Neuronal Effects of
Microbial Toxins
Health Effects, Pathology, Epidemiology
Ecology, Detection and Identification Problems of Moulds in Indoor
Environments
Occupational Exposure to Molds, Diseases and Diagnosis
Indoor Moulds:
a Public Health Problem in Belgium
Pilot Analysis of the Immune Response to Fungal Antigens in Subjects Working
in Humidity Damaged Houses
Can Microbial Volatile Metabolites Cause Irritation at Indoor Air
Concentrations?
Growth Conditions of Streptomyces Anulatus Regulate Induced Inflammatory
Responses and Cyto Toxicity in Macrophages
Clinical Findings Related to Indoor Fungal Exposure - Review of Clinic Data
of a Specialty Clinic
Pulmonary Hemorrhage Among Infants with Exposure to Toxigenic Molds
IAQ and
Human Toxicosis: Empirical Evidence and Theory
Cognitive Impairment Associated with Exposure to Toxigenic Fungi
Symptoms Associated to Work in a Water Damaged School Building
Sensory Irritation of Microbially Produced Volatile Organic Compounds in
Mice During Repeated Exposures
Immunological Biomonitoring in the Assessment of Exposure to Airborne Fungi
from Waste Handling
Chronic Toxic Encephalopathies Apparently Related to Exposure to Toxigenic
Fungi
Building-Related Illness in Occupants of Mold-Contaminated Houses
Diagnosing the Cause of a "Sick Building:" a Case Study of an
Epidemiological and Microbiological Investigation
Fungal Exposure and IGg-levels of Occupants in Houses with and without Mold
Problems
The
Immunopathology of Hypersensitivity Reactions
Exposure to Stachybotrys Chartarum Induces Immunoglobulin a Antibody
Response in Man
Sensitization to Molds and Respiratory Symptoms in School Children
Mycotoxin
Cytotoxicity Screening of Field Samples
The Effect-Inhaled Spores of Mycotoxin Producin Fungi on Animals
Trichothecenes as
a Potent Inducer of Apoptosis
Analysis for Stachybotrys
Toxins
Assessing
Bioaerosols in Elementary School Classrooms
Anatomy of a Fungal Problem
Prevalence of Fungi
in Carpet Dust Samples
Detection and Decontamination of a Facility Contaminated with Fungi
Including Stachybotrys chartarum
Airborne Concentrations of Trichoderma and Stachybotrys linked to
Mycotoxicosis
Exposure Measures for Studies of Mold and Dampness and Respiratory Health
Fungal Growth in Buildings: The Aerobiological Perspective
Why
are there Still Problems with Fungal Allergen Extracts?
Comparative studies of fungal media for the recovery of Stachybotrys
Chartarum from Environmental Samples
Heteroduplex DNA Fingerprinting of Penicillium Brevicompactum from House
Dust
The Trichodiene Synthase Gene from Stachybotrys Chartarum : A Potential
Diagnostic Indicator of Indoor Contamination
Microscopic Fungi and Metabolites in Dwellings-a Bioassay Study
Moisture, Mold and
Health in Apartment Homes
Toxigenic Microbes in Indoor Environment: Identification, Structure and
Biological Effects of the Aerosolizing Toxins
Evaluation of
Exposure to Environmental Bacteria
Cellular and Humoral Responses in an Animal Model Inhaling Penicillium
Chrysogenum Spores
Sporulation of the Hyphomycete Stachybotrys chartarum Under Three Light
Conditions
Mycotoxin Spectra as a Biochemical Parameter for Occupational and
Environmental Fungus Exposure
Membrane Toxic Substances in Water-damaged Construction Materials and Fungal
Pure Cultures
Different
Methods to Characterize Moldy Buildings
Comparative Studies of Collection Efficiency of Airborne Fungal using
Andersen Single-Stage Sampler and Air-O-Cell Cassettes
Trichothecene Mycotoxins in Some Water-Damaged Buildings
Immunochemical Detection of Mycotoxins Associated with Stachybotryotoxicosis
Mitigation of Visible Fungal Contamination in Buildings: Experience From
1993 - 1998
Microbes and Moisture Content of Materials from Damaged Building
Concentrations of Viable Spores of Fungi and Actinomycetes in Ventilation
Channels
Air
Quality Restoration in a Fungal Contaminated Building
Sampling,
Results & Remediation in 300 "Sick Houses"
Identifying and Preventing Fungal Contamination Problems in New Home
Construction
A Toxic Mold Cleanup Guide
Molds as an
Environmental Factor in Infant Leukemia?
Mechanisms of Adverse Health Effects of Moldy House Microbes: in vitro and
in vivo studies on toxic effects and inflammatory responses.
Exposure to Bioaerosols
Schools, Mould
and Health - An Intervention Study
Development of Methods to Monitor the Success of Repair Measures
Neurotoxic Effects of
Microbial Toxins
The Biological Activities of the Metabolites of Microbes Present in the
Indoor Air
Environment, Decision-Making and Well-Being - Insecurity, Uncertainty and
Crisis of Expertise
Radonsafe Foundation, Moisture Prevention and Air Exchange in a Healthy
Building
Adsorption, Desorption, and Chemical Reactions in the Particulate Matter
Collected on Air Filters and Ducts
Fungal Allergens and Antigens - Their Characterization and Biological
Effects in Mice after Inhalation Exposure
Indoor Air Quality Control
Mold and Moisture Transfer in Building Structures and Buildings with
Particular Regard to the Prevention of Health Hazards
Stachybotrys Induced Hemorrhage in the Developing Lung
Date study started January, 1999; Date Study Completed January, 2004
Recruitment status verified February, 2001 This study is currently
recruiting patients. Sponsored by National Institute of Environmental Health
Sciences (NIEHS)
Purpose: The majority of the workscope of this project is focused on an
infant animal model of toxigenic mold induced pulmonary hemorrhage.
Clinically related studies are directed only to the description of human
infants diagnosed with idiopathic pulmonary hemorrhage regarding their
clinical parameters, and collecting samples of secretion, blood, and urine
for analysis for fungal spores and mycotoxins. These latter analyses are
being developed using the infant rat model.
Condition: Idiopathic Pulmonary Hemorrhage
Further Study Details:
Over the past seven years in the Cleveland, Ohio area there have been 47
cases of unexplained pulmonary hemorrhage in young infants. Sixteen of the
infants have died. A CDC case-control study found an association with
water-damaged homes and the toxigenic fungus, Stachybotrys chartarum, which
requires water soaked cellulose to grow. The spores of this fungus are not
infectious in the lung but do contain very potent mycotoxins which appear to
be particularly toxic to the rapidly developing lungs of young infants.
Secondary stresses, e.g. environmental tobacco smoke, appear to be important
triggers of overt hemorrhage. Concern that there may be a larger number of
undetected young infants with this disorder led to the examination of all
infant coroner cases, which revealed six sudden infant death syndrome cases
with major amounts of pulmonary hemosiderin-laden macrophages, indicating
extensive hemosiderosis existing prior to death. All of these infants had
lived in the eight zip code area where all but fifteen of the patients have
lived. This disorder may extend beyond Cleveland since toxigenic fungi are
widespread. We are aware of a total of 138 infants with idiopathic pulmonary
hemorrhage across the country over the past four years. The purpose of this
proposal is to establish an infant animal model for this
stachybotryomycotoxicosis which can be used to understand the developmental
pathophysiology by which the fungal spores induce hemorrhage and to address
practical problems faced in the clinical care of these infants and in public
health prevention. The model uses tracheal instillation of toxic
Stachybotrys spores in neonatal to weanling rats to initiate the
pathological process, followed by stresses to trigger acute hemorrhage.
Capillary fragility to transmural pressures will be assessed by morphometric
analysis of electron micrographs. Markers of Stachybotrys exposure which can
be applied to clinical cases are being developed and tested in the rats.
Dorr G Dearborn, MD,PhD, dxd9@po.cwru.edu
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The
Immunopathology of Hypersensitivity Reactions
Vincent A. Marinkovich, M.D. Clinical Associate Professor, Stanford
Medical School, Redwood City, CA
Abstract
Overactivity of the immune system, either allergy (IgE) or hypersensitivity
(non-IgE) is responsible for more illness than is generally appreciated,
even by the medical profession. The least understood are the non-IgE
mechanisms which involve either immune complex formation (type III of Gell
and Combs) or direct killer T-cell involvement (type IV). Type III reactions
may be localized with a large deposition of antigen at a focal point where
immune complexes are formed and tissue damage ensues including necrosis.
This is termed the Arthus reaction. A systemic dissemination of antigens
will provoke a systemic inflammatory reaction which is most closely modeled
by the well studied acute and chronic serum sickness reaction. Serum
sickness was identified as the constellation of symptoms which followed the
administration of antitoxins (antiserum given for infectious disease before
the advent of antibiotics) which were derived from non-human sources, most
often horses. Chronic serum sickness was observed when otherwise healthy
subjects were given repeat doses of antiserum experimentally over relatively
short periods of time. The symptoms observed in spontaneous and experimental
serum sickness included fatigue, rash, cognitive changes, myositis,
arthritis, headache, weight-loss, cardiovascular symptoms etc., which are
often seen during heavy chronic exposure to fungal spores. The dynamic
nature of circulating immune complexes, their complexity, their rapidly
changing equilibrium patterns and their pathogenicity must be appreciated
before the clinician can properly interpret the patterns of illness his
patients describe. The best simple test identifying and thereby allowing the
avoidance of serum sickness is a specific IgE test to a panel of high
exposure antigens including fungi, food and occupational antigens.
