Using the systematic evolution of ligands by exponential enrichment (SELEX) method, we have identified oligonucleotides that bind to human IgE with high affinities and high specificity. These ligands were isolated from three pools of... more
Using the systematic evolution of ligands by exponential enrichment (SELEX) method, we have identified oligonucleotides that bind to human IgE with high affinities and high specificity. These ligands were isolated from three pools of oligonucleotides, each representing 10(15) molecules: two pools contained 2'-NH2 pyrimidine-modified RNA with either 40 or 60 randomized sequence positions, and the third pool contained ssDNA with 40 randomized sequence positions. Based on sequence and structure similarities, these oligonucleotide IgE ligands were grouped into three families: 2'-NH2 RNA group A ligands are represented by the 35-nucleotide truncate IGEL1.2 (Kd = 30 nM); 2'-NH2 RNA group B ligands by the 25-nucleotide truncate IGEL2.2 (Kd = 35 nM); and the ssDNA group ligands by the 37-nucleotide truncate DI 7.4 (Kd = 10nM). Secondary structure analysis suggests G quartets for the 2'-NH2 RNA ligands, whereas the ssDNA ligands appear to form stem-loop structures. Using rat ...
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Drawing evidence from epidemiology and exposure assessment studies and recommendations from expert practice, we describe a process to guide health care providers helping their patients who present with symptoms that might be associated... more
Drawing evidence from epidemiology and exposure assessment studies and recommendations from expert practice, we describe a process to guide health care providers helping their patients who present with symptoms that might be associated with living in damp housing. We present the procedures in the form of a guided 2-part interview. The first part has 5 questions that triage the patient toward a more detailed questionnaire that reflects features of housing conditions known to be reliably associated with exposures to mold and dampness contaminants. We chose the questions based on the conditions associated with moisture problems in homes across the United States and Canada. The goal is to facilitate the clinician's effort to help patients reduce exposure to environmental triggers that elicit symptoms to better manage their disease.
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Research Interests: Immunology, Asthma, Medicine, Methods, Humans, and 4 moreAllergens, Immunoglobulin E, Epitopes, and Allergen
Awareness of the relationship of fungi to asthma in indoor air is very old and well documented. There is substantial evidence that mold and dampness exacerbate asthma in sensitized individuals. Many governmental and nongovernmental... more
Awareness of the relationship of fungi to asthma in indoor air is very old and well documented. There is substantial evidence that mold and dampness exacerbate asthma in sensitized individuals. Many governmental and nongovernmental organizations around the world have issued guidelines to the effect that the elimination of moisture intrusion and the removal of moldy items from living space can improve respiratory health. The process of home assessment for moisture and mold presence is discussed along with factors that can be used to guide fungal exposure reduction efforts. An approach to the assessment process itself is outlined, and common causes of moisture and mold damage are described. Points that should be included in a report resulting from a home assessment and rudimentary elements of report interpretation are discussed. Emphasis is that interpretation of sampling for moisture and fungal presence should be provided by the person performing the assessment. We conclude that mult...
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Research Interests: Immunology, Cell line, Method, Soybean, Optometry and Ophthalmology, and 3 moreIGE, Rat, and Model System
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Research Interests: Immunology, Air pollution, Multiple Instance Learning, Standardization, Allergy, and 13 moreHumans, Allergens, Immunoglobulin E, Coefficient of Variation, Accuracy, Immunoassay, Reproducibility of Results, Precision, Epitopes, Confidence Interval, Air Pollutants, Clinical Allergy and Immunology, and Reference standards
Research Interests: Immunology, Food Allergy, Allergy, Humans, FISH, and 15 moreAllergies, Infant, Immunoglobulin E, Antibody, IGE, Immunoassay, Assay, Atopic Dermatitis, Quantitative Analysis, Hypersensitivity, Food and Drug Administration, Positive predictive value, Clinical Allergy and Immunology, Child preschool, and Negative predictive value
Research Interests: Physical Chemistry, Immunology, Mass Spectrometry, Air pollution, Automobiles, and 15 moreAir Sampling, Allergy, Humans, Respiratory Disease, Optical microscopy, Allergens, Immunoglobulin E, Rubber, Colorado, Particle Size, Urban Population, Particulate Air Pollution, Air Pollutants, Mortality rate, and Clinical Allergy and Immunology
The allergist/immunologist judiciously diagnoses allergic disease by using confirmatory IgE antibody data from in vivo and in vitro assays after the collection of a clinical history. After an overview of historical events, clinically... more
The allergist/immunologist judiciously diagnoses allergic disease by using confirmatory IgE antibody data from in vivo and in vitro assays after the collection of a clinical history. After an overview of historical events, clinically available allergen-specific IgE assays from Phadia, Siemens, and Hycor are contrasted by their design and performance characteristics. The assays share comparable working ranges, analytical sensitivities, and excellent precision, reproducibility, and linearity to a performance standard of <15% coefficients of variation. However, multiple interlaboratory studies have confirmed that the 3 IgE antibody assays either detect different populations of IgE antibody or do not measure the same antibodies with comparable efficiencies. The clinical consequence is that IgE antibody results from the 3 assays are not interchangeable or equivalent. Data generated with one assay cannot be directly extrapolated to published predictive outcomes based on IgE antibody levels from a different assay. The transition from allergen extract-based to allergenic components reagents is discussed, emphasizing the chip-based microarray's strength in identifying IgE antibody cross-reactivity. US Food and Drug Administration-cleared point-of-care IgE antibody lateral flow cassettes are overviewed. Finally, IgE antibody concentration, affinity, clonality (epitope specificity), and specific activity (specific/total IgE ratio) are examined as humoral immune response parameters measured by serologic assays that affect effector cell degranulation and ultimately allergic disease expression.
