|
Molds, Mycotoxins, and Human Health
Michael R. Gray, M. D., M. P. H.,
C. I. M. E.
There are two hundred
thousand different molds and fungi. They have been present on
this planet for 3 billion years, and certainly, many of us love
our bleu cheese. Most molds are quite harmless, aside from their
tendency to induce allergies in those of us who are prone to
develop allergies in the first place.
HOWEVER:
There truly were good
reasons why we are warned in Leviticus: that if your house be
contaminated with plagues, mold and Leprosy, you should put the
contents in the middle of it, and set it aflame. The spores
from Stachybotrys chartarum (a.k.a. atra), a mold capable of
producing some of the most toxic substances known to human-kind,
can survive temperatures up to 500 degrees Fahrenheit, as well
as acid, caustics, and bleach without being destroyed. Spores
from molds have been removed from 2,000,000-year-old sedimentary
rock and grown when placed on appropriate media. And, every
nation that has developed biological warfare capability, has
harvested mycotoxins from molds, some of which are so toxic that
microgram quantities are capable of killing within twenty-four
hours, while being so completely metabolized that they are
undetectable at autopsy.
From 1987 through the present Dr.
Gray has developed a reasonably uniform database on 350 patients
with exposures to a variety of haptogenic (immunologically
reactive), xenobiotic (toxic) compounds, including 75 patients
with confirmed exposure to toxigenic structural molds. These
patients have been evaluated in the context of individual
clinical encounters, with the workup including standardized
comprehensive Internal Medicine Database questionnaires with an
extensive Occupational History gathering component,
Environmental History gathering questionnaires, kindly provided
by Grace Ziem, M.D., Dr. P.H., direct interviews, physical
examinations, extensive laboratory testing including complete
blood counts with differentials (CBCs), comprehensive metabolic
profiles (CMPs), arthritis and thyroid profiles, lymphocyte
phenotype studies including total white cell counts, total
lymphocyte counts, T-cell and B-cell counts, T-cell subsets,
T-cell activation levels using both CD26 and HLA-DR markers,
evaluation of natural killer cell counts and functional status,
audits for auto antibody production, anti herpes viral titers,
anti volatile organic compound (VOC) antibody titers, evaluation
of stimulated lymphocyte mitogen response, and pulmonary
function testing when indicated, electrocardiograms and chest
x-rays as indicated, neuropsychological evaluations,
quantitative electroencephalograms (QEEGs), and in the cases in
which excessive mold exposure was confirmed by environmental
hygiene evaluations with quantification and identification of
the specific molds present, appropriate audits were conducted
for specific anti mold antibody levels. Excel spreadsheets were
prepared including the laboratory data of the confirmed mold
exposed patients evaluated between 1994 and February 2001. This
exercise revealed patterns of abnormalities consistent with what
has been reported in the literature in the last several
centuries relating to the adverse health effects of toxigenic
molds and fungi in man and other species. These include, but
are not limited to, Alimentary toxic aleukia,
Dendrodochiotoxicosis, Kashin Beck disease, 'Usov's disease,'
Stachybotryotoxicosis, Cardiac beriberi, Ergotism, Balkan
nephropathy, Reye's syndrome, hepatocellular carcinoma, Pink
Rot, and Onyalai.
Specifically, Dr. Gray's
clinical evidence confirmed the presence of B-cell
proliferation, excessive T-cell activation, inhibition of
suppressor cell complement receptor sites, suppression of
Natural Killer Cell populations which are centrally involved in
cancer cell surveillance and destruction, and excessive mitogen
suppression, confirmed by inhibition of stimulated lymphocyte
mitosis in the presence of extracts of pokeweed, concanavillin A
(Con-A), and phytohemagglutinin (PHA) implying the inhibition of
immune cell reproduction, generally considered necessary to
mounting a competent immune response. In short, the immune
system is showing signs of being excessively stimulated by the
inhalation of respirable spores, and simultaneously is being
partially inhibited by the effects of the mycotoxins released by
those spores.
In addition, pulmonary
function testing (PFTs) confirmed excessive small airways
obstruction, the hallmark of mold induced hypersensitivity
pneumonitis, and a review of the neuropsychological evaluations,
and QEEGs performed on the mold exposed individuals confirmed
the presence of central nervous system impairments consistent
with what is expected based on numerous animal and human
toxicological studies found in the many peer reviewed articles
readily available in the extensive world literature on the toxic
effects of mycotoxins.