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Hypersensitivity Pneumonitis from Toxic Mold Exposure
Fungal Spores: Hazardous to Health? W.G. Sorenson
National Institute for Occupational Safety and Health, Morgantown, West
Virginia USA
Fungi have long been known to affect human well being in various ways,
including disease of essential crop plants, decay of stored foods with
possible concomitant production of mycotoxins, superficial and systemic
infection of human tissues, and disease associated with immune stimulation
such as hypersensitivity pneumonitis and toxic pneumonitis. The spores of a
large number of important fungi are less than 5 µm aerodynamic diameter, and
therefore are able to enter the lungs. They also may contain significant
amounts of mycotoxins. Diseases associated with inhalation of fungal spores
include toxic pneumonitis, hypersensitivity pneumonitis, tremors, chronic
fatigue syndrome, kidney failure, and cancer. Key words: mold, fungi,
mycotoxin, lung disease, toxic pneumonitis. -- Environ Health
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Cognitive Impairment Associated with Exposure to Toxigenic Fungi
Wayne A. Gordon, Ph.D., Eckardt Johanning, M.D.,M.Sc. Lisa Haddad, B.A.
Professor, Department of Rehabilitation Medicine, Mount Sinai School of
Medicine; Eckardt Johanning, M.D., Adjunct Instructor, Department of
Community Medicine, Mount Sinai School of Medicine; Lisa Haddad, B.A.,
Research Assistant, Department of Rehabilitation Medicine, Mount Sinai
School of Medicine; Research performed at Mount Sinai School of Medicine,
Correspondence: Wayne A Gordon Ph.D., Department of Rehabilitation Medicine,
Mount Sinai School of Medicine
The objective of the study was to examine whether cognitive impairment was
associated with exposure to Stachybotrys atra. 20 individuals were examined
using a standard neuropsychological battery and a symptom checklist. Results
indicate that all individuals seen meet at least 1 of the criteria for a
cognitive impairment, with 13 of the 20 (65%) meeting at least 3 of the
criteria for cognitive impairment. Preliminary findings suggest that
exposure to toxigenic molds are associated with cognitive impairment,
specifically deficits in verbal memory, verbal learning,
attention/concentration and set shifting. In addition to these cognitive
deficits, the sample reported a high number of cognitive, physical and
behavioral symptoms. Validation on a larger sample of individuals is
indicated.
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Prevention
and Treatment of Skin Lesion of T-2 Toxin
Author: Dr. A. Khaboshany, Dr. A. Omidi, Dr. S.M. Morsali
Institution: Medical Science University, Mashhad
Trichothesin mycotoxins are a group of fungal metabolites which are produced
by the same species of fusarium. These compounds have a common structure and
depending on various substitutions on the ring, different toxins with
special function are produced. These toxins cause many cellular damages in
contaminated men and animals. These damages will appear in animal organs
which have grown faster. For example, most damages will cause to bone
marrow, skin and digestive tract cells. These toxins react with - SH group
of enzyme. For example, peptidy transpheras, which have a role important in
the synthesis of cellular proteins and inhibited action of the enzymes. In
this investigation, we chose compounds for prevention and treatment which
react with toxins and compete in their reaction with - SH group of enzymes.
Thiol compounds were the best and from these four Thiol compounds, N-
Acetylcysteine, sodium hyposulfatl, cysteine hydrochloride and menthionine
were chosen and their effects in prevention and treatment. Application of
NAC pomad to the contaminated position after 30 min., decreased 50-70
percent of lesions. Also, application of pomad after 60 min., decreased
40-60 percent of lesions.
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Building-Related Illness in Occupants of Mold-Contaminated Houses
Toxic Mold Exposure- Case Study Investigation
James Craner, M.D., M.P.H. Consultant in Occupational & Environmental
Medicine, Verdi, Nevada, Assistant Clinical Professor, Department of
Medicine, Division of Occupational Medicine, University of California, San
Francisco School of Medicine, Address for correspondence: P.O. Box 1161,
Verdi, NV 89439
The clinical presentation and course of individuals and families who
developed illnesses related to non-infectious fungal exposures inside their
homes is described. Occupants developed their illnesses shortly after their
homes had been water damaged. A few occupants had a specific
building-related illness, such as hypersensitivity pneumonitis or asthma
exacerbation, but most had a "sick building syndrome" symptom complex
involving irritation/inflammation of the mucous membranes, respiratory
tract, and skin; fatigue; and/or neurocognitive dysfunction. All cases
required months or years to correctly diagnose. Air, surface, and/or bulk
microbiological sampling in most of the homes yielded high concentrations of
toxigenic fungi, including Stachybotrys chartarum and Penicillium and
Aspergillus species, emanating from water-damaged building materials. Most
of the ill individuals had complete clinical improvement shortly after their
removal from the contaminated indoor environment, but a few individuals
continued to experience symptoms in response to a variety of environmental
irritants. The author proposes a new clinical syndrome entity to describe
the non-infectious, mold-related, building-related illness.
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Diagnosing the Cause
of a "Sick Building:"
Case Study of an Epidemiological and Microbiological Investigation
James Craner, M.D., M.P.H., Linda d. Stetzenbach, Ph.D. Consultant in
Occupational & Environmental Medicine, Verdi, Nevada Director, Department of
Microbiology, Harry Reid Center for Environmental Studies, University of
Nevada-Las Vegas, Las Vegas, Nevada
This report describes the methods and outcome of a physician-led
investigation of occupants' prolonged, unexplained illnesses associated with
working inside a large, modern office building. Occupants (cases) complained
of building-related symptoms including eye, nose, and throat mucous membrane
irritation; rashes; respiratory symptoms; profound, unexplained fatigue; and
neurocognitive symptoms, including difficulty concentrating and short-term
memory impairment. No functional ventilation problems or chemical
contamination were detected in a walk-through evaluation and basic air
quality testing. An epidemiological survey of the building's 700 occupants
was then conducted. With 86% of the occupants responding to the survey,
there was an average case prevalence of health-related complaints of nearly
25%, evenly distributed among floors. Cases were geographically distributed
in a pattern which coincided with the location of the ceiling-mounted
variable air volume (VAV) boxes which distributed ventilated air to the
occupied spaces. Re-inspection revealed previously undetected, focal
water-staining of 40% of ceiling tiles located underneath the VAV boxes
throughout the building. Active growth of Stachybotrys chartarum (atra) and
other fungi was detected on many of the damaged tiles. All water-damaged
tiles were replaced and VAV hot water valves were tightened. Occupants
reported significant improvement of symptoms within weeks after these
changes.
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Effects of Mycotoxins on Human Immune Functions in Vitro
Berek L, Petri IB, Mesterhazy A A, Teren J, Molnar J.
Immunosuppressive and carcinogenic Fusarium mycotoxins may appear in
domestic food products. Therefore, the immunological effects of Fusarium
mycotoxins were tested on human peripheral blood mononuclear cells from
different blood donors. In the present study we investigated deoxynivalenol
(DON), 3-acetyldeoxynivalenol, fusarenon-X, T-2 toxin, zearalenone,
alpha-zearalenol, beta-zearalenol and nivalenol for their effects on T and B
cells in a proliferation assay, antibody-dependent cellular cytotoxicity
(ADCC) and natural killer (NK) cell activity on human peripheral blood
mononuclear cells. The concentrations applied in our experiments were
similar to those which can be found in normal human peripheral blood system
(0.2-1800 ng/ml). Among the eight mycotoxins tested, T-2 toxin, fusarenon X,
nivalenol and deoxynivalenol exerted the highest immunosuppressing effect on
human peripheral blood mononuclear cells in vitro. Mycotoxin-induced
immunosupression was manifested as depressed T or B lymphocyte activity.
Furthermore, by virtue of inhibition of NK cell activity, the protection
against tumor development may also be attenuated.
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Agonistic and Antagonistic effects of Zearalenone, an Etrogenic Mycotoxin,
Human Cancer Cell lines
Withanage GS, Murata H, Koyama T, Ishiwata I.
Zearalenone (ZEA) is a nonsteroidal estrogenic compound mainly produced by
the molds Fusarium graminearium and Fusarium culmorum found in a variety of
host plants and soil debris around the world. ZEA is usualy non-lethal to
animals but is important to livestock producers because its hyperestrogenic
effects adversely influence the reproductive performance of animals. There
have been suggestions of possible involvement of ZEA in the progression of
breast malignancies and tumors of the female reproductive tract in humans.
The toxic or stimulatory effects of ZEA and its metabolites alpha-zearalenol
and 17-beta-estradiol on SKN, HHUAand HepG2 cells were studied using rapid
colorimetric MTT assay. In general, both concentrations of 17-beta-estradiol
(100M and 10 nM) were toxic to SKN and HHUA cell cultures. Both ZEA and
alpha-zearalenol stimulated the proliferation of SKN and HHUA cells. On
HepG2 cells, lower concentrations (10 nM) of 17-beta-estradiol and higher
concentrations (100 microM) of ZEA exhibited toxic effects, whereas
treatment with higher concentrations of 17-beta-estradiol and lower
concentration of ZEA did not show toxic effects. A dose dependent
antagonistic effect was observed when the cell cultures were pre-incubated
with ICI 182,780, a synthetic estrogen receptor blocker, before estradiol or
mycotoxin treatments.
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Trichothecenes
This Page is part of the CU Toxic Plant Pages and was constructed by
Yuan-Kuo Chen.
Trichothecenes are produced by several common molds including species in the
genera Acremonium (Cephalosporium), Cylindrocarpon, Dendrodochium,
Myrothecium, Trichoderma, Trichothecium, and most numerously in Fusarium.
Trichothecenes are composed of a tetracyclic sesquiterpene skeleton
containing a six-membered oxane ring, a stable epoxide group in positions 12
and 13 and a 9,10 olefinic bond. They have been classified into four groups.
