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The application of an action system model to destructive behaviour: the examples of arson and terrorism.

This article argues that criminal and deviant behaviour can be productively viewed through an action system framework. The idea is developed by considering two forms of destructive behaviour: arson and barricade-hostage terrorist incidents. Two studies are presented. The first study tests the hypothesis that different forms of arson will reflect the four dominant states that an action system can take; integrative, expressive, conservative, and adaptive. A smallest space analysis was performed on 46 variables describing 230 cases of arson and the results identified the four themes of action system functioning. An examination of the personal characteristics of the arsonists also produced four variable groupings and a combined analysis of the four action scales and four characteristics scales also supported the structural hypothesis of the action system model. The second study applied the action system model to the study acts of terrorist barricade-hostage incidents. A smallest space analysis of 44 variables coded from 41 incidents again revealed four distinct forms of activity, which were psychologically similar to the four modes of arson identified in study one. Overall, these two studies provide support for the appropriateness of the action system framework as a way of classifying different forms of deviant behaviour.

Behavior↗

G protein-mediated signal transduction as a target of antidepressant and antibipolar drug action: evidence from model systems.

While the molecular locus of antidepressant and antibipolar drug action has not yet been established, it has become increasingly likely that the targets of such drugs lie distal to neurotransmitter receptors along the signal transduction pathway. These targets are likely to involve G protein-mediated signal transduction systems such as adenylyl cyclase and phospholipase C. This article will demonstrate model systems that have been developed in an attempt to determine how and where these drugs work. It appears that these model systems not only represent good experimental paradigms for studying the mechanisms of antibipolar and antimanic drugs, but are useful as simplified, yet realistic venues in which to test the speed and efficacy of suspected therapeutic agents.

Adenylyl Cyclases↗

A model system for optimising the selection of membrane antigen-specific human antibodies on intact cells using phage antibody display technology.

The functional expression of human antibody fragments on the surface of filamentous bacteriophage, and selection of phage antibodies (PhAbs) with antigens, has provided a powerful tool for generating novel antibodies. Applications of phage antibody display technology have increased over the past decade. Successful isolation of phage antibodies has been reported mostly using purified antigens. Isolation has proven to be more complicated with complex mixtures of antigens, such as intact cells. A given cell type contains thousands of different epitopes, each capable in theory of binding phage antibodies. Often antigens are not known or cannot be purified without disrupting their conformational integrity. To overcome problems involving phage antibody selections on intact cells, we have developed an experimental model system that allows for optimisation and comparison of various selection strategies. The model system comprises labelling of intact cells with the fluorescently labelled phospholipid fluorescein-DHPE. Upon incubation, this phospholipid is readily incorporated in the membrane of any cell type. Labelling intensity is regulated by varying the phospholipid concentration. After optimisation of key steps in the selection procedure, we were able to isolate fluorescein-DHPE specific phage from a synthetic library using intact cells. This model system can be applied to any cell type and we demonstrate that it can be used to efficiently compare and optimise selection strategies.

Antibodies↗

Model systems for investigating mucin gene expression in airway diseases.

