Basidiospore aeroallergens.
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Air Microbiology↗
Biomedical subjects
S B Lehrer
Publications and source records attributed to S B Lehrer.
Passive cigarette smoke-challenge studies: increase in bronchial hyperreactivity.
Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke-sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 +/- 283 micrograms/m3), and airborne nicotine levels (226 +/- 49 micrograms/m2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke-sensitive subjects without asthma reacted to cigarette-smoke challenge (greater than or equal to 20% fall from baseline FEV1). Thirty-two percent (10/31) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% (9/31) at 24 hours, and 13% (4/31) up to day 14 after ETS challenge. Of the subjects without asthma, 18% (7/39) demonstrated increased BHR at 6 hours, 10% (4/39) at 24 hours, and 8% (3/39) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS.
Adolescent↗
Effects of a GnRH agonist on fertility following administration to prepubertal male and female rats.
Leuprolide, a GnRH agonist, was administered daily to male and female rats for 90 days. Animals were sexually immature (25 days old) at the outset. Dosages were 20 and 200 micrograms/kg/day. Five males and five females were euthanized on Day 91. Sex organs were weighed and evaluated for histopathologic changes. These procedures were repeated 140 days later. Following a recovery period lasting 45 days (onset of normal-appearing estrous cycles) in females and 140 days (two spermatogenic cycles) in males, the fertility of these rats was assessed by mating with untreated animals. Treated males gained less weight while treated females gained more weight than controls. Weights of primary and secondary sex organs were reduced below control, but returned to normal following 140 days of recovery. Treated males were fertile and produced normal litters. Reproductive performance of low-dosage (20 micrograms/kg/day) females was normal 45 days after treatment cessation, but half of the high-dosage (200 micrograms/kg/day) females failed to become pregnant. However, reproductive performance of this group compared well with control performance after an additional 6 weeks of recovery. Atrophic changes were noted in male and female sex organs. Following 140 days of recovery, ovaries, uterus, vagina, prostate, and seminal vesicle were normal. Although testes and epididymides showed partial recovery at this time, multifocal or segmental atrophy and mineralization were noted in portions of some seminiferous tubules.
Animals↗
Assessment of multiple markers of environmental tobacco smoke (ETS) in controlled, steady-state atmospheres in a dynamic test chamber.
Controlled test atmospheres of sidestream and mixed mainstream/sidestream tobacco smoke were produced in a dynamic test chamber of 16.9 m3 volume. University of Kentucky 1R4F research cigarettes were automatically smoked by a Borgwaldt smoking machine. Different target levels of smoke were attained by varying the number of cigarettes being smoked (one or two cigarettes continuously) and dilution airflow through the chamber (1.6 to 7.4 m3/min). For each level, a "smoke index" was calculated as the number of cigarettes being smoked divided by the dilution flow rate. Ultraviolet light-absorbing particulate matter (UVPM); aerosol counts and size distribution; and concentrations of CO, NO2, NH3, formaldehyde, acetaldehyde, acrolein, and nicotine were determined in the test atmospheres and background dilution air. Parameters exhibiting the highest correlations with smoke index (r2 > 0.98) included UVPM, aerosol counts, formaldehyde, and acetaldehyde. The other parameters were also highly correlated with r2 > 0.9 in each case. Differences in concentration for sidestream and mixed mainstream/sidestream atmospheres were statistically significant for acetaldehyde, formaldehyde, and CO; in each case the level was higher in mixed mainstream/sidestream smoke. These results demonstrate the utility of employing multiple markers for assessment of environmental tobacco smoke levels and for dichotomizing the contributions of sidestream and mainstream smoke to these levels. The generation factors developed in this work can be used for estimating required ventilation rates for attainment of target air quality conditions in smoking rooms.
Air Pollutants↗
Chronological assessment of asbestos exposure on cell composition in murine lung.
To elucidate immune pathogenic mechanisms in asbestosis, lung and spleen lymphoid cell populations were analyzed at defined time intervals (1, 2, 3, 6, and 12 weeks during exposure and 4, 24, and 48 weeks post-exposure) in asbestos-exposed and unexposed (control) mice. Polymorphonuclear leukocytes and macrophages were increased in the lung tissue histologic sections of asbestos-exposed mice compared to controls. No consistent changes were observed in percentages of lung or spleen helper, suppressor, or total lymphocyte populations after asbestos exposure. The numbers of B cells (identified by anti-IgG) in minced lung preparations of asbestos-exposed animals were increased after 12 weeks of exposure. There also was an increase in IgG production in asbestos-exposed mice after 12 weeks exposure and at 4 weeks post-exposure with a return to near baseline levels 24 and 48 weeks after initial exposure. Collectively, these studies demonstrate stimulatory effects of inhaled asbestos fibers on B cells and IgG production after 12 weeks of continuous inhalation of asbestos fibers in a dust generation chamber.
