DNA clone showed that p25 is a truncated form of a larger protein precursor, p35, which seems to be the predominant form of the protein in crude brain extract. Cdk5/p35 is the first example of a Cdc2-like kinase with neuronal function.

581 citations


Journal ArticleDOI
TL;DR: In this article, the authors examined how the task, cultural, and political characteristics of acquisitions influence decisions about levels of integration and concluded that an understanding of acquisition integration is best achieved by viewing integration design decisions through multiple theoretical lenses.
Abstract: Executives of 56 acquiring organizations participated in policy-capturing research that examined how the task, cultural, and political characteristics of acquisitions influence decisions about levels of integration. Although task-related characteristics entered most heavily into managers' decision models, cultural and political factors were also important. These results suggest that an understanding of acquisition integration is best achieved by viewing integration design decisions through multiple theoretical lenses. Furthermore, although industry and acquisition experience explained some variation in integration decision policies, results suggest that other individual or organization-level factors are also at work.

577 citations


Journal ArticleDOI
Kevin J. Leco1, Rama Khokha1, N Pavloff1, S P Hawkes1, Dylan R. Edwards1 
TL;DR: It is proposed that TIMP-3 functions in a tissue-specific fashion as part of an acute response to remodeling stimuli in murine tissue inhibitor of metalloproteinases-3.

490 citations


Proceedings ArticleDOI
22 Oct 1994
TL;DR: The paper considers both human and technical considerations that designers should ponder before choosing a particular concurrency control method and reviews the work-in-progress designing and implementing a library of concurrency schemes in GROUPKIT, a groupware toolkit.
Abstract: This paper exposes the concurrency control problem in groupware when it is implemented as a distributed system. Traditional concurrency control methods cannot be applied directly to groupware because system interactions include people as well as computers. Methods, such as locking, serialization, and their degree of optimism, are shown to have quite different impacts on the interface and how operations are displayed and perceived by group members. The paper considers both human and technical considerations that designers should ponder before choosing a particular concurrency control method. It also reviews our work-in-progress designing and implementing a library of concurrency schemes in GROUPKIT, a groupware toolkit.

453 citations


Journal ArticleDOI
TL;DR: The present article reports a series of experiments in which the temporary attentional deficits that ensue when humans are required to select a target from among a temporal stream of stimuli presented at a rapid rate.
Abstract: To investigate the temporal allocation of attention, a series of 7 experiments using rapid serial visual presentation (RSVP) was designed to examine the relationship of the attentional demands of various target tasks to the production of the subsequent visual attentional deficit, or "attentional blink" (AB), recently reported by J. E. Raymond, K. L. Shapiro, and K. M. Amell (1992). The principal finding is that AB occurs only when a target is an object and does not occur when the target is defined by a temporal interval. Target detection difficulty as estimated by d' analysis reveals no relationship between the attentional demands of the target and the production of the AB. A late-selection account of this phenomenon is offered in place of the early-selection account advanced in Raymond et al.'s previous report. Many studies of visual attention have addressed issues concerning the allocation of attention to spatially distributed visual information that is presented for brief intervals. The experiments reported in this article, however, are concerned with how attention is allocated to visual information that is distributed over time but presented in a restricted area of the visual field. The present article reports a series of experiments in which we investigated the temporary attentional deficits that ensue when humans are required to select a target from among a temporal stream of stimuli presented at a rapid rate. The task used in all experiments is that of rapid serial visual presentation (RSVP). In the generic task, stimuli are presented briefly in the same location at a rate of between 6-20 items/s. The subject's task is to identify one or more target(s) that is(are) differentiated in some way from the background, or nontarget, stimulus stream. Stimuli that have been investigated with this method include letters, digits, words, and pictures (e.g., D. E. Broadbent & M. H. P. Broadbent, 1987; Intraub, 1985; Kanwisher, 1987; Lawrence, 1971; Reeves & Sperling, 1986; Weichselgartner & Sperling, 1987). Thus the RSVP procedure could be construed as the temporal analogy to spatial search in that a subject must detect a target from among a set of nontargets or distractors.