Overproduction of mucus and of mucin glycoproteins and goblet cell hyperplasia occurs in chronic obstructive airway diseases, including asthma and cystic fibrosis. Mucus overproduction results from alterations in several cellular processes, including altered regulation of airway mucin genes on exposure to environmental and infectious agents and to inflammatory mediators. Seven of the nine identified MUC genes (which encode the protein backbone of mucins) are normally expressed in human respiratory tract tissues. Several inflammatory mediators have now been shown to regulate expression of MUC2, MUC5AC, and MUC5B genes. Importantly, mucin gene expression can be regulated both transcriptionally and posttranscriptionally. Current information on airway mucin gene expression is summarized in this review along with an overview of airway epithelial model systems. In vitro model systems include airway epithelial carcinoma cell lines and primary normal human bronchial epithelial (NHBE) cells. In vivo systems include human respiratory tract tissues and rodent airways. Our laboratory has begun to investigate the role of cytokines on mucin gene expression in vitro and in vivo and on goblet cell metaplasia in vivo. Because cytokines can alter cell proliferation, we characterized the effect of interleukin (IL)-4 and IL-13 on the proliferation of NHBE cells and three human lung carcinoma cell lines--A549, NCI-H292, and Calu-3--that are frequently used for analyses of airway mucin gene expression. Both IL-4 and IL-13 had cell-specific effects. They increased proliferation moderately (1.2-3.0-fold) in NHBE and Calu-3 cells, but markedly inhibited proliferation of A549 cells in a dose-dependent manner. IL-4 increased proliferation of NCI-H292 cells moderately, although IL-13 had no significant effect. We also examined the role of IL-13 and IL-4 on MUC5AC messenger RNA (mRNA) expression in A549, Calu-3, and H292 cell lines and did not observe any significant effect. However, we recently showed an increase in Muc-5ac mRNA and protein expression in a murine model of ovalbumin-induced allergic asthma and in murine airways when IL-13 was delivered intranasally (Alimam, N.Z., et al. Am J. Respir. Cell Mol. Biol. 22:253--260). Thus, we speculate that IL-13 plays a role in the differentiation of murine airway epithelial cells into goblet cells, which then express Muc-5ac mRNA. A detailed analysis of the role of cytokines in airway cell differentiation and mucin gene expression both in vitro and in vivo is required to elucidate the roles of mucins in airway health and diseases. Identification of Muc-5ac as a major gene and gene product in goblet cell metaplasia should facilitate delineation of the molecular mechanisms underlying the induction and reversal of airway goblet cell metaplasia and goblet cell hyperplasia.

Animals↗

Albumin-eicosanoid interactions. A model system to determine their attributes and inhibition.

A model system was developed to (a) reflect the chemical attributes of the microenvironment involved in albumin-eicosanoid interactions and (b) determine the effects of other ligands on these interactions. Albumin-dependent modulation of prostaglandin stability was chosen as the basis for this system. 15-Ketoprostaglandin E2 (PGE2) was evaluated as a model ligand because under special conditions it decomposes with formation of a visible chromophore. Human serum albumin, in a concentration-dependent fashion, catalyzed the dehydration of 15-keto-PGE2 with the concurrent generation of this chromophore (lambda max = 505 nm, epsilon = 35,000). Since chromophore production from 15-keto-PGE2 in albumin-free solution occurs only at pH greater than 10, the results suggest that albumin-eicosanoid interactions involve a microenvironment with alkaline attributes. The effect of other ligands on albumin-15-keto-prostaglandin E2 interactions was determined by monitoring their ability to inhibit the spectral component of these interactions. Inhibition correlated with an affinity for specific binding sites on albumin. At mole ratios of ligand/albumin below 1, only phenylbutazone, its analogs, and warfarin inhibited chromophore development. Other ligands including fatty acids, steroids, tryptophan, and drugs with an affinity for other binding sites were ineffective inhibitors.

Alprostadil↗

Nuclear magnetic resonance studies of Ba1 bacterium and some model systems.

Lithium NMR relaxation times of some model systems and E. coli cells in high LiCl concentration were measured. The lithium NMR relaxation times were compared to the relaxation times in the holotolerant bacterium Ba1 (Goldberg, M., Risk, M. and Gilboa, H. (1983) Biochim. Biophys. Acta 763, 35-40). Complementary studies of the water protons NMR relaxation times were carried out. It is suggested that the lithium in the H.S. Ba1 bacterium is occulated in small pores of the cell envelope.

Chlorides↗

A dynamic system model of an off-road cyclist.

To optimize the performance of off-road bicycle suspension systems, a dynamic model of the bicycle/rider system would be useful. This paper takes a major step toward this goal by developing a dynamic system model of the cyclist. To develop the cyclist model, a series of four vibrational tests utilizing random inputs was conducted on seven experienced off-road cyclists. This allowed the transfer functions for the arms and legs to be determined. To reproduce the essential features (i.e., resonance peaks) of the experimental transfer functions, the system model included elements representing the visceral mass along with the arms and legs. Through simulations, the frequency responses of the system model of the rider in each of the four tests were computed. Optimal stiffness and damping parameter values for each subject were determined by minimizing the difference between the experimental and simulation results. Good agreement between experimental and simulation results indicates that modeling the rider as a lumped parameter system with linear springs and dampers is possible.