Several types of mycotoxins,
including trichothecenes, ochratoxins, patulins, and aflatoxins
induce human illnesses, which resemble radiation sickness and
result from the random effects of being DNA "adduct formers."
Adduct formers are compounds whose molecular size and
configuration allow them to insert themselves randomly into DNA,
and RNA, thus resulting in the inhibition of protein synthesis,
bone marrow suppression, coagulation defects and bleeding
disorders resulting in nasal, pulmonary, and gastrointestinal
hemorrhaging, bleeding into the adrenal glands, uterus, vagina,
and the brain.
In addition, many mycotoxins
are potently neurotoxic, producing central nervous system
effects including behavioral and cognitive changes, ataxia, and
convulsions. This has been extensively described in
peer-reviewed literature in the early and mid twentieth
century-although this literature is not readily accessible on
computerized databases, such as the Medline, and Toxline search
systems, because these sources often do not include titles
before the 1960's. Nonetheless, mycotoxicosis has clearly been
demonstrated to have been the cause of several major human
epidemics, usually involving ingestion of foods prepared with
mold infested grains and cereals, or from the consumption of
livestock which had been fed mold infested feed. Inhalation
and absorption of mycotoxins have also been clearly demonstrated
to be causative of human illnesses.
Throughout the course of
almost thirty years of medical practice, Dr. Gray has treated
hundreds of patient with mold-induced diseases. Until 1994,
most of those patients were people with mold-related allergies
and asthma, and cases of symptomatic coccidiomycosis (valley
fever). In 1994, he treated a group of employees manifesting
building related illnesses, which were ultimately confirmed to
have been caused by several molds, most prominently Stachybotrys
atra, Penicillium, Aspergillus, Chaetomium, and several others,
usually referred to as structural molds. He has since seen
several dozen patients with building-related mold exposures
resulting in a wide variety of illnesses.
The biological function of
mycotoxins is to enhance the probability of survival of the next
generation of mold. The mycotoxins are typically "packaged" in
the spores with the DNA of the organism. This process almost
always takes place under adverse environmental conditions: when
nutrient substrates are becoming less available, or when arid
conditions prevail. We see this with regularity in the Sonoran
Desert climate experienced in Tucson. With every rain the molds
grow. Within less than a day, when the humidity returns to the
teens (10 to 20% being the norm in the desert), the ambient
environmental spore counts reported by our local meteorologists
dramatically increases: it is a common species-specific survival
mechanism. When spores are forming, mycotoxins are being
produced. The mycotoxins-many of which are antibiotics or
antifungal agents-provide an increased probability that any
given spore will be likely to survive in a very competitive
environment with many micro organisms competing for the same
ecological "nitch." Because many of the molds also produce
solvent carriers they are not only a source of significant
solvent exposure, but, whether the mycotoxins do volatilize or
not, the do aerosolize and become air born via aerosol. In
addition, the spores in which the mycotoxins often reside do
take flight as they are released from the hyphae, hair like
processes of the parent cell, and even the 7 by 4 micra
Stachybotrys atra spore must be considered respirable (able to
penetrate to the respiratory surfaces of the lung-the alveoli)
because these particles tend to orient themselves parallel to
the long dimension of the progressively smaller bronchi as they
travel down to the lungs tiny air sacs. While the kinetics
associated with spherical particles dictates that only particles
between 5 and 0.005 micron are capable of penetrating to the
alveoli, the size range of mold spores is from 7 to 0.003
micron, and they are uniquely capable of penetrating to the
alveoli. Once having arrived in the alveoli, they stimulate a
dramatic immune response. This is also a site in which they are
able to release their mycotoxins, allowing them to be absorbed
into the blood flowing through the prolific capillary beds found
adjacent to the air sacs. The mycotoxins then circulate
throughout the body.