449 citations


Journal ArticleDOI
TL;DR: In this article, a l'aide de deux exemples, l'A. essaie de prouver que l'equivalence proclamee entre les enonces attribuant des dispositions ou pouvoirs causaux and les enonce conditionnels n'est pas defendable si l'enonce conditionnel est formule d'une certaine facon.
Abstract: A l'aide de deux exemples, l'A. essaie de prouver que l'equivalence proclamee entre les enonces attribuant des dispositions ou pouvoirs causaux et les enonces conditionnels n'est pas defendable si l'enonce conditionnel est formule d'une certaine facon. Cela peut etre evite par une reformulation triviale du conditionnel

Journal ArticleDOI
TL;DR: A method to monitor mRNA expression that is based upon the reverse transcriptase-polymerase chain reaction (RT-PCR) and includes multiple sets of primer pairs in coamplification reactions is developed and demonstrated the utility by monitoring the expression kinetics of cyclins A, B1, D1, and E, and of the immediate-early genes c-fos, c-myc, and beta-actin.

Journal ArticleDOI
TL;DR: Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p<0.001), which led to an improvement in serum markers of cholestasis.

Journal ArticleDOI
TL;DR: It is suggested that prolonged nitric oxide synthesis inhibition in HUVECs causes an oxidant- and PAF-associated rise in adhesion on the surface of these endothelial cells for neutrophils.
Abstract: The objective of the present study was to determine whether prolonged inhibition of nitric oxide synthesis in endothelial cells increased the surface adhesion of these cells for neutrophils. Human umbilical vein endothelial cells (HUVECs) were grown to confluence in 48-well microtiter plates. Exposure of HUVECs to the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) did not cause neutrophil adhesion at 1 hour but increased adhesion at 4 hours in a dose-dependent manner. The increased adhesion was prevented with L-arginine or nitric oxide donors but not an analogue of cGMP. The increased adhesion was inhibited by monoclonal antibodies directed against the beta 2-integrin CD18 and endothelial cell adhesion molecule ICAM-1. Platelet-activating factor (PAF) receptor antagonist WEB 2086 also prevented the L-NAME-induced neutrophil adhesion. Intracellular oxygen radical scavengers (dimethyl sulfoxide, butylated hydroxytoluene, and alpha, alpha'-dipyridyl), the iron chelator desferrioxamine, and the mitochondrial inhibitor azide inhibited the L-NAME-induced neutrophil adhesion, whereas extracellular oxygen radical scavengers (superoxide dismutase and catalase) had no effect. HUVECs were loaded with 2',7'-dichlorodihydrofluorescein diacetate, and oxidation to the fluorescent dichlorodihydrofluorescein (DCHF) was monitored. Fluorescence was enhanced in the L-NAME-treated HUVECs throughout the 4-hour incubation, an event inhibitable by an antioxidant and azide. The magnitude of the intracellular oxidation of DCHF was equivalent to approximately 0.8 mumol/L H2O2. These data suggest that prolonged nitric oxide synthesis inhibition in HUVECs causes an oxidant- and PAF-associated rise in adhesion on the surface of these endothelial cells for neutrophils.

Journal ArticleDOI
TL;DR: The data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia and predictors of response to these drugs could not be determined.
Abstract: Objective. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. Methods, Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. Results. After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2—9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response. Conclusion. Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.

Proceedings ArticleDOI
24 Jul 1994
TL;DR: The paper extends Lindenmayer systems in a manner suitable for simulating the interaction between a developing plant and its environment by modeling the response of trees to pruning, which yields synthetic images of sculptured plants found in topiary gardens.
Abstract: The paper extends Lindenmayer systems in a manner suitable for simulating the interaction between a developing plant and its environment. The formalism is illustrated by modeling the response of trees to pruning, which yields synthetic images of sculptured plants found in topiary gardens.


Journal ArticleDOI
TL;DR: It was found that a combination of physical neglect, physical abuse, and verbal abuse had the greatest impact on children, affecting such things as their enjoyment of living and hopes for the future.

Journal ArticleDOI
TL;DR: It is concluded that activity-dependent increases in light transmittance across brain slices primarily reveal glial and neuronal swelling associated with excitatory synaptic input and action potential discharge.