Bicycling↗

Fluorescence depolarization in a model system: carbonic anhydrase-dansyl sulphonamide.

The model system, carbonic anhydrase to which dansyl sulphonamide is specifically adsorbed, was chosen to test the fundamentals of the fluorescence depolarisation method. Fluorescence decay was shown to be satisfactorily represented by a single exponential decay term and the derived lifetime did not seem to vary significantly with mean excitation or emission wavelength. Depolarisation measurements were quite reproducible and those made with varying temperature were consistent with those performed with varying solution viscosity, thus excluding localised dye rotation. The calculated relaxation time, which was independent of wavelength of excitation or emission, was in conformity with a rigid spherical molecule of molecular weight 29 000 with 30% hydration.

Carbonic Anhydrases↗

Acrylamide formation from asparagine under low-moisture Maillard reaction conditions. 1. Physical and chemical aspects in crystalline model systems.

The formation of acrylamide in crystalline model systems based on asparagine and reducing sugars was investigated under low-moisture reaction conditions. The acrylamide amounts were correlated with physical changes occurring during the reaction. Molecular mobility of the precursors turned out to be a critical parameter in solid systems, which is linked to the melting behavior and the release of crystallization water of the reaction sample. Heating binary mixtures of asparagine monohydrate and anhydrous reducing sugars led to higher acrylamide amounts in the presence of fructose compared to glucose. Differential scanning calorimetry measurements performed in open systems indicated melting of fructose at 126 degrees C, whereas glucose and galactose fused at 157 and 172 degrees C, respectively. However, glucose was the most reactive and fructose the least efficient sugar in anhydrous liquid systems, indicating that at given molecular mobility the chemical reactivity of the sugar was the major driver in acrylamide formation. Furthermore, reaction time and temperature were found to be covariant parameters: acrylamide was preferably formed by reacting glucose and asparagine at 120 degrees C for 60 min, whereas 160 degrees C was required at shorter reaction time (5 min). These results suggest that, in addition to the chemical reactivity of ingredients, their physical state as well as reaction temperature and time would influence the formation of acrylamide during food processing.

Acrylamide↗

The effects of phenytoin on rat development: an animal model system for fetal hydantoin syndrome.

An animal model system has been established which reproduces some of the features of the Fetal Hydantoin Syndrome. This pattern of altered growth and development includes growth retardation, craniofacial anomalies, distal phalangeal hypoplasia, and mental deficiency. Rats exposed in utero to phenytoin on gestational days 9, 11, and 13 exhibited fetal onset growth retardation, abnormalities of the craniofacial region and axial skeleton. In addition, the exposed offspring had significantly lower fetal weights, a shortened snout and a high-arched, irregular palate, and significant delays in skeletal maturation. These abnormalities resemble those reported for the Fetal Hydantoin Syndrome and provide a means to study the effect of phenytoin on the morphological and biochemical development of the fetus.

Abnormalities, Drug-Induced↗

The south central center for public health preparedness training system model: a comprehensive approach.

The South Central Center for Public Health Preparedness (SCCPHP) is a collaboration among the schools of public health at Tulane University and the University of Alabama at Birmingham and the state health departments in Alabama, Arkansas, Louisiana, and Mississippi. The SCCPHP provides competency-based training via distant delivery methods to prepare public health workers to plan for and rapidly respond to public health threats and emergency events. This article presents the training system model used by the SCCPHP to assess, design, develop, implement, and evaluate training that is both competency driven and practice based. The SCCPHP training system model ensures a standardized process is used across public health occupations and geographic regions, while allowing for tailoring of the content to meet the specific training needs of the workforce in the respective state and local health departments. Further, the SCCPHP training system model provides evidence of the reciprocal nature between research and practice needed to advance the area of emergency preparedness training and workforce development initiatives in public health.

Competency-Based Education↗

Measurement of circulating Clq precipitable immune complexes by a nephelometric type assay after polyethylene glycol extraction in model system.