Animals↗
Comparison of cockroach allergenic activity in whole body and fecal extracts.
Previous studies have established cockroach allergens as important sensitizing agents in the induction/exacerbation of urban asthma. The present investigation compared saline extracts of American cockroach (Periplaneta americana) whole bodies and feces and German cockroach (Blattella germanica) whole bodies and feces as important sources of allergens. All extracts were tested before or after gel filtration on Sephadex G-75 columns (fraction 2) as previously described. Skin test studies of 69 subjects with asthma with extracts of American or German cockroaches demonstrated a significant correlation of reactivity to whole body and fecal extracts for both species. Direct RASTs of 13 sera from cockroach skin test-positive subjects were generally greater to both German whole body extracts (GWBEs) and German fecal extracts (GFEs) as compared to American whole body and fecal extracts. There was a good correlation of RAST reactivity to GWBE with GFE. RAST inhibition demonstrated that GFE contained most of the allergenic activity present in GWBE. These studies demonstrate the allergenic similarities of cockroach whole body and fecal extracts and suggest that cockroach feces are an important sensitizing agent in atopic asthma.
Allergens↗
Asthmatic responses to passive cigarette smoke: persistence of reactivity and effect of medications.
The present study assessed the persistence of cigarette-smoke reactivity and the effects of drug pretreatment on bronchial responsiveness to environmental tobacco smoke (ETS). Two groups of subjects were chosen for the study. Group I consisted of 15 atopic smoke-sensitive subjects with asthma, six of whom were defined "reactors" and nine "nonreactors" to ETS challenge. Group II consisted of 15 atopic subjects without asthma and with documented upper respiratory tract symptoms on exposure to ETS. All subjects were challenged for 2 to 6 hours with mechanically generated ETS in a static inhalation chamber. Five/six subjects in group I, who were previously demonstrated as reactors 24 months earlier, remained reactive within 1 to 2 hours of continuous ETS exposure. Pretreatment with albuterol, cromolyn, and a combination of albuterol and cromolyn 30 minutes before ETS exposure significantly diminished airway reactivity to ETS. All nine previous nonreactors in group I remained nonreactive despite rechallenge with ETS for up to 6 hours. Group II subjects challenged under identical conditions did not reveal a significant decline in FEV1 on challenge with ETS. These studies demonstrate the persistence of ETS reactivity during a 2-year period. Although cromolyn sodium and/or albuterol can protect against reactivity, mechanisms of ETS-induced airway reactivity remain unknown.
Adult↗
Cockroach allergenic activity: analysis of commercial cockroach and dust extracts.
Previous investigations demonstrated that cockroach whole bodies and feces are important sources of allergens in the induction/exacerbation of bronchial asthma. The current study investigated different cockroach source materials, commercial extracts, and house dust extracts for cockroach allergenic activity. In general, extracts from four different sources of either American or German cockroaches contained similar amounts of allergenic activity by RAST inhibition. Three commercial American cockroach extracts compared by RAST inhibition had similar allergenic activity on an equal protein basis. Skin test results correlated house dust reactivity to both commercial and inhouse cockroach wholebody extracts and to fecal extracts. Six different samples of house dust obtained from vacuum cleaners in the New Orleans area and three commercially obtained house dust extracts contained varying quantities of cockroach allergenic activity by RAST inhibition. These studies demonstrate that commercial cockroach extracts vary in allergenic activity and that all house dust extracts tested contain cockroach allergens.
Allergens↗
Basidiomycete allergy: identification and characterization of an important allergen from Calvatia cyathiformis.
