Dorr Dearborn - Academia.edu (original) (raw)

Papers by Dorr Dearborn

Environmental Research, Feb 1, 2010

Background: Housing conditions can contribute to allergen exposures that are linked to asthma, bu... more Background: Housing conditions can contribute to allergen exposures that are linked to asthma, but little is known about which of those conditions are most likely to predict high levels of allergens in settled house dust. Methods: We pooled allergen, housing condition, occupant behavior, demographic, and other data from nine asthma studies (n =950 homes in 6 US cities). Dust mite (Der f 1 or Der p 1), cockroach (Bla g 1 or Bla g 2), mouse (Mus m 1), cat (Fel d 1) and dog (Can f 1) allergens were measured in settled dust from kitchens or bedrooms, and concentrations were categorized according to previously published asthma symptom thresholds. We calculated odds ratios (OR) using logistic regression to identify those housing conditions and occupant behaviors that were associated with clinically significant allergen levels, after adjusting for numerous confounding variables. Results: The adjusted results show that high cockroach allergen was associated with cracks or holes in walls (OR =2.1), high dust mite allergen was associated with mold odor (OR= 2.5), housing built before 1951 (OR= 2.1), and single-family home with slab on grade (OR =1.9); and mouse allergen was associated with rodent control or signs of rodents (OR =3.62) and inversely associated with presence of a cat (OR =0.20). Water leaks and below average housekeeping had unadjusted high odds ratios for high cockroach allergen. Conclusion: We have identified a number of housing conditions that are consistently associated with increased allergen dust concentrations. This study indicates that screening for housing-based asthma triggers should include presence of cats, dogs, cockroaches, or rodents; water leaks; mold or mold odor; holes or cracks in walls; and below average housekeeping. Single family houses that have basements or crawl spaces or are built before 1951are also important predictors for increased allergens in housing.

Radiology, Jul 1, 1986

Magnetic resonance (MR) imaging of the trachea and main bronchi was performed in seven infants (a... more Magnetic resonance (MR) imaging of the trachea and main bronchi was performed in seven infants (aged 3-15 months) with symptoms of airway obstruction. Diagnoses made clinically, radiologically, and by transnasal flexible fiberoptic endoscopy included vascular ring (one patient), tracheal compression by the innominate artery (five patients), and tracheomalacia (one patient). MR images in sagittal and axial sections clearly demonstrated tracheal compression at the level of the innominate artery in three infants and tracheal narrowing due to a vascular ring in one patient. The other three patients had airway narrowing apparently unrelated to aberrant vascular structures on MR images. The appearance of the airways on MR images corresponded closely to endoscopic observations. It is conc!uded that MR imaging is capable of demonstrating airway obstruction in infants and delineating any relationship to major mediastinal blood vessels. Index terms: Magnetic resonance (MR), in infants and children #{149} Trachea, MR studies, 671.1299

Oxford University Press eBooks, Dec 1, 2013

Mold DORR DEARBORN Abstracts Mold (fungus) is important in the outdoor, natural world, but indoor... more Mold DORR DEARBORN Abstracts Mold (fungus) is important in the outdoor, natural world, but indoor exposure to mold is not healthy. Indoor mold is ubiquitous. It becomes a hazard for children's health when it is amplifi ed by water intrusion or chronic dampness. Infants and children can develop fungal infections caused by mold. Immune-compromised children and children with chronic lung diseases such as cystic fi brosis are at especially high risk for fungal infections. Children are also susceptible to irritant and toxic reactions caused by fungal mycotoxins, toxic metabolites that are released into indoor air by many molds especially in damp or wet environments. Airborne mycotoxins can sensitize allergic children and trigger immune reactions, allergic rhinitis, and acute asthmatic att acks. Mycotoxins can also cause toxic infl ammation of the airways in nonallergic children through direct irritation of the airways not mediated by the immune system. Diagnostic tools for assessment of inhalation exposure to mold are limited and not well validated. Th e only specifi c treatment for fungal-derived disorders is cessation of exposure, which typically requires remediation of the water intrusion or chronic dampness that amplifi es mold growth. Antibiotics are used to treat fungal infections. Evaluation and remediation of indoor mold require expert assistance and oversight.

Journal of Clinical Toxicology, 2015

Objective: Very low birth weight (VLBW) infants frequently receive blood transfusions. We hypothe... more Objective: Very low birth weight (VLBW) infants frequently receive blood transfusions. We hypothesize that toxic metals in donor blood may pose a health risk with potential adverse neurologic effects on the developing brain of a vulnerable VLBW infant. Study design: Samples from 100 donor blood units were collected from a large urban hospital. Blood was analyzed for aluminum, arsenic, beryllium, cadmium, manganese, mercury, nickel, lead and polonium. The estimated upper limit of acceptable metal concentration in donor blood was calculated assuming a transfusion volume of 20 ml/kg and using either previously published acceptable intravenous doses or oral reference doses with a conservative estimate of 10% gastrointestinal absorption. Ingested mercury was assumed to be 95% absorbed. Results: Eight of the nine metals were detectable. Concentrations of arsenic, beryllium, cadmium, mercury and polonium were not of concern for any single blood transfusion. Concentrations of aluminum, manganese, nickel and lead exceeded the estimated upper limit of acceptable concentration in 5, 11, 4 and 26 units respectively. Of the 100 units, 31 had at least one toxic metal concentration high enough to pose a potential health risk. Conclusions: VLBW infants are exposed to heavy metals that are toxic from blood transfusion. The number of units with concerning levels of toxic metals was higher than expected. Neonatologists should be aware of this potential exposure to toxic metals from donor blood when decision is made to administer blood transfusion. Neurodevelopmental studies of toxic metal exposed infants from blood transfusion are warranted.