Journal ArticleDOI
TL;DR: The findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that avoids pulmonary angiography, identifies patients with proximal-vein thrombosis who require treatment, and avoids the need for treatment and further investigation in the majority of patients.
Abstract: Background: Pulmonary embolism has historically presented a formidable diagnostic problem because of the nonspecificity of the clinical findings associated with this disorder and the diagnostic uncertainties and challenges presented by both ventilation-perfusion lung scanning and pulmonary angiography. We have reported previously that serial noninvasive leg testing provides a practical noninvasive alternative to pulmonary angiography in patients with nonhigh probability (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have reevaluated this observation prospectively to (1) confirm or refute our original observation in an independent cohort and (2) to increase the numbers sufficiently to provide narrow confidence limits for the observed outcomes. Methods: A prospective comparative study in 1564 consecutive patients with suspected pulmonary embolism who underwent ventilation-perfusion lung scanning and objective testing for proximal-vein thrombosis. Results: On long-term follow-up of 627 patients with the following characteristics: (1) abnormal, nondiagnostic lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95% confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95% confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits, 1.8% to 9.2%) with high probability lung scans who received anticoagulant therapy. Conclusions: Our findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies patients with proximal-vein thrombosis who require treatment, and (3) avoids the need for treatment and further investigation in the majority of patients. (Arch Intern Med. 1994;154:289-297)

Journal ArticleDOI
TL;DR: Addition of a nitroxybutyl moiety to two NSAIDs markedly reduced the ability of these agents to induce short-term gastric injury but did not interfere with their ability to suppress inflammatory processes, inhibit prostaglandin synthesis, or inhibit platelet aggregation.

Journal ArticleDOI
TL;DR: A set of shape factors to measure the roughness of contours of calcifications in mammograms and for use in their classification as malignant or benign as well as for classification as benign or benign are developed.
Abstract: The authors have developed a set of shape factors to measure the roughness of contours of calcifications in mammograms and for use in their classification as malignant or benign. The analysis of mammograms is performed in three stages. First, a region growing technique is used to obtain the contours of calcifications. Then, three measures of shape features, including compactness, moments, and Fourier descriptors are computed for each region. Finally, their applicability for classification is studied by using the three shape measures to form feature vectors. Classification of 143 calcifications from 18 biopsy-proven cases as benign or malignant using the three measures with the nearest-neighbor method was 100% accurate. >