Just as psilicybin
containing mushrooms and lysergic acid (LSD) are capable of
inducing hallucinations, and cognitive distortions, a number of
mycotoxins are capable of causing both transient, and permanent
neurotoxicity. Approximately 70% of the patients with confirmed
exposure to toxigenic structural mold have been demonstrated to
have significant neurotoxicity. Neurological problems
encountered among these patients have included optic neuritis,
multiple sclerosis, basal ganglion and midbrain based movement
disorders--developing in some cases within months of occupancy
of contaminated residences. In two female patients from
Phoenix, blindness was demonstrated in one or both eyes, and
then within several months of the onset of the optic neuritis,
both were diagnosed with MRI confirmed multiple sclerosis, first
manifesting in the spinal cord of one of them. Four of the
patients in the same group were confirmed to have serious
movement disorders thought to be arising from midbrain
structures. Another patient was confirmed to have developed
occulomotor nerve palsy on three separate occasions, each time
in conjunction with documented exposure to Stachybotrus, and
other structural molds and their associated mycotoxins. Others
were diagnosed with variable toxic encephalopathies by QEEG
brain mapping, neuropsychological testing, and specialized
techniques measuring specific quantifiable neurological
parameters.
Toxic encephalopathy is a
fluctuant neurological condition manifested by cognitive
impairments, which are the direct result of the recurrent and
paroxysmal activity of the immune system and the central nervous
system interacting with each other to cause episodic cognitive
and neurological dysfunction in the form of abnormal brainwave
activity and associated variable signs and symptoms of cognitive
dysfunction such as memory loss, dyslexia, word finding
difficulties and attention deficit disorders. These neurological
abnormalities, which are triggered by exposure to concentrations
of haptogenic, xenobiotic, volatile, organic compounds at sub-osmic
threshold levels, have been demonstrated, by the work of Iris
Bell M.D., Ph. D., at the University of Arizona, as well as
other researchers, to trigger abnormal brainwave activity that
is regionally specific, affecting the temporal lobes
bilaterally, the right parietal lobe and the frontal lobes of
the brain. These three central nervous system structures are
involved in memory function, spatial relations, and cognitive
integrative functions respectively. These effects are recurrent
and can be demonstrated through the use of multiple diagnostic
modalities, including electroencephalograms (EEGs), quantitative
electroencephalograms (QEEGs), PET scans, SPECT scans, and other
objective neurophysiologic modalities. When a patient is
exposed to a haptogenic (immunologically active), xenobiotic
(toxic) trigger to which they are historically reactive,
abnormalities are observed on electroencephalographic tracings
within fifteen seconds of said exposure, even when administered
in a double blind fashion. It is now becoming clear that this
paroxysmal activity can, in fact, take the form of complex
partial seizures, and often leads to immediate, transient
cognitive impairment, followed by a "post-ictal" condition,
characterized by excessive fatigue.
Because the victim of these
episodes does not lose consciousness, as occurs in grand mal
seizures, they are often unaware that these episodes are
occurring, but an astute observer watching the individual would
see what in essence is described in the literature as an
"absence seizure." In many of the patients who suffer from
toxic encephalopathy that have been tested with 24-hour,
ambulatory electroencephalograms, multiple seizures per hour in
some cases, and certainly multiple seizures in a 24-hour period
have been demonstrated.
Brain mapping, done by
quantitative electroencephalographic techniques (QEEG), also has
demonstrated consistent abnormalities in several types of
brainwaves. This mode of analysis has become the clinically
relevant standard in the assessment of patients suffering from
toxic encephalopathy, and actually offers the potential for
therapeutic intervention using neurotherapy with QEEG-gated
biofeedback techniques. Neurotherapeutic intervention has been
shown to reduce the frequency and severity of these episodes,
and may improve cognitive function and memory.
A wealth of literature in the
field of Occupational Medicine has appeared over a more than a
century confirming the significance of molds in both residential
and workplace environments. Molds have long been known to lead
to the development of a severe debilitating lung disease known
as hypersensitivity pneumonitis. Hypersensitivity pneumonitis is
an inflammatory condition which involves inflammation in the
smallest of the airways in the lungs, triggered by exposure to
commonly encountered volatile organic compounds of a chemical
nature, as well as several types of biological dusts, pollens,
mold spores and mycotoxins "packaged" within the spores. The
ensuing inflammation results in small airways spasms, and
obstruction occurring in regular and repetitive episodes. This
condition which causes shortness of breath, and often severe
debilitating chest pain, is generally treatable with medications
commonly used for asthma, and is only preventable by avoidance
of exposure to the triggering agents such as mold spores.