JAMA: The Journal of the American Medical Association, 1995

Pulmonary Hemorrhage/Hemosiderosis-Continued Hemosiderosis is an uncommon childhood disease chara... more Pulmonary Hemorrhage/Hemosiderosis-Continued Hemosiderosis is an uncommon childhood disease characterized by spontaneous pulmonary hemorrhage often associated with iron deficiency anemia. During January 1993-November 1994, eight cases of acute pulmonary hemorrhage/hemosiderosis were diagnosed among infants at a children's referral hospital in Cleveland. In comparison, during 1983-1993, a total of three cases of pulmonary hemosiderosis were diagnosed among infants and children at this hospital. This report summarizes the preliminary results of the ongoing epidemiologic, clinical, and laboratory investigations by pediatric pulmonologists in Cleveland,

Journal of Pregnancy and Child Health, 2014

Evidence has been accruing to indicate that young children are vulnerable to noise in their physi... more Evidence has been accruing to indicate that young children are vulnerable to noise in their physical environment. A literature review identified that, in addition to hearing loss, noise exposure is associated with negative birth outcomes, reduced cognitive function, inability to concentrate, increased psychosocial activation, nervousness, feeling of helplessness, and increased blood pressure in children. While increasing attention has been given to the health effects of noise in children, research about noise exposure is sparse and often the measure of exposure is simply proximity to a noise source. The U.S. National Children's Study (NCS) provides a unique opportunity to investigate noise exposures to pregnant women and children using a number of assessment modalities at different life stages. Measurement of noise levels in homes and other environments, personal dosimetry measurements made over a period of days, and questionnaires addressing sources of noise in the environment, annoyance to noise, perceived noise level, use of head phones and ear buds, noisy activity exposures, and occupational exposures, are planned for evaluation within the NCS Vanguard pilot study. We describe the NCS planned approach to addressing noise exposure assessment in study visits over a child's lifetime.

New England Journal of Medicine, 1981

Journal of Immunology, May 15, 1987

Pseudomonas aeruginosa and its products have been shown to inhibit mitogen-induced human lymphocy... more Pseudomonas aeruginosa and its products have been shown to inhibit mitogen-induced human lymphocyte blastogenesis as measured by [3H]TdR uptake. The phenazine pigment pyocyanine has been identified as one of the inhibitors present in cellfree culture Supernatants. To determine the mechanism of the inhibitory action of pyocyanine, we studied its effect on the early stages of T cell activation. Pyocyanine inhibited lymphocyte stimulation induced by specific antigens, the lectin concanavalin A and the calcium ionophore, ionomycin, suggesting that its inhibitory effect is not dependent on interference with the T cell antigen receptor complex itself. Using quin-2, we showed that pyocyanine did not interfere with the mitogen-induced increase in cytosolic-free Ca2+. We also showed that pyocyanine did not interfere with the function of calmodulin stimulated Ca2+-Mg2+ ATPase activity, indicating that the mechanism of action of pyocyanine differs from that of the structurally related phenothiazine compounds. Analysis of IL 2 production and IL 2 receptor expression clearly showed that pyocyanine inhibits the production of this essential lymphokine as well as the expression of IL 2 receptors on the T cell membrane. This inhibition is dose dependent and not due to cellular toxicity. There was parallel inhibition of growth in cell volume as well as [3H]TdR uptake. Thus, our results demonstrate that pyocyanine inhibits T cell proliferation by decreasing the production of the critical lymphokine IL 2 and by decreasing the expression of the IL 2 receptor. Local suppression of lymphocyte stimulation by phenazine pigments such as pyocyanine may interfere with cellular immune responses that may be necessary for eradication of chronic infection with P. aeruginosa. Chronic pulmonary infection with Pseudomonas aeruginosa is a major cause of morbidity and mortality

Toxicological Sciences, Jan 19, 2005

Stachybotrys chartarum has been linked to building-related respiratory problems including pulmona... more Stachybotrys chartarum has been linked to building-related respiratory problems including pulmonary hemorrhage in infants. The macrocyclic trichothecenes produced by S. chartarum have been the primary focus of many investigations. However, in addition to trichothecenes this fungus is capable of producing other secondary metabolites and a number of protein factors. This study examines the effects of intact, autoclaved, and ethanol-extracted spores on the lungs of infant rats as an approach to differentiate between secondary metabolites and protein factors. Seven-day-old infant rats were exposed intratracheally to 1 3 10 5 spores/g body weight (toxic strain JS58-17) and sacrificed at various times up to 72 h. The inflammatory response was measured by morphometric analysis of the lungs and determination of inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid. Alveolar space was greatly reduced in animals exposed to fungal spores compared to phosphate buffered saline (PBS)-treated controls. The largest effects were observed in pups treated with intact spores where alveolar space 24 h after treatment was 42.1% compared to 56.8% for autoclaved spores, 51.1% for ethanol-extracted spores, and 60.6% for PBS-treated controls. The effects of different spore preparations on inflammatory cells, cytokine, and protein concentrations in the BAL fluid can be ranked as intact > autoclaved > extracted. Tumor necrosis factor alfa (TNF-a), interleukin 1-beta (IL-1b), and neutrophils were the most sensitive indicators of inflammation. The difference between autoclaved (100% trichothecene toxicity, denatured/enzymatically inactive proteins) and intact (100% trichothecene activity, unaltered/released proteins) spores indicates the involvement of fungal proteins in the inflammatory response to S. chartarum and sheds new light on the clinical importance of ''nontoxic'' strains.