Fusarium spp. contain several well known trichothecenes including two highly
toxic members of group A, diacetoxyscirpenol (DAS) and T-2 toxin, and toxins
in group B including deoxynivalenol (DON) and nivalenol. DON is the most
common but least toxic of these. Trichothecenes are strong inhibitors of
protein synthesis in mammalian cells. However, DOM received its common name,
vomitoxin, from the vomiting that generally accompanies trichothecene
poisoning. (D'Mello, et.al., 1991)
DON resulted in feed refusal in swine. In lambs, consumption of a wheat diet
containing DON at 15.6 mg/kg of BW for 28 d did not alter feed consumption,
weight gain, or feed efficiency. Oral administration of DON showed that it
was rapidly passed essentially unchanged (95%) and excreted primarily in
urine. Incubation of DON with ruminal microorganisms in vitro for 48 h
resulted in partial conversion to deepoxy DON. These results indicate that
the impact of DON on ruminants is lower than initially suspected. DON caused
no organ damages to animals. Extremely low amounts of DON(<4ng/ml) were
transmitted to milk after a single oral dose of 920 mg to a dairy cow.
(Diekman and Green, 1992)
The FDA issued an "advisory" to federal and state officials recommending a
level of concern for DON of 2 micrograms of DON/ gm for wheat entering the
milling process, 1 microgram/ gm in finished wheat products for human
consumption, and 4 microgram/ gm for wheat and wheat milling by-products
used in animal feed. (Wood, 1992)
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Toxigenic Fungi: Which
are Important?
Pitt JI.
Growth of commonly occurring filamentous fungi in foods may result in
production of mycotoxins, which can cause a variety of ill effects in
humans, from allergic responses to immunosuppression and cancer. According
to experts, five kinds of mycotoxins are important in human health around
the world: aflatoxins, ochratoxin A, fumonisins, certain trichothecenes, and
zearalenone. These toxins are produced by only a few species of fungi, in a
limited range of commodities. Aflatoxins are potent carcinogens, produced by
Aspergillus flavus and A. parasiticus in peanuts, maize and some other nuts
and oilseeds. Ochratoxin A is a kidney toxin and probable carcinogen. It is
produced by Penicillium verrucosum in cereal grains in cold climates, by A.
carbonarius in grapes, wines and vine fruits, and by A. ochraceus sometimes
in coffee beans. Fumonisins, which may cause oesophageal cancer, are formed
by Fusarium moniliforme and F. proliferatum, but only in maize.
Trichothecenes are highly immunosuppressive and zearalenone causes
oestrogenic effects; both are produced by F. graminearum and related
species. Current reporting probably underestimates the effect of mycotoxins
as a cause of human mortality.
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Toxigenic Fungi and Mycotoxins
Pitt JI.
Growth of commonly occurring filamentous fungi in foods may result in
production of toxins known as mycotoxins, which can cause a variety of ill
effects in humans, from allergic responses to immunosuppression and cancer.
The most important mycotoxins are aflatoxins, ochratoxin A, fumonisins,
trichothecenes and zearalenone. Aflatoxins are potent carcinogens and, in
association with hepatitis B virus, are responsible for many thousands of
human deaths per annum, mostly in non-industrialised tropical countries.
Ochratoxin A is a probable carcinogen, and may cause urinary tract cancer
and kidney damage in people from northern and eastern Europe. Fumonisins
appear to be the cause of oesophageal cancer in southern Africa, parts of
China and elsewhere. Trichothecenes are highly immunosuppressive and
zearalenone causes oestrogenic effects in animals and man. Currently
available records and statistics do not reflect the major role played by
mycotoxins in mortality attributable to food-borne micro-organisms.
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Exposure Biomarkers in Chemoprevention Studies of Liver Cancer
Wild CP, Turner PC.
Molecular Epidemiology Unit, Epidemiology and Health Services Research,
School of Medicine, University of Leeds, UK.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, the
major risk factors being hepatitis B and C viruses and aflatoxins; other
factors such as alcohol are also of importance in some populations.
Aflatoxin exposure biomarkers include urinary aflatoxin metabolites and
aflatoxin-albumin adducts in peripheral blood. These biomarkers are well
validated and have been applied in studies of many populations worldwide.
They are proving to be valuable end-points in intervention studies,
including chemoprevention studies. The biomarkers permit assessment of
primary prevention measures to reduce aflatoxin intake. In addition, the
determination of individual urinary aflatoxin metabolite profiles means that
the effectiveness of chemopreventive agents designed to modulate aflatoxin
metabolism can also be evaluated. Both aflatoxin-albumin adducts and urinary
aflatoxin metabolites have been associated with increased HCC risk in
prospective studies, indicating the predictive value of these biomarkers at
the group level. However, given the multifactorial and multistep nature of
HCC, it is unlikely that these exposure biomarkers will be predictive at the
individual level or be of value as surrogate end-points in longer-term
intervention trials aimed at reducing disease incidence. Aflatoxin-related
mutations at codon 249 of the p53 gene in plasma may be more relevant in
this regard but their application requires further understanding of the
temporal appearance of this biomarker in relation to the natural history of
the disease.
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Mechanisms of
Aflatoxin B1 Lung Tumorigenesis
Massey TE, Smith GB, Tam AS.
Department of Pharmacology and Toxicology, Queen's University, Kingston,
Ontario, Canada. masseyt@post.queensu.ca
Although aflatoxin B1 (AFB1) is best known as a hepatocarcinogen, the
respiratory system can also be a target of this mycotoxin. In isolated lung
cells from rabbits and mice, AFB1 is bioactivated by cytochromes P450,
primarily in nonciliated bronchiolar epithelial (Clara) cells. However,
mutagenesis experiments suggest that the DNA-binding AFB1 epoxide metabolite
can leave the cells of origin, and potentially interact with other cell
types. Consistent with DNA adduct studies, AFB1-induced AC3F1 mouse lung
tumors contain point mutations at guanine residues in K-ras, with the
anticipated bias for the A/J allele. Furthermore, following AFB1 treatment
but prior to tumor development, K-ras mutations occur preferentially in
mouse Clara cells. However, in contrast to findings with other carcinogens,
AFB1-induced mouse lung tumors demonstrate frequent, but heterogeneously
distributed, overexpression of p53 protein as well as p53 point mutations,
suggesting a carcinogen-specific response. Unlike lung tissue from mice and
rabbits, human peripheral lung bioactivates AFB1 primarily by prostaglandin
H synthase--and/or lipoxygenase-catalyzed cooxidation, with activity
concentrated in macrophages. In addition, although glutathione S-transferase
M1-1 has high specific activity for AFB1 epoxide conjugation, lung tissues
from GSTM1-null individuals do not demonstrate diminished rates of
conjugation, compared to tissues from GSTM1-positive individuals. In
summary, AFB1 tumorigenesis in mice demonstrates unique properties, and
processes of bioactivation show significant species differences.
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Relationship
Between Lung Cancer and Aflatoxin B1
Georggiett OC, Muino JC, Montrull H, Brizuela N, Avalos S, Gomez RM.
Catedra de Cirugia II-UA Cirugia H. Misericordia Fac. Cs. Medicas U.N.C.
The relationship between aflatoxins and liver cancer is well established. In
addition the inhalation exposure to carcinogen aflatoxin B1 (AFB 1) is
considerable. Genotoxic chemical is known to react with DNA either directly
or after metabolic activation to form adducts, a step thought to be relevant
with respect to chemical carcinogenesis. The presence and the amount of
specific DNA adducts provide a good indication of chemical exposure and
genetic damage resulting the exposure to carcinogens and account for same of
factors affecting individual susceptibility to cancer. Analysis of DNA
adducts requires that the sensitivity of the methods to be sufficient high
to allow detection of about 1 adduct/109 normal nucleotides. Most suitable
method is based in physiochemical technique such as HPLC. Because
circumstantial epidemiological evidence suggests that AFB1 inhalation may
cause primary lung cancer. We investigate AFB1 by HPLC in three different
tobacco sources, and in 39 patients with compatible lung cancer or chronic
bronchitis. The patients were divided by clinical manifestations in lung
cancer (n: 25) and chronic bronchitis (n: 14). Twenty-three of 25 patients
presented epidermoid lung cancer within smoking habit, and 2 of 25 presented
adenocarcinoma without smoking habit. In chronic bronchitis group 12 of 14
cases presented smoking habit. The control PBS liquid was negative to AFB1;
the different tobacco sources, a) Virginia of Jujuy, b) Brasilero and c)
black of Salta presented AFB1 positive determinations respectively. The
bronchial tissues obtained by lung biopsies presented positive AFB1 in lung
epidermoid cancer at 0.68 +/- 0.82 mg/L. The adenocarcinoma presented AFB1
negative determinations. In chronic bronchitis patients with smoking habit
(n: 12) presented AFB1 positive with a level less than the epidermoid lung
cancer group, 0.21 +/- 0.109 mg/L, p < .025.
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Neuronal Effects of
Microbial Toxins
Project leader Kai Savolainen, Department of Industrial Hygiene and
Toxicology
Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland Researchers H. Stockmann
Completed by May 2002
Collaborating parties Finnish Research Programme on Environmental Health,
Kuopio University
Objectives: Fungal growth in moisture problem houses often leads to exposure
to microbes which produce microbial toxins. Besides the typical respiratory
tract disorders, recent findings suggest that microbial toxins may cause
serious effects in the central nervous system of animals and man. The
objective of the study is to try to explore the mechanisms whereby the
toxins affect neuronal cells.
Subjects: Neuroblastoma and glioblastoma cells.
Methods: Studying the effects of microbial toxins on oxidarive stress,
transcription factors and cell viability (necrosis and apoptosis).
Fluorescent probes and different gel separation methods.
Effect of Individual Metabolic Characteristics on Genotoxicity
Project leader Hannu Norppa, Department of Industrial Hygiene and Toxicology
Helsinki, Finland. Researchers S. Bernardini, G. Falck, A. Hirvonen, H.
Järventaus, J. Tuimala
Completed by Dec. 2005
Objectives: The goal of the project is to clarify the influence of metabolic
polymorphisms on the genotoxicity of chemicals in humans.