Basidiomycetes were not considered as major aeroallergen sources until spore traps revealed the prevalence of basidiospores, which were in some cases associated with epidemic outbreaks of asthma. More recently, we established that approximately one third of subjects with respiratory allergic disease were skin prick test positive to basidiospore extracts. Bronchial challenge with these extracts induced reversible immediate and late phase bronchospasm in sensitive subjects. Screening individual RAST-positive sera for reactivity to immunoprinted Calvatia cyathiformis spore extract indicated that a basic component with pI 9.3 reacted with 63% of test sera. Further analysis by RAST and immunoprint (IP) inhibition showed that this component, Cal c Bd9.3, appeared to cross-react with spore extracts from 3 of 5 other species tested. To isolate this component for additional analysis, a protocol was used with two sequential stages of preparative isoelectric focusing (IEF) followed by hydrophobic interaction chromatography. This yielded purified Cal c Bd9.3 that retained IgE-binding activity by IP, was a single band by IEF and SDS-PAGE (16 kD) analysis when stained with Coomassie blue. Double diffusion in gel with rabbit antiserum to Cal c BD9.3 demonstrated a single precipitin band in crude extract that was identical to that obtained with purified Cal c Bd9.3. By IP this antiserum recognized pure Cal c Bd9.3 and the 9.3 band in crude extracts from C. cyathiformis and 3 other species, corroborating the cross-reactivity. However, other bands were also recognized. These studies indicate that basidiospores are major fungal aeroallergens, many of which contain a common basic allergen to which most sensitized subjects react.
Allergens↗
Skin test reactivity to whole body and fecal extracts of American (Periplaneta americana) and German (Blatella germanica) cockroaches in atopic asthmatics.
Forty-six atopic asthmatic subjects aged 3 to 58 years attending the allergy clinic of a university hospital were evaluated for prick skin test reactivity with commercially available extracts of cockroach (CCE) and house dust (HD). Additionally, skin testing was performed with American cockroach whole body (AWBE) and fecal extracts (AFE) as well as German cockroach whole body (GWBE) and fecal extracts (GFE) prepared in our laboratory. Commercial cockroach extract was prepared from American, German, and Oriental cockroach whole bodies. Skin test reactivity to the different extracts were as follows: 83% to HD, 70% to CCE, 70% to AWBE and/or GWBE, 63% to AWBE, 57% to GWBE, 63% to AFE and/or GFE, 52% to AFE, 50% to GFE, 48% to both AWBE and GWBE, and 39% to both AFE and GFE. The subjects with positive skin tests to AWBE and/or GWBE (70%) were the same individuals who showed skin test reactivity to CCE (70%). Subjects from lower income families (less than $10,000) had a significantly higher skin test reactivity to cockroach allergens than those from families with an annual income of $11,000 to $24,000 (P = .04). These results demonstrate the significance of cockroach sensitization in atopic asthmatics, suggest the importance of fecal cockroach allergens, and support earlier observations of shared interspecies allergens between American and German cockroach whole bodies.
Adolescent↗
Developmental toxicity of temafloxacin hydrochloride in the long-tailed macaque (Macaca fascicularis).
The potential developmental toxicity of temafloxacin hydrochloride was studied in the long-tailed macaque (Macaca fascicularis). Ten animals in each of the three drug-treated groups (25, 50, and 100 mg/kg) were administered temafloxacin via nasogastric intubation during gestational days (GD) 20-50. A control group of ten animals received vehicle only. The dams were monitored daily for adverse physical signs and maternal blood samples were collected for analyses of serum progesterone (P), 17 beta-estradiol (E2), and chorionic gonadotropin (CG). In addition, the conceptus was monitored periodically by ultrasound during gestation to confirm growth and viability. Increased maternal toxicity (weight loss, anorexia, emesis) and embryolethality were observed at 100 mg/kg, and a no-observable-adverse-effect-level (NOAEL) of 50 mg/kg was established. The incidence of prenatal mortality was as follows: Control = 1/10 (10%); 25 mg/kg = 1/10 (10%); 50 mg/kg = 2/10 (20%); and 100 mg/kg = 5/10 (50%). Analysis of P, E2, and CG indicated no significant effect of treatment. In addition, no significant differences were observed in embryonic/fetal growth and development when compared to historical controls. No gross structural changes were observed in fetuses exposed to 50 or 100 mg/kg, although one fetus exposed to 25 mg/kg exhibited microphthalmia. This anomaly was considered spontaneous and, therefore, unrelated to treatment.
4-Quinolones↗
Characterization of water-soluble shrimp allergens released during boiling.
Water-soluble shrimp allergens released during boiling (shrimp water) were characterized and compared to allergen extracts from boiled shrimp (shrimp meat). Both shrimp extracts contained acidic proteins (isoelectrofocusing) and demonstrated similar allergenic activity (RAST and RAST inhibition). Shrimp-water extract was analyzed further by immunoprinting with sera from 14 shrimp-sensitive, RAST-positive subjects, and six nonsensitive, RAST-negative individuals. Although none of the sera from shrimp-tolerant individuals reacted, 12/14 sera (85.7%) from shrimp-sensitive subjects reacted with shrimp-water proteins with acid isoelectric points. Shrimp-water extract was fractionated by chromatofocusing with pH and NaCl gradients. A number of eluted ultraviolet-absorbing peaks contained allergens as determined by RAST inhibition. Isoelectrofocusing demonstrated many protein bands present in these peaks, some of which bound IgE from a RAST-positive sera pool. These studies indicate that shrimp water is an excellent source of shrimp allergens, that chromatofocusing is a useful method for fractionation of shrimp allergens, and that shrimp allergens are generally protein molecules with acid isoelectric points.