Protein Engineering Design & Selection, 1993

Journal of Natural Products, 1996

An investigation of a cluster of cases of pulmonary hemosiderosis in infants in Cleveland, OH, le... more An investigation of a cluster of cases of pulmonary hemosiderosis in infants in Cleveland, OH, led to the isolation of many isolates of Stachybotrys atra and two isolates of a related toxigenic fungus, Memnoniella echinata. M. echinata produces two cytotoxic trichothecene mycotoxins, trichodermol (1a) and trichodermin (1b), as well as several griseofulvins. Dechlorogriseofulvin (2a) and epidechlorogriseofulvin (2b) were the major compounds isolated. This is the first report of a fungus outside the Penicillium genus producing griseofulvins.

Journal of Occupational and Environmental Medicine, Jun 1, 2004

ABSTRACT Fungal concentrations were measured in the dust of 6 homes in Cleveland, Ohio, where an ... more ABSTRACT Fungal concentrations were measured in the dust of 6 homes in Cleveland, Ohio, where an infant developed pulmonary hemorrhage (pulmonary hemorrhage homes [PHH]) and 26 reference homes (RH) with no known fungal contamination. Quantitative polymerase chain reaction assays for 82 species (or assay groups) were used to identify and quantify fungal concentrations. The ratios of the geometric means of PHH to RH were >1 for 26 species (group I). However, the same ratios were <1 for 10 species (group II). Probit analysis of the sum of the logs of the concentrations of these 2 groups resulted in a 95% probability range for separating PHH from RH homes. The same 82 fungal species were also tested for hemolysin production on sheep's blood agar (incubated at 37 degree C). Hemolysins were more commonly produced by group I species (42%) compared with group II species (10%).

Applied and Environmental Microbiology, Jul 1, 1999

Stachybotrys chartarum is an indoor air, toxigenic fungus that has been associated with a number ... more Stachybotrys chartarum is an indoor air, toxigenic fungus that has been associated with a number of human and veterinary health problems. Most notable among these has been a cluster of idiopathic pulmonary hemorrhage cases that were observed in the Cleveland, Ohio, area. In this study, 16 strains of S. chartarum isolated from case (n ‫؍‬ 8) or control (n ‫؍‬ 8) homes in Cleveland and 12 non-Cleveland strains from diverse geographic locations were analyzed for hemolytic activity, conidial toxicity, and randomly amplified polymorphic DNA banding patterns. In tests for hemolytic activity, strains were grown at 23°C on wet wallboard pieces for an 8-week test period. Conidia from these wallboard pieces were subcultured on sheep's blood agar once a week over this period and examined for growth and clearing of the medium at 37 or 23°C. Five of the Cleveland strains (all from case homes) showed hemolytic activity at 37°C throughout the 8-week test compared to 3 of the non-Cleveland strains. Five of the Cleveland strains, compared to two of the non-Cleveland strains, produced highly toxic conidia (>90 g of T2 toxin equivalents per g [wet weight] of conidia) after 10 and 30 days of growth on wet wallboard. Only 3 of the 28 strains examined both were consistently hemolytic and produced highly toxic conidia. Each of these strains was isolated from a house in Cleveland where an infant had idiopathic pulmonary hemorrhage.

PubMed, Mar 1, 1988

Phosphoinositide content was measured in erythrocyte membranes from 11 patients with cystic fibro... more Phosphoinositide content was measured in erythrocyte membranes from 11 patients with cystic fibrosis (CF) and from 12 control subjects to determine whether altered levels of phosphatidylinositol-4-phosphate (Ptdlns4P) or phosphatidylinositol-4,5-bisphosphate (Ptdlns(4,5)P2) are responsible for the decrease in Ca2+-adenosine triphosphatase (Ca2+-ATPase) activity in this disorder. Isolated membranes were extracted with an acidified chloroform-methanol solvent system. The recovered lipids were separated by one-dimensional thin-layer chromatography and quantified with a colorimetric assay for phosphorus. The results are expressed in molar percent, moles of phosphoinositide times 100 divided by the total number of moles of phospholipid per membrane. The means +/- SEM of Ptdlns(4,5)P2, Ptdlns4P, and phosphatidylinositol (Ptdlns) in CF membranes (1.07 +/- 0.18, 1.02 +/- 0.22, and 2.32 +/- 0.36 molar percent, respectively) were indistinguishable from controls (0.91 +/- 0.14, 0.85 +/- 0.12, and 2.21 +/- 0.32 molar percent, respectively) (P greater than 0.20 for all three pairs). The accuracy of quantitative recovery throughout the procedure was determined by adding a radioactive internal standard, L-3-phosphatidyl[2-3H]inositol to 10 membrane preparations. Although quantitative recoveries, as determined by percent radioactivity recovered, varied from 54% to 92%, mean Ptdlns(4,5)P2, Ptdlns4P, and Ptdlns levels appropriately corrected from tracer loss were still indistinguishable between the two groups. We conclude that absolute phosphoinositide levels are not altered in cystic fibrosis erythrocyte membranes and that the differences in Ca2+-ATPase activity cannot be explained on this basis.