Materials: The importance of genetic polymorphisms is studied among smokers,
foundry workers, bus drivers exposed to vehicle exhaust and nuclear power
plant employees, and also among control persons. In addition, the genotoxic
metabolites of some industrial chemicals are examined in lymphocyte cultures
of donors representing different genotypes.
Methods: The genotoxicological methods applied include cytogenetic analyses
from peripheral lymphocytes. Genotype determinations are carried out by
means of techniques based on polymerase chain reaction.
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Health Effects, Pathology, Epidemiology
Effects after Mold Exposure – Which are the Causative Agents?
Ragnar Rylander, M.D. e-mail: ragnar.rylander@envmed.gu.se
This presentation reviews the most well known specific agents in molds and
their relation to the different effects caused by exposure to molds. It is
emphasized that field studies in principle only describe relationships and
that such relationships not always support conclusions regarding causality
for individual agents. At present, the general strategy to prevent the
mold-related diseases airways inflammation, increased risk for infections,
hypersensitivity pneumonitis and neurological disorders must therefore be to
remove the mold contamination, viable as well as dead organisms.
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Ecology, Detection and Identification Problems of Moulds in Indoor
Environments
Robert A. SAMSON Ph.D.
Centraalbureau voor Schimmelcultures, The Netherlands, e-mail:
samson@cbs.knaw.nl
For many people working in the building industry or those who are consulting
for indoor problems, identification of moulds does not seem a problem. In
their opinion mould applying disinfectants or antifungal paints can easily
solve problems. Furthermore, it is often recommended to modify the
construction and adding ventilation with the result that the conditions for
fungal growth can be reduced. However, if we like to know the cause and the
degree of biodeterioration, in particular when health implications are
involved, it is important to know which organisms are causing the problem.
This is particularly true for species of Stachybotrys, Penicillium,
Aspergillus and Fusarium.
Identification of mould isolates or specimens is problematic for the
inexperienced researcher. This is partly due to the fact that the methods
for identification are still based on the phenotypical characters of the
moulds, which requires many skills in microscopical observations. In
addition the mould flora of indoor environments consists of some problematic
genera such as Penicillium, Aspergillus and Fusarium of which there is no
general taxonomic consensus. Even experienced mycologists might reach
different conclusions hence different names for an isolate.
Several surveys of moulds in indoor environments have revealed that we are
dealing with a known and relatively low number of species. To detect these
relevant species it is, however, essential to apply the appropriate methods.
This paper is focused on the ecology and taxonomic problems of indoor moulds
also related to methods of detection.
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Occupational Exposure to Molds, Diseases and Diagnosis
Kari Reijula, M.D., Ph.D.
Director, Indoor Air & Environment Program; Finnish Institute of
Occupational Health; Finnish institute of Occupational Health, email:
krei@occuphealth.fi
Exposure to molds has become a significant health risk to an increasing
number of workers in various occupations throughout the nations. Fungal
antigens are able to cause occupational asthma, rhinoconjunctivitis,
hypersensitivity pneumonitis and organic dust toxic syndrome (ODTS) for
instance among farmers, construction workers, housekeeping personnel as well
as factory and sawmill workers who have to handle moldy and contaminated
materials. In recent years, an increasing incidence of mold-induced diseases
has been encountered in moldy contaminated water-damaged buildings. This has
occured both in homes and workplaces. Symptomatic persons occupying moisture
problem buildings may develop asthma, rhinitis, ODTS and HP. However, the
majority of the exposed individuals present with conjunctival, respiratory
or systemic reactions the immune mechanisms of which remain unclear. In the
present summary some aspects will be presented on health effects which
appear among workers exposed especially to fungal antigens.
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Indoor
Moulds: a Public Health Problem in Belgium
Nicole Nolard, Ph. D.
Introduction
This paper is a summary of highlights recorded from 15 years’ experience of
surveys in home environments of patients with respiratory disorders linked
with allergy, mainly asthma. Actually, after the 1st oil crisis, in the
1970’s, people began to renovate their house with the aim of best insulating
every part from cellar to attic and we registered a continuing increase in
complaints correlated with the presence of fungi, not only in damp houses
but also in renovated and even new houses. Each survey responded to a
specific case with different situation standards (house/flat; city /
country, underprivileged / luxurious; pets / no pets) Moreover, taking into
account the evolution of the sampling methods, a standard methodology was
rather difficult to elaborate. Under these circumstances, in 1982, a scheme
was set up in our laboratory at the Institute of Public Health, which
belongs to the Belgian Ministry of Health, for environmental control in
homes. It includes:
a visit to the home
a standardized home environment form,
the sampling of air, surfaces, furniture, wall paper, mattress and carpet
dust for fungal moulds
the isolation, purification and placing in our collection of fungal strains
for immunological testing (more than 2000 strains are stored either freeze
dried or under liquid nitrogen in the IHEM collection),
the creation of a serum bank containing not only the serum of the allergic
patient but also the sera of people living in the same surroundings,
the standardisation of a mini-method for preparing fungal extracts from
selected strain,
finally, the immunological analysis from allergic patients, from subjects
exposed to the same environment but not symptomatic and from a pool of test
sera. Prick tests and antibody research (IgE and IgG) are carried out, or
are in the process of being carried out, with our own extracts and have
confirmed the role, in greater and greater numbers, of moulds as
pneumoallergens in the home. Our objective is to present in this article a
synthesis of our work at the Institute and to inform about the interest of
environmental surveys.
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Pilot Analysis of the Immune Response to Fungal Antigens in Subjects Working
in Humidity Damaged Houses
Professor of Clinical Immunology and Microbiology e-mail:
Anja.Tiilikainen@oulu.fi
Abstract
Although the proportion of anti-mold IgG antibody producers was largely the
same among different groups of subjects tested, the highest OD-readings in
EIA technique were seldom seen in symptomless controls, but generally in
association with any allergy of the "mold exposed" subjects or in patients
referred to specialist analysis at the Oulu University Hospital outpatient
clinic for oto-rhino-laryngology. Some subjects in each group were
distinctly multi-immune ("responders" = R) and some just occasionally
reactive ("low responders" = LR) against a panel of 12-16 mold antigens; of
the 34 allergic subjects 6 were R and 3 LR. In vitro cultures of patient
lymphocytes usually responded with a lower cytokine production to
Aspergillus fumigatus antigen than to other mold antigens, in contrast to
responses of lymphocytes from healthy controls. More often than not, R
lymphocytes showed higher cytokine production than did LR lymphocytes; more
frequently in healthy controls than in patients.
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Can Microbial Volatile Metabolites Cause Irritation at Indoor Air
Concentrations?
University of Kuopio, Department of Environmental Sciences, Kuopio, Finland;
Corresponding author: Prof. Anna-Liisa Pasanen; University of Kuopio,
Department of Environmental Sciences, email: annal.pasanen@uku.fi
Sensory irritation potency of selected volatile organic compounds assumed to
be of microbial origin (MVOCs) was estimated theoretically by using the data
of the recent chamber experiments and the results of volatile organic
compounds (VOCs) measurements in water-damaged buildings. According to the
estimations, a possible risk for complaints of irritation caused by exposure
to the mixtures of those MVOCs in moisture problem buildings was evaluated.
Exposure to mixtures of the selected non-reactive VOCs at the theoretical
airborne concentrations calculated from the data of the chamber experiments
would not result in sensory irritation in humans, and, thus, microbial
growth in constructions should not increase the probability of irritating
symptoms considerably. The data on MVOC concentrations measured in some
problem buildings also supported this hyphothesis. Irritation would be
expected when the airborne concentrations of single assumed MVOC approach a
level of hundreds of m g/m3 or mg/m3.
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Growth Conditions of Streptomyces Anulatus Regulate Induced Inflammatory
Responses and Cyto Toxicity in Macrophages.
Division of Environmental Health, National Public Health Institute, Division
of Environmental Health Maija-Riitta Hirvonen, Ph.D, National Public Health
Institute, email Maija-Riitta.Hirvonen@ktl.fi
Abstract
RAW264.7 macrophages were exposed for 24 hrs to the spores of Streptomyces
anulatus (doses of 105 106, 107 spores/million cells), isolated from a moldy
building and grown on 23 different kind of media. Production of nitric oxide
(NO) in macrophages was induced dose dependently by spores of S. anulatus
reaching the level from 4.2 mM to 39.2 mM depending on the composition of
the medium. The expression of inducible NO synthase (iNOS) was detected in
the macrophages after the exposure to the spores collected from all tested
growth media. The production of reactive oxygen species (ROS) was
significantly increased when compared to controls by the highest dose of the
spores from two media. The growth media affected the production of cytokines
as well; the highest dose dependent levels of IL-6 varied from 400 to 7500
pg/ml and the levels of TNF a from 450 to 3100 pg/ml. The amount of death
macrophages after the exposure varied from 11 % to 98% depending on the
growth media of the microbe. Altogether, our results suggest that the growth
conditions of S. anulatus, have a fundamental role in the ability of spores
to induce inflammatory responses and cytotoxicity in RAW264.7 cells.
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Clinical Findings Related to Indoor Fungal Exposure - Review of Clinic Data
of a Specialty Clinic
Eckardt Johanning M.D., M.Sc., Paul Landsbergis Ph.D. johanni2@crisny.org
Objective: Review of symptoms, clinical abnormalities and laboratory
findings of building occupants with abnormal indoor fungal exposure,
primarily allergenic and toxigenic fungi (Stachybotrys atra, Penicillium,
Aspergillus).
Design: Descriptive review of 151 cases evaluated at a specialty clinic.
Analyses of a standardized health symptom questionnaire and immunological
laboratory data.
Subjects: Pediatric and adult specialty clinic population with verified
abnormal indoor fungal exposure.