Although the condition of hypersensitivity pneumonitis was first
described in association with mold spore exposure in conditions
varyingly described as reactive airways disease, silo filler's
disease, farmer's lung, bird fancier's disease--which rarely
occurs among individuals keeping a single bird as a pet, but
frequently is seen among those maintaining pigeon coups with
hundreds of birds present at a time--and byssinosis or "Brown
Lung Disease" in cotton mill workers. If not treated
aggressively, hypersensitivity pneumonitis will lead to the
progressive development of emphysema. In the case of structural
mold-exposed individuals, treatment with antifungal medication,
such as ketaconazole, itraconazole, and/or fluconazole-each
produced or derived from mold mycotoxins themselves-may be
appropriate and necessary.
There is allegedly
"disagreement within the scientific community as to whether the
relatively large size of Stachybotrys spores prevents it from
penetrating to the deepest areas of the lung." However, this
controversy was resolved by the documented presence of
Stachybotrys spores in the alveoli and small airways of the lung
of an infant suffering and dying from mold-induced hemorrhagic
pneumonitis a rare lung disease, found to have occurred in a
series of nine infants in Cleveland, Ohio by Dr. Dorr Dearborn,
who confirmed the presence of Stachybotrys mold in each of the
infants' homes. These cases were reported by the Centers for
Disease Control (CDC), in their 1998 Morbidity and Mortality
Weekly Reports (MMWR). There has been some controversy raised
by some researchers claiming that they cultured the organism
from these homes, and were unable to detect mycotoxins in the
resultant cultures. The problem is that they are not
acknowledging that molds in general do not produce mycotoxins
when they are growing under "ideal" conditions, such as those
that usually obtain in laboratory settings. They generally
produce their toxins when austere living conditions bring about
sporulation, for example when nutrients are depleted, or when
arid conditions prevail.
The clinical observations from the
patients in Dr. Gray's practice who presented between 1994 and
the present with environmental hygiene documentation of exposure
to structurally-related molds in their homes or workplaces
provides clear evidence of the presence of consistent
abnormalities in the clinically relevant workup. These
abnormalities include, but are not limited to, the immunologic,
pulmonary, and neurological workup, that is clearly parallel to
the findings in both human and animal studies recorded in the
local, national, and international medical literature. Similar
findings were reported in the case of Ron Allison-Melinda
Ballard's husband-who suffered debilitating memory loss, which,
to a reasonable medical certainty, was causally related to the
confirmed and relevant mold exposure in their home. The
congruency of the findings in these cases, collectively have
confirmed the presence of a "clinical fingerprint" that allows
for the clinical diagnosis of mycotoxicosis-within reasonable
medical certainty. It is quite clear, when the clinical
fingerprint is evident, that "but for the exposure to mixed
toxigenic structural molds" these constellations of illness
would not be occurring. One Tucson based neurotherapist, who
has career long experience treating patients with blunt head
trauma, strokes, and toxin induced trauma, stated that never in
his experience has he seen entire families present demonstrating
cognitive deficits of such severity. The variety of
abnormalities reported is consistent with the random nature of
the damage induced by "adduct formers" discussed below. The
random mutagenic events encountered with mycotoxins is
reminiscent of radiation induced damage, and the same
constellation of bone marrow suppression, interference with
protein synthesis resulting in failure to thrive, weight loss
and weakness, easy bruising, frequent nosebleeds, and increased
susceptibility to infections, skin lesions, and rashes is
clinically similar.
In reply to the assertions
that the symptoms reported by the victims of toxigenic
structural mold exposure, sick building syndromes, or chemical
hyper-reactivity are psychosomatic, or somatoform disorders, Ann
Davidoff (l994) clearly demonstrated the absence of any data
supporting such hypotheses. In addition, rebutting assertions
of malingering by "litigenous" victims of exposure to
environmental toxins, powerful data has been filed with the
Federal Agency for Toxic Substances Disease Registry (ATSDR) in
relation to the sub-registry on the benzene exposed residents of
the Three Lakes Subdivision north of Houston, which clearly
demonstrated that there was no shift in the symptoms reported by
this cohort of 1100 residents when they were surveyed both
before and after litigation was filed in that matter. Thus
claims of somatoform origins of patients complaints are
seriously flawed, misleading, and biased, and represent an
unsubstantiated hypothesis which is at best without merit, and
at worst cruel, as it demeans patients who are suffering from
serious, organic, physiologic problems usually affecting
multiple organ systems.