Biochemistry, Jun 1, 1984

The rates of hydrolysis of N-[(alpha-L-rhamnopyranosyloxy)phospho]-L-leucyl-L-tryptophan (phospho... more The rates of hydrolysis of N-[(alpha-L-rhamnopyranosyloxy)phospho]-L-leucyl-L-tryptophan (phosphoramidon), N alpha-phosphoryl-L-leucyl-L-tryptophan (PO3LeuTrp), N alpha-phosphoryl-L-leucyl-L-phenylalanine (PO3LeuPhe), and N alpha-phosphoryl-L-leucyl-L-phenylalaninamide (PO3LeuPheNH2) were followed by proton nuclear magnetic resonance spectroscopy. The rates of hydrolysis (kobsd) of PO3LeuTrp, PO3LeuPhe, and PO3LeuPheNH2 were all first order in phosphorylamide concentration over the pH range studied (3.8-9.5). The values for kobsd at pH 7.3 and 37 degrees C are as follows: PO3LeuTrp, 0.35 h-1; PO3LeuPhe, 0.63 h-1; PO3LeuPheNH2, 0.73 h-1. The values for kobsd do not significantly change between pH 5 and pH 8 but dramatically decreased with increasing pH. The hydrolysis of PO3LeuPhe and PO3LeuPheNH2 above a pH of approximately 5 was positively correlated with the concentration of monoanionic species (NHRPO3H)1-, and the values for the first-order rate constants for the respective monoanionic species were calculated to be 0.66 +/- 0.03 h-1 and 1.07 +/- 0.10 h-1. Phosphoramidon was not found to hydrolyze after 6 days at 37 degrees C at a pH of 4.6 and 7.7, while the phosphorylamide PO3LeuTrp, synthesized by the removal of L-rhamnose from phosphoramidon by base hydrolysis, was found to rapidly hydrolyze under these conditions. Solvolysis in aqueous methanol of PO3LeuPhe and PO3LeuPheNH2 indicates that the hydrolysis reaction is bimolecular, proceeding by way of direct attack of solvent (H2O, CH3OH) on phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal of Biological Chemistry, Mar 1, 1982

Portions of this paper (including "Experimental Procedures," "Results," Figs. 1-7, and Tables 1-1... more Portions of this paper (including "Experimental Procedures," "Results," Figs. 1-7, and Tables 1-111) are presented in miniprint as prepared by the authors. Miniprint is easily read with the aid of a standard magnifying glass. Full size photocopies are available from the Journal of Biological Chemistry, 9650 RockviUe Pike, Bethesda, MD 20814. Request Document No. 81M-1479, cite authors, and include a check or money order for $11.60 per set of photocopies. Full size photocopies are also included in the microfilm edition of the Journal that is available from Waverly Press.

Advances in Applied Microbiology, 2004

Publisher Summary Stachybotrys chartarum is one of the several environmental fungi that can produ... more Publisher Summary Stachybotrys chartarum is one of the several environmental fungi that can produce very potent toxic compounds. Animal models provide physicians and environmental scientists with useful tools for assessing risks associated with the respiratory effects of air pollutants. The animal studies to date support the view that pulmonary exposure to the spores of S. chartarum leads to hemorrhagic inflammation and impairment of growth. This has been demonstrated by increases in bronchoalveolar lavage (BAL) fluid of inflammatory cells, proinflammatory mediators, hemoglobin, and proteins along with changes in pulmonary surfactant. Although the earlier experiments were conducted with relatively high doses, recent findings indicate that lower doses, which appear to be closer to the concentrations encountered in indoor air, can elicit similar symptoms. The results of animal studies based on different experimental designs are difficult to compare because of many variables—including spore toxicity, viability, and content of fungal proteins in addition to species, strains, age of animals, and route of administration.

Journal of Biological Chemistry, Feb 1, 1983

A peptide from sperm whale myoglobin, residues 132-153, and a chromogenic substrate, H-D-valyl-L-... more A peptide from sperm whale myoglobin, residues 132-153, and a chromogenic substrate, H-D-valyl-L-leucyl-L-lysyl-p-nitroanilide diacetate, were selected to investigate the susceptibility of peptide bonds adjacent to N',iVdimethyllysyl residues to tryptic hydrolysis. The peptides were exhaustively methylated using formaldehyde and sodium cyanoborohydride (N. J e n t o f t and D. G. Dearborn (1979) J. Biol. Chem. 254, 4359-4365). Unmodified and methylated peptides were digested with trypsin or submaxillary protease, an enzyme that catalyzes the hydrolysis of only arginyl bonds in proteins. Trypsin catalyzed the hydrolysis of the methylated apomyoglobin peptide only at the single arginyl residue and not at any of the four W,N-dimethyllysyl residues. Trypsin also failed to catalyze the hydrolysis of reductively methylated H-D-valyl-L-leucyl-L-lysyl-pnitroanilide. Even a 17-fold molar excess of the methylated substrate did not appear to alter the rate of tryptic hydrolysis of the unmodified substrate. These results are discussed with regard to the interactions of substrates within the specificity site of trypsin.