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The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing,... more
The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.
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Endotoxin is an inflammatory made by gram negative bacteria that can irritate the skin, induce respiratory problems, fever, and shock. It is an adjuvant for both delayed hypersensitivity and IgE production and has been shown to magnify... more
Endotoxin is an inflammatory made by gram negative bacteria that can irritate the skin, induce respiratory problems, fever, and shock. It is an adjuvant for both delayed hypersensitivity and IgE production and has been shown to magnify antigen specific mediator release. Since many of the clinical problems associated with natural latex products involve similar clinical sequelae, we investigated the possibility that latex gloves might be contaminated with endotoxin. To measure the endotoxin content of a variety of natural latex gloves, investigate the its distribution and origin, associated with latex proteins, and determine the particle sizes associated with its release. Endotoxin, protein, and allergen were measured using a quantitative kinetic Limulus assay, modified Lowry, and RAST inhibition, respectively. Particle size and density were determined using an Anderson multistage air sampler and CsCl2 gradient. Endotoxin was found to be a highly significant contaminant of some latex gloves. Levels ranged from 0.09 ng to 2.8 micrograms/g of glove. Protein levels ranged from < 25 to 1150 micrograms/g of glove while allergen levels ranged from < 1 to 837 micrograms/g of glove. Endotoxin and protein eluted rapidly from the interior of the gloves tested. Greater than 70% of the endotoxin was found to be associated with particles in the < 7 microns aerodynamic diameter range. The highest levels of endotoxin were found in nonsterile examination gloves with a tendency towards powdered gloves containing more endotoxin and protein. A slurry containing cross-linked dextran through which gloves were dipped revealed very high endotoxin contamination (64 micrograms/mL) while unused cross-linked dextran has very little associated endotoxin. These data demonstrate that some natural rubber latex gloves, particularly nonsterile examination gloves, are contaminated with high amounts of endotoxin and proteins. These were found mostly on the inside of gloves and were released as very small respirable particles that were not physically associated with the powder. These findings support the hypothesis that endotoxin may be responsible for some of the tissue irritation associated with latex glove use. In addition, this material may be responsible for the enhancement of delayed and immediate hypersensitivity reactions to chemicals and proteins found in these products and offers a possible explanation for the disproportionate severity of these reactions.
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To enable the readers to recognize some of the history, problems, progress, interpretation, and present status of assays for specific IgE (s-IgE) antibodies. Peer-reviewed literature in the field. Key articles were selected by the author.... more
To enable the readers to recognize some of the history, problems, progress, interpretation, and present status of assays for specific IgE (s-IgE) antibodies. Peer-reviewed literature in the field. Key articles were selected by the author. Clinical and analytical studies have differed widely in their conclusions as to the performance of tests for s-IgE. Study conclusions depend on the testing method used, the allergen(s) studied, patient selection, and, most importantly, the standards used for comparison. Today, only a handful of the once commercially developed assays still exist, and some of these still do not compare well to an analytical ideal standard. However, with the extent of regulation and economic pressures, most of the surviving s-IgE tests are considerably improved over what had existed before them. Allergic diseases with multiple symptom patterns seem to be increasing in modern societies. Objective methods are needed to differentiate allergic origins from other mechanisms that cause similar symptoms. Accurate, quantitative, and objective methods for s-IgE measurement are now available and can be used effectively in clarifying allergic diagnoses when interpreted in conjunction with the clinical history.
