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Biomedical subjects

R E Biagini

Publications and source records attributed to R E Biagini.

At least 19 recordsLinked to original sources
PubMed2006

Allergen concentration in natural rubber latex.

BACKGROUND: Hevea brasiliensis latex serum is commonly used as the in vivo and in vitro reference antigen for latex allergy diagnosis as it contains the full complement of latex allergens. OBJECTIVE: This study quantifies the concentrations of the significant allergens in latex serum and examines its suitability as an antigen source in latex allergy diagnosis and immunotherapy. METHODS: The serum phase was extracted from centrifuged latex that was repeatedly freeze-thawed or glycerinated. Quantitation of latex allergens was performed by two-site immunoenzymetric assays. The abundance of RNA transcripts of the latex allergens was estimated from the number of their clones in an Expressed Sequence Tags library. RESULTS: The latex allergens, Hev b 1, 2, 3, 4, 5, 6, 7 and 13, were detected in freeze-thawed and glycerinated latex serum at levels ranging from 75 (Hev b 6) to 0.06 nmol/mg total proteins (Hev b 4). Hev b 6 content in the latex was up to a thousand times higher than the other seven latex allergens, depending on source and/or preparation procedure. Allergen concentration was reflected in the abundance of mRNA transcripts. When used as the antigen, latex serum may bias the outcome of latex allergy diagnostic tests towards sensitization to Hev b 6. Tests that make use of latex serum may fail to detect latex-specific IgE reactivity in subjects who are sensitized only to allergens that are present at low concentrations. CONCLUSION: Latex allergy diagnostics and immunotherapy that use whole latex serum as the antigen source may not be optimal because of the marked imbalance of its constituent allergens.

Allergens↗
PubMed2005

Simultaneous measurement of specific serum IgG responses to five select agents.

Select Agents are defined by CDC and the USDA Animal and Plant Health Inspection Service (APHIS) as biological agents or toxins deemed a threat to public, animal, or plant health, or to animal or plant products. They are classified on the basis of their ease of dissemination, mortality/morbidity rate, and potential for social disruption. A subset of these agents includes Bacillus anthracis, Yersinia pestis, Francisella tularensis, ricin toxin (RT), and staphylococcal enterotoxin B (SEB). Infection or intoxication with these agents has been shown to elicit an antigen-specific serum IgG response. We describe a fluorescent covalent microsphere immunoassay (FCMIA) for measurement of specific IgG antibodies to seven different antigens from five different select agents; B. anthracis [protective antigen (PA) and lethal factor (LF)], Y. pestis (F1 and V antigens), F. tularensis, RT and SEB simultaneously in human B. anthracis vaccinee sera (containing anti-PA and anti-LF IgG) which had been spiked with animal specific IgG antibodies to the other select agents. Inter-assay and intra-assay coefficients of variation were 6.5 and 13.4%, respectively (N = 4). There were no significant differences (P > 0.70) between assay responses when the assays were performed individually or multiplexed. When the observed versus expected interpolated concentrations were compared, highly linear relationships were observed (r2 values from 0.981 to 0.999, P < 0.001). Minimum detectable concentrations (MDC) ranged from 0.3 ng mL(-1) (Y. pestis F1) to 300 ng mL(-1) (RT). Finally, the curves showed responses were linear for most analytes from their MDC to 125 (SEB) to 1,300 (Y. pestis F1) x their MDC. These data indicate that multiplexed FCMIA is a sensitive and accurate method for simultaneous measurement of specific IgG in serum to CDC select agents and may be of value in screening either decontamination workers or the general population for exposure to/infection with these agents.

Animals↗
PubMed2004

Development of a sensitivity enhanced multiplexed fluorescence covalent microbead immunosorbent assay (FCMIA) for the measurement of glyphosate, atrazine and metolachlor mercapturate in water and urine.