Mycotoxins produced by
structural molds-meaning molds imported into the residences,
workplaces, and public buildings on the paper covering the
drywall, and other wood based composite materials-- often
represent some of the most toxic substances known to humankind.
The molds imported on building materials are not the same as
molds commonly encountered in outdoor environments. The wood
chips, and wood pulp imported from the Amazon rain forests bring
with them their own varieties of mold spores. The climate of
"deregulation" that has prevailed since the early eighties has
favored the proliferation of new construction in which building
codes requiring pretreatment of building materials with
anti-fungal agents have simply not been adequately enforced.
This in turn has led to circumstances, which when coupled with
"corner-cutting" structural defects, have led to the conditions
which favor water intrusion that has all to often allowed the
appearance of truly toxic levels of mold spores and mycotoxins,
which are, in turn, capable of inducing serious diseases
resulting from the presence of agents with the potential for
damaging the human immune system, inducing allergies,
gastrointestinal disorders, skin disease, neurological disease,
endocrine disruption, birth defects, cancer, pulmonary, renal,
hepatic, and general metabolic disorders.
Treatment protocols for the
problems seen must be individualized, and carefully constructed,
taken great care to avoid overuse of antibiotics with infection
mimicking inflammatory conditions. This is particularly
relevant, because inappropriate antibiotic use may foster
further mold and fungal growth in an already compromised host.
One of the most frustrating
problems relating to dealing with patients experiencing illness
from exposure to structural molds, and bioaerosols from gray
water contamination is the inability to mobilize a proactive
response from public agencies. The issue is like the "hot
potato." In the apartment complex alluded to above in the
Phoenix area, when tenants complained to the County Health
officials, they came to inspect without the instrumentation
required for the detection of moisture or mold. And when
attempts were made to report cases of illness to the State
Health Department, after being told by a Deputy Assistant
Director that the problem would be referred to the Director of
the Division of Epidemiology and Chronic Disease, no return call
was forthcoming. Similarly, when Dr. Gray raised the issue of
structural mold, which resulted in the closure of the Bella
Vista Elementary School in Sierra Vista with the Cochise County
Board of Health--on which he served for six years-- the only
physician member of the Board opined that "mold was not a public
health issue!" Clearly, education is the order of the day.
Michael R. Gray, M.D.,
M.P.H., C.I.M.E.
Preventive Medicine and
Occupational Medicine, Board Certified
Internal Medicine, Emergency
Medicine, and Toxicology, Board Prepared
Certified Independent
Medical Examiner, and
Commissioner, Medical
Direction Commission, Arizona State Division of Emergency
Medical Services.
Bibliography:
1. Andersson, M.A., M.
Nikulin, U. Koljalg, M.C. Andersson, F. Rainey, K. Reijula, E.L.
Hintikka, and M. Salkinoja-Salonen, "Bacteria, and Toxins in
Water-Damaged Building Materials," Applied and Environmental
Microbiology, 1997 Vol. 63, No. 2: pps 387-393.
2. Ayada, A. "Iraqi
Research on New Mycotoxicosis in Humans" Dept. Of Defence
3. Brunekreef, B. "Home
Dampness and Respiratory Morbidity in Children" Am. Rev. Respir
Dis. 1989 Vol. 140 pg 196-203.
4. Coppock, R.W., DVM,
PhD; W. E. Hoffmann, DVM, PhD; H.B. Gelberg, DVM, PhD; D. Bass,
PhD; B. Buck, Koritz, DVM, MS, 1989 "Hematologic Changes Induced
by intravenous administration of diacetoxyscirpenol in pigs,
dogs, calves" Am. J. Vet. Res. 1989 Vol. 50#3 Pg.
