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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.
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PMID:Evaluation of immunotoxicity induced by single or concurrent exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel. 1253 64

Plaque rupture with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death. Endothelial disruption leading to plaque rupture may relate to mechanical fatigue associated with cyclic flexion of plaques. A novel method is proposed to assess stress and strain distribution using the finite element (FE) analysis and in vivo patient-specific dynamic 3D coronary arterial tree reconstruction from cine angiographic images. The local stresses were calculated on the diseased arterial wall which was modeled as consisting of a central fibrotic cap subjected to the cyclic flexion from cardiac contraction. Various parameters characterizing the plaque were chosen including vessel diameter, percentage narrowing, and lesion length. According to the FEA simulations, the results show that the smaller vessel diameter, greater percentage narrowing, and/or larger lesion size may result in higher stress on the plaque cap, with the vessel diameter as the dominant factor.
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PMID:Stress analysis using anatomically realistic coronary tree. 1465 40

A three-dimensional (3D) MRI-based computational model with multicomponent plaque structure and fluid-structure interactions (FSI) is introduced to perform mechanical analysis for human atherosclerotic plaques and identify critical flow and stress/strain conditions which may be related to plaque rupture. Three-dimensional geometry of a human carotid plaque was reconstructed from 3D MR images and computational mesh was generated using Visualization Toolkit. Both the artery wall and the plaque components were assumed to be hyperelastic, isotropic, incompressible, and homogeneous. The flow was assumed to be laminar, Newtonian, viscous, and incompressible. The fully coupled fluid and structure models were solved by ADINA, a well-tested finite element package. Results from two-dimensional (2D) and 3D models, based on ex vivo MRI and histological images (HI), with different component sizes and plaque cap thickness, under different pressure and axial stretch conditions, were obtained and compared. Our results indicate that large lipid pools and thin plaque caps are associated with both extreme maximum (stretch) and minimum (compression when negative) stress/strain levels. Large cyclic stress/strain variations in the plaque under pulsating pressure were observed which may lead to artery fatigue and possible plaque rupture. Large-scale patient studies are needed to validate the computational findings for possible plaque vulnerability assessment and rupture predictions.
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PMID:3D MRI-based multicomponent FSI models for atherosclerotic plaques. 1529 32

The objective of this study was to evaluate the safety and activity of the intratumoral administration of the immune costimulatory molecule, B7.1, encoded by a vector derived from the canarypox virus, ALVAC (ALVAC-B7.1), alone and with the intratumoral injection of ALVAC encoding the immune-stimulatory cytokine, interleukin 12 (ALVAC-IL-12). Fourteen patients with metastatic melanoma who had s.c. nodules received intratumoral injections on days 1, 4, 8, and 11. Nine patients were given escalating doses of up to 25 x 10(8) plaque-forming units of ALVAC-B7.1. Five patients were given 25 x 10(8) plaque-forming units of ALVAC-B7.1 combined with ALVAC-IL-12 50% tissue culture infective dose of 2 x 10(6). Toxicity was mild to moderate and consisted of inflammatory reactions at the injection site and fever, chills, myalgia, and fatigue. Higher levels of B7.1 mRNA were observed in ALVAC-B7.1-injected tumors compared with saline-injected control tumors. Higher levels of intratumoral vascular endothelial growth factor and IL-10, cytokines with immune suppressive activities, were also observed in ALVAC-B7.1- and ALVAC-IL-12-injected tumors compared with saline-injected controls. Serum levels of vascular endothelial growth factor increased at day 18 and returned to baseline at day 43. All patients developed antibody to ALVAC. Intratumoral IL-12 and IFN-gamma mRNA decreased. Changes in serum IL-12 and IFN-gamma levels were not observed. Tumor regressions were not observed. The intratumoral injections of ALVAC-B7.1 and ALVAC-IL-12 were well tolerated at these dose levels and at this schedule and resulted in measurable biological response. This response included the production of factors that may suppress the antitumor immunologic activity of these vectors.
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PMID:Phase I study of the intratumoral administration of recombinant canarypox viruses expressing B7.1 and interleukin 12 in patients with metastatic melanoma. 1593 Mar 53