Clq precipitins were assayed in a model system by absorption nephelometry. Polyethylene glycol was used to extract immune complexes so that sufficient sensitivity with minimal interference could be achieved. Using a double beam spectrophotometer, we found that the reaction of immune complexes with Clq occurred rapidly and plateaued between 5-20 minutes. The optimal concentration of sodium in the reaction mixture was between 0.155-0.165 M, while chloride and EDTA did not affect the reaction significantly. Standard curves generated from heated aggregated gamma globulin showed a high degree of linearity, between 12.5-400 mg/L. Need for conductivity meters, radioisotopes, and other special equipment was eliminated because highly purified Clq is not required for nephelometric assay, and all necessary parameters can be monitored by flame photometry and electrophoresis, which are available in most clinical laboratories. Day to day reproducibility showed CVs of 5.4, 9.5, and 11.4% at control levels of 210, 160, and 70 mg/ L of immune complexes, respectively. Twelve patients with elevated levels of immune complexes by other methods were differentiated from normals by the present method. Nephelometry may offer a simplified approach for testing immune complexes and may become more widespread in clinical laboratories.

Antigen-Antibody Complex↗

A system model for halothane closed-circuit anesthesia. Structure considerations and performance evaluation.

BACKGROUND: Previously, the authors described a physiologic model for closed-circuit inhalational anesthesia. The basic version of this system model was clinically validated for isoflurane. An extended version adopted nonpulmonary elimination causing a constant fraction of anesthetic to be irreversibly lost. This version improved the accuracy of the model for enflurane. The model's performance for other inhalational anesthetics that are not biochemically inert, such as halothane, remained to be evaluated. METHODS: The current study quantified the predictive performance of four versions of the model by comparison of the predicted and measured alveolar halothane concentration-time profiles in 53 patients. Version A did not incorporate nonpulmonary elimination, whereas version D adopted a nonlinear hepatic nonpulmonary elimination following Michaelis-Menten kinetics. A and D used fixed partition coefficients. Their counterparts, A' and D', were formulated to examine the impact of age-adjusted partition coefficients on the accuracy of our model. Each concentration measured by mass spectrometry was compared to four predicted concentrations calculated by four computer simulations (one per version). For each patient, the authors calculated the root mean squared error (rmse; typical error size), bias (systematic component), and scatter of the prediction errors. RESULTS: Fifty-three patients were anesthetized with 330 ml of liquid halothane via 426 bolus injections during more than 61 h; 21,890 alveolar concentrations (average 0.6 vol%) were measured. Version D' showed the best overall performance with an rmse of 19.6 +/- 7.2%, a bias of 0.5 +/- 15.9%, and a scatter of 13.2 +/- 3.5% (mean +/- SD). CONCLUSIONS: The model incorporating nonpulmonary elimination and age-adjusted partition coefficients (D') is sufficiently reliable and accurate to represent halothane closed-circuit anesthesia. This system model, with its various versions, is a valuable tool to predict the dynamics of isoflurane, enflurane, and halothane for clinical, educational, and research purposes.

Adult↗

Capsaicin-evoked CGRP release from rat buccal mucosa: development of a model system for studying trigeminal mechanisms of neurogenic inflammation.

Many of the physiological hallmarks associated with neurogenic inflammatory processes in cutaneous tissues are similarly present within orofacial structures. Such attributes include the dependence upon capsaicin-sensitive sensory neurons and the involvement of certain inflammatory mediators derived therein, including calcitonin gene-related peptide (CGRP). However, there are also important differences between the trigeminal and spinal nervous systems, and the potential contributions of neurogenic processes to inflammatory disease within the trigeminal system have yet to be fully elucidated. We present here a model system that affords the ability to study mechanisms regulating the efferent functions of peptidergic terminals that may subserve neurogenic inflammation within the oral cavity. Freshly dissected buccal mucosa tissue from adult, male, Sprague-Dawley rats was placed into chambers and superfused with oxygenated, Krebs buffer. Serial aliquots of the egressing superfusate were acquired and analysed by radioimmunoassay for immunoreactive CGRP (iCGRP). Addition of the selective excitotoxin, capsaicin (10-300 microm), to the superfusion buffer resulted in a significant, concentration-dependent increase in superfusate levels of iCGRP. Similarly, release of iCGRP from the buccal mucosa could also be evoked by a depolarizing concentration of potassium chloride (50 mm) or by the calcium ionophore A23187 (1 microm). The specific, capsaicin receptor antagonist, capsazepine (300 microm), completely abolished the capsaicin-evoked release of iCGRP while having no effect whatsoever on the potassium-evoked release. Moreover, capsaicin-evoked release was dependent upon the presence of extracellular calcium ions and was significantly, though incompletely, attenuated by neonatal capsaicin denervation. Collectively, these data indicate that the evoked neurosecretion of iCGRP in response to capsaicin occurs via a vanilloid receptor-mediated, exocytotic mechanism. The model system described here should greatly facilitate future investigations designed to identify and characterize the stimuli that regulate the release of CGRP or other neurosecretory substances in isolated tissues. This system may also be used to elucidate the role of these mediators in the aetiology of inflammatory processes within the trigeminal field of innervation.

