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Polysymptomatic syndromes and autonomic reactivity to nonfood stressors in individuals with self-reported adverse food reactions.

This study compared symptom reports and cardiovascular reactivity of a group of 24 individuals recruited from the community who reported a cognitive or emotional symptom caused by at least one food (food-sensitivity reporters, FSR) vs those of 15 controls (C) without a history of food, chemical, drug, or inhalant sensitivities. The main findings were: 1) FSR indicated sensitivities not only to foods, but also to environmental chemicals, drugs, and natural inhalants, as well as significantly more symptoms than C in multiple systems; 2) more FSR than C noted recent state depression and anxiety, as well as higher trait anxiety on the Bendig form of the Taylor Manifest Anxiety Scale; 3) however, on multiple regression analysis, not only depression, but also the number of sensitivities (foods, chemicals, drugs, inhalants), accounted for part of the variance in total number of symptoms (38 and 17%, respectively), whereas none of the affective measures accounted for any of the variance in total number of sensitivities over all subjects; 4) after controlling for depression and anxiety, FSR still showed a trend toward poorer performance on a timed mental arithmetic task (p = 0.16); and 5) FSR and C showed opposite patterns of heart rate change to two different stressful tasks (mental arithmetic and isometric exercise) (group by task interaction, p < 0.05). The data are discussed in terms of a time-dependent sensitization (TDS) process that predicts a cross-sensitizing and cross-reactive role for xenobiotic agents (e.g., foods, chemicals, drugs, and inhalants) and for salient psychological stress in the expression of psychophysiological dysfunctions of FSR. As in other chronically ill populations, negative affect in food-sensitive individuals may explain greater symptom reporting, but not necessarily account for the illness itself. For either a food or a psychological stimulus to begin to elicit sensitized responses, e.g., marked physiological differences from C, FSR may require multiple, intermittent exposures spaced over 5-28 days rather than on only 1 day.

Adult↗

New multiple antigenic peptide-based enzyme immunoassay for detection of simian immunodeficiency virus infection in nonhuman primates and humans.

Infections with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2, respectively) are zoonotic infections. In Africa, the potential exists for additional cross-species transmissions from at least 33 different species of simian immunodeficiency virus (SIV)-infected nonhuman primates (NHPs) through hunting and butchering of these animals for food. Here we describe a highly sensitive and specific enzyme immunoassay (EIA) with chemically modified, multiple antigenic peptides (MAPs) developed for the detection and discrimination of antibodies to SIV genetic lineages. The SIV EIA was developed by using a comprehensive array of MAPs covering two envelope gene regions from all of the SIV lineages for which env sequences were available. Assay sensitivity was evaluated by using 63 plasma or serum samples obtained from primates naturally or experimentally infected with SIVs from 10 genetic lineages. Assay specificity was determined by using 97 known SIV-negative plasma specimens from these same species. Also used in the evaluations were 369 human samples: 198 HIV seronegative, 170 HIV-1 and/or HIV-2 seropositive, and 1 from a human SIVsm infection. Overall assay sensitivity and specificity were 100% with both immunodominant region (IDR) and V3 region MAPs. Although SIV env sequences from talapoin monkeys were not available for specific MAP inclusion, 5 (100%) of 5 SIVtal-infected samples were detected through cross-reactivity with other SIV IDR MAPs used in the assay. The one human SIVsm infection was identified. In conclusion, our SIV MAP EIA proved to be highly sensitive and specific for detecting SIV infections in NHPs and humans. As shown with SIV-infected talapoin monkeys, this assay has the potential to detect previously unidentified SIV strains and should be suitable for sentinel surveillance for potential new cross-species transmissions of SIVs to humans.

Amino Acid Sequence↗

Brain temperature measured by 1H-NMR in conjunction with a lanthanide complex.

In vivo data on temperature distributions in the intact brain are scarce, partly due to lack of noninvasive methods for the region of interest. NMR has been exploited for probing a variety of brain activities in vivo noninvasively within the region of interest. Here we report the use of a thulium-based thermometric sensor, infused through the blood, for monitoring absolute temperature in rat brain in vivo by (1)H-NMR and validated by direct temperature measurements with thermocouple wires. Because the (1)H chemical shifts also demonstrate pH sensitivity, detection of multiple resonances was used to measure both temperature and pH simultaneously with high sensitivity. Examination of blood plasma and cerebral spinal fluid samples removed from rats infused with the thermometric sensor suggests that the complex, despite its negative charge, crosses the blood-brain barrier to enter the extracellular milieu. In the future, the thulium-based thermometric sensor may be used for monitoring temperature (and pH) distributions throughout the entire brain, examining response to therapy and evaluating changes induced by alterations in neuronal activity.