Main outcome measures: Self-reported symptom-complexes, Immunoglobulin E and
G, T- lymphocyte enumeration and function.
Results: Widespread contamination of water-damaged building materials
primarily with toxin producing fungi were identified in the patients
exposure history, who are reporting from a variety of nonspecific"sick
building"-like complaints to a history of more serious morbidity of the
respiratory system, skin, eye, chronic fatigue-like symptoms (CFIDS) and
central nervous system dysfunctions (vertigo, memory, irritability,
concentration, verbal dysfunctions). In some cases abnormalities of
enumeration and functional laboratory tests (flow-cytology), mainly of the
white blood cell system were identified. IgE or IgG antibodies used as
exposure markers, were positive in about less than 25% of all cases. Removal
from exposure typically resulted in improvement in the majority of cases.
Conclusion: Indoor air exposure to mycotoxin and allergen producing fungi
results in a high frequency of health complaints, variant multi-organ and
laboratory abnormalities requiring a detailed exposure assessment and
clinical evaluation. Removal from fungal exposure and symptomatic treatment
generally results in noticeable improvement of most patients. I propose to
name these presentations and clinical findings-if certain criteria are met:
"fungal syndrome".
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Pulmonary Hemorrhage Among Infants with Exposure to Toxigenic Molds
Ruth A. Etzel1, M.D., Ph.D., Dorr G. Dearborn2, Ph.D., M.D.
Case Western Reserve University, Cleveland, Ohio 44106
In 1994, we investigated a geographic cluster of 10 cases of acute
idiopathic pulmonary hemorrhage among infants in Cleveland, Ohio. Our
matched case-control study demonstrated that infants with this condition
were more likely than control infants to live in homes with toxigenic
Stachybotrys chartarum and other fungi in the indoor air. The risk appeared
to increase when both S. chartarum and environmental tobacco smoke were
present in the home. Since the completion of the 1994 investigation, 27
additional infants in the Cleveland area have been diagnosed with acute
idiopathic pulmonary hemorrhage. Of the 37 infants, 30 were African-American
infants, all of whom lived in a limited geographic area of eastern
metropolitan Cleveland, an area of older housing stock. Twelve deaths with
extensive idiopathic pulmonary hemosiderosis have been identified, including
seven originally thought to be due to Sudden Infant Death Syndrome (SIDS).
To determine how common this problem might be, we actively solicited reports
of idiopathic pulmonary hemorrhage in infants from pediatricians throughout
the United States. We have received physician reports of an additional 101
cases of acute idiopathic pulmonary hemorrhage among infants under 1 year of
age. This paper reviews the risk factors for this condition and discribes
the ongoing surveillance efforts.
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IAQ and
Human Toxicosis: Empirical Evidence and Theory
Harriet M. Ammann, Ph.D., D.A.B.T.
Washington State Department of Health, e-mail: HMA0303@doh.wa.gov
Studies of injury, illness and death occurring in mold-exposed animals and
people in the field, observe that the illness called mycotoxicosis results
from more complex exposures than can be observed in laboratory experiments
with pure mold toxins. Response in field exposures occurs at lower exposure
concentrations than those from controlled experiments. Occurrence of signs
and symptoms at low exposure levels may result from a number of factors,
including a greater spectrum of susceptibility in heterogeneous populations,
additive or synergistic actions of multiple toxins, actions of other toxic
microbial compounds, allergic and irritant response, as well as concomitant
exposure to other contaminants. Changes in the immune system, often
reflected as increased susceptibility to infectious illness, are a common
finding of low level exposure to toxigenic molds that inhibit protein
synthesis. Changes in the immune system are extremely complex, but changes
in the endocrine and nervous system accompany them, and may reflect changes
in the central neuroendocrine-immune control system. Evaluation of illness
of individuals exposed to a combination of irritant, allergenic and
toxigenic biological contaminants in wet buildings requires more information
about basic effects of individual agents as well as interactive effects of
the complex mixtures. In the meantime, case definition for such illness
needs to include exposure parameters that actually reflect the nature of the
agents capable of effecting illness, rather than some isolated component
such as a single mycotoxin. A definition of mycotoxicosis borrowed from
agricultural animal and worker exposures, "illness resulting from exposure
to one or more toxic molds and their products," could serve. A case
definition should also include location of individuals relative to the
location of suspect contaminants, time of contact with or exposure to molds
and their products, and a list of signs and symptoms gleaned from
investigations of known animal or human toxic exposures. Commonality of
signs and symptoms in those who show similar time and place exposure
parameters could be used to further focus definition of a case. Prudent
public health practice recognizes the potency of the toxic agents produced
by toxigenic molds, and seeks to protect occupants of buildings once
moisture incursion with resultant microbial growth has been discovered.
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Cognitive Impairment Associated with Exposure to Toxigenic Fungi
Wayne A. Gordon, Ph.D., Eckardt Johanning, M.D.,M.Sc. Lisa Haddad, B.A.
The objective of the study was to examine whether cognitive impairment was
associated with exposure to Stachybotrys atra. 20 individuals were examined
using a standard neuropsychological battery and a symptom checklist. Results
indicate that all individuals seen meet at least 1 of the criteria for a
cognitive impairment, with 13 of the 20 (65%) meeting at least 3 of the
criteria for cognitive impairment. Preliminary findings suggest that
exposure to toxigenic molds are associated with cognitive impairment,
specifically deficits in verbal memory, verbal learning,
attention/concentration and set shifting. In addition to these cognitive
deficits, the sample reported a high number of cognitive, physical and
behavioral symptoms. Validation on a larger sample of individuals is
indicated.
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Symptoms Associated to Work in a Water Damaged School Building
T.Sigsgaard MD.,PhD., H.L.C.Jensen B.Sc., E.Nichum B.Sc, S.Gravesen
M.Sc., L.Larsen M.Sc., M..Hansen B.Sc. Copenhagen, Environmental E-mail:
TS@mil.au.dk
This paper describes a cross sectional study of employees from a school,
where an annex had a long history of water damage. The annex had
infestations by a range of moulds with Penicillium, Aspergillus,
Cladosporium most often encountered. The employees filled in a questionnaire
with questions on sick building syndrome extended with symptoms of toxic
alveolitis. After allocating the employees into three groups according to
the weekly hours spent in the annex of 0-7 h/week, 8-15h/week and more than
15 hours/week. We found a positive trend for headache, tiredness, nausea and
sleeping difficulties with increasing time spent in the annex. This was also
true for episodes of fever, shivering or a flue-like feeling. This study
emphasises the need for a standardised way to perform investigations of
water damaged buildings and indicates a dose response relationship between
exposure to water damaged buildings and symptoms of inflammation and
CNS-irritation even in low exposure situations.
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Sensory Irritation of Microbially Produced Volatile Organic Compounds in
Mice During Repeated Exposures
Anne Korpi, PH. LIC., Jukka-Pekka Kasanen, M.Sc., Anna-Liisa Pasanen, Ph.D.
Department of Environmental Sciences, Kuopio, Finland; email:
anne.korpi@uku.fi
Microbially produced volatile organic compounds (MVOCs) are suspected to
cause eye, nose and throat irritation in occupants of moldy buildings. The
effect of repeated exposures (30 minutes per day during 4 consecutive days)
of mice to 3-octanone (3531 mg/m3), 1-octen-3-ol (36 mg/m3), or to a mixture
of five MVOCs (58 mg/m3) via inhalation was studied with a standardized
method (ASTM E 981-84). With single MVOCs, no changes in the responses
between repetitions of exposure were seen, and only a very slight adaptation
in the respiratory response was noted along with the repetition of exposure
to a mixture of MVOCs. Thus, during a short-term experiment, repeated
exposure to MVOCs did not provoke changes in the sensation of irritation nor
cause permanent effects on upper respiratory tract.
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Immunological Biomonitoring in the Assessment of Exposure to Airborne Fungi
from Waste Handling
J. Bünger1, M.D., M. Müller, Ph.D., K. Stalder, M.D., Prof., E. Hallier,
M.D., Prof.
Center of Environmental and Occupational Medicine, Department of
Occupational and Social Medicine, Georg-August-University, Göttingen,
Germany e-mail: ehallie@gwdg.de
The immunologic reaction of workers in different waste treatment facilities
to inhalation of mold antigens was studied by determination of specific IgG
antibody levels and compared to exposures. Antigens were prepared from
cultures of fungi which were dominant in dust samples at these workplaces.
In 520 waste workers, 32 patients with symptoms of hypersensitivity
pneumonitis (HP), and 98 control subjects, serum concentrations of specific
IgG antibodies to antigens of molds (Aspergillus and Penicillium species)
were determined by an indirect immunofluorescence test (IIFT). The highest
antibody levels were found in workers in compost plants, followed by
employees of garbage sorting facilities. Lower levels were determined in
workers at landfills and lowest in collectors of household biowaste. This
order reflects the ranking according to the exposure measurements. About 5%
of workers had elevated antibody levels, but none complained about typical
symptoms of HP. The IIFT proved to be a very sensitive method of antibody
detection since even IgG levels of persons subjected to environmental
exposure alone (control) could be measured. High exposure to organic dust at
workplaces with waste handling is correlated with elevated mold-specific IgG
antibody levels.
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Chronic Toxic Encephalopathies Apparently Related to Exposure to Toxigenic
Fungi
Pierre L. Auger M.D., Pierrot Pépin H.I., J. David Miller Ph.D., Manfred
Gareis D.V.M., Ph.D., Julien Doyon Ph.D., Rémi Bouchard M.D., Marie-France
Pinard Ph.D., Claude Mainville Ing.
This report concerns four cases of neurotoxic encephalopathies possibly
caused by a prolonged exposure to toxin producing filamentous fungi (molds)
in the workplace. We will also demonstrate that complete fungal evaluation
with species identification and complementary cytotoxicity testing can be
useful to identify possible causes of health effects of mold exposures.