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UniCAP Phadiatop is a single laboratory test designed to determine the presence or absence of specific IgE to a variety of common inhalants. Its purpose is to aid in the differentiation of patients with symptoms attributable to allergic... more
UniCAP Phadiatop is a single laboratory test designed to determine the presence or absence of specific IgE to a variety of common inhalants. Its purpose is to aid in the differentiation of patients with symptoms attributable to allergic disease from other common causes. Consecutive children and adolescent patients (n = 145) at two centers were examined by having their history and physical examination performed by two board certified allergists. Their conclusions along with skin prick tests and specific IgE measurements regarding seven common inhalants (mite, oak, ragweed, grass, dog, cat, Alternaria) were compared with UniCAP Phadiatop test results. This was done using concordance of all test results. Attempts to resolve test discrepancies, when found, included specific RAST inhibitions, total IgE values, and physicians' judgment after testing. All patients with resolved diagnoses (143 of 145, 103 positive and 40 negative) were identified correctly by the UniCAP Phadiatop test. Skin test results and specific IgE measurements correlated well, but neither correlated well with the history by itself, suggesting a minimal false-positive component of the history of 23%. UniCAP Phadiatop results demonstrated a quantitative relationship between the patient's score and the amount of IgE specific to these individual allergens. The UniCAP Phadiatop test was shown to be highly sensitive and specific in differentiating individuals who are sensitized to common inhalants from those who are not. This test is recommended to all physicians as an aid in diagnostic and referral decisions for patients suspected of having an inhalant allergic diathesis.
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Studies have demonstrated that the magnitude of sensitization as evidenced by specific IgE (sIgE) levels provides significant information as to whether a sensitized individual is likely to be truly reactive. However, it is not clear that... more
Studies have demonstrated that the magnitude of sensitization as evidenced by specific IgE (sIgE) levels provides significant information as to whether a sensitized individual is likely to be truly reactive. However, it is not clear that quantitative sIgE results provided by different laboratories using different technologies are comparable. To investigate whether similar results were obtained from Clinical Laboratory Improvement Act-certified laboratories that used 3 common systems for sIgE antibody determination with serum samples and mouse-human IgE chimeric antibodies with known specificity and quantity. Sixty samples for peanut and 20 for soy were submitted for sIgE determination on 3 different systems: ImmunoCAP, Immulite, and Turbo radioallergosorbent test (RAST). Mouse-human chimeric IgE antibodies specific for the major birch allergen Bet v 1 and for the dust mite allergen Der p 2 were also included. A qualitative evaluation using a cutoff of 0.35 kUA/L showed some differences in the ability to detect sIgE sensitization, with the Turbo RAST being most variable. However, considerable differences were found with quantitative evaluation, with Immulite overestimating and Turbo RAST underestimating sIgE compared with ImmunoCAP. Similar discrepancies were seen with the mouse-human chimeric IgE antibody samples. These findings have potentially serious clinical implications, since each of these systems is widely used. It is therefore important that all laboratories clarify which system they are using. Just because 2 systems present their results in the same units does not mean that the results are necessarily correct or interchangeable.
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Accurate and reliable evaluation of the presence or absence of allergen-specific IgE is important in the differential diagnosis of allergic disease. A variety of different commercial tests are available for this purpose. There are few... more
Accurate and reliable evaluation of the presence or absence of allergen-specific IgE is important in the differential diagnosis of allergic disease. A variety of different commercial tests are available for this purpose. There are few data available to judge how the results of these different tests compare with one another in everyday use. To examine prospectively the extent of comparability among specific IgE results from different laboratories. Six diagnostic laboratories employing five different methods to assay specific IgE were selected. Aliquots from 26 serum samples that contained variable levels of IgE specific to 17 common aeroallergens were sent in triplicate to each study laboratory during a 6-week time period. Results were reported numerically and by class scores and then compared by examining their concordance using Kendall's W nonparametric statistical test. In addition, cut-off values were compared by a best agreement analysis using reported results. Reproducibility was determined using precision profiles based upon the coefficient of variation among triplicates for each allergen across the range of reported results. In all, 7,813 tests were analyzed. Concordance among different assays in commercial use with one exception was not good. This was particularly true around the cut-off region where most assays demonstrated high imprecision. The Pharmacia CAP System used by two different laboratories demonstrated highly comparable results with good precision. Some assays were reproducible but not accurate. Others were neither reproducible nor accurate. The results of this study indicate that not all commercial laboratories/assays for specific IgE provide reproducible and accurate data. Significant potential for misdiagnosis was detected for some reported results. Methods were identified that do give sensitive, accurate, and reproducible results.