Environmental Research, Feb 1, 2010

Background: Housing conditions can contribute to allergen exposures that are linked to asthma, bu... more Background: Housing conditions can contribute to allergen exposures that are linked to asthma, but little is known about which of those conditions are most likely to predict high levels of allergens in settled house dust. Methods: We pooled allergen, housing condition, occupant behavior, demographic, and other data from nine asthma studies (n =950 homes in 6 US cities). Dust mite (Der f 1 or Der p 1), cockroach (Bla g 1 or Bla g 2), mouse (Mus m 1), cat (Fel d 1) and dog (Can f 1) allergens were measured in settled dust from kitchens or bedrooms, and concentrations were categorized according to previously published asthma symptom thresholds. We calculated odds ratios (OR) using logistic regression to identify those housing conditions and occupant behaviors that were associated with clinically significant allergen levels, after adjusting for numerous confounding variables. Results: The adjusted results show that high cockroach allergen was associated with cracks or holes in walls (OR =2.1), high dust mite allergen was associated with mold odor (OR= 2.5), housing built before 1951 (OR= 2.1), and single-family home with slab on grade (OR =1.9); and mouse allergen was associated with rodent control or signs of rodents (OR =3.62) and inversely associated with presence of a cat (OR =0.20). Water leaks and below average housekeeping had unadjusted high odds ratios for high cockroach allergen. Conclusion: We have identified a number of housing conditions that are consistently associated with increased allergen dust concentrations. This study indicates that screening for housing-based asthma triggers should include presence of cats, dogs, cockroaches, or rodents; water leaks; mold or mold odor; holes or cracks in walls; and below average housekeeping. Single family houses that have basements or crawl spaces or are built before 1951are also important predictors for increased allergens in housing.

Radiology, Jul 1, 1986

Magnetic resonance (MR) imaging of the trachea and main bronchi was performed in seven infants (a... more Magnetic resonance (MR) imaging of the trachea and main bronchi was performed in seven infants (aged 3-15 months) with symptoms of airway obstruction. Diagnoses made clinically, radiologically, and by transnasal flexible fiberoptic endoscopy included vascular ring (one patient), tracheal compression by the innominate artery (five patients), and tracheomalacia (one patient). MR images in sagittal and axial sections clearly demonstrated tracheal compression at the level of the innominate artery in three infants and tracheal narrowing due to a vascular ring in one patient. The other three patients had airway narrowing apparently unrelated to aberrant vascular structures on MR images. The appearance of the airways on MR images corresponded closely to endoscopic observations. It is conc!uded that MR imaging is capable of demonstrating airway obstruction in infants and delineating any relationship to major mediastinal blood vessels. Index terms: Magnetic resonance (MR), in infants and children #{149} Trachea, MR studies, 671.1299

Oxford University Press eBooks, Dec 1, 2013

Mold DORR DEARBORN Abstracts Mold (fungus) is important in the outdoor, natural world, but indoor... more Mold DORR DEARBORN Abstracts Mold (fungus) is important in the outdoor, natural world, but indoor exposure to mold is not healthy. Indoor mold is ubiquitous. It becomes a hazard for children's health when it is amplifi ed by water intrusion or chronic dampness. Infants and children can develop fungal infections caused by mold. Immune-compromised children and children with chronic lung diseases such as cystic fi brosis are at especially high risk for fungal infections. Children are also susceptible to irritant and toxic reactions caused by fungal mycotoxins, toxic metabolites that are released into indoor air by many molds especially in damp or wet environments. Airborne mycotoxins can sensitize allergic children and trigger immune reactions, allergic rhinitis, and acute asthmatic att acks. Mycotoxins can also cause toxic infl ammation of the airways in nonallergic children through direct irritation of the airways not mediated by the immune system. Diagnostic tools for assessment of inhalation exposure to mold are limited and not well validated. Th e only specifi c treatment for fungal-derived disorders is cessation of exposure, which typically requires remediation of the water intrusion or chronic dampness that amplifi es mold growth. Antibiotics are used to treat fungal infections. Evaluation and remediation of indoor mold require expert assistance and oversight.

Journal of Clinical Toxicology, 2015

Objective: Very low birth weight (VLBW) infants frequently receive blood transfusions. We hypothe... more Objective: Very low birth weight (VLBW) infants frequently receive blood transfusions. We hypothesize that toxic metals in donor blood may pose a health risk with potential adverse neurologic effects on the developing brain of a vulnerable VLBW infant. Study design: Samples from 100 donor blood units were collected from a large urban hospital. Blood was analyzed for aluminum, arsenic, beryllium, cadmium, manganese, mercury, nickel, lead and polonium. The estimated upper limit of acceptable metal concentration in donor blood was calculated assuming a transfusion volume of 20 ml/kg and using either previously published acceptable intravenous doses or oral reference doses with a conservative estimate of 10% gastrointestinal absorption. Ingested mercury was assumed to be 95% absorbed. Results: Eight of the nine metals were detectable. Concentrations of arsenic, beryllium, cadmium, mercury and polonium were not of concern for any single blood transfusion. Concentrations of aluminum, manganese, nickel and lead exceeded the estimated upper limit of acceptable concentration in 5, 11, 4 and 26 units respectively. Of the 100 units, 31 had at least one toxic metal concentration high enough to pose a potential health risk. Conclusions: VLBW infants are exposed to heavy metals that are toxic from blood transfusion. The number of units with concerning levels of toxic metals was higher than expected. Neonatologists should be aware of this potential exposure to toxic metals from donor blood when decision is made to administer blood transfusion. Neurodevelopmental studies of toxic metal exposed infants from blood transfusion are warranted.