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Building-Related Illness in Occupants of Mold-Contaminated Houses
James Craner, M.D., M.P.H.
Consultant in Occupational & Environmental Medicine, Verdi, Nevada,
The clinical presentation and course of individuals and families who
developed illnesses related to non-infectious fungal exposures inside their
homes is described. Occupants developed their illnesses shortly after their
homes had been water damaged. A few occupants had a specific
building-related illness, such as hypersensitivity pneumonitis or asthma
exacerbation, but most had a "sick building syndrome" symptom complex
involving irritation/inflammation of the mucous membranes, respiratory
tract, and skin; fatigue; and/or neurocognitive dysfunction. All cases
required months or years to correctly diagnose. Air, surface, and/or bulk
microbiological sampling in most of the homes yielded high concentrations of
toxigenic fungi, including Stachybotrys chartarum and Penicillium and
Aspergillus species, emanating from water-damaged building materials. Most
of the ill individuals had complete clinical improvement shortly after their
removal from the contaminated indoor environment, but a few individuals
continued to experience symptoms in response to a variety of environmental
irritants. The author proposes a new clinical syndrome entity to describe
the non-infectious, mold-related, building-related illness.
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Diagnosing the Cause of a "Sick Building:" a Case Study of an
Epidemiological and Microbiological Investigation
James Craner, M.D., M.P.H., Linda d. Stetzenbach, Ph.D.
Consultant in Occupational & Environmental Medicine, Verdi, Nevada
Director, Department of Microbiology, Harry Reid Center for Environmental
Studies, University of Nevada-Las Vegas, Las Vegas, Nevada
This report describes the methods and outcome of a physician-led
investigation of occupants’ prolonged, unexplained illnesses associated with
working inside a large, modern office building. Occupants (cases) complained
of building-related symptoms including eye, nose, and throat mucous membrane
irritation; rashes; respiratory symptoms; profound, unexplained fatigue; and
neurocognitive symptoms, including difficulty concentrating and short-term
memory impairment. No functional ventilation problems or chemical
contamination were detected in a walk-through evaluation and basic air
quality testing. An epidemiological survey of the building’s 700 occupants
was then conducted. With 86% of the occupants responding to the survey,
there was an average case prevalence of health-related complaints of nearly
25%, evenly distributed among floors. Cases were geographically distributed
in a pattern which coincided with the location of the ceiling-mounted
variable air volume (VAV) boxes which distributed ventilated air to the
occupied spaces. Re-inspection revealed previously undetected, focal
water-staining of 40% of ceiling tiles located underneath the VAV boxes
throughout the building. Active growth of Stachybotrys chartarum (atra) and
other fungi was detected on many of the damaged tiles. All water-damaged
tiles were replaced and VAV hot water valves were tightened. Occupants
reported significant improvement of symptoms within weeks after these
changes.
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Fungal Exposure and IGg-levels of Occupants in Houses with and without Mold
Problems
Hyvärinen A., M.Sc., Reiman M., Ph.D., Meklin1 T, M.Sc., Husman T., M.D,
Vahteristo M, M.Sc., MD., Nevalainen A, Ph.D.
National Public Health Institute, Email: Anne.Hyvarinen@ktl.fi
The aim of the study was to evaluate the relevance of serum antifungal-IgG
antibodies to reflect the individual“s exposure to building related fungi.
The concentrations of viable fungi were higher and composition of fungal
flora was different in the index houses with moisture problem compared to
those in the reference houses. Positive IgG-findings were common in both
groups, although higher antibody levels against most of the fungi were found
in the study group than in the control group. However, compatibility between
fungal flora found in each house and elevated IgG-levels of its occupants
were seldom found in either of the groups. This study suggests that
microbial sampling gives information of the building at the time of the
measurements, whereas IgG-antibodies reflect long-term integrated exposure
of an individual from total environment including the work place.
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The
Immunopathology of Hypersensitivity Reactions
Vincent A. Marinkovich, M.D.
Clinical Associate Professor, Stanford Medical School,
Overactivity of the immune system, either allergy (IgE) or hypersensitivity
(non-IgE) is responsible for more illness than is generally appreciated,
even by the medical profession. The least understood are the non-IgE
mechanisms which involve either immune complex formation (type III of Gell
and Combs) or direct killer T-cell involvement (type IV). Type III reactions
may be localized with a large deposition of antigen at a focal point where
immune complexes are formed and tissue damage ensues including necrosis.
This is termed the Arthus reaction. A systemic dissamination of antigens
will provoke a systemic inflammentory reaction which is most closely modeled
by the well studied acute and chronic serum sickness reaction. Serum
sickness was identified as the constellation of symptoms which followed the
aadministration of antitoxins (antisera given for infectious disease before
the advent of antibiotics) which were derived from non-human sources, most
often horses. Chronic serum sickness was observed when otherwise heaalthy
subjects were given repeat doses of antisera experimentally over relatively
short periods of time. The symptoms observed in spontaneous and experimental
serum sickness included fatigue, rash, cognitive changes, myositis,
arthritis, headache, weight-loss, cardiovascular symptoms etc., which are
often seen during heavy chronic exposure to fungal spores. The dynamic
nature of circulating immune complexes, their complexity, their rapidly
changing exquilibrum patterns aaand their pathogenicity must be appreciated
before the clinican can properly interpret the patterns of illnes his
patients’ describe. The best simple test identifying and thereby allowing
the avoidance of serum sickness is a specific IgE test to a panel of high
exposure antigens including fungi, food and occupational antigens.
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Exposure to Stachybotrys Chartarum Induces Immunoglobulin a Antibody
Response in Man
Päivi Raunio M.Sc, Anna Pasanen Prof., Tuula Husman M.D., Tuomas Virtanen
M.D. University of Kuopio, e-mail: Paivi.Raunio@uku.fi
The levels of serum immunoglobulin (Ig) E, G and A antibodies against
Stachybotrys chartarum were measured in patients with asthmatic or
mycotoxicosis symptoms (n=6), their family members (n=10) and control
subjects (n=18) with indirect enzyme-linked immunosorbent assays. The
Stachybotrys-specific IgG and IgA levels correlated with each other
significantly (r=0.71, p<0.01) in the group of exposed subjects (patients
and family members), but not in the control group. The IgA levels were
significantly higher (p<0.01) and the IgG levels slightly higher (p<0.05) in
the patient group than in the control group. IgE levels did not differ
between the subject groups. The results of this study suggest that the
exposure to Stachybotrys does not cause IgE-mediated allergy in humans. It
is possible that the IgA response reflects better exposure to the fungus
than the IgG response does.
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Sensitization to Molds and Respiratory Symptoms in School Children
Taskinen1 T., M.D., Hyvärinen A., M.Sc., Meklin T., M.Sc., Husman T., M.D.,
Nevalainen A., Ph.D., Korppi1 M. M.D.
Kuopio University Hospital, E-mail: Taina.Taskinen@ktl.fi,
taina.taskinen@kiuruvesi.fi
We performed a questionnaire study in 622 school children; asthma or
asthmatic symptoms were present in 208 (33%) children. Moisture and mold
problems weredocumented in the index school (N=414; 168 (41%) were
symptomatic); the control school (N=208; 40 (19%) were symptomatic, p<0.001)
had no such problems. Skin prick tests to 13 molds (9 occurring in
environment and 4 indicating moisture problems in buildings) were performed
in the 208 symptomatic children. A positive reaction (>3mm) was observed in
only 5 (2%) children. Children who were exposed to molds in the school had
more often emergency visits (OR=2.0, p<0.01) and also they had used more
antibiotic courses (OR=2.1, p<0.01) than nonexposed pupils, but only during
spring. Our results show that skin test positivity to molds is rare in
school children. This is true in pupils with asthmatic symptoms, and also in
the pupils from the school with moisture or mold problems. In addition,
respiratory infections seem to be associated with mold exposure.
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Mycotoxin
Cytotoxicity Screening of Field Samples
Manfred Gareis, D.V.M., Ph.D., Prof., Eckardt Johanning, MD., M.Sc. Ritchie
Dietrich, Ph.D. Institute for Microbiology and Toxicology, e-mail:
gareis.baff@t-online.de
Several hydrophil fungi produce very potent chemical metabolites
(mycotoxins) that may pose a particular health risk in indoor settings.
However, these properties have not been routinely assessed in similar field
investigations, due to a lack of readily available screening test methods. A
total of 166 moulded samples of building materials (gypsum boards,
wallpaper, ceiling tiles, fiberglass and other insulating materials,
carpets, dust and air filters) from 44 case investigations conducted during
the time period from 1993 to 1998 in various areas of the United States were
tested with the MTT-cytotoxicity screening assey for the presence of
cytotoxic mycotoxins and compared with controls. A subset of samples was
analysed by an enzyme-immune assay (EIA) for occurrence of macrocyclic
trichothecenes produced by strains of Stachybotrys chartarum. In addition,
presence of fungi were examined by culture methods and scanning electron
microscopy. Different levels of cytotoxicity were detected in particular of
field samples of gypsum board or wall paper visibly contaminated with fungal
growth. Samples with highly cytotoxic effects reacted positive in the
MTT-bioassay at concentrations of less than 5 mg of sample aliquot per ml of
cell culture medium and indicated the presence of cytotoxic contaminants.
Twentythree field samples (52%) of all case investigations were positive for
cytotoxicity compared with controls. Most frequently detected fungi in toxic
samples were Stachybotrys chartarum (85%), Trichoderma sp. (31%) and
Chaetomium sp. (38%) compared to non-cytotoxic samples with a proportion of
38%, 10% and 5%, respectively. These results indicated the presence of
non-toxigenic strains or alternatively the non-production of cytotoxic
mycotoxins by toxigenic strains on these particular samples. The level of
toxicity obtained by the MTT-bioassay highly correlated with the amount of
macrocyclic trichothecenes detected by use of the EIA in the samples
contaminated with or without Stachybotrys chartarum. Toxicity detected in
samples not contaminated with Stachybotrys chartarum indicates the presence
of cytotoxic mycotoxins produced by other fungi. In conclusion, the results
support the usefulness of the MTT cytotoxicity assay as an important
diagnostic tool for the assessment of potential mycotoxin exposure inside
buildings with fungal contamination.