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To compare the diagnostic value of two commercial in vitro tests for the detection of latex-specific IgE antibodies. Serum samples were collected from latex-allergic and nonlatex-allergic individuals. Persons were classified as latex... more
To compare the diagnostic value of two commercial in vitro tests for the detection of latex-specific IgE antibodies. Serum samples were collected from latex-allergic and nonlatex-allergic individuals. Persons were classified as latex allergic if they had a positive clinical history and a positive skin prick test with a latex extract. Persons with no latex-related symptoms and negative skin tests were classified as nonlatex allergic. The serum samples were tested in a blinded fashion by a laboratory using the CAP (Pharmacia-Upjohn) and AlaSTAT (Diagnostic Products Company) assays. Values of 0.35 kA U/L or greater were considered positive in both tests. The 143 sera studied came from 83-latex allergic and 60 nonallergic persons. The in vitro tests were found to have sensitivities of 79.5% and 73.8%, and specificities of 90.2% and 91.7%, for CAP and AlaSTAT, respectively. The positive predictive values were 91.7% and 92.5%, while the negative predictive values were 76.4% and 71.4% for the CAP and AlaSTAT, respectively. In individuals classified by the combination of clinical history and skin test results, both the Pharmacia CAP and the DPC AlaSTAT demonstrated acceptable sensitivities, specificities, and predictive values for detection of antilatex IgE antibodies. These findings suggest that both assays can be useful adjuncts to the diagnosis of latex allergy.
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To determine the impact of feedyards on endotoxin concentration, fecal coliform count, and other water quality measurements during winter and summer in feedyard playas (shallow lakes). Water samples obtained from 7 feedyard playas and 3... more
To determine the impact of feedyards on endotoxin concentration, fecal coliform count, and other water quality measurements during winter and summer in feedyard playas (shallow lakes). Water samples obtained from 7 feedyard playas and 3 nonfeedyard control playas. Surface water samples were collected from each playa and at various depths from 3 feedyard playas. Endotoxin concentrations, 22 water quality variables, and fecal coliform counts were determined in samples collected in summer and winter from various combinations of playas. Cattle numbers per feedyard ranged from 40,000 to 175,000 head/y. Mean endotoxin concentrations were significantly lower in control playas than in feedyard playas in winter and summer. Endotoxin concentration appeared to be homogenous at various water depths. Values for 20 of 22 water quality variables were higher in the feedyard playas than in control playas in winter and summer. In winter only, mean total fecal coliform concentration in feedyard playas was significantly greater than in control playas. Results indicated that feedyards have the potential to impact water quality in playas, and cattle should not be allowed access to them. Feedyard playa water should not be used under high pressure to settle dust in pens with cattle or to cool cattle, because aerosols containing pathogens and high concentrations of endotoxin are a health hazard for humans and cattle?
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Patients exhibit a multitude of symptoms that may or may not be allergy related. In this study, we examined the consistency between results obtained by a multiallergen-specific immunoglobulin E (IgE) test and frequent use (3 months or... more
Patients exhibit a multitude of symptoms that may or may not be allergy related. In this study, we examined the consistency between results obtained by a multiallergen-specific immunoglobulin E (IgE) test and frequent use (3 months or more) of prescribed antihistamines. A retrospective examination of 1-year prescription claims records from January 1, 2000, through December 31, 2000, for 4,643 patients enrolled in a 115,000-member managed care organization who received 1 or more prescriptions for an oral antihistamine (loratadine, fexofenadine, or cetirizine). A total of 1,343 health plan enrollees who received an oral antihistamine prescription were continuously enrolled during the year 2000 and diagnosed with allergic rhinitis. Of these patients, 246 (18%) consented to a multiallergen- specific IgE test, and 159 patients (64.6%) had a negative IgE test result. A total of 163 patients were classified as frequent antihistamine users (3 or more antihistamine prescriptions), and 101 (6...
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This report discusses discusses the withdrawal of the United States as a signatory from the Trans-Pacific Partnership (TPP) agreement as directed by President Trump.