Book
09 Sep 1994
TL;DR: Parry and Doan as discussed by the authors argue that since there are no metapositions anywhere in the universe, all we can know are systems in a never-ending process of "perturbing" and coupling with one another to form new systems.
Abstract: Stories of the Self: Surviving In a World With No Truth Story Revisions: Narrative Therapy in the Postmodern World A. Parry and R.E. Doan. New York: The Guilford Press, 1994, 216 pp., $15.95 (softcover). Postmodern writings, for the most part have earned reputations for thick, impenetrable, overly intellectualized styles which belie most mortal Attempts at understandings. The standard postmodern sentence, it seems, contains no less than six dependent clauses and encompasses at least one full page text. Rife with nonoffensi ve language, neologisms and round-about sentence constructions, such writings have alienated a large majority of readers who have been raised on modernist, straightforward svelte and words which arc actually included m Webster's New World Dictionary (Guralnik, 1982) And rightfully so. Thankfully, Parry and Doan have largely forgone such convoluted writing us their book. In actuality, this is two books under one corer. The first part, written largely by Alan Parry, focuses on the literary and epistemological precedents for narrative therapy. In this section, Parry points to the fundamental differences between "paradigmatic"-modernist therapy and "narrative" postmodern therapy, suggesting that the chief goal of modernist therapy and, thus, language is to reduce, to limit one word to one clear, strictly operartionally defined meaning. On the other fund, the central goal of postmodernist therapy and language is to elaborate, to allow a word more than one possible met, to invite the client to use words as he or she interprets them. In the first chapter of this book, Parry succinctly outlines the heart of what he sees as the big problem of modernist thinking in a postmodern world-all of our stories, our "grand narratives" have been invalidated and rendered impotent. Parry asserts that as science, truth and progress supplanted sacred and mythical stories as the operative "grand narratives" in the modern age, we had no choice but to begin comparing our own personal stories against those "meta-stories." However, as the world developed and became more complex, even these stories became insufficient to explain the tangled intricacy of events surrounding us. Thus, as the more cynical populace of the world moved into the postmodern era, we were left with "no single story, however understood, [which was] able to provide either legitimacy or sufficiency equal to the pace of change" (p. 11) Therefore, Parr, advocates an adaptation of therapeutic technique to the postmodern world, where the ideals and certainties of the modernist search for truth have given way to a more individual search for meaning. In Chapter 2, Parry turns his discussion to the challenges of doing story-based narrative therapy in a world which has largely been stripped of its grand stories Parry uses the theme of family therapy, which he suggests is "for postmodernism what psychoanalysis was for modernism" (p. 5), presumably because it exemplifies the demonic interplay of different "stories" within a system, none of which can be assumed to have superiority over any other. He asserts that, even within an individual, there are many stories influencing the person at any one time, in the same way that there are many stories and voices within a family system. Paraphrasing Maturana, Parry indicates that: since there are no metapositions anywhere in the universe, all we can know are systems in a never-ending process of "perturbing" and coupling with one another to form new systems. Furthermore, we can only know what our own biological structures permit us to "know." But since it is our structurally determined capacity for language that even enables us to make such distinctions as systems in the first place, all our perceived truths are, in the very first instance, constructed Truths, (p. 16) By endorsing this perspective, Parry situates narrative therapy in a broadly constructivist (see Kelly, 1955). Parry goes on to suggest that, Whether the viewer is a person, a family, a community, or a people, the world is unavoidable viewed through the lens of a succession of stories-not only 3 personal story, but gender, community, class, and cultural stories (p. …

Journal ArticleDOI
TL;DR: This article conducted surveys to reveal perceptions and attitudes of residents of the Spey Valley, Scotland towards tourism and related issues, and found that a remarkable stability in attitudes persisted over the 14-year period and, although most residents are positive towards tourism, through use of an index of consensus it was revealed that negative views had somewhat increased.

Journal ArticleDOI
TL;DR: The paper analyzes how Gini-style indices are optimally used in the evaluation of economic spatial models designed to predict where health care practitioners are likely to locate under competitive market conditions to establish one particular geographic distribution of health practitioners which is empirically dominant.

Journal ArticleDOI
TL;DR: The principles concerning the prophylaxis, diagnosis, and clinical management of venous thromboembolic disease in neurosurgery and neurology patients are dealt with in this review.
Abstract: Thromboembolism is a common problem in neurosurgery and neurology patients. Within this diverse population are subpopulations of patients with varying degrees of thromboembolic risk: low, moderate, and high. Patients at substantial risk for deep vein thrombosis and pulmonary embolism include those with spinal cord injury, brain tumor, subarachnoid hemorrhage, head trauma, stroke, and patients undergoing a neurosurgical operation. There are prophylactic strategies that can be applied to these various risk groups that will dramatically reduce the incidence of thromboembolism. The risk of pulmonary embolism or fatal pulmonary embolism typically exceeds the risk of severe or fatal bleeding from adequate prophylaxis, and these techniques should be applied on a routine basis. To adequately care for patients with deep venous thrombosis and pulmonary embolism, the physician requires a thorough understanding of the methods of diagnosis, the pharmacokinetics of heparin and warfarin, and a knowledge of their role in the treatment strategies that have proven efficacy and safety. In addition, an awareness of the low molecular weight heparins and heparinoids is becoming essential. These new agents have a potentially promising role in both the prophylaxis and treatment of patients with neurological disease. The principles concerning the prophylaxis, diagnosis, and clinical management of venous thromboembolic disease in neurosurgery and neurology patients are dealt with in this review.

