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.

Integrative medicine and systemic outcomes research: issues in the emergence of a new model for primary health care.

Clinicians and researchers are increasingly using the term integrative medicine to refer to the merging of complementary and alternative medicine (CAM) with conventional biomedicine. However, combination medicine (CAM added to conventional) is not integrative. Integrative medicine represents a higher-order system of systems of care that emphasizes wellness and healing of the entire person (bio-psycho-socio-spiritual dimensions) as primary goals, drawing on both conventional and CAM approaches in the context of a supportive and effective physician-patient relationship.

US military veterans' perceptions of the conventional medical care system and their use of complementary and alternative medicine.

Background: Use of complementary and alternative medicine (CAM) is growing quickly in the USA, prompting hypotheses about why people turn to CAM. One reason for increasing use of CAM modalities may be dissatisfaction with the conventional care system. However, recent studies suggest that dissatisfaction is not a major factor.

Design and biological activity of (S)-4-(5-([1-(3-chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl)imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency.

The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-aminopyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs.

Evaluation of amino acid-based linkers in potent macrocyclic inhibitors of farnesyl-protein transferase.

A series of amino acid-based linkers was used to investigate the effects of various substituents upon the potency, pharmacokinetic properties, and conformation of macrocyclic farnesyl-protein transferase inhibitors (FTIs). As a result of the studies described herein, highly potent FTIs with improved pharmacokinetic profiles have been identified.

EEG beta 1 oscillation and sucrose sensitization in fibromyalgia with chemical intolerance.

Patients with fibromyalgia (FM) have diffuse musculoskeletal pain; half report concomitant intolerance for low levels of environmental chemicals (CI). Previous investigators have hypothesized that the chronic pain and chemical intolerance reflect sensitization of different central nervous system limbic and/or mesolimbic reward pathways. We evaluated electroencephalographic (EEG) beta activity and blood glucose responses of FM patients with and without CI and normals during three repeated sucrose ingestion sessions and during a final, water-only session (testing for conditioning).

Down-modulation of the costimulatory molecule, CD28, is a conserved activity of multiple SIV Nefs and is dependent on histidine 196 of Nef.

In this study Nef proteins derived from simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) were compared to assess their abilities to down-modulate the cell surface levels of the T-cell costimulatory molecule CD28. We demonstrate that in addition to Nef derived from the prototypic SIVmac239, Nef proteins encoded by the pathogenic SIVsmmPBj molecular clone and the SIVsmmB670 isolate also down-modulate cell surface CD28. In contrast, Nef proteins derived from HIV failed to down-modulate CD28.

Electroencephalographic registration of low concentrations of isoamyl acetate.

Previous research has demonstrated electroencephalogram (EEG) changes in response to low-odor concentrations, resulting in near-chance detection. Such findings have been taken as evidence for olfaction without awareness. We replicated and extended previous work by examining EEG responses to water-water control, 0.

Plausibility of homeopathy and conventional chemical therapy: the systemic memory resonance hypothesis.

The controversy surrounding clinical observations and double-blind studies on homeopathic treatments is lessened when modern dynamical systems analysis is applied to high-dilution therapies. The logic of recurrent feedback loops, which applies to all dynamical network systems, inexorably leads to the systemic memory hypothesis - that complex patterns of emergent information and energy are stored to various degrees in physical, chemical, and biological systems. The addition of resonance, a dynamic pattern recognition process, explains many classic observations using high-dilution therapies.

The T-cell receptor zeta chain contains two homologous domains with which simian immunodeficiency virus Nef interacts and mediates down-modulation.

We have recently demonstrated that simian immunodeficiency virus (SIV) Nef binds to the zeta chain of the T-cell receptor (TCR), leading to its down-modulation from T-cell surfaces (I. Bell, C. Ashman, J.

Patterns of waking EEG spectral power in chemically intolerant individuals during repeated chemical exposures.

Previous studies indicate that low level chemical intolerance (CI) is a symptom of several different controversial conditions with neuropsychiatric features, e.g., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and "Persian Gulf Syndrome".

Subjective ratings of odorants by women with chemical sensitivity.

The purpose of the present study was to investigate whether women with chemical sensitivity rated the intensity and pleasantness of three odorants [peppermint, vanilla, and propylene glycol (PG)] and odorless room air differently than women without chemical sensitivity. The ratings of the experimental group (women with self-reported chemical sensitivity and no history of sexual abuse) were compared to those of two control groups who did not report chemical sensitivity [sexually abused (SA) women and healthy women without sexual abuse history]. All subjects were exposed to odorants and odorless control stimuli once a week for 3 consecutive weeks.

The association of energy intake bias with psychological scores of women.

Objective: Assess the association between reporting bias of dietary energy intake and the behavioral and psychological profiles in women.