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On March 8, 2018, the 11 remaining signatories of the Trans-Pacific Partnership (TPP) agreement, excluding the United States, signed the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP). The CPTPP parties... more
On March 8, 2018, the 11 remaining signatories of the Trans-Pacific Partnership (TPP) agreement, excluding the United States, signed the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP). The CPTPP parties announced the outlines of the agreement in November 2017 and concluded the negotiations in January 2018. The CPTPP, which requires ratification by 6 of the 11 signatories to become effective, would be a vehicle to enact much of the TPP, signed by these countries and the United States in February 2016 and from which President Trump withdrew in January 2017. The withdrawal was the first action under the President's new trade policy approach, which includes a stated preference for bilateral free trade agreement (FTA) negotiations over multiparty agreements like TPP, a critical view of many existing U.S. FTAs, and a prominent focus on bilateral U.S. trade deficits as an indicator of the health of trade relationships. The Trump Administration has also be...
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This report provides information about the early August 2014 U.S.-Africa Leaders Summit in Washington, DC, and policy issues likely to be addressed by participants in the summit and other events being held in conjunction with it.
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Genetic hemoglobinopathies are the most common single-gene disorder worldwide. Some automated hematology analyzers have the capability of flagging individuals who may have hematological disorders based on complete blood count (CBC)... more
Genetic hemoglobinopathies are the most common single-gene disorder worldwide. Some automated hematology analyzers have the capability of flagging individuals who may have hematological disorders based on complete blood count (CBC) biomarkers. We aimed to evaluate the accuracy of a hematology analyzer in identifying genetic hemoglobinopathies in Cambodian women and to determine which hematological biomarkers are the best predictors. A CBC was completed using a Sysmex XN-1000 analyzer and hemoglobinopathies were determined with capillary hemoglobin electrophoresis for 808 nonpregnant Cambodian women. Sysmex XN-1000 Interpretive Program (IP) messages, which flag potential hematological disorders, were produced from CBC results. Then, 2 × 2 tables were used to determine sensitivity and specificity of the IP message “Hemoglobin defect” to detect a genetic hemoglobinopathy. Receiver operating characteristic (ROC) analyses assessed the diagnostic ability of six CBC biomarkers to predict a...
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This report discusses the African Growth and Opportunity Act (AGOA), which is a nonreciprocal trade preference program that provides duty-free treatment to U.S. imports of certain products from eligible sub-Saharan African (SSA) countries.
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This report briefly summarizes some of the key controversial issues of the Trans-Pacific Partnership (TPP), including select market access issues (such as on dairy and other agricultural products, autos, and textiles and apparel) as well... more
This report briefly summarizes some of the key controversial issues of the Trans-Pacific Partnership (TPP), including select market access issues (such as on dairy and other agricultural products, autos, and textiles and apparel) as well as the level of intellectual property protection, the scope and enforcement of environment and worker rights provisions, investor-state dispute settlement, access to government procurement, and the potential inclusion of provisions on currency valuation and exchange rates. The TPP is a proposed free trade agreement (FTA) among 12 Asia-Pacific countries, which the Obama Administration casts as comprehensive, with economic and strategic significance for the United States.
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This report discusses the Trans-Pacific Partnership (TPP), which is a proposed free trade agreement (FTA) among the United States and 11 Asia-Pacific countries. It examines the key provisions of the proposed Trans-Pacific Partnership... more
This report discusses the Trans-Pacific Partnership (TPP), which is a proposed free trade agreement (FTA) among the United States and 11 Asia-Pacific countries. It examines the key provisions of the proposed Trans-Pacific Partnership (TPP), related policy and economic contexts, and issues of potential interest to Congress.
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In higher education, Learning Assistants (LAs)—a relatively recent evolution grounded in peer mentorship models—are gaining popularity in classrooms as universities strive to meet the needs of undergraduate learners. Unlike Teaching... more
In higher education, Learning Assistants (LAs)—a relatively recent evolution grounded in peer mentorship models—are gaining popularity in classrooms as universities strive to meet the needs of undergraduate learners. Unlike Teaching Assistants, LAs are undergraduate students who receive continuous training from faculty mentors in content-area coaching and pedagogical skills. As near-peers, they assist assigned groups of undergraduates (students) during class. Research on LAs suggests that they are significant in mitigating high Drop-Fail-Withdrawal rates of large enrollment undergraduate science, technology, engineering, mathematics, and medical (STEMM) courses. However, there is a dearth of description regarding the learning between LAs and STEMM faculty mentors. This paper reports on perspectives of faculty mentors and their cooperating LAs in regard to their learning relationships during a Calculus II at a research-oriented university during Spring of 2020. Using an exploratory-d...