Animals↗

Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

OBJECTIVE: To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. METHODS: Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. RESULTS: The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. CONCLUSIONS: Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

Adenosine↗

Tissue temperature monitoring with multiple gradient-echo imaging sequences.

The inherent sensitivity of multiple gradient-echo sequences to the chemical shift is exploited to rapidly map muscle water frequency shifts caused by ultrasonic heating. The use of multiple echoes is shown to offer several advantages over single gradient-echo approaches previously proposed for temperature measurement. An increase in the effective bandwidth significantly reduces aliasing problems observed with single gradient-echo methods in high temperature applications. Of greater significance is the improved immunity to intrascan motion found for multi-echo versus single echo gradient methods, making the former more attractive for clinical applications. Finally, a sensitivity to the presence of multiple spectral components unavailable with single gradient-echo methods is obtained.

Animals↗

Chemically sensitive high throughput parallel analysis of solid phase supported library members

This paper introduces Fourier transform infrared imaging as a powerful spectroscopic tool for the parallel identification of members of resin-supported combinatorial libraries. This technique combines the chemical specificity and high sensitivity of FTIR with the ability to rapidly analyze multiple supported resin beads simultaneously. It is shown here that the chemical identity of ligands on a variety of supported resin beads can be identified in a single experiment without destroying or otherwise perturbing the system.

Journal Article↗

Some strategies for improving specificity and sensitivity in the analysis of anti-cancer drugs.

Some approaches are discussed for introducing specificity and sensitivity into analytical methods for anti-tumour agents which include a liquid chromatographic step. Various modes of HPLC have been exploited to monitor these drugs specifically and at therapeutically low levels. The use of column switching technology and chemical derivatization techniques to enhance both specificity and sensitivity are discussed. Multiple columns (linked through switching valves) containing packings exhibiting different affinities for the analytes cisplatin and riboxamide provide (a) a high degree of selectivity with convenient analysis times, (b) the opportunity for preconcentration of analytes, (c) improved longevity of analytical columns, (d) a solution to the 'general elution problem', and (e) allow direct application of biological fluid to the HPLC system. The use of chemical derivatization techniques (pre- and post-column) to achieve improved sensitivity and altered chromatographic and chemical properties of these and other anti-tumour agents (galactitol, tamoxifen, emetine) is also described. The high chemical reactivity of many anti-tumour agents often requires their rapid derivatization after a biological sample is drawn to prevent chemical degradation in the sample vial. The use of chemical and photochemical derivatization techniques combined with spectrophotometric, fluorometric and voltammetric detectors illustrates the power and utility of derivatization technology in trace drug analysis.

Journal Article↗

Chemosensing in Escherichia coli: two regimes of two-state receptors.

The chemotaxis network in Escherichia coli is remarkable for its sensitivity to small relative changes in the concentrations of multiple chemical signals. We present a model for signal integration by mixed clusters of interacting two-state chemoreceptors. Our model results compare favorably to the results obtained by Sourjik and Berg with in vivo fluorescence resonance energy transfer. Importantly, we identify two distinct regimes of behavior, depending on the relative energies of the two states of the receptors. In regime I, coupling of receptors leads to high sensitivity, while in regime II, coupling of receptors leads to high cooperativity, i.e., high Hill coefficient. For homogeneous receptors, we predict an observable transition between regime I and regime II with increasing receptor methylation or amidation.

Chemotaxis↗

Chemical modification of DNA: quantitation of O6-methyldeoxyguanosine by tandem mass spectrometry.

Methodology is described which allows quantitation of O6-methyldeoxyguanosine generated as a product of in vitro methylation of calf thymus DNA by methyl methanesulfonate (MeMS). Quantitative precision of 10% is achieved on samples of 10(-11)-10(-12) mol generated in 0.02% yield (expressed as O6-methyldeoxyguanosine versus deoxyguanosine) when DNA is treated with the weak carcinogen MeMS. These results show the potential application of this method to the analysis of DNA chemical modifications at the low levels that are relevant to the induction of biological effects of many alkylating agents. The methodology utilizes enzymatic degradation, reverse-phase chromatography and finally analysis by tandem mass spectrometry using desorption chemical ionization. Multiple reaction monitoring was used to increase sensitivity and the CD3-labeled nucleoside was used as an internal standard for quantification.

Chromatography, High Pressure Liquid↗

Immunotoxicity testing: an economical multiple-assay approach.