5. Coppock, R.W., DVM,
PhD; W. E. Hoffmann, DVM, PhD; H.B. Gelberg, DVM, PhD; D. Bass,
PhD; B. Buck, DVM, MS "Pharmacokinetics if Diacetoxyscirpenol in
Cattle and Swine Effects of Halothane. Am. J. of Vet Res. 1987,
Vol. #48 Pg. 41.
6. Dales, R., Richard
Burnett, Harry Zwanenburg and, Claire A. Franklin. "Respiratory
Health Effects of Home Dampness and Mold Among Canadian
Children" Am. J. of Epidemology. 1991, Vo. 134 #2 Pg. 196-203.
7. Dales, R., Richard
Burnett, and Harry Zwanenburg. "Adverse health Effects Among
Adults Exposed to Home Dampness and Mold" Am Rev, Respir Dis.
1991 Vol. 143 Pg. 505-509.
8. Davidoff, A.
"Psychogenic Origins of Multiple Chemical Sensitivities Syndrom:
A Critical Review of Research Lit" Arch. Of Environ. Health 1994
Vol. #5 Pg. 316-325.
9. Dunn,a. et al. "Endotoxins
Induced Activation of Cerebral Catecholamine and Serotonia
Metabolism Comparison with Interlukin-1 J of Pharmacology & Exp.
Therpy 1992 Feb.
10. Elidemir, O.
"Isolation of Stachbotrys from the Lung of Child with Pulmonary
Hemosiderosis" Pediatrics April 5 1999 964-966.
11. Frisvad, J. "The
Connection Between Penicillia and Aspergilli and Mycotoxins with
Special Emphasis on Misidentified Isolates" Arch. Of Envirom.
Contam. Toxicol 1989 Vol. 18 452- Pg. 452-467.
12. Edwards,J. F."
Humidifier Fever " Thorax 1977 32, 653-663
13. Flappan S, Jay
Portnoy, Patricia Jones Charles Barnes "Infant Pulmonary
Hemorrhage in Suburban home with water Damage and Mold
Environmental Health Perspectives Vol. 107,#11 Nov. 1999
14. Hendry,M. Cole, Eugene
"A Review of Mycotoxins in Indoor Air" J. of Toxicology and
Environmental Health 1993 38: 183-198
15. Jarvis Bruce, W.G.
Sorenson, Eev-Lisa Hintikka, Marjo Nikulin, Yihong, Zhou, Jian
Jiang, Shengun Wang, Simon Hinkey, Ruth Etzel, D. Dearborn
"Study of toxin production by Isolates of Stachybotrys chartarum
and Memnoniella echinata Isolated during a Study of Pulmonary
Hemosiderosis in Infants" Applied Environ. Microbiology 1998
Vol. 64,#10 pps 3620-3625
16. R.M. Karr M. R. Wilson, V. R.
Anicetti, B.A. S. B. Lehrer, Ph.D B. T> Butcher, P.D. and J. E.
Salvaggio, M.D. "An Approach to Fungal Antigen Relationships by
Radioallergosorbent" J. Allergy Clin. Immunol 1981 March Vol. 67
No 3. pp 194-198
17. Johanning E. Phillip
Morey, Bruce Jarvis, Ray Biagini, DeLon Hull, Paul Landsbergis,
"Health and Immunology Study Following Exposure to Toxigenic
Fungi Stachybotrys chartarum in a Water -Damaged Office
Environment "Int. Arch Occup. Environ health 1996 68: 207-218
18. Lappalainen S,
Nikulin,M Berg,Seija,Paivi Parikka Eeva-Lissa Hintikka Anna
-Lisa Pasanen "Fusarium Toxins and Fungi Associated with
Handling of Grain on Eight Finnish Farms"Atmos. Environ. Vol. 30
No. 17 pp 3059=3065 1996
19. Llicorish, Kenrick,
Harold Novey, Peter Kozak, Ronald Fairshter and Archie Wilson
"Role of Alternaria and Penicillium Spores in the Pathogenesis
of Asthma" J. of Allergy Clin. Immunol. Dec. 1995 Pg.819-824
20. M Mahmoudi, D.O and
Eric GershwinM.D. "Sick Building Syndrome. III Stachybotrys
chartum" Journal of Astma 37 {2} 191-198 (2000)
21. Nielsen K.F., M.O.
Hansen, T.O. Larsen, U. Tharne "Production of Trichothecene
Mycotoxins on Water Damaged Gypsum Boards In Danish Buildings"
Int. Biodeterioration & Biodegradation 42 1998 1-7
22. Nielsen, K.F., M.O.
Hansen, T.O. Larsen, U. Tharne "Production of Mycotoxins on
Artificially Inoculated Building Materials" Int.