Design: At baseline a series of questionnaires were administered to 37 women, (the Marlowe-Crowne Social Desirability Scale, Weinberger Adjustment Inventory (WAI), the Eating Disorder Inventory (EDI), the Restraint Scale and Sorensen-Stunkard's silhouettes). Subjects received training on how to record dietary records.

Odor sensitivity and respiratory complaint profiles in a community-based sample with asthma, hay fever, and chemical odor intolerance.

This is a community-based study of odor sensitivity and respiratory complaints for persons reporting asthma (n = 14/141), hay fever (n = 72/140), and chemical odor intolerance (CI) (n = 41/181). CI, a symptom of multiple chemical sensitivity (MCS), was determined from self-ratings of feeling 'moderately' to 'severely' ill using the Chemical Odor Intolerance Index (CII). Index odors included perfume, pesticide, drying paint, new carpet odor, and car exhaust.

EEG sensitization during chemical exposure in women with and without chemical sensitivity of unknown etiology.

This study tested the sensitization model proposed by Bell et al. [Bell I.R.

Neural sensitization model for multiple chemical sensitivity: overview of theory and empirical evidence.

This paper summarizes theory and evidence for a neural sensitization model of hyperresponsivity to low-level chemical exposures in multiple chemical sensitivity (MCS). MCS is a chronic polysymptomatic condition in which patients report illness from low levels of many different, structurally unrelated environmental chemicals (chemical intolerance, CI). Neural sensitization is the progressive host amplification of a response over time from repeated, intermittent exposures to a stimulus.

Infrared Diode-Laser Spectroscopy of Phosphoryl Bromide (BrPO).

Many lines of the nu1 P&dbond;O stretching fundamental of the transient molecule BrPO have been detected between 1251 and 1266 cm-1. The band resembles a parallel band of a near-prolate asymmetric top. Although it was not possible to obtain the A rotational constant exactly, both B and C were precisely determined subject to an assumed value of A = 1.

Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitization model.

This study (ntotal = 35) compared early life stress ratings, parental relationships, and health status, notably orthostatic blood pressures, of middle-aged women with low-level chemical intolerance (CI group) and depression, depressives without CI (DEP group), and normals. Environmental chemical intolerance is a symptom of several controversial conditions in which women are overrepresented, that is, sick building syndrome, multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia. Previous investigators have postulated that people with CI have variants of somatization disorder, depression, posttraumatic stress disorder (PTSD) initiated by childhood abuse or a toxic exposure event.

Repressive and defensive coping styles predict resting plasma endorphin levels in the elderly.

Jamner, L.D., Schwartz, G.

Association of simian immunodeficiency virus Nef with the T-cell receptor (TCR) zeta chain leads to TCR down-modulation.

The Nef protein of simian immunodeficiency virus (SIV) is dispensable for replication in established T-cell lines but essential for high level virus replication in the adult host, though the mechanism by which Nef contributes to this has remained unclear. We demonstrate here that SIV Nef binds to the zeta chain of the T-cell receptor (TCR). SIV Nef proteins that interact with TCR zeta in a yeast two-hybrid system also reduce T-cell surface expression levels of TCR alphabeta, CD3 and CD4.

Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings.

This cross-sectional telephone survey study assessed prevalence rates of current chemical sensitivity, frequency of chemical odor intolerance, and self-reported Persian Gulf chemical exposures among 41 randomly sampled Department of Veterans Affairs outpatients who were Persian Gulf War (PGW) and PGW-era veterans. The participants were drawn from an initial random list of 100 veterans, of whom 28 PGW and 20 era veterans had correct telephone data on file. Of those contacted, 86% of PGW veterans (24/28) and 85% of era veterans (17/20) agreed to participate.

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia.

This article summarizes (1) epidemiologic and clinical data on the symptoms of maladies in association with low-level chemicals in the environment, i.e., environmental chemical intolerance (CI), as it may relate to chronic fatigue syndrome (CFS) and fibromyalgia; and (2) the olfactory-limbic neural sensitization model for CI, a neurobehavioral synthesis of basic and clinical research.

Positive perceptions of parental caring are associated with reduced psychiatric and somatic symptoms.

Objective: In a previous 35-year follow-up investigation to the Harvard Mastery of Stress Study, positive ratings of parental caring obtained in healthy male college students were found to be predictive of substantially reduced disease incidence (including cardiovascular disease, ulcers, and alcoholism) in mid-life. The present cross-sectional study examined the relationship between perceptions of parental caring, current psychiatric and somatic symptoms, and defensiveness, in a University of Arizona sample of females and males.

Method: The Harvard Parental Caring Scale (HPCS), the SCL90R, and the Marlowe-Crowne (MC) scale (a measure of defensiveness) were administered to 398 students at the University of Arizona.