A model for assessing immunotoxicologic effects of chemicals and drugs was developed in the Sprague-Dawley rat whereby multiple concomitant immunoassays were performed in a single animal. The multiple parameters of immunity assessed in each rat included T cell-dependent IgG antibody production, delayed hypersensitivity, natural killer cell cytotoxicity, and production of three potent immune regulating immunocytokines: macrophage-derived interleukin 1 and prostaglandin E2, and lymphocyte-derived interleukin 2. Splenocyte and resident peritoneal macrophage numbers were also quantitated and spleen and thymus weights recorded. The sensitivity of this animal model was tested by treating rats with the immune-potentiating drugs, NPT 15392 (erythro-9-[2-hydroxy,3-nonyl]hypoxanthine) and avridine (N,N-dioctadecyl-N',N'-bis-[2-hydroxyethyl]propanediamine, or the immune-suppressive drugs, cyclophosphamide (N,N-bis[2-chloroethyl]tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine -2-oxide) and dexamethasone. Rats treated with NPT 15392 or avridine generally had enhanced immune responses, while those treated with cyclophosphamide or dexamethasone had decreased immune responses. Differential responsiveness of various immunocyte populations within individual rats to different drugs, or to doses of the same drug, indicates the efficacy of measuring multiple responses within the same animal. The multiassay-single animal approach represents an economical, versatile, sensitive, and relatively comprehensive paradigm for assessing immunotoxicologic/pharmacologic properties of chemicals and drugs. The approach is extremely economical since multiple immune responses are evaluated in each animal. The approach is versatile because it is amenable to incorporation of a variety of in vitro and in vivo assays and could be applied to almost any species. The model is relatively comprehensive because major types of immune responses/immunocyte populations and immunoregulatory pathways are tested. Finally, the model is sensitive for detecting immunosuppression as well as immunoenhancement, as validated by the use of known immune response modifiers in this study.

Animals↗

Illustrating sensitivity and uncertainty in environmental fate models using partitioning maps.

Variations of model predictions of the environmental fate of organic contaminants are usually analyzed for only one or at most a few selected chemicals, even though parameter sensitivity and contribution to uncertainty are widely different for different chemicals. A graphical method is introduced that allows for the comprehensive investigation of model sensitivity and uncertainty for all persistent organic nonelectrolytes at the same time. This is achieved by defining a two-dimensional hypothetical "chemical space" as a function of the equilibrium partition coefficients between air, water, and octanol (KOW, KAW, KOA), and plotting sensitivity and/or uncertainty of a specific model result to each input parameter as a function of this chemical space. The approach is illustrated for the bulk phase concentrations in air, water, soil, and sediment calculated by a level III model. Colored contour maps facilitate the identification of those input parameters that cause a high output variation of hypothetical and real chemicals. They also allow for the easy categorization of chemicals in terms of common parameter sensitivities, and thus comparable environmental behavior. Sensitivity varies with the mode of emission and the degradability of the chemicals, making it necessary to develop multiple sets of contour maps. Comparison of these sets of maps in turn allows the investigation of how parameter sensitivities change as a result of changes in mode of emission and persistence. The presented method can be used for investigating the sensitivity of any prediction obtained with any linear fate model that characterizes the partitioning behavior of organic chemicals with KAW, KoW, and KOA. Once the sensitivity maps have been constructed for a given environmental scenario, it is possible to perform a sensitivity analysis for a specific chemical by simple. placement of the substances' partitioning combinations within the chemical space. The maps can further contribute to the mechanistic understanding of a model's behavior, can aid in explaining observations of divergent environmental behavior of related substances, and can provide a rationale for grouping chemicals with similar model behavior, or for selecting representative example chemicals for a model investigation. They can also help in deciding when accurate and precise knowledge of physical chemical property data is crucial and when approximate numbers suffice to conduct a model investigation.

Air↗

Plasma polyamines determined by negative-ion chemical ionization/mass spectrometry.

We have developed an accurate and highly sensitive gas-chromatographic/mass-spectrometric procedure for determining di- and polyamines (putrescine, spermidine, and spermine) in plasma and erythrocytes. Deuterium-labeled analogs of putrescine, spermidine, and spermine were synthesized for use as internal standards. Trifluoroacetyl derivatives of the polyamines were formed during the procedure and then detected with negative-ion chemical ionization/mass spectrometry in combination with multiple ion monitoring. Limits of sensitivity ranged from 0.25 to 1.0 pmol of analyte injected into the instrument.

Chromatography, Gas↗

Differential activation of the c-Jun N-terminal kinase pathway in arsenite-induced apoptosis and sensitization of chemically resistant compared to susceptible B-lymphoma cell lines.

