Idiopathic environmental intolerances. American Academy of Allergy, Asthma and Immunology (AAAAI) Board of Directors.
Explore the source record for details and available documents.
Environmental Exposure↗
SEARCH · Search PubMed
Results for “Multiple Chemical Sensitivity”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Sensitization studies in chemically intolerant individuals: implications for individual difference research.
Chemical intolerance (CI) is an individual difference trait in which persons report feeling ill in multiple physiological systems from low levels of a wide range of chemically unrelated environmental substances. This paper discusses the neural sensitization model for progressive host amplification of polysymptomatic responses elicited by chemical exposures following an initiating event. The sensitization model accommodates hypotheses for initiating and eliciting CI in human populations that involve both environmental chemicals and physical or psychological stressors. Recent studies in this laboratory have demonstrated sensitization in individuals with CI over repeated sessions for dependent variables such as electroencephalographic (EEG) activity and diastolic blood pressure. Psychological distress variables alone do not explain these findings. Individuals with CI and/or vulnerability to sensitization share specific characteristics, for example, female gender, certain genetic background (offspring of alcohol-preferring parents), and personal preference for high sugar/ carbohydrate intake. Overall, the data suggest that the 15-30% of the general population who report heightened CI are highly sensitizable. Sensitizability may serve an adaptive, sentinel function in threatening environments with poor signal-to-noise ratios. However, as sensitization gradually shifts operating set points of physiological systems out of the normal range in response to allostatic load, this process may contribute to the development of chronic, polysymptomatic health conditions such as multiple chemical sensitivity and/or fibromyalgia. Individual response specificity and stereotypy rather than toxicant properties may determine which types of central, autonomic, and/or peripheral nervous system dysfunctions manifest at subclinical and clinical levels.
Age of Onset↗
Identification of gene expression changes induced by chemical allergens in dendritic cells: opportunities for skin sensitization testing.
Cellular changes within resident skin dendritic cells (DCs) after allergen uptake and processing are critical events in the acquisition of skin sensitization. Here we describe the development of a set of selection criteria to derive a list of potential target genes from previous microarray analyses of human peripheral blood-derived (peripheral blood mononuclear cells (PBMCs)-DCs) treated with dinitrobenzene sulfonic acid for predicting skin-sensitizing chemicals. Based on those criteria, a probing evaluation of the target genes has been conducted using an extended chemical data set, comprising five skin irritants and 11 contact allergens. PBMCs-DCs were treated for 24 hours with various concentrations of chemicals and in each instance the expression of up to 60 genes was examined by real-time PCR analysis. Consistent allergen-induced changes in the expression of many genes were observed and further prioritization of the targets was conducted by analysis of the same genes in DCs treated with non-sensitizing chemicals to determine their specificity for skin sensitization. Real-time PCR analyses of multiple chemical allergens, irritants, and non-sensitizers have identified 10 genes that demonstrate reproducibly high levels of selectivity, specificity, and dynamic range consistent with providing the basis for robust and sensitive alternative approaches for the identification of skin-sensitizing chemicals.
Allergens↗
Food sensitivity, a search for underlying causes. Case study of 12 patients.
Twelve cases of multiple food sensitivity were studied. All had responded to food elimination and a number were receiving sublingual food desensitization drops. An underlying cause was postulated and looked for. The method used was an electrical recording technique called the segmental electrogram. All of the cases were seen to have a primary colonic dysfunction which has been described as Dysbiosis. It was assumed that the colonic dysfunction was due to abnormal intestinal flora and this was corrected by a repopulation of the bowel with normal commensals and the simultaneous stimulation of liver and pancreatic function. This resulted in all of the patients losing at least a number of their sensitivities and those who were on sublingual desensitization drops were able to stop these drops and tolerate the foods without any further problem. It has postulated that much of multiple food and chemical sensitivity is due to underlying causes of which Dysbiosis is one.
Adolescent↗
The vomeronasal organ and chemical sensitivity: a hypothesis.
Environmental exposures to very low levels of airborne chemicals are associated with adverse symptoms, often affecting multiple organ systems, in the phenomenon of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of chemically sensitive subjects in the United States, but the mechanism linking exposure to symptoms remains unclear, despite the advancement of a variety of theoretical models. In many of these models, exposure of the nasal respiratory system to an airborne agent is the first step in the pathway leading to symptoms. In this article, we advance the hypothesis that interactions between environmental chemicals and the vomeronasal organ (VNO) may play a role in the etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves in animals as part of a sensitive chemosensory system; however, evidence suggesting that the VNO retains a functional role in the adult human is controversial. Reported characteristics of the human VNO relevant to CS, including location, prevalence, selective sensitivity to airborne chemical exposure, and capacity to produce systemic effects, are discussed within the context of this ongoing debate. Beyond relevance to CS, the demonstration of an active, adult VNO could have significant impact on environmental toxicology.