Alefacept is a selective immunomodulating, antipsoriatic drug that blocks the LFA-3/CD2 interaction necessary for the activation and proliferation of memory effector T cells by binding to CD2 expressed on the T cell surface. Because the CD4+ count is reduced by alefacept, it is recommended that this count be monitored on a regular basis to ensure that it does not drop below 250 cells/mul. Few side effects have been related to the use of alefacept that differ from placebo even when CD4+ counts drop below 250 cells/microl. The side effects that have been reported are minor and include: headache, nasopharyngitis, rhinitis, influenza, upper respiratory tract infections, pruritus, arthralgias, fatigue, nausea, accidental injury and increases in liver enzymes. Serious infections and malignancies do not appear linked to the use of alefacept. The percentage of patients who developed antibodies against alefacept is very low. Alefacept is a very safe biological therapy for moderate-to-severe chronic plaque psoriasis with few side effects reported. The utility of checking CD4 counts while administering alefacept for 12 weeks appears minimal.
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PMID:Alefacept: a safety profile. 1625 57

Plaque rupture plays a role in the majority of acute coronary syndromes. Rupture has been associated with stress concentrations, which are affected by tissue properties and anatomy. In this study rupture was not approached as an acute syndrome, but rather as the culmination of a chronic injury or fatigue process. The aim of our study was to investigate the impact of anatomy, tissue properties, and blood pressure on a fatigue mechanism. Incremental crack propagation was dynamically simulated based on evolving stress distributions. Stresses were resolved by a finite element solver, using vessel stiffness properties derived from in vivo data. Plaque fatigue crack growth per pressure pulse was estimated using an adapted Paris-relation. It was demonstrated that cracks begin at the lumen wall at areas of stress concentration, depending on the shape of the lumen, thickness of the fibrous cap and stiffness of the plaque components. Mean or pulse pressure did not affect initiation location. Cracks extended radially and grew at a rate that was highly dependent on both mean and pulse pressure and on lipid stiffness. Rupture rate depended on blood pressure and lipid stiffness. It was concluded that a fatigue mechanism in a pulsatile cardiovascular pressure environment reconciles clinical evidence of acute plaque rupture at seemingly low stress levels, and it could provide a framework for developing strategies to create a biomechanically benign environment which is least conducive to plaque rupture.
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PMID:Fatigue and plaque rupture in myocardial infarction. 1632 36

Psoriasis is a chronic, inflammatory disease affecting 1-3% of the world's population. Joints can be affected in up to 30% of patients. About one third of patients have either severe or moderate (involving more than 10% of body surface area) disease. Patients affected with extensive psoriasis have an impaired quality of life. Psoriasis has a large spectrum of clinical features and evolution, so no complete agreement on the classification of the clinical variants exists. Plaque psoriasis is the commonest form (more than 80% of affected patients). The course of plaque psoriasis varies. Spontaneous resolution is possible, but rarely occurs. Plaques tend to remain static or slowly enlarge. Flexural (inverse, intertriginous) psoriasis manifests with lesions thinner than those of plaque form with no or minimal scaling, and is localized in the skin folds. Guttate (eruptive) psoriasis has frequently a sudden onset and frequently appears abruptly after a bacterial or viral febrile episode of inflammation of the upper ways. Pustular and erythrodermic psoriasis are the most severe clinical variants. In the diffuse pustular form recurrent episodes of fever occur, followed by new outbreaks of pustules. Erythrodermic psoriasis corresponds to the generalized form of the disease. The entire skin is bright red and is covered by superficial scales. Fatigue, myalgia, shortness of breath, fever and chills may also occur. In sebopsoriasis (seborrheic dermatitis + psoriasis) the lesions tend to occur at the same sites as seborrheic dermatitis; greasy scales predominate, but silvery scales can be found in some areas. Nail psoriasis shows various features: nail pits; oil spots; subungual hyperkeratosis; onycholysis. Rare forms include psoriasis circinata, lip psoriasis and oral psoriasis. Differential diagnosis includes many other dermatological conditions.
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PMID:Clinical presentation of psoriasis. 1782 42