Journal ArticleDOI
TL;DR: There was an overall decrease in protein synthesis with the induction of drought stress, followed by a resumption of synthesis upon rehydration, and the synthesis of a number of specific polypeptides was found to decrease upon water loss in the leaves.
Abstract: Changes in the concentrations of free amino acids and specific organic acids were analysed during the induction of drought stress in Brassica napus. Most of the amino acids showed a characteristic linear increase with the induction of drought stress in Brassica leaves, increasing an average of 5.9-fold over control levels, followed by a reduction in concentration upon rehydration of the plants. Pyruvate concentrations doubled after 4 days of drought stress whereas 2-oxoglutarate concentrations remained relatively constant. The activities of two of the enzymes involved in amino acid biosynthesis, alanine aminotransferase (EC 2.6.1.2) and aspartate aminotransferase (EC 2.6.1.1), were also measured. Neither enzyme showed any increase in activity, except when the plants were rehydrated. This suggests that the increase in both alanine and aspartate levels results from the increase in their precursors pyruvate and glutamate and may not require increased enzyme activity. The effect of drought stress upon changes in protein synthesis was analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. We found that there was an overall decrease in protein synthesis with the induction of drought stress, followed by a resumption of synthesis upon rehydration. In addition, the synthesis of a number of specific polypeptides was found to decrease upon water loss in the leaves.

Journal ArticleDOI
TL;DR: It is concluded that the CDS achieves a useful degree of separation between measures of depression, negative and extrapyramidal symptoms in subjects with schizophrenia, when combined with the other measures used in this study.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the role played by group attitudes in mediating the impact of GDSS designs on group decision-making performance and found that group attitudes were influential in affecting group decision making performance.
Abstract: Empirical investigations of the effects of group decision support systems (GDSS) accord relatively little attention to the role of attitudes developed by groups toward the GDSS. This study draws upon the theory of social influence to examine the role played by group attitudes in mediating the impact of GDSS designs on group decision-making performance. We found that, in addition to capabilities of GDSS designs, group attitudes toward GDSS were influential in affecting group decision-making performance. The managerial implications of the study are: (1) effective GDSS designs for supporting groups in equivocal decision-making contexts should include structures for communication and consensus support and (2) attempts should be made to enhance user attitudes toward the GDSS through design features of the GDSS, training, and facilitation of positive social influences within the group. The study also provides encouraging evidence about the value of social theories, such as the social influence model and the adaptive structuration theory, in investigating GDSS effects. Further, this study illustrates the value of the partial least squares (PLS) analysis method for testing holistic structural models of GDSS effects.

Journal Article
TL;DR: This study demonstrates for the first time that histamine induces leukocyte rolling via a P-selectin-dependent mechanism in vivo, a prolonged, H1 receptor-mediated event that may contribute significantly to the early phase of inflammation.
Abstract: The objective of this study was to systematically assess the molecular mechanisms and kinetics of histamine-induced leukocyte rolling in rat mesenteric venules using intravital microscopy. A complicating factor in these studies is surgical preparation-induced leukocyte rolling (spontaneous rolling), which leads to a lack of effect of histamine on this parameter. Therefore, we identified the source of the surgery-induced leukocyte rolling (partial mast cell degranulation) and established that pretreatment of animals with sodium cromoglycate (connective tissue mast cell stabilizer) inhibited spontaneous leukocyte rolling. Superfusion of the mast cell-stabilized rat mesentery with histamine caused a profound increase in leukocyte rolling which persisted for the entire hour of experimentation. Diphenhydramine (H1-receptor antagonist) but not cimetidine (H2-receptor antagonist) prevented the rise in histamine-induced leukocyte rolling. An anti-P-selectin Ab but not an anti-CD18 Ab reversed the histamine-induced leukocyte rolling in a dose-dependent fashion. In this model of low base line rolling, exposure of the mesentery to the chemotactic agent platelet-activating factor did not induce leukocyte rolling or adhesion. However, co-administration of histamine with platelet-activating factor did indeed promote leukocyte adhesion suggesting that the presence of at least one effector of P-selectin is a minimal requirement for chemotactically-stimulated leukocytes to adhere to postcapillary venules. This study demonstrates for the first time that histamine induces leukocyte rolling via a P-selectin-dependent mechanism in vivo. This is a prolonged, H1 receptor-mediated event that may contribute significantly to the early phase of inflammation.