Air Pollutants↗
Assessing adherence to a rotary diversified diet, a treatment for 'environmental illness'.
OBJECTIVES: To develop and test a method to assess adherence to a rotary diversified diet (RDD), a treatment for environmental illness, which is a putative disorder characterized by multiple sensitivities to foods, chemicals, or inhalants. The RDD requires the elimination of prohibited foods and rotation of remaining nonprohibited foods and their "food families" within a 4- to 7-day cycle. The regimen has yet to be validated to the satisfaction of the scientific community. DESIGN: Details of the 2 components of the RDD prescription, elimination and rotation, were documented, and a food record method of assessing adherence was developed. Adherence to the RDD was then assessed in a cohort of women who were enrolled in a larger prospective study. Test-retest reliability of the adherence assessment method was determined by calculating ratings twice on the same set of patient food records, with 1 week between trials. SUBJECTS/SETTING: All patients were contacted through a private environmental medicine clinic in Toronto, Canada. Eight patients provided the food records needed for development of the method; adherence was then assessed in 22 women aged 25 to 67 years. STATISTICAL ANALYSES: Means, standard deviations, and 95% confidence intervals for adherence ratings were calculated. The reliability of the adherence assessment method was determined by calculating Pearson correlation coefficients for adherence ratings from each trial. A paired t test was also used to determine if the mean differences in ratings between trials were significant. RESULTS: Patients experienced difficulties following both components of the RDD: 37% to 44% of foods consumed were either prohibited or allowed, but were consumed on the incorrect day. The adherence assessment method was found to have high levels of reliability. APPLICATIONS: The adherence assessment method can be used in future evaluations of the RDD, although further testing of the method is recommended. Increased involvement of dietitians with patients diagnosed with environmental illness is recommended.
Adult↗
Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
Amino Acid Sequence↗
Putting chemical and environmental sensitivities in perspective.
Chemical sensitivity has been recognized for an extended period. Over the last 30 years or more, there has been a growing number of chemicals to which humans are being exposed. Some people have become sensitive to one or more of these chemicals and present this sensitivity in a wide variety of signs or symptoms. Single or multiple organ systems may become involved. This article is intended to give an overview on the existence and recognition of chemical sensitivities and how they may be diagnosed and treated. The important item is to educate physicians to the existence of chemical sensitivity and to consider this in their differential diagnosis when the patient presents with the signs, symptoms, or clinical pattern that is explained.
Allergens↗
Multiple-quantum relaxation dispersion NMR spectroscopy probing millisecond time-scale dynamics in proteins: theory and application.
New relaxation dispersion experiments are presented that probe millisecond time-scale dynamical processes in proteins. The experiments measure the relaxation of (1)H-(15)N multiple-quantum coherence as a function of the rate of application of either (1)H or (15)N refocusing pulses during a constant time relaxation interval. In contrast to the dispersion profiles generated from more conventional (15)N((1)H) single-quantum relaxation experiments that depend on changes in (15)N((1)H) chemical shifts between exchanging states, (1)H-(15)N multiple-quantum dispersions are sensitive to changes in the chemical environments of both (1)H and (15)N spins. The resulting multiple-quantum relaxation dispersion profiles can, therefore, be quite different from those generated by single-quantum experiments, so that an analysis of both single- and multiple-quantum profiles together provides a powerful approach for obtaining robust measures of exchange parameters. This is particularly the case in applications to protonated proteins where other methods for studying exchange involving amide proton spins are negatively influenced by contributions from neighboring protons. The methodology is demonstrated on protonated and perdeuterated samples of a G48M mutant of the Fyn SH3 domain that exchanges between folded and unfolded states in solution.
Magnetic Resonance Spectroscopy↗
Long-lasting reductions of ethanol drinking, enhanced ethanol-induced sedation, and decreased c-fos expression in the Edinger-Westphal nucleus in Wistar rats exposed to the organophosphate chlorpyrifos.