Body burdens from exposures to pesticides may be estimated from urinary analyses of pesticide parent/metabolite concentrations. Pesticide applicators and others are often exposed to numerous unrelated pesticides, either sequentially or simultaneously. Classically, body burdens of pesticides are analyzed using chemical/instrumental analysis (CIM) or enzyme immunoassays (EIAs). Both of these technologies can usually be used to quantitate one analyte (or closely related groups of analytes) per analysis. Alternatively, multiple analytes can be measured simultaneously using a multiplexed fluorescence covalent microbead immunoassay (FCMIA). We developed a multiplexed FCMIA to simultaneously measure glyphosate (Gly), atrazine (Atz), and metolachlor mercapturate (MM) in water and urine. The assay had least detectable doses (LDDs) in water/diluted urine of 0.11/0.09 ng/ml (Gly, water/urine LDD), 0.10/0.07 ng/ml (Atz) and 0.09/0.03 ng/ml (MM). The sensitivity for the measurement of Gly was enhanced by derivatization. All assays gave linear responses from the LDDs for each respective pesticide to 300 ng/ml. There was no cross-reactivity between the three analytes. Using a 96-well microplate and an autosampler, as many as 288 separate analyses can be completed in approximately 120 min with precision, sensitivity, and specificity equivalent to, if not better, than that found when these same analytes are measured by CIM or EIA.

Acetanilides↗
PubMed2004

Determination of serum IgG antibodies to Bacillus anthracis protective antigen in environmental sampling workers using a fluorescent covalent microsphere immunoassay.

AIMS: To evaluate potential exposure to Bacillis anthracis (Ba) spores in sampling/decontamination workers in the aftermath of an anthrax terror attack. METHODS: Fifty six serum samples were obtained from workers involved in environmental sampling for Ba spores at the American Media, Inc. (AMI) building in Boca Raton, FL after the anthrax attack there in October 2001. Nineteen sera were drawn from individuals both pre-entry and several weeks after entrance into the building. Nine sera each were drawn from unique individuals at the pre-entry and follow up blood draws. Thirteen donor control sera were also evaluated. Individuals were surveyed for Ba exposure by measurement of serum Ba anti-protective antigen (PA) specific IgG antibodies using a newly developed fluorescent covalent microsphere immunoassay (FCMIA). RESULTS: Four sera gave positive anti-PA IgG results (defined as anti-PA IgG concentrations > or = the mean microg/ml anti-PA IgG from donor control sera (n = 13 plus 2 SD which were also inhibited > or = 85% when the serum was pre-adsorbed with PA). The positive sera were the pre-entry and follow up samples of two workers who had received their last dose of anthrax vaccine in 2000. CONCLUSION: It appears that the sampling/decontamination workers of the present study either had insufficient exposure to Ba spores to cause the production of anti-PA IgG antibodies or they were exposed to anthrax spores without producing antibody. The FCMIA appears to be a fast, sensitive, accurate, and precise method for the measurement of anti-PA IgG antibodies.

Adult↗
PubMed2001

Exposure to protein aeroallergens in egg processing facilities.

Proteinaceous materials in the air can be highly allergenic and result in a range of immunologically mediated respiratory effects, including asthma. We report on the largest evaluation of exposure to date of airborne egg protein concentrations in an egg breaking and processing plant that had cases of occupational asthma. Personal air samples for egg protein were analyzed in duplicate on each PTFE filter using two analytical methods: (1) a commercial assay for non-specific total protein, and (2) indirect competitive inhibition assay using an ELISA method to quantify specific egg protein components. The highest concentrations were found in the egg washing room (mean exposure 644 microg/m3) and breaking room (255 microg/m3), which were also the areas where the risk of being sensitized was the greatest. There was excellent quantitative agreement between the airborne concentrations of total protein and sum of the specific protein antigens (ovalbumin, ovomucoid, and lysozyme). The correlation coefficient of the log-transformed data from the two methods was 0.88 (p < 0.0001). Size-selective sampling also indicated that most of the aerosol was capable of reaching the small airways. The methods described can be utilized to evaluate employee exposure to egg proteins. Exposure documentation, coupled with recommended exposure reduction strategies, could facilitate prevention of future employee sensitization and allergic respiratory responses by identifying high-exposure jobs and evaluating control measures.

Aerosols↗
PubMed2001

Receiver operating characteristics analyses of Food and Drug Administration-cleared serological assays for natural rubber latex-specific immunoglobulin E antibody.