Animals↗

Violent traumatic brain injury: occurrence, patient characteristics, and risk factors from the Traumatic Brain Injury Model Systems project.

OBJECTIVES: To examine the occurrence of and characteristics associated with violent traumatic brain injury (TBI) in the Traumatic Brain Injury Model Systems (TBIMS) project for 4 of the 5 original Model Systems centers and to determine the patient characteristics of this group, as well as the risk factors for sustaining such an injury. DESIGN: Prospective evaluation of individuals with violent TBI over a 10-year period. SETTING: Four TBIMS centers. PARTICIPANTS: A total of 1,229 individuals who received acute hospitalization and inpatient rehabilitation care for TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The occurrence of a violent TBI. RESULTS: Twenty-six percent of the participants in the TBIMS project sustained a violent TBI. This type of injury was more common in African-American men who were single and slightly older than the average TBI patient, were unemployed before injury, and had had a previous TBI. A higher injury rate was noted in the earlier part of the evaluation period. Those who sustained a violent TBI had higher levels of caregiver burden and disability, as well as decreased productivity and community reintegration at rehabilitation discharge and at 1 and 2 years postinjury. CONCLUSIONS: The occurrence of violent TBI in the TBIMS project is consistent with national trends of decreasing incidence of violent injuries in the 1990s. These results present a profile of those who have been injured through violence. The relative risks for sustaining such an injury appear to be well defined when considering demographic and temporal factors.

Adult↗

A new model system for measuring intracanal temperatures.

A new model system was developed which allows intracanal temperature measurements to be recorded during repeated obturations of a human tooth root canal. A human central incisor was embedded in clear orthodontic resin and sectioned longitudinally. Sixteen thermocouples were secured at 2-mm intervals along two surfaces of the root canal. The thermocouples were connected to a computerized temperature recording system to measure intracanal temperatures produced by high-temperature thermoplasticized injectable gutta-percha. The system was capable of recording 16 simultaneous temperatures every second with an accuracy of a hundredth degree centigrade. There was a linear increase in the recorded temperatures in the root canal. However, the actual temperatures were lower than expected.

Body Temperature↗

Comparison of volatile generation in serine/threonine/glutamine-ribose/glucose/fructose model systems.

Thermal generation of volatiles in nine model reactions was studied and compared. Each of the model systems contained one amino acid and one monosaccharide. The amino acid was serine, threonine, or glutamine, and the monosaccharide was ribose, glucose, or fructose. More unsubstituted pyrazine was generated in serine-sugar systems than threonine-sugar systems. The formation of several furfuryl-substituted pyrazines and pyrroles was observed in some of the studied systems. Total pyrazines were generated more in glutamine-containing systems than in serine- and threonine-containing systems, and the reverse was true for generation of furfuryl-substituted compounds. Acetylpyrazine was generated in serine/threonine/glutamine-glucose and serine/glutamine-fructose systems.

Fructose↗

Introduction: the Traumatic Brain Injury Model Systems of Care.

The Traumatic Brain Injury Model Systems of Care (TBIMS) is a program that has been funded by the National Institute on Disability and Rehabilitation Research (US Department of Education) since 1987. The program is a collaborative effort of rehabilitation centers across the United States to further knowledge about the natural history of recovery and outcomes over the life course of individuals with traumatic brain injury, as well as to provide comprehensive services across the continuum of care and to foster innovative research programs. This introduction describes the underlying principles of the TBIMS program and the research initiatives carried out in the 1997/1998-2002 funding cycle.

Brain Injuries↗