Allergens↗
The relationships among shrimp-specific IgG subclass antibodies and immediate adverse reactions to shrimp challenge.
High levels of shrimp-specific IgE, in association with a positive prick test, are not always predictive of a positive, immediate response to double-blind, placebo-controlled, food challenge (DBPCFC) with shrimp. The observation that shrimp-sensitive individuals in general have increased levels of circulating shrimp-specific IgG is of interest because antigen/allergen-specific IgG subclasses have been associated with adverse reactions to foods. Therefore, this current study measured shrimp-specific IgG subclass and IgE antibodies in 31 individuals with histories of immediate, adverse reactions to shrimp immediately before DBPCFC and 20 shrimp-tolerant subjects. Individuals with a history of shrimp sensitivity had significantly raised shrimp-specific IgG2 and IgG4 compared to shrimp-tolerant individuals. Challenge-positive subjects were distinguished from subjects with negative or equivocal responses by an increased IgG2 (p less than or equal to 0.001). Specific IgG4 was not raised (p less than or equal to 0.065). These studies indicate that some shrimp-specific IgG subclass levels are increased in shrimp-sensitive subjects. However, none of the subclass responses were significantly predictive of a positive response to DBPCFC and therefore were not diagnostic of shrimp intolerance.
Adult↗
Evidence for cross-reactive allergens among basidiomycetes: immunoprint-inhibition studies.
Allergenic cross-reactivity among six basidiomycete species (Calvatia cyathiformis, Coprinus quadrifidus, Psilocybe cubensis, Pleurotus ostreatus, Ganoderma meredithae, and Pisolithus tinctorius) was determined by immunoprint inhibition. Extensive cross-reactivity was demonstrated among Coprinus quadrifidus, Psilocybe cubensis, and Pleurotus ostreatus of the order Agaricales, and Calvatia cyathiformis of the order Lycoperdales. However, G. meredithae (order Aphyllophorales) and Pisolithus tinctorius (order Sclerodermatales) did not demonstrate significant cross-reactivity with the other basidiomycete species. Generally, the two most potent inhibitors were Psilocybe cubensis and Pleurotus ostreatus. Inhibitory dose-response curves of a major allergenic band (isoelectric point, 9.3) were obtained by densitometry. Significant cross-reactivity was demonstrated for the 9.3 band among the species of the order Agaricales and with Calvatia cyathiformis. The most potent inhibitors were again Psilocybe cubensis and Pleurotus ostreatus. Thus, there is substantial allergenic cross-reactivity among the species of the order Agaricales tested and with Calvatia cyathiformis but not between these four species and G. meredithae or Pisolithus tinctorius. These studies support earlier RAST-inhibition observations of shared allergenic epitopes among basidiomycetes, especially epitopes within the Agaricales. The presence of shared epitopes suggests the possibility of devising a panel of skin test reagents representative of a large group of basidiomycetes.
Allergens↗
The natural history of shrimp hypersensitivity.
Sera collected sequentially during a 24-month interval from 11 individuals with shrimp hypersensitivity and 10 nonhypersensitive control subjects were evaluated for shrimp-specific IgE, IgG, IgM, and IgA reactivity. Shrimp-hypersensitive subjects underwent double-blind, placebo-controlled shrimp challenges; seven exhibited positive challenges, and four subjects reported the subjective symptom of oropharyngeal pruritus. Shrimp-specific IgE levels in all subjects were relatively constant during the 24 months of this study and not affected by shrimp challenge, although some fluctuation in the shrimp-specific IgG, IgM, and IgA reactivity were noted, apparently unrelated to shrimp challenge. Shrimp-specific IgE and IgG, but not IgM and IgA, were significantly higher in the group with shrimp hypersensitivity as compared to the control subjects. Moreover, the challenge-positive subjects had higher levels of both shrimp-specific IgE and IgG than subjects reporting pruritus. The levels of shrimp-specific IgG correlated directly with shrimp-specific IgE reactivity. These studies indicate that serum levels of shrimp-specific IgE are significantly elevated in shrimp-hypersensitive subjects who exhibit positive food challenges, and these baseline levels did not appear to be altered long term by isolated shrimp challenge. Furthermore, baseline shrimp-specific antibody (IgG, IgM, and IgA) levels noted in normal subjects were not markedly affected by frequent ingestion of shrimp.