Receiver operating characteristics (ROC) analyses to evaluate and compare the diagnostic accuracy of Food and Drug Administration (510K)-cleared natural rubber latex (NRL)-specific immunoglobulin E (IgE) antibody immunoassays have not been performed using well-characterized skin-testing reagents. Sera were collected from 311 subjects (131 latex puncture skin test [PST] positive and 180 PST negative). All masked, coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, HYCOR HY-TEC RAST, and Pharmacia-Upjohn CAP System RAST FEIA (CAP). Diagnostic accuracy was evaluated using GraphRoc for Windows software to construct and analyze ROC curves in relation to the subjects' PST status and the results of the immunoassays. The ROC areas under the curve (AUCs) +/- standard error based on PST for the three diagnostic tests were 0.858 +/- 0.024, 0.869 +/- 0.024, and 0.924 +/- 0.017, respectively, for AlaSTAT, CAP, and HY-TEC. The HY-TEC system had a significantly greater AUC based on PST than those observed for AlaSTAT (P < 0.05) and CAP (P < 0.05) analyses. When the diagnostic tests were probed as to the cutoffs giving maximal diagnostic efficiency compared to PST, CAP and AlaSTAT yielded values of <0.35 kU of allergen IgE (kU(A))/liter and <0.35 kU/liter while the HY-TEC assay yielded 0.11 kU/liter. The diagnostic efficiencies based on PST in our cohort at these cutoffs were 87.1, 88.1, and 88.7%, respectively. The HY-TEC assay had a significantly greater AUC than CAP and AlaSTAT using PST as a diagnostic discriminator in our cohort. When the HY-TEC system was probed at its maximally efficient cutoff (0.11 kU/liter) versus HYCOR's recommended cutoff of 0.05 kU/liter, a loss of sensitivity of 8.4% was observed with a gain in specificity of 19.5%.

Antibodies, Anti-Idiotypic↗
PubMed1999

Diagnostic performance of Food and Drug Administration-cleared serologic assays for natural rubber latex-specific IgE antibody. The Multi-Center Latex Skin Testing Study Task Force.

BACKGROUND: In the absence of Food and Drug Administration-approved natural rubber latex skin testing reagents, latex-specific IgE antibody immunoassays are used in the diagnosis of latex allergy. Comparative diagnostic performance of these tests has not been definitively determined. OBJECTIVE: We sought to study the predictive value of available Food and Drug Administration (510K)-cleared latex-specific IgE antibody immunoassays in the diagnosis of latex allergy. METHODS: Subjects (n = 312) were classified as having a positive (n = 117) or a negative (n = 195) latex allergy history (Hx) or having a positive (n = 131) or a negative (n = 181) puncture skin test (PST) response (Greer reagent). The 14 subjects with a negative Hx and a positive PST response had negative responses to glove provocation testing and thus were considered sensitized but asymptomatic. Sera from 22 subjects were split to evaluate intra-assay variation. All 334 coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, Hycor HY-TEC EIA System, and Pharmacia-UpJohn CAP System. Variance and diagnostic performance parameters of each test were computed with 95% confidence intervals in relation to the subjects' Hx and PST status. RESULTS: Intra-assay concordance of split sera results was 96.0% for all 3 assays, with coefficients of variation of less than 25% and between-assay coefficients of variation of less than 21%. The diagnostic performance of the CAP and AlaSTAT assays were equivalent in comparison with PST results: sensitivity, CAP 76.3% and ALASTAT 73. 3% and specificity, CAP 96.7% and AlaSTAT 97.2% (P = NS). The HY-TEC assay was more sensitive (91.6%) and less specific (73.3%) than the CAP and AlaSTAT assays (P <.001). From 9% to 25% of the sera were discordant, being positive in at least 1, but not all 3, assays. CONCLUSION: The CAP and AlaSTAT assays produce 24% and 27% of false-negative results, respectively, whereas the HY-TEC produces 27% of false-positive results when compared with the PST.

Antibodies, Anti-Idiotypic↗
PubMed1999

Evaluation of postural stability in workers exposed to lead at a secondary lead smelter.