Intermittent or continuous exposure to a wide variety of chemically unrelated environmental pollutants might result in the development of multiple chemical intolerance and increased sensitivity to drugs of abuse. Interestingly, clinical evidence suggests that exposure to organophosphates might be linked to increased ethanol sensitivity and reduced voluntary consumption of ethanol-containing beverages in humans. The growing body of clinical and experimental evidence emerging in this new scientific field that bridges environmental health sciences, toxicology, and drug research calls for well-controlled studies aimed to analyze the nature of the neurobiological interactions of drugs and pollutants. Present study specifically evaluated neurobiological and behavioral responses to ethanol in Wistar rats that were previously exposed to the pesticide organophosphate chlorpyrifos (CPF). In agreement with clinical data, animals pretreated with a single injection of CPF showed long-lasting ethanol avoidance that was not secondary to altered gustatory processing or enhancement of the aversive properties of ethanol. Furthermore, CPF pretreatment increased ethanol-induced sedation without altering blood ethanol levels. An immunocytochemical assay revealed reduced c-fos expression in the Edinger-Westphal nucleus following CPF treatment, a critical brain area that has been implicated in ethanol intake and sedation. We hypothesize that CPF might modulate cellular mechanisms (decreased intracellular cAMP signaling, alpha-7-nicotinic receptors, and/or cerebral acetylcholinesterase inhibition) in neuronal pathways critically involved in neurobiological responses to ethanol.
Alcohol Drinking↗
Ultraviolet-induced chemical vapor deposition of silica films studied by surface-sensitive multiple-internal-reflection spectroscopy.
Explore the source record for details and available documents.
Journal Article↗
Occupational dermatoses among fibreglass-reinforced plastics factory workers.
Fibreglass-reinforced plastics (FRP) factory workers are at high risk of developing occupational dermatoses because of their exposure to many chemicals used in the manufacture of plastics as well as to glass fibre or dust. Patch tests were carried out on 29 workers involved in FRP manufacturing processes where unsaturated polyester (UP) resin was used, to investigate the causes of their skin problems. Of the 22 workers who reported experiencing skin problems, 16 showed positive results to at least 1 chemical, including 6 cases of multiple sensitivity. 2 showed positive reactions to UP base resin, 6 to cobalt chloride, 5 to benzoyl peroxide (BPO), 4 to methyl ethyl ketone peroxide (MEKPO), 2 to para-tertiary butyl catechol (PTBC), 1 to styrene and 1 to formaldehyde. After taking into account their exposures and reported causes by questionnaires and their patch test results, 7 cases were diagnosed as allergic contact dermatitis (ACD) due to chemicals, 3 as irritant contact dermatitis (ICD) due to chemicals, and 3 as dermatitis due to mechanical irritation (MI) from glass fibre or dust, as well as 9 as ACD and/or MI. 18 of the total of 29 subjects (62.1%), including 2 workers without a history of skin problems, were sensitized to at least 1 chemical. Cobalt, peroxides, PTBC and UP base resin were the common causes of ACD.
Adult↗
Development and applications of a model for cellular response to multiple chemotactic cues.
The chemotactic response of a cell population to a single chemical species has been characterized experimentally for many cell types and has been extensively studied from a theoretical standpoint. However, cells frequently have multiple receptor types and can detect and respond chemotactically to more than one chemical. How these signals are integrated within the cell is not known. and we therefore adopt a macroscopic phenomenological approach to this problem. In this paper we derive and analyze chemotactic models based on partial differential (chemotaxis) equations for cell movement in response to multiple chemotactic cues. Our derivation generalizes the approach of Othmer and Stevens [29], who have recently developed a modeling framework for studying different chemotactic responses to a single chemical species. The importance of such a generalization is illustrated by the effect of multiple chemical cues on the chemotactic sensitivity and the spatial pattern of cell densities in several examples. We demonstrate that the model can generate the complex patterns observed on the skin of certain animal species and we indicate how the chemotactic response can be viewed as a form of positional indicator.
Animals↗
Single photon emission computed tomography of the brain in patients with chemical sensitivities.