JAMA: The Journal of the American Medical Association, 1995

Pulmonary Hemorrhage/Hemosiderosis-Continued Hemosiderosis is an uncommon childhood disease chara... more Pulmonary Hemorrhage/Hemosiderosis-Continued Hemosiderosis is an uncommon childhood disease characterized by spontaneous pulmonary hemorrhage often associated with iron deficiency anemia. During January 1993-November 1994, eight cases of acute pulmonary hemorrhage/hemosiderosis were diagnosed among infants at a children's referral hospital in Cleveland. In comparison, during 1983-1993, a total of three cases of pulmonary hemosiderosis were diagnosed among infants and children at this hospital. This report summarizes the preliminary results of the ongoing epidemiologic, clinical, and laboratory investigations by pediatric pulmonologists in Cleveland,

Journal of Pregnancy and Child Health, 2014

Evidence has been accruing to indicate that young children are vulnerable to noise in their physi... more Evidence has been accruing to indicate that young children are vulnerable to noise in their physical environment. A literature review identified that, in addition to hearing loss, noise exposure is associated with negative birth outcomes, reduced cognitive function, inability to concentrate, increased psychosocial activation, nervousness, feeling of helplessness, and increased blood pressure in children. While increasing attention has been given to the health effects of noise in children, research about noise exposure is sparse and often the measure of exposure is simply proximity to a noise source. The U.S. National Children's Study (NCS) provides a unique opportunity to investigate noise exposures to pregnant women and children using a number of assessment modalities at different life stages. Measurement of noise levels in homes and other environments, personal dosimetry measurements made over a period of days, and questionnaires addressing sources of noise in the environment, annoyance to noise, perceived noise level, use of head phones and ear buds, noisy activity exposures, and occupational exposures, are planned for evaluation within the NCS Vanguard pilot study. We describe the NCS planned approach to addressing noise exposure assessment in study visits over a child's lifetime.

New England Journal of Medicine, 1981

Journal of Immunology, May 15, 1987

Pseudomonas aeruginosa and its products have been shown to inhibit mitogen-induced human lymphocy... more Pseudomonas aeruginosa and its products have been shown to inhibit mitogen-induced human lymphocyte blastogenesis as measured by [3H]TdR uptake. The phenazine pigment pyocyanine has been identified as one of the inhibitors present in cellfree culture Supernatants. To determine the mechanism of the inhibitory action of pyocyanine, we studied its effect on the early stages of T cell activation. Pyocyanine inhibited lymphocyte stimulation induced by specific antigens, the lectin concanavalin A and the calcium ionophore, ionomycin, suggesting that its inhibitory effect is not dependent on interference with the T cell antigen receptor complex itself. Using quin-2, we showed that pyocyanine did not interfere with the mitogen-induced increase in cytosolic-free Ca2+. We also showed that pyocyanine did not interfere with the function of calmodulin stimulated Ca2+-Mg2+ ATPase activity, indicating that the mechanism of action of pyocyanine differs from that of the structurally related phenothiazine compounds. Analysis of IL 2 production and IL 2 receptor expression clearly showed that pyocyanine inhibits the production of this essential lymphokine as well as the expression of IL 2 receptors on the T cell membrane. This inhibition is dose dependent and not due to cellular toxicity. There was parallel inhibition of growth in cell volume as well as [3H]TdR uptake. Thus, our results demonstrate that pyocyanine inhibits T cell proliferation by decreasing the production of the critical lymphokine IL 2 and by decreasing the expression of the IL 2 receptor. Local suppression of lymphocyte stimulation by phenazine pigments such as pyocyanine may interfere with cellular immune responses that may be necessary for eradication of chronic infection with P. aeruginosa. Chronic pulmonary infection with Pseudomonas aeruginosa is a major cause of morbidity and mortality

Toxicological Sciences, Jan 19, 2005

Stachybotrys chartarum has been linked to building-related respiratory problems including pulmona... more Stachybotrys chartarum has been linked to building-related respiratory problems including pulmonary hemorrhage in infants. The macrocyclic trichothecenes produced by S. chartarum have been the primary focus of many investigations. However, in addition to trichothecenes this fungus is capable of producing other secondary metabolites and a number of protein factors. This study examines the effects of intact, autoclaved, and ethanol-extracted spores on the lungs of infant rats as an approach to differentiate between secondary metabolites and protein factors. Seven-day-old infant rats were exposed intratracheally to 1 3 10 5 spores/g body weight (toxic strain JS58-17) and sacrificed at various times up to 72 h. The inflammatory response was measured by morphometric analysis of the lungs and determination of inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid. Alveolar space was greatly reduced in animals exposed to fungal spores compared to phosphate buffered saline (PBS)-treated controls. The largest effects were observed in pups treated with intact spores where alveolar space 24 h after treatment was 42.1% compared to 56.8% for autoclaved spores, 51.1% for ethanol-extracted spores, and 60.6% for PBS-treated controls. The effects of different spore preparations on inflammatory cells, cytokine, and protein concentrations in the BAL fluid can be ranked as intact > autoclaved > extracted. Tumor necrosis factor alfa (TNF-a), interleukin 1-beta (IL-1b), and neutrophils were the most sensitive indicators of inflammation. The difference between autoclaved (100% trichothecene toxicity, denatured/enzymatically inactive proteins) and intact (100% trichothecene activity, unaltered/released proteins) spores indicates the involvement of fungal proteins in the inflammatory response to S. chartarum and sheds new light on the clinical importance of ''nontoxic'' strains.