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The Effect-Inhaled Spores of Mycotoxin Producin Fungi on Animals
Eeva-Liisa Hintikka, D.V.M., Ph.D.
Head of the Department of Bacteriology, National Veterinary and Food
Research Institute, Helsinki, FINLAND
Animals in contact with a mouldy environment are exposed to respiratory
fungal infection, lung mycosis. Toxic fungal spores in the air create a risk
of respiratory effect. Animal experiments have shown that pure mycotoxins
administered to the respiratory organs have only a transient or no effect in
the lungs. Toxin-containing spores of Stachybotrys atra administered to the
respiratory organs of mice cause severe haemorrhages and lung inflammation.
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Trichothecenes
as a Potent Inducer of Apoptosis
Hiroki Okumura, Naoto Yoshino, Yoshitsugu Sugiura, Masao Sugamata,
Eeva-liisa Hintikka, Bruce Jarvis, Yoshio Ueno
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical
Sciences, Science University of Tokyo, Ichigaya, E-mail
youeno@kagu.sut.ac.jp
Induction of apoptosis by the trichothecenes was examined in promyelotic
leukemia cell line HL-60 and mice. An early elevation of intracellular Ca++
ion followed by disruption of observed mitochondrial transmembrane
potential, induction of caspase-3, and DNA fragmentaion was oberved in T-2
toxin-treated cells. An induction of apoptotic cell death in the tissues of
mice given T-2 toxin was confirmed by electron microscopic analysis. The
induction of apoptosis was proposed as a novel cell death mechanism of T-2
toxin as well as macrocyclic trichothecenes.
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Analysis for Stachybotrys
Toxins
Bruce B. Jarvis1, Ph.D., Prof., Simon F. Hinkley
Department of Chemistry and Biochemistry, and Joint Institute for Food
Safety and Nutrition, University of Maryland, College Park, MD e-mail
address: bj6@umail.umd.edu
Analytical conditions have been developed for the detection and quantitation
of several classes of mycotoxins produced by the toxigenic mold,
Stachybotrys atra (S. chartarum). Fungal cultures or environmental samples
are extracted with methanol-chloroform and the crude extracts passed through
a PEI silica cleanup column. The fractions from this cleanup column are
analyzed by reversed phase chromatography (C-18, acetonitrile-water-formic
acid) coupled to a diode array detector. Three major classes of mycotoxins
are produced by S. atra: trichothecenes, phenylspirodrimanes, and, a new
class of diterpenoids, the atranones. Thirty-eight isolates of S. atra were
assayed for their mycotoxin production, and the S. atra isolates fell into
two distinct classes: those that produce trichothecenes (12/38) and those
that produce atranones (22/38).
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Assessing Bioaerosols in Elementary School Classrooms
K.H. Bartlett, Ph.D., S.M. Kennedy, Ph.D., M. Brauer, Sc.D., B. Dill, Ph.D.,
C. VanNetten, Ph.D. K.H. Bartlett, Ph.D kbartlet@interchange.ubc.ca
A two year study of elementary school classrooms was begun in 1996. Data
collected included: number of occupants and patterns of occupancy, CO2
levels, temperature and percent relative humidity (%RH), total particulate,
and air exchange rates using tracer gas (SF6). Indoor and outdoor
bioaerosols were collected using an Andersen N-6 impactor.
The effect of measured indoor air quality parameters and building
characteristics on the airborne concentrations of indoor bacteria and
mesophilic fungi were evaluated using multiple linear regression. The
variable with the highest predictive value for bacterial concentrations was
indoor CO2 concentration, with the final equation having a R2 of 0.59. In
contrast, outdoor temperature had the highest predictive value for indoor
mesophilic fungi with the final equation having a R2 of 0.61.
Variables commonly measured during an indoor air quality investigation can
be used to understand bioaerosol concentrations. High commensal bacterial
counts are clearly related to inadequate ventilation of the occupied space.
In a similar manner, the use of mechanical or natural ventilation in
buildings and the concentration of fungi in the outdoor environment is
related to indoor fungal counts. These data would suggest that indoor air
quality investigations benefit from an integrated investigative approach.
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Anatomy of a Fungal Problem
Neil Carlson1, M.S., C.I.H., Arif Quraishi2, B.S.M.E., M.B.A.
University of Minnesota, 410 Church Street S.E., Minneapolis
Sampling was performed in a school with extensive visible fungal growth to
evaluate exposure potential to building occupants. Musty odors and
allergy-type symptoms were reported by building occupants. Initial testing
using fungal sampling was not successful in identifying risks to building
occupants. Additional sampling was conducted using total spore trap
sampling, tape sampling and microbial volatile organic compound (MVOC)
sampling. Analysis of the samples using total spore trap and tape sampling
methods identified exposure potential to Acremonium spp., Alternaria spp.,
Paecilomyces spp., Aspergillus niger and others. Measurement of MVOCs showed
that the indoor MVOCs were almost double the outside level. While sampling
performed by traditional viable methods suggested no exposure potential,
tape, spore trap and MVOC sampling data revealed greater exposure potential.
Based on the results of this study, viable fungal sampling should not be the
only method for conducting risk assessments relating to exposure to fungal
spores and their bioeffluents.
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Prevalence of
Fungi in Carpet Dust Samples
Mark Hodgson LRSC, Richard Scott AIA
Senior Consultant, Occupational Health and Safety; Clayton Environmental
Consultants, mail: Mhodgson@claytongrp.com or Rscott@Claytongrp.com
Samples of dust collected from carpeting can provide an indication of the
microbial condition of a building with the carpet material having potential
to be both an amplifier (growth site) and reservoir for fungi.
Interpretation of the data obtained from analysis of the dust is helpful
when making a determination as to the overall condition of both the building
and the carpet material. The authors have collated data from 243 samples
collected in both problem and control buildings across the USA. A comparison
is made between the results obtained from both problem and control
buildings, with particular emphasis on the biodiversity found and the
regional differences observed. The study concludes that despite the
ubiquitous nature of fungi there are a number of key indicators which can be
used to determine if the dust from a carpet suggests a contaminated
building.
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Detection and Decontamination of a Facility Contaminated with Fungi
Including Stachybotrys chartarum
Ling-Ling Hung, Ph.D. US Public Health Service, Division of Federal
Occupational Health, Philadelphia, PA Email: lhung@foh.dhhs.gov
A facility indoor environmental quality investigation was initiated in 1996
due to onset of employees' health symptoms after fifteen minutes exposure in
the facility. The investigation was to determine the extent of
contamination, identify the causative agents, design decontamination
specifications, and develop and implement a monitoring strategy for
clearance sampling.
Massive fungal growth was observed on various surfaces. Many types of
microbiological samples were collected throughout this two-story facility.
Very high fungal levels were detected on bulk and wipe samples (107 CFU/g
and 106 CFU/in2). Three rounds of air samplings were conducted. Outdoor
fungal levels were at 102 CFU/m3 with Cladosporium as the predominant fungi.
However, indoor fungal levels were consistently at least 104 CFU/m3. Indoor
fungal flora was dominated by Aspergillus, Penicillium, and Stachybotrys
chartarum. Analytical results showed that basement, ground floor, and
ductwork were contaminated.
Specifications were developed to decontaminate the facility and the
ductwork. Ten percent (10%) bleach solution and Oxine® brand of chlorine
dioxide (500 ppm) was used as the disinfectant for the facility and the
ductwork, respectively. Final clearance samples were taken to evaluate the
effectiveness of the cleaning. Air sampling results showed that airborne
fungal levels in the facility were compatible to those of outdoors (230 and
224 CFU/m3, respectively), with a similar fungal flora. Results from final
clearance surface samples, taken after completion of second ductwork
cleaning, showed that surface fungal burden of this facility was not
different from that of a reference building.
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Airborne Concentrations of Trichoderma and Stachybotrys linked to
Mycotoxicosis
Larry D. Robertson, M.S., B.S. Mycotech Biological, Inc., Jewett, TX
The affected individual developed symptoms approximately 55 days after
exposure to a working environment containing significant fungal
contamination. Initial symptoms included bronchitis, swelling, spastic
colon, severe headaches, and fatigue. Later, abdominal pain, nausea,
diarrhea, and loose teeth were reported. Three physicians having specialties
in internal medicine, toxicology, and neurology independently diagnosed
exposure to an "unknown" environmental toxin; however, the physicians were
not provided with environmental results from the work place. The work
environment indicated airborne concentrations of Trichoderma viride and
Stachybotrys chartarum at 494 CFU/m3 and 212 CFU/m3, respectively. Active
Trichoderma viride and Stachybotrys chartarum growth sites were documented
at levels of 3.3 x 104 CFU/g and 2.0 x 107 CFU/g; respectively. Although
these contaminants were exclusive to the individuals work area, the CIH/CSP
represented the data as "typical" for indoor environments. As a result, no
exposure data was provided to the attending physicians. After 5 months of
exposure the individual became too ill to return to work. Within 1 month of
removal the symptoms begin to subside. Complete symptom cessation resulted
after 12 months. The absence of specific human dose-exposure data relative
to the various mycotoxins produced by Trichoderma viride and Stachybotrys
chartarum does not support a valid medical claim relative to an
aerosol-induced mycotoxicosis. However, anecdotal, circumstantial, and
environmental information strongly supports the potential for this event to
have occurred. This study demonstrates the current void that exists relative
to both the knowledge and availability of mycotoxin diagnostic methods in
the medical field and suggests the immediate need for education, training,
and research relative to aerosol generated mycotoxicoses.