Postural sway testing was carried out on a group of 145 workers exposed to lead in a secondary lead smelter and 84 workers not exposed to lead in a hinge manufacturing plant. All workers were measured for blood lead levels (BLL) and erythrocyte zinc protoporphyrin (ZPP) concentrations at the time of testing and both a total cumulative and a time-weighted average BLL value was constructed for the lead exposed workers. The lead exposed workers mean BLL at the time of testing was 38.9 microg/dl and the non-exposed workers mean was 2.3 microg/dl. ZPP levels averaged 55.2 microg/dl for exposed workers and 18.9 microg/dl for non-exposed workers. Total cumulative BLL averaged 83476 microg/dl days for the exposed workers, with a mean time-weighted average BLL of 35.1 microg/dl. Six tests of postural stability, four two leg conditions and two single leg conditions were administered to all subjects using a force platform to produce measurements of sway for comparison purposes. The two leg conditions also manipulated the visual and proprioceptive systems. A statistically significant association was observed for sway measurements and the current BLL for all workers, but not with the current BLL of only the lead exposed workers. No statistically significant associations were present with the cumulative measures of long-term exposure. Of the six tests of sway, only the single leg conditions showed significant exposure effects. The results suggest effects of lead exposure among those with average BLL near 40.0 microg/dl, but only in the most challenging one leg conditions.

Enzyme Inhibitors↗
PubMed1998

Epidemiology studies in immunotoxicity evaluations.

Studies in humans designed to detect immunomodulation from exposure to xenobiotics present challenging problems to epidemiologists and immunotoxicologists. Exposed and control groups must be carefully selected, exposure to the xenobiotic must be sufficiently high and well-documented, and the referent group should be as similar as possible to the exposed. Immune markers/functional tests in an individual may be influenced by sunlight exposure, medication, illness and use of recreational drugs; all of these potential confounding factors must be addressed. Sample acquisition is usually performed at sites geographically distant from the controlled environment of an investigator's laboratory, yielding an assortment of new problems that would not occur in clinical or hospital situations. Regulations and guidelines concerning the transport of biological samples and potential hazards of HIV and HBV exposures to personnel must be adapted to field conditions. Since the application of immunotoxicological techniques to populations exposed to xenobiotics is relatively new, and the ability to measure an increasing number of immune biomarkers of activation, suppression, autoimmunity or hypersensitivity is rapidly expanding, there are difficulties in the interpretation of statistically positive results (sometimes within the normal range) and their potential health significance. Finally, both biological and methodological factors complicate the assessment of dose-response/concentration effect relationships in human immunotoxicity studies, and traditional dose-response relationships may not always be present.

Drug Evaluation↗
PubMed1998

Immunologic findings among lead-exposed workers.

A comprehensive panel of immune parameters was evaluated among 145 lead-exposed workers with a median blood lead level (BLL) of 39 micrograms/dL (range: 15-55 micrograms/dL) and 84 unexposed workers. After adjusting for covariates, we found no major differences in the percentage of CD3+ cells, CD4+ T cells, CD8+ T cells, B cells, or NK cells between lead-exposed and unexposed workers, although the association between lead exposure and the number of CD4+ T cells was modified by age. We also found no differences between exposed and unexposed workers in serum immunoglobulin levels, salivary IgA, C3 complement levels, or lymphoproliferative responses. However, among exposed workers, the percentage and number of B cells were positively associated with current BLL, serum IgG was negatively associated with cumulative lead exposure, and the percentage and number of CD4+/CD45RA+ cells were positively associated with cumulative lead exposure. We found no evidence of a marked immunotoxic effect of lead at the exposure levels studied, although some subtle differences in immunologic parameters were noted.

Adult↗
PubMed1992

Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non-human primate animal model.