Protein Engineering Design & Selection, 1993

Journal of Natural Products, 1996

An investigation of a cluster of cases of pulmonary hemosiderosis in infants in Cleveland, OH, le... more An investigation of a cluster of cases of pulmonary hemosiderosis in infants in Cleveland, OH, led to the isolation of many isolates of Stachybotrys atra and two isolates of a related toxigenic fungus, Memnoniella echinata. M. echinata produces two cytotoxic trichothecene mycotoxins, trichodermol (1a) and trichodermin (1b), as well as several griseofulvins. Dechlorogriseofulvin (2a) and epidechlorogriseofulvin (2b) were the major compounds isolated. This is the first report of a fungus outside the Penicillium genus producing griseofulvins.

Journal of Occupational and Environmental Medicine, Jun 1, 2004

ABSTRACT Fungal concentrations were measured in the dust of 6 homes in Cleveland, Ohio, where an ... more ABSTRACT Fungal concentrations were measured in the dust of 6 homes in Cleveland, Ohio, where an infant developed pulmonary hemorrhage (pulmonary hemorrhage homes [PHH]) and 26 reference homes (RH) with no known fungal contamination. Quantitative polymerase chain reaction assays for 82 species (or assay groups) were used to identify and quantify fungal concentrations. The ratios of the geometric means of PHH to RH were >1 for 26 species (group I). However, the same ratios were <1 for 10 species (group II). Probit analysis of the sum of the logs of the concentrations of these 2 groups resulted in a 95% probability range for separating PHH from RH homes. The same 82 fungal species were also tested for hemolysin production on sheep's blood agar (incubated at 37 degree C). Hemolysins were more commonly produced by group I species (42%) compared with group II species (10%).

Applied and Environmental Microbiology, Jul 1, 1999

Stachybotrys chartarum is an indoor air, toxigenic fungus that has been associated with a number ... more Stachybotrys chartarum is an indoor air, toxigenic fungus that has been associated with a number of human and veterinary health problems. Most notable among these has been a cluster of idiopathic pulmonary hemorrhage cases that were observed in the Cleveland, Ohio, area. In this study, 16 strains of S. chartarum isolated from case (n ‫؍‬ 8) or control (n ‫؍‬ 8) homes in Cleveland and 12 non-Cleveland strains from diverse geographic locations were analyzed for hemolytic activity, conidial toxicity, and randomly amplified polymorphic DNA banding patterns. In tests for hemolytic activity, strains were grown at 23°C on wet wallboard pieces for an 8-week test period. Conidia from these wallboard pieces were subcultured on sheep's blood agar once a week over this period and examined for growth and clearing of the medium at 37 or 23°C. Five of the Cleveland strains (all from case homes) showed hemolytic activity at 37°C throughout the 8-week test compared to 3 of the non-Cleveland strains. Five of the Cleveland strains, compared to two of the non-Cleveland strains, produced highly toxic conidia (>90 g of T2 toxin equivalents per g [wet weight] of conidia) after 10 and 30 days of growth on wet wallboard. Only 3 of the 28 strains examined both were consistently hemolytic and produced highly toxic conidia. Each of these strains was isolated from a house in Cleveland where an infant had idiopathic pulmonary hemorrhage.

PubMed, Mar 1, 1988

Phosphoinositide content was measured in erythrocyte membranes from 11 patients with cystic fibro... more Phosphoinositide content was measured in erythrocyte membranes from 11 patients with cystic fibrosis (CF) and from 12 control subjects to determine whether altered levels of phosphatidylinositol-4-phosphate (Ptdlns4P) or phosphatidylinositol-4,5-bisphosphate (Ptdlns(4,5)P2) are responsible for the decrease in Ca2+-adenosine triphosphatase (Ca2+-ATPase) activity in this disorder. Isolated membranes were extracted with an acidified chloroform-methanol solvent system. The recovered lipids were separated by one-dimensional thin-layer chromatography and quantified with a colorimetric assay for phosphorus. The results are expressed in molar percent, moles of phosphoinositide times 100 divided by the total number of moles of phospholipid per membrane. The means +/- SEM of Ptdlns(4,5)P2, Ptdlns4P, and phosphatidylinositol (Ptdlns) in CF membranes (1.07 +/- 0.18, 1.02 +/- 0.22, and 2.32 +/- 0.36 molar percent, respectively) were indistinguishable from controls (0.91 +/- 0.14, 0.85 +/- 0.12, and 2.21 +/- 0.32 molar percent, respectively) (P greater than 0.20 for all three pairs). The accuracy of quantitative recovery throughout the procedure was determined by adding a radioactive internal standard, L-3-phosphatidyl[2-3H]inositol to 10 membrane preparations. Although quantitative recoveries, as determined by percent radioactivity recovered, varied from 54% to 92%, mean Ptdlns(4,5)P2, Ptdlns4P, and Ptdlns levels appropriately corrected from tracer loss were still indistinguishable between the two groups. We conclude that absolute phosphoinositide levels are not altered in cystic fibrosis erythrocyte membranes and that the differences in Ca2+-ATPase activity cannot be explained on this basis.