Adult↗
Identification and characterization of important cockroach allergens.
Allergens extracted from American and German cockroach species have been identified as significant sensitizing agents in the induction/exacerbation of asthma. In the present study, gel-filtration fractions of saline extracts of American cockroach (Periplaneta americana) whole bodies (AWBE fraction 2) and German cockroach (Blattella germanica) whole bodies (GWBE fraction 2) were used to identify and characterize important cockroach allergens by immunoprinting. In addition, allergens from AWBE and GWBE fractions 2 were additionally fractionated by chromatofocusing on polybuffer exchanger. Immunoprinting studies demonstrated several important acidic allergens in cockroach whole body extracts. All but one allergen had an acid isoelectric point (pH 2.80 to 5.20). Two allergens, one that focused at pH 3.50 and another allergen (or group of isoallergens) that focused between pH 4.15 to 4.55 were reactive with most sera obtained from cockroach-sensitive subjects. Chromatofocusing and subsequent skin test and RAST studies of AWBE and GWBE confirmed the presence of significant cockroach allergens with isoelectric points within the zone of pH 3.75 to 4.50. RAST-inhibition studies demonstrated the similarity of these allergens between AWBE and GWBE. Collectively, these observations identify the presence of several acidic cockroach allergens presumably shared between AWBE and GWBE.
Allergens↗
Respiratory and immunological reactions among Shiitake (Lentinus edodes) mushroom workers.
Four workers, the total work force employed at a Shiitake farm, developed cough and sputum production following a variable period of exposure to Shiitake mushrooms. All four had abnormal diffusing capacity and three had abnormal spirometry values. Chest roentgenograms demonstrated an interstitial pattern in one worker. Pulmonary function tests performed before and during several days of work demonstrated a significant decrease (greater than 20%) in forced vital capacity (FVC) and/or maximal mid-expiratory flow (MMEF) in three workers. Although specific antibodies to an extract of Shiitake spores were detected in sera from three workers none were IgE. High levels of Shiitake spores were detected in growing rooms (greater than 10(6)/m3) as well as other locations at the farm. Shiitake spore airborne antigen, detected by an immunochemical assay, was present in dust collected with a volumetric sampler from different locations at the farm. Antigenic determinants of Shiitake spore antigens, in common with antigens from other cultivated mushrooms (Agaricus and Pleurotus) were demonstrated by ELISA inhibition assay. This study demonstrates that workers exposed to high levels of Shiitake spores develop symptoms and laboratory findings suggestive of hypersensitivity pneumonitis (HP). Strict environmental control and the wearing of a face mask is probably needed to reduce the high risk of sensitization and possible development of immunological lung disease. Shiitake spores must be considered as an aetiological agent of mushroom workers' lung.
Agricultural Workers' Diseases↗
Evaluation of Basidiomycete and Deuteromycete (Fungi Imperfecti) extracts for shared allergenic determinants.
Aqueous extracts of select members of the Basidiomycetes and Deuteromycetes (Fungi Imperfecti) were evaluated for the presence of shared allergenic determinants using skin prick and radio-allergosorbent test (RAST) inhibition. Twenty adults with perennial symptoms of rhinitis, with or without asthma, were skin-prick tested with six species of Deuteromycetes and seven species of Basidomycetes. Positive weal-and-flare reactivity to Pleurotus ostreatus was associated with Alternaria alternata, Fusarium solani and Epicoccum purpurescens. Positive skin reactivity to Calvatia cyathiformis was also associated with A. alternata and F. solani. Coprinus quadrifidus was associated only with F. solani, and Psilocybe cubensis was only associated with Aspergillus fumigatus. No other skin test associations were demonstrated. For every allergen tested by RAST inhibition, significant dose-dependent homologous inhibition was demonstrated. Although the ability of an individual heterologous extract to inhibit the direct RAST varied, inhibition was generally minimal. In the most extreme example, no heterologous allergen inhibited the A. alternata RAST. However, the Armillaria tabescens RAST was inhibited 52.6%, 38.1% and 25.1% by A. fumigatus, E. purpurescens, and Penicillium notatum, respectively, suggesting significant cross-reactivity. These results suggest that, although shared allergenic determinants exist between select species of Basidiomycetes and Deuteromycetes, crossreactivity is minimal and its clinical significance is not clear. These data confirm that for reliable diagnosis of fungal allergy, representatives of both major groups must be used.
Adult↗