An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5 through the use of provocation challenges, and compared V2O5 reactivity before and after subchronic V2O5 exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5-exposed groups (n = 8 each) received equal weekly V2O5 exposures (concentration x time) with different exposure profiles. One V2O5-exposed group received 0.1 mg V2O5 m-3 on Mondays, Wednesday and Fridays, with a twice-weekly peak exposure of 1.1 mg V2O5 m-3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper-reactivity. The other V2O5-exposed group received a constant daily concentration of 0.5 mg V2O5 m-3. A control group (n = 8) received filtered, conditioned air. Pre-exposure challenges with V2O5 produced a concentration-dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5 inhalation did not produce an increase in V2O5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Evaluation of cutaneous responses and lung function from exposure to opiate compounds among ethical narcotics-manufacturing workers.

We recently demonstrated morphine-6-hemisuccinate-human serum albumin conjugate (M-6-HS-HSA)-specific IgG in serum from ethic narcotics-manufacturing workers. In this article, we present results of epicutaneous tests to opiate compounds and lung-function studies in these same workers. Thirty-nine workers, exposed to opiates, were evaluated for possible work-related changes in lung function and were administered a questionnaire concerning opiate exposure and health history in February 1988. In December 1988, 33 employees with occupational exposure to opiates, six other workers (New Jersey referent) employed at the same factory with minimal exposure to opiate compounds, and 17 nonexposed individuals from Cincinnati, Ohio, were subjected to epicutaneous threshold testing with a panel of six opiate compounds and nine common aeroallergens. In opiate-exposed workers, significantly lower epicutaneous threshold concentrations were detected (compared to New Jersey referent and Cincinnati control subjects) for dihydrocodeine (p less than 0.01), hydrocodone (p less than 0.05), codeine (p less than 0.01), and morphine (p less than 0.05). Significant associates existed among epicutaneous threshold concentrations between the agents tested; that is, individuals with a positive morphine skin test would generally have a positive codeine skin test, etc. Atopic status (positive cutaneous test results to two or more of nine common aeroallergens) was not significantly associated (p greater than 0.05) with positive opiate skin sensitivity. Although the mean cross-shift decrements in FEV1 for all workers were nonsignificant, five opiate-exposed individuals demonstrated cross-shift decrements in FEV1 of greater than 10%. Daily maximum-minus-minimum changes in workweek PEFR (PEFRmax-min) were significantly reduced for Monday through Thursday (p less than 0.05) compared to PEFRmax-min changes during a nonwork, nonexposure 3-day weekend. Ten exposed workers demonstrated daily PEFRmax-min changes of greater than 20%, suggesting acute airway obstruction. Increased cutaneous reactivity to opiate compounds among opiate-exposed workers may reflect development of pharmacologic hyperresponsiveness to opiate compounds.

Adult↗
PubMed1991

Evaluation of the onset and duration of response to cold air inhalation challenge in cynomolgus monkeys (Macaca fascicularis).

Cold air inhalation challenge (CAIC) for the evaluation of bronchial reactivity has been proposed as a physical agent alternative to chemical agent challenges (methacholine or histamine), especially suitable for the occupational environment. The present investigation describes and evaluates a method for performing cold air inhalation challenge in Cynomolgus monkeys (Macaca fascicularis), a species shown to be useful in animal modeling studies of occupational asthma. Six adult male anesthetized monkeys were ventilated by changes in external pressure while breathing cold air (-25 degrees C to -30 degrees C). Pulmonary function testing was performed at 10, 25, 40 and 55 min post-challenge. Significant increases (P less than 0.05) in average pulmonary flow resistance (RL) and decreases in dynamic compliance (CL dyn) were observed, with maximum impairment occurring at 25 min post-challenge, with a trend towards a return to baseline values at 55 min post-challenge. Peak expiratory flow rate (PEFR), forced expiratory volume in 0.5 s/forced vital capacity (FEV0.5/FVC) and forced expiratory flow at 50% forced vital capacity (FEF50) showed the same general pattern of reduction as seen with RL; however, these results were not statistically significant, most probably owing to individual monkey variability and the small number of monkeys (N = 6) used. A repeat challenge at 25 min after a primary challenge yielded increased RL in one monkey, suggesting that no absolute refractory period is present from CAIC. Results of these studies demonstrate that CAIC causes bronchoconstriction in monkeys and may be useful in further animal modeling studies designed to determine the asthmogenic/airway irritant potential of occupational toxicants.

Air↗