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Exposure Measures for Studies of Mold and Dampness and Respiratory Health
J. David Miller M.Sc., Ph.D., Robert Dales M.D., M.Sc. Jim White, P.
Eng. Department of Chemistry, Carleton University, Ottawa, Ontario.
This paper reviews some basic principles underlying the measurement of fungi
in air samples and dust to describe their quantitative and qualitative
value. We compare the results of such measurements with our experience in
the Wallaceburg study wherein ca. 400 homes in southern Ontario were studied
for various exposure and health outcomes. Until more powerful methods to
determine quantitative and qualitative exposures to fungi are developed, the
attributable risk of fungal contamination in residential housing for public
health cannot be estimated with accuracy. The most reliable information on
mold exposures in residential housing can be obtained by measuring moisture
source strength, detailed study of areas of visible mold plus some
mycological testing of building materials to determine where the growth is
occurring beyond that visible to the naked eye and qualitative and
quantitative analysis of molds in settled dust.
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Fungal Growth in Buildings: The Aerobiological Perspective
Harriet A. Burge Ph.D. Harvard School of Public Health, Boston,
In the search for inexpensive shelter, we have developed indoor environments
that are conducive to fungal contamination. While active fungal growth
indoors is usually inappropriate and should be controlled, assessing
specific health risks associated with such growth remains a challenge.
Epidemiological tools are often used to determine relative risks associated
with occupancy by groups of people in environments with or without certain
factors, including fungal growth, but do not always make clear the role of
the growth in the disease process in indiviudals. Aerobiologists assess
relationships along a pathway that includes sources, dispersion and decay of
aerosols, exposuree to individuals, doses of agents, and responses. Both
approaches yield valuable information, but require the development of
testable hypotheses.
As a model, we can apply the epidemiological and aerobiological processes to
the Cleveland hemosiderosis outbreak, and consider the following hypotheses:
The Cleveland babies that develop hemosiderosis are more likely to live in
moldy homes than those that did not develop the diseease, all other things
being equal.
The Cleveland babies that developed hemosiderosis are more likely to live in
homes with Stachybotrys than those that did not develop the disease, all
other things being equal.
Aerobiology Babies that developed disease were likely to have received a
dose of Stachybotrys chartarum toxins sufficient to cause the reported
symptoms.
Some evidence exists to support Hypothesis 1.
Hypothesis 2 is suppored by very little evidence
Hypothesis 3 has not been tested.
Until Hypotheses 2 and 3 areadequately tested and verified, assuming a
cause/effect relationshipfor Stachybotrys toxins in these cases is
premature. Premature establishement of cause/effect relationships may lead
to unneccessaary conceern, and prevent discovery of actual caauses of
disease. This hypothesis development and testing process is essential if we
are to accurately determine the role of indoor fungi in human disease.
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Why are there Still Problems with Fungal Allergen Extracts?
W. Elliott Horner, Samuel B. Lehrer Air Quality Sciences, Inc., Atlanta,
GA, and Tulane University Medical Center, New Orleans, LA email
aqs@mindspring.com
It has long been axiomatic that reliable allergen extracts of fungi are more
difficult to produce and work with than extracts of pollen, dander, or other
allergen sources (Salvaggio, 1981; Burge, 1985; D’Amato, Spieksma, 1995;
Feinberg, 1946). Features of fungi that contribute to this include their
number and variety, the identification is sometimes difficult, their
phenotypic plasticity, and the presence of endogenous proteases that can
degrade allergens in crude extracts. All of these problems can be addressed
to an extent, albeit some with difficulty. Indeed, with the few fungi with
which molecular techniques are being used, recombinant allergens are readily
being produced. Unfortunately, adequate resources and resolve are lacking
for a concerted effort at producing well-characterized allergen extracts.
Further, the extracts that are available correspond poorly with the fungi
that are often a problem indoors.
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Comparative studies of fungal media for the recovery of Stachybotrys
Chartarum from Environmental Samples
Stella M. Tsai1, M.Sc., Chin S. Yang, Ph.D., Patricia Heinsohn, Ph.D.,
CIH P&K Microbiology Services, Inc., Cherry Hill, NJ
Five commonly used fungal media were used to determine the relative recovery
efficiencies of Stachybotrys chartarum (SC) by culturing sixty-five unknown
environmental samples from building materials. These fungal media were
cornmeal agar (CMA), Czapek cellulose agar (CCA), 2% malt extract agar (2%
MEA), 1% malt extract agar (1% MEA) and rose bengal agar (RBA). The samples
were first examined microscopically for the presence of SC. It was found
that all five fungal media were all suitable for the recovery of SC from the
environmental samples. The recovery frequency of SC from bulk samples ranged
from 87.7% on 2% MEA to 95.4% on CMA. Qualitative differences of colony
growth and interaction between S. chartarum and other fungi were observed on
the media. CMA yielded the best sporulation and highest recovery rate of SC
from the environmental samples. The other four media also supported the
isolation and recovery of SC but at reduced rates.
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Heteroduplex DNA Fingerprinting of Penicillium Brevicompactum from House
Dust
James A. Scott, Neil A. Straus1, Bess Wong Department of Botany,
University of Toronto E-mail: jscott@sporometrics.com
It is widely believed that many osmotolerant microfungi, including toxigenic
species of Aspergillus and Penicillium proliferate on indoor substrata such
as dust and broadloom even in the absence of appreciable moisture. This
hypothesis has been offered as an explanation for the disproportionate
abundance of propagules of these species in indoor environments, relative to
their representation in outdoor reservoirs such as air and soil.
We obtained several thousand isolates of Penicillium from 367 homes in
southwestern Ontario, Canada. From these, 75 isolates of P. brevicompactum
representing 54 houses were selected based on micromorphological and
physiological uniformity. Sequences of PCR-amplification products of
polymorphic genetic loci were compared between isolates using heteroduplex
mobility assay (HMA), demonstrating two primary, genetically divergent
groups which appear to be stable, clonally-reproduced lineages within the
dust mycoflora. These clones are distributed throughout the sample
population and co-exist at several sites, suggesting that in absence of
objective moisture problems, the principal amplifiers of P. brevicompactum
lie outside the building environment. It is possible that mechanical /
filtration effects (e.g. differential removal of propagules by vacuum
cleaning and elutriation in air conveyance systems), and the relatively long
spore viabilities of trichocomaceous anamorphs play a significant role in
concentrating propagules of these microfungi in homes.
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The Trichodiene Synthase Gene from Stachybotrys Chartarum : A Potential
Diagnostic Indicator of Indoor Contamination
Neil A. Straus PhD, James Scott, Bess Wong MSc Department of Botany,
University of Toronto, Canada Email: straus@botany.utoronto.ca
The hyphomycete Stachybotrys chartarum readily grows on damp cellulosic
areas in buildings producing spores that may contain highly toxic
trichothecenes. Here we report the cloning, sequencing of the gene for
trichodiene synthase which is the first enzyme of the pathway uniquely
dedicated to the synthesis of trichothecenes. The predicted amino acid
sequence shows regions of high conservation. Nucleotide sequence divergence
permits the selection of PCR primers that can detect the trichodiene
synthase gene of S. chartarum in DNA diagnostic strategies.
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Microscopic Fungi and Metabolites in Dwellings-a Bioassay Study
Ing. Elena Pieckovį, M.P.H., Ph.D., MUDr. Zdenka Jesenskį, Dr., Sc., Ken
Wilikins, Ph.D. Institute of Preventive and Clinical Medicine, Bratislava,
Slovakia
The ciliostatic effect of chloroform-extractable endo- and exocellular
metabolites of the most frequently isolated fungal strains from growth in
dwellings: Alternaria sp., Aspergillus glaucus group, A. versicolor,
Cladosporium sphaerospermum, Penicillium sp., P. chrysogenum, Stachybotrys
chartarum, Trichoderma viride and Ulocladium sp. was studied on tracheal
cilia from day old chicks in vitro. Biomass extracts from Alternaria sp. and
A. versicolor as well as exocellular extracts from P. chrysogenum, S.
chartarum I, T. viride and Ulocladium sp. stopped cilia movement during the
first 24 hours. Biomass extracts of P. chrysogenum, S. chartarum I and T.
viride as well as media extracts from Alternaria sp., C. sphaerospermum and
Penicillium sp. stopped cilia movement between 24 and 48 hours. Between 48
and 72 hours the biomass extract of an A. glaucus gr. isolate and media
extracts of A. versicolor and S. chartarum II showed activity while the
other extracts (cellular from C. sphaerospermum, S. chartarum II and
Ulocladium sp. and media one from A. glaucus gr.) showed no activity. The
results are discussed in relationship with health status of people
living/working in moldy buildings.
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Moisture, Mold
and Health in Apartment Homes
A. Nevalainen, Ph.D., M. Vahteristo, M.Sc., J. Koivisto, Civ.Eng., T.
Meklin, M.Sc., A. Hyvärinen, M.Sc., J. Keski-Karhu, M.Sc., T. Husman, M.D.
National Public Health Institute, Division of Environmental Health e-mail
aino.nevalainen@ktl.fi
The prevalence of observations of moisture or mold, and the respiratory
health status of the occupants, was surveyed in a random sample of 120
apartment buildings. The buildings and two apartments from each were given a
walk-through inspection and all the signs of moisture and mold recorded
using questionnaires and checking lists by civil engineers. A health
questionnaire was sent to the occupants. In 60% of the apartments, signs of
moisture damage could be observed, and 42% of the apartments were assessed
to be in need of repair because of the moisture observations. Respiratory
symptoms, such as cough, nocturnal cough and dyspnea, sore throat,
hoarseness, rhinitis, nasal bleeding and impaired sense of smell were
significantly associated with the observa
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RESEARCH and STUDIES