Chemical sensitivities display a recurrent pattern on scintigraphic examinations of the brain. The pattern can include mismatching between early and late imaging, multiple hot and cold foci distributed throughout the cortex without regard to lobar distribution (salt and pepper pattern), temporal asymmetries, and sometimes increased activity in the basal ganglia. This study used Desert Shield/Desert Storm veterans who present with abnormal neurological and psychological symptoms as a model to exhibit abnormalities by brain scintigraphy. These are typical of those seen in patients with documented exposure to neurotoxic compounds who develop a clinical syndrome that has been termed "chemical sensitivity." Exposure to cocaine, alcohol, and other substances of abuse can result in abnormal scintigrams of the brain using tracers such as [technetium-99m]hexamethylpropyleneoxime. This study used techniques combining regional cerebral blood flow data with delayed distributional data after the intracellular conversion of the tracer into a hydrophilic molecule. In addition to delayed image abnormalities, a mismatch occurs in the regional activity between the two image sets of the veterans. This degree of mismatch was not seen in control subjects who were screened for avoidance of neurotoxic agents. Patterns identified from examinations performed on patients with known exposure to petroleum distillates, pesticides and other materials linked with neurotoxicity were identified in some veterans of the Desert Shield/Desert Storm operation. A single case of repeated examinations on a veteran showed a reversion of these patterns toward normal after therapy. This reversion followed independent assessments of clinical improvement.
Adult↗
Precise adaptation in bacterial chemotaxis through "assistance neighborhoods".
The chemotaxis network in Escherichia coli is remarkable for its sensitivity to small relative changes in the concentrations of multiple chemical signals over a broad range of ambient concentrations. Key to this sensitivity is an adaptation system that relies on methylation and demethylation (or deamidation) of specific modification sites of the chemoreceptors by the enzymes CheR and CheB, respectively. It was recently discovered that these enzymes can access five to seven receptors when tethered to a particular receptor. We show that these "assistance neighborhoods" are necessary for precise adaptation in a model for signaling by clusters of chemoreceptors. In agreement with experiment, model clusters composed of receptors of different types exhibit high sensitivity and precise adaptation over a wide range of chemical concentrations and the response of adapted clusters to addition/removal of attractant scales with free-energy change. We predict two limits of precise adaptation at large attractant concentrations: Either receptors reach full methylation and turn off, or receptors become saturated and cease to respond to attractant but retain their adapted activity.
Adaptation, Physiological↗
Sensitivity to some rubber additives.
The frequency of positive patch tests to 13 rubber accelerators in Poland was recorded. Of particular interest was the relatively large group of patients positive to several, mostly chemically unrelated, accelerators. The mechanism of this multiple sensitivity is discussed. Positive tests to N-isopropyl-N-phenyl-p-phenylenediamine were observed in more than half of the patients reacting to several aromatic amines. Anamnesis indicated that in the case of cross-reactions to many aromatic amines, none of the patients positive to N-isopropyl-N-phenyl-p-phenylenediamine had complained of a reaction to rubber products.
Age Factors↗
Multiple quantum two-dimensional 1H--15N nuclear magnetic resonance spectroscopy: chemical shift correlation maps for exchangeable imino protons of Escherichia coli tRNAMetf in water.
A procedure based on multiple quantum two-dimensional nuclear magnetic resonance spectroscopy is described for generation of 1H--15N chemical shift correlation maps. The method is used to obtain 15N chemical shifts for the exchangeable imino protons in 1H--15N units of site-specifically labeled Escherichia coli tRNAMetf in water. The high sensitivity and excellent chemical shift dispersion of the multiple quantum two-dimensional technique make it ideally suited for studying protonated nitrogens by NMR.
Escherichia coli↗
Comparison of dose-responses of contact allergens using the guinea pig maximization test and the local lymph node assay.
The guinea pig maximization test (GPMT) has been used as a method for the prediction of skin sensitizing potential for over 30 years. Besides hazard identification, risk assessment of sensitizing chemicals requires the assessment of potency. For the determination of potency based on lowest effective dose levels, dose-response studies are required. In the standard GPMT a single concentration is used for intracutaneous and topical induction and the assay provides a qualitative assessment of allergenicity. This paper presents data derived from quantitative evaluation of the sensitizing potency of chemicals in the GPMT, based on multiple concentrations. We performed the GPMT in accordance with the original procedure of Magnusson and Kligman; and included in this procedure a range of intradermal and topical concentrations for induction. Three allergens with different sensitizing potencies, diethylamine (DEA), tetramethyl thiuram disulfide (TMTD) and zinc dimethyl dithiocarbamate (ZDMC) were tested. The data obtained with this test procedure were compared to data we previously obtained using the local lymph node assay (LLNA). Both the GPMT and the LLNA showed dose response relationships for the three chemicals tested. For the chemicals tested, both tests differed in the relative potencies based on benchmark concentrations. While both tests ranked DEA as the least potent allergen, the GPMT ranked ZDMC more potent than TMTD, the reverse being found in the LLNA. The nature of the data provided in the LLNA makes it likely that benchmarks as defined with this test are more reliable than that defined in the GPMT. However, further validation with human data is necessary.
Allergens↗