Biodeterioration & Biodegradation 42 1998 9-16
23. Nikulin, Marjo, Kari
Reijula Bruce Jarvis, Pirjo Veijalainen, and Eeva-Lisa Hintikka
"Effects of Intranasal Exposure to Spores of Stachybotrys atra
in Mice," Fundamental and Applied Toxicology 35, 182-188 1997
24. Ogawa, Kiyoshi. Masto
Nakamura, Mitsuo Hayashi, Satoshi Yaginuma, Syui Yamamoto, Kazu
Furihata, Kazuo Shin-Ya and Hauo Seto Stachybocins, "Novel
Endothelial Receptor Antagonists, Produced by Stachybotrys sp.
M6222," J. of Antibiotics Dec. 1995 p 1396 - 1400
25. Pang, V "Experimental
T-2 Toxicosis in Swine Following Inhalation Exposure: Clinical
Signs & Effects on Hematology-Serum Biochemistry and Immune
Response" Fundamental and Applied Toxicology {11} 100-109 1988
26. Pang,V. "Toxicology of
T-2 Toxin in Swine following Topical Application," Fundamental
and Applied Toxicology 11 pp 50-59 1988
27. Carol, Rao, Joseph
Brain and Harriet Burge, "Reduction of Pulmonary Toxicity of
Stachybotrys chartarum Spores by Methanol Extraction of
Mycotoxins" Applied and Environmental Microb. July 2000 p
2817-2821 Vol 66 #7
28. Rautiala, Sirpa, Tiina
Reponen, Anne Hyvarinen,Aino Nevalainen, Tuula Husman,Anu
Vehvilainen, Pentti Kalliokoski "Exposure to Airborne Microbes
During the Repair of Moldy Buildings" Am Ind. Hygiene
Association (57) March 1996 p279-284
29. Rowen, Niel, Cameron
Johnstone, Craig McLean John Anderson, Joe Clarke, "Prediction
of Toxigenic Fungal Growth in Buildings by Using a Novel
Modeling System," Appl. Environ. Microb. Nov. 1999 Vol 65 #11 p
4814- 4821
30. Savilahti, Risto,
Jukka Uitti, Pekka Lippala, Tula Husman, Pekka Roto,
"Respiratory Morbidity among Children Following Renovation of a
Water-Damaged School," Archives of Environmental Health Nov.
Dec. Vol.55 (6) Nov. Dec. p 405-409
31. Sakamotto, Kazutoshi,
Eisku Tsuji, M. Miyauchi, Tomoko Nakanishi, M. Yamashita, N
Shigematsu, Toshihaur Tada, S. Izuma,and M. Okuhara "FR 901459,
A Novel Immunosuppressant Isolated from Stachybotrys chartarum
No. 19392," Journal of Antibiotics Dec. 1993 p 1788
32. Sudakin, M.D., D.
"Stachybotrys chartarum: Current Knowledge of It's Role in
Disease" Med Gen. Med Feb. 29 2000
33. Michael Sweeney, Alan
Dobson, "Molecular Biology of Mycotoxins Biosynthesis" FEMS
Microbiology Letters 175 1999 p 149-163
34. Steyn, The
Biosyntheses of Mycotoxins a Study in Secondary Metabolism
Academic Press
35. T, Tuomi, K . Reijula,
T Johnsson, K. Hemminki, E Hintikka O, Lindroos S. Kalso. P,
Koukila-Kahkola, H, Mussalo-rauhamaa and T. Haahtel "Mycotoxins
in Crude Building Materials from Water -Damaged Buildings,"
Appl. Environ. Microb. May 2000 Vol 66 #5 p 1899-1904
36. Thorn, Jorgen, Ragner
Rylander "Inflammatory response after Inhalation of Bacterial
Endotoxins Assesed by the Induced Sputum Technique," Thorax Aug.