Vulnerable plaque morphology has been described by gross pathology and intravascular ultrasound, but morphological criteria cannot fully explain vulnerability, which involves four distinct factors: 1) inflammatory and biological processes; 2) geometry; 3) composition; and 4) hemodynamic stress. These last three aspects underlie the biomechanical study of vulnerable plaque. By virtue of the nature of their evolution, atherosclerotic plaques tend to be excentric, and this is a crucial morphological feature, causing circumferential stress to peak in very specific juxta-luminal locations, where it can exceed the rupture threshold of collagen, the basic constituent of arterial architecture. The lipido-necrotic core covered by a fibrous cap, formed in young plaques, is another morphological feature, which, can also increase and concentrate circumference stress in the juxta-luminal fibrous cap. The larger the lipid core, the thinner the fibrous cap and the greater is the stress. There are also inflammatory processes in such areas, which tend to reduce cap thickness. Ruptures occur when this thickness falls below 65 microns. Heart rate, blood pressure and pulse pressure are all biomechanical factors affecting vulnerable arterial walls, increasing circumferential stress and material fatigue. Vulnerable plaques are almost always associated with positive arterial remodeling. Numerical simulation has shown such so-called compensatory remodeling to be exclusively due to the healthy arc stretching in vulnerable plaques. Positive remodeling is optimal when the healthy arc is around 170 degrees, which keeps the lumen area relatively stable as long as the plaque does not exceed 40% to 50%. This mechanism does not apply to concentric plaques. In conclusion, the mechanism of vulnerable plaque rupture is highly complex and multifactorial. This complexity more or less precludes prediction in individual cases: we are in the realms of chaos theory and acute sensitivity to initial conditions. The greatest caution is therefore required in any attempt to predict rupture from diagnostic imagery, which provides only morphological data on plaque's nature.
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PMID:Morphological and biomechanical aspects of vulnerable coronary plaque. 1789 37

The analysis of plaque mechanics along the longitudinal axis (bending strain) may provide useful information because repetitive bending strain of an atherosclerotic plaque can fatigue the wall material and result in plaque rupture. Whether essential hypertension is associated with a specific pattern of bending strain has not yet been determined. The study included 92 patients with an atherosclerotic plaque on the common carotid artery: 66 patients with essential hypertension, either treated or not, and 26 normotensive patients. A novel noninvasive echotracking system (ArtLab; Esaote, The Netherlands) was used to measure intima-media thickness, diameter, and distensibility at 128 sites on a 4-cm-long carotid segment. Carotid plaque was either less elastic than adjacent carotid artery (inward strain) or more elastic (outward strain). Inward strain was more frequently associated with an inward plaque remodeling, whereas an outward strain was more frequently associated with an outer remodeling. In multivariate logistic regression analysis, patients with essential hypertension were more likely to exhibit an inward strain of carotid plaque (odds ratio=6.9 [1.4 to 34.9]; P<0.02), independently of 2 factors favoring inward strain: an outer remodeling (odds ratio=4.6 [1.7 to 13.4]; P<0.005) and the absence of renin-angiotensin system blockers (odds ratio=4.8 [1.1 to 20.4]; P<0.05). In conclusion, arterial wall material of hypertensive patients was less elastic at the site of the plaque than upstream, and carotid was inwardly strained in the zone affected by plaque. This may generate a high level of stress concentrations and fatigue, exposing the plaque to a greater risk of rupture.
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PMID:Carotid plaque, arterial stiffness gradient, and remodeling in hypertension. 1877 39

We hypothesized that acute exercise stress would exacerbate immunosuppressive effects of sub-acute exposure to dietary deoxynivalenol (DON). Male BALB/c mice were fed 0 or 2 mg DON/kg diet for 14 days, 12 animals per dose, and then exercised to fatigue on a treadmill. Mice were euthanized by decapitation, trunk blood and spleens were collected. Single-cell suspensions of splenocytes were used to quantify immune function by plaque hemolysis and conconavalin-A (ConA) stimulated lymphocyte proliferation assays. Serum corticosterone level was determined by enzyme immunoassay. Only the nonexercised DON-fed mice showed significant splenocyte proliferation suppression, 32.9 +/- 17.9% of nonexercised controls (p = 0.021). Exercised controls and DON-fed exercised animals showed splenocyte proliferation of 68-75% of nonexercised controls. Antibody response to a T-dependent antigen, sheep red blood cells, was significantly less for exercised DON-fed mice than in controls (p = 0.031). Serum corticosterone levels were significantly higher for both exercised groups compared to the unexercised groups (p < 0.001). IL-4 secretion from mitogen-stimulated splenocytes was elevated by DON alone (p < 0.05) while IL-2 was elevated by DON with exercise stress (p < 0.05). Our hypothesis was confirmed with respect to T-lymphocyte-dependent antibody production, but not for splenocyte proliferation. Exercise stress abrogated DON-mediated suppression of splenocyte proliferation, perhaps mediated by induction of elevated stress hormones counteracting cytokine expression alterations of DON.
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PMID:Low-level dietary deoxynivalenol and acute exercise stress result in immunotoxicity in BALB/c mice. 1895 98


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