Biochemistry, Jun 1, 1984

The rates of hydrolysis of N-[(alpha-L-rhamnopyranosyloxy)phospho]-L-leucyl-L-tryptophan (phospho... more The rates of hydrolysis of N-[(alpha-L-rhamnopyranosyloxy)phospho]-L-leucyl-L-tryptophan (phosphoramidon), N alpha-phosphoryl-L-leucyl-L-tryptophan (PO3LeuTrp), N alpha-phosphoryl-L-leucyl-L-phenylalanine (PO3LeuPhe), and N alpha-phosphoryl-L-leucyl-L-phenylalaninamide (PO3LeuPheNH2) were followed by proton nuclear magnetic resonance spectroscopy. The rates of hydrolysis (kobsd) of PO3LeuTrp, PO3LeuPhe, and PO3LeuPheNH2 were all first order in phosphorylamide concentration over the pH range studied (3.8-9.5). The values for kobsd at pH 7.3 and 37 degrees C are as follows: PO3LeuTrp, 0.35 h-1; PO3LeuPhe, 0.63 h-1; PO3LeuPheNH2, 0.73 h-1. The values for kobsd do not significantly change between pH 5 and pH 8 but dramatically decreased with increasing pH. The hydrolysis of PO3LeuPhe and PO3LeuPheNH2 above a pH of approximately 5 was positively correlated with the concentration of monoanionic species (NHRPO3H)1-, and the values for the first-order rate constants for the respective monoanionic species were calculated to be 0.66 +/- 0.03 h-1 and 1.07 +/- 0.10 h-1. Phosphoramidon was not found to hydrolyze after 6 days at 37 degrees C at a pH of 4.6 and 7.7, while the phosphorylamide PO3LeuTrp, synthesized by the removal of L-rhamnose from phosphoramidon by base hydrolysis, was found to rapidly hydrolyze under these conditions. Solvolysis in aqueous methanol of PO3LeuPhe and PO3LeuPheNH2 indicates that the hydrolysis reaction is bimolecular, proceeding by way of direct attack of solvent (H2O, CH3OH) on phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal of Biological Chemistry, Mar 1, 1982

Portions of this paper (including "Experimental Procedures," "Results," Figs. 1-7, and Tables 1-1... more Portions of this paper (including "Experimental Procedures," "Results," Figs. 1-7, and Tables 1-111) are presented in miniprint as prepared by the authors. Miniprint is easily read with the aid of a standard magnifying glass. Full size photocopies are available from the Journal of Biological Chemistry, 9650 RockviUe Pike, Bethesda, MD 20814. Request Document No. 81M-1479, cite authors, and include a check or money order for $11.60 per set of photocopies. Full size photocopies are also included in the microfilm edition of the Journal that is available from Waverly Press.

Advances in Applied Microbiology, 2004

Publisher Summary Stachybotrys chartarum is one of the several environmental fungi that can produ... more Publisher Summary Stachybotrys chartarum is one of the several environmental fungi that can produce very potent toxic compounds. Animal models provide physicians and environmental scientists with useful tools for assessing risks associated with the respiratory effects of air pollutants. The animal studies to date support the view that pulmonary exposure to the spores of S. chartarum leads to hemorrhagic inflammation and impairment of growth. This has been demonstrated by increases in bronchoalveolar lavage (BAL) fluid of inflammatory cells, proinflammatory mediators, hemoglobin, and proteins along with changes in pulmonary surfactant. Although the earlier experiments were conducted with relatively high doses, recent findings indicate that lower doses, which appear to be closer to the concentrations encountered in indoor air, can elicit similar symptoms. The results of animal studies based on different experimental designs are difficult to compare because of many variables—including spore toxicity, viability, and content of fungal proteins in addition to species, strains, age of animals, and route of administration.

Journal of Biological Chemistry, Feb 1, 1983

A peptide from sperm whale myoglobin, residues 132-153, and a chromogenic substrate, H-D-valyl-L-... more A peptide from sperm whale myoglobin, residues 132-153, and a chromogenic substrate, H-D-valyl-L-leucyl-L-lysyl-p-nitroanilide diacetate, were selected to investigate the susceptibility of peptide bonds adjacent to N',iVdimethyllysyl residues to tryptic hydrolysis. The peptides were exhaustively methylated using formaldehyde and sodium cyanoborohydride (N. J e n t o f t and D. G. Dearborn (1979) J. Biol. Chem. 254, 4359-4365). Unmodified and methylated peptides were digested with trypsin or submaxillary protease, an enzyme that catalyzes the hydrolysis of only arginyl bonds in proteins. Trypsin catalyzed the hydrolysis of the methylated apomyoglobin peptide only at the single arginyl residue and not at any of the four W,N-dimethyllysyl residues. Trypsin also failed to catalyze the hydrolysis of reductively methylated H-D-valyl-L-leucyl-L-lysyl-pnitroanilide. Even a 17-fold molar excess of the methylated substrate did not appear to alter the rate of tryptic hydrolysis of the unmodified substrate. These results are discussed with regard to the interactions of substrates within the specificity site of trypsin.