1998 pps 1047-1052
37. Smedje, D. Norback
"New Ventilation System at Select Schools in Sweden- Effects on
Asthma and Exposure," Archiv. Of Environmental Health Jan. Feb
2000 Vol 55 no1 pps 19-25
38. Thuvander,A.C.,
Wikman,I, Gadhasson, "In Vitro Exposure of Humans Lymphocytes to
Trichothecenes: Individual Variations in Senstvity and Effects
of Combined Exposure on Lymphocyte Function" Food and Chem,".
Toxicology 37 1999 p 639-648
39. Ueno, "Toxicological
Features of T-2 Toxin and Related Trichothecenes," Fundamental
of Applied Toxicology4 s124-s132 1984
40. Vesper. S Et al. "
Evaluation of Stachybotrys in the House of an Infant with
Pulmonary Hemorrhage: Quantitative Assessment Before, During and
After Remediation," Jn. of Urban Health Vol: 77 No. 1 March 2000
41. Vesper, S Dorr
Dearborn, O Elidermir, and R. Haugland "Quantification of
Siderophore and Hemolysin from Stachybotrys chartarum Strains,
Including a Strain Isolated from the Lung of a Child with
Pulmonary Hemorrhage and Hemosiderosis," Applied and
Environmental Microbiology June 2000 Vol 66 No 6 Pg 2678-2681
42. Velazco, V., G. Faifer
and Godoy " Differential Effects of T-2 Toxin on Bone marrow and
Spleen Erythropoiesis in Mice," Food and Chem Toxicology 34 1996
p 371-375
43. Verhoeff, A. P., R. T
Van Strien j. H van Wijen, B. Brunekreef "Damp Housing and
Childhood Respiratory Symptoms: the Role of Sensitization to
Dust Mites and Mold," Am J of Epidemiology Vol. 141 No .2 pps
103110
44. Wang, J.D., W.
Fitzpatrick and J. Wilson "Effects of Trichothecene Mycotoxin
T-2 Toxin on the Neurotransmitters and Metabolites in Discrete
Areas of the Rat Brain," Food and Chemical Toxicology 36 1998 p
947-953
45. Yike, I., T Allen, W.
Sorenson D. Dearborn "Highly Sensitive Protein Translation Assay
for Trichothecene Toxicity in Airborne Particulates: Comparison
with Cytotoxicity Assays," Applied Environmental Microb. Jan
1999 Vol 65, No1 pp 88-94
46. Yan, D.K., Rumbeiha J.
Pestka "Experimental Murine IgA Nephropathy Following Passive
Administration of Vomitoxin-Induced IgA monoclonal Antibodies,"
Food and Chemical Toxicology 36 1998 1095-1106
47. Zhou, G., W. Whong,
T. Ong, B. Chen, "Development of a fungal specific PCR Assay for
Detecting Low-Level Fungi in an Indoor Environment," Molecular
and Cellular Probes, Vol 14 No 6 Nov. 2000 339-348
Book References:
1. "Symposium On
Mycotoxins In Human Health," edited by J F.H. Purchase Macmillan
1971
2. "Environmental Health
Criteria II Mycotoxins," W. H. O. 1979
3. "Toxicology
Biochemistry and Pathology of Mycotoxins," edited by; Uraguchi
and Yamazaki Halstead Press 1978
4. "Moulds Fungi and
Bronchial Asthma," P. J. Van Der Werff 1958
5. "Mycotoxins in Human
and Animal Health," 1977 Pathotox Press
6. "Clinical and
Experimental Aspects of Fungal Poisoning,"1977 Han Publishers
7. "Guide to Clinically
Significant Fungi," Deanna A. Sutton, A Fothergill, M Rinaldi
Williams and Wilkins
8. "Mycotoxins," V. Berina,
Elsevier, 198I PCS Environmental Health Criteria WHO 1990
9. "The Biosynthesis Of
Mycotoxins A study In Secondary Metabolism," Editor: Pieter
Steyn
10. "Molds, Mushrooms, And
Mycotoxins," By Christensen 1975
11. "Toxicology of Plant
and Fungal Compounds," edited by Richard Keeler
12. "Mould Fungi and
Bronchial Asthma," P.J. Van Der Werff
©2001-2005 Mold-Help
|