Various forms of inorganic arsenic are significant environmental contaminants that have multiple effects on cells, including the induction of apoptotic cell death. Induction of apoptosis in lymphoid cells can mediate immunotoxicity following exposure to chemicals. However, the mechanisms regulating the sensitivity of B-lymphocytes to arsenic-induced apoptosis are not understood. Therefore, we investigated the involvement of key mitogen-activated protein kinase pathways and apoptosis induction by sodium arsenite in a model system of chemically resistant and susceptible B-lymphoma cell lines. These studies revealed a differential requirement for the c-Jun N-terminal kinase (JNK) pathway for apoptosis induction by sodium arsenite in the resistant EW36 versus sensitive ST486 cell lines. Specifically, activation of the JNK pathway was not required for arsenite-induced apoptosis in ST486 cells, whereas JNK pathway activation was always associated with apoptosis induction in EW36 cells. Importantly, we found that EW36 cells, which overexpress the Bcl-2 protein, can be substantially sensitized to arsenite-induced apoptosis by prior exposure to nonlethal hyperthermia. Moreover, pretreatment with an inhibitor of p38 kinase acted synergistically with hyperthermia to further sensitize EW36 cells. The inhibition of p38 prolonged a transient period of JNK phosphorylation that occurred immediately after heat shock treatment and involved the persistent activation of SEK1, one of the kinases upstream of JNK. Significantly, the sensitization of resistant cells is characterized by a lowering of the threshold concentration of arsenite required to activate the JNK pathway and induce apoptosis.

Apoptosis↗

High-resolution X-ray fluorescence and excitation spectroscopy of metalloproteins.

A spectrograph has been developed with sufficient efficiency to make high-resolution fluorescence experiments on metalloproteins possible. The resolution of this spectrometer can reach 0.45 eV at 7.1 keV emission energy. The focus images of this multiple curved-crystal array spectrometer are presented. The chemical sensitivity of Kbeta emission spectra can be used to identify chemical states, and the spin-polarized near-edge structure provides a new measure of the spin density. The high-resolution fluorescence metalloprotein studies should become routine with third-generation synchrotron facilities, and the strength of both site and spin selectivity should complement the structural information from other spectroscopies.

Journal Article↗

[Utilization of embryo development technique of Brachydanio rerio to evaluating toxicity on various chemicals].

The application of Brachydanio rerio embryo development technique to research on environmental science was summarized in this paper. This testing technique was approved as one of standard methods for chemical toxicity test, especially for teratogensis, by international organizations (OECD, DIN). There are many advantages of this testing, e.g., low cost, easy operation, high sensitivity and multiple sensible endpoints, comparing with other toxicity testing. Also, it was used to judge toxic mechanism of chemicals. The embryo development of zebrafish can be affected obviously by heavy metal, pesticide, organic reagent and complex chemicals. Among them, Cu and Hg appeared stronger toxicity, and Cr was weaker for heavy metals. TPTA and Lindane were higher toxicity within pesticide, and they were higher toxicity if the organic reagent with one or more halogen substituent(s) and aminobenzene. These results were correspondent with other toxicity testing, and it showed higher sensitivity, especially a sublethal endpoint was selected. Therefore, it can be expected to test toxicity and teratogensis on mixed pollutant monitoring.

Animals↗

Alterations in hematopoietic responses in B6C3F1 mice caused by drinking a mixture of 25 groundwater contaminants.

Myelotoxicity parameters were monitored in female B6C3F1 mice exposed to 0, 1, 5, and 10% of a chemical mixture stock in drinking water for 2.5 to 31.5 weeks. The mixture consisted of 25 groundwater contaminants frequently found near toxic waste dumps, as determined by U.S. Environmental Protection Agency (EPA) surveys. Water consumption, body and organ weights, and hematological and histopathological examinations were conducted. No animals developed overt signs of toxicity after 2.5 weeks of treatment. No significant effect on bone marrow cellularity was observed after 2.5, 15.5, or 31.5 weeks of exposure; however, mice exposed to 5% or higher concentrations of the chemical mixture stock solution for 15.5 weeks showed significant suppression of granulocyte-macrophage progenitor cells (CFU-GM) and erythroid precursors (CFU-E) with no changes in body weight, histopathological or hematological parameters. Decreases occurred in erythrocyte mean corpuscular volume of mice exposed to a 10% solution for 15.5 weeks and to 5 and 10% solutions following 31.5 weeks of treatment. In addition, dose-related decreases were found in body, liver, and thymus weights in the 5 and 10% solutions exposure groups after 31.5 weeks. These results suggest that bone marrow may be a sensitive indicator for long-term, low-level exposure of multiple chemicals in mice. Furthermore, long-term exposure to highly contaminated groundwater may present a subtle risk to the hematopoietic system.

Animals↗