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At least 343 records · Page 19Linked to original sources
PubMed2002

Molecular mechanism of satratoxin-induced apoptosis in HL-60 cells: activation of caspase-8 and caspase-9 is involved in activation of caspase-3.

Satratoxins have been recognized as potential immunomodulatory agents in outbreaks of building-related illness. Here we report that satratoxin G-treated human leukemia HL-60 cells underwent apoptosis through the action of caspase-3 which was activated by both caspase-8 and caspase-9. Western blot analysis of caspase-3 in the satratoxin G-treated cells apparently indicated the appearance of a catalytically active fragment of 17 kDa. Increased caspase-3 activity was also detected by using a fluorogenic substrate, DEVD-AMC. Next, exposure to satratoxin G led to cleavage of PARP from its native 116 kDa form to a 85 kDa product. Moreover, DFF-45/ICAD were cleaved into a 12.5 kDa fragment via satratoxin G treatment. Enzymic assay on IETD-AMC revealed that caspase-8 is strongly activated by exposure to satratoxin G while T-2 toxin (T-2) could not activate caspase-8 at an early stage of apoptosis. Furthermore, satratoxin G caused a release of cytochrome c from mitochondria into the cytosol and increased the activity of caspase-9 against LEHD-AMC. These findings indicate that satratoxin G-induced apoptosis involves activation of caspase-3 and DFF-40/CAD through both activation of caspase-8 and cytosolic accumulation of cytochrome c along with activation of caspase-9.

Apoptosis↗
PubMed2003

Indoor air quality and health does fungal contamination play a significant role?

Fungal contamination in buildings can vary greatly, and their presence in a dwelling does not necessarily constitute exposure. Measurement of mold spores and fragments varies depending on the methodology and instruments used. Meaningful comparison of data is rarely possible. The presence of a specific immune response to a fungal antigen only connotes that exposure to one or more related species has occurred, but not that there is a symptomatic clinical state. The response of individuals to indoor bioaerosols is complex and depends on age, gender, state of health, genetic makeup, and degree and time of bioaerosol exposure. In general, mold contamination in buildings is associated with incursion of water or moisture, which should be remedied as efficiently as possible. When disease occurs, it more likely is related to transient annoyance or irritational reactions. Allergic symptoms may be related to mold proliferation in the home environment. Because molds are encountered both indoors and outdoors, it is difficult to determine where the sensitivity initially arose and if the response is solely provoked by either an indoor or outdoor source. As an indoor allergen, mold is considered to be an infrequent participant in the induction of allergic disease when compared with housedust mites, animal dander, and cockroach allergens. Infection in healthy individuals is rare and usually is caused by an outdoor source. Building-related disease caused by mycotoxicosis has not been proved in the medical literature.

Air Pollution, Indoor↗
PubMed2003

Toxic mold: phantom risk vs science.

OBJECTIVE: To review the available literature on the subject of fungi (molds) and their potential impact on health and to segregate information that has scientific validity from information that is yet unproved and controversial. DATA SOURCES: This review represents a synthesis of the available literature in this area with the authors' collective experience with many patients presenting with complaints of mold-related illness. STUDY SELECTION: Pertinent scientific investigation on toxic mold issues and previously published reviews on this and related subjects that met the educational objectives were critically reviewed. RESULTS: Indoor mold growth is variable, and its discovery in a building does not necessarily mean occupants have been exposed. Human response to fungal antigens may induce IgE or IgG antibodies that connote prior exposure but not necessarily a symptomatic state. Mold-related disease has been discussed in the framework of noncontroversial and controversial disorders. CONCLUSIONS: When mold-related symptoms occur, they are likely the result of transient irritation, allergy, or infection. Building-related illness due to mycotoxicosis has never been proved in the medical literature. Prompt remediation of water-damaged material and infrastructure repair should be the primary response to fungal contamination in buildings.

Air Pollution, Indoor↗
PubMed1995

Design, synthesis, and evaluation of A/C/D-ring analogs of the fungal metabolite K-76 as potential complement inhibitors.

The terpenoid 6,7-diformyl-3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'-trihydrox y-2',5',5', 8a'-tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran] (1a; K-76), a natural product of fungal origin, and its monocarboxylate sodium salt 1c (R = COONa; K-76COONa) inhibit the classical and alternative pathways of complement, and 1c was shown to inhibit the classical pathway at the C5 activation step. In an attempt to elucidate the essential pharmacophore of 1a,c, the natural product was used as a "topographical model" for the design of partial analogs retaining the desired complement inhibiting potency. Therefore, A/C/D-ring analogs have been synthesized, as shown in Scheme 1 using 3-methoxyphenol (3) and limonene chloride (5) as starting materials, which contain functional groups similar to those found on the natural product. The use of (4R)-(+)- and (4S)(-)-limonene chloride (5a,b, respectively) provided two series of compounds differing in the stereochemistry of the C-4 chiral center (limonene moiety numbering). The in vitro assay results of the inhibition of anaphylatoxin production and classical complement-mediated hemolysis revealed that 7-carboxy-2-(R,S)-methyl-2-(1'-methylcyclohexen-(4'R)-yl)-4-met hoxybenzofuran (13a) and 7-carboxy-2-(R,S)-methyl-2-(1'-methylcyclohexen-(4'S)-yl)-4-met hoxybenzofuran (13b) were active in the same range of concentrations as the natural product.

Animals↗
PubMed2006

Carneic acids A and B, chemotaxonomically significant antimicrobial agents from the xylariaceous ascomycete Hypoxylon carneum.

Carneic acids A and B (1, 2) are polyketide antibiotics structurally related to phomopsidin. They were isolated as major constituents of the stromata of Hypoxylon carneum, a species that had shown a highly specific secondary metabolite profile in a survey of xylariaceous ascomycetes based on HPLC profiling. Their chemical structures were elucidated by a combination of spectroscopic methods and by preparation of derivatives. An X-ray crystal structure of the dinitrobenzoate of carneic acid B methyl ester (8) was obtained, even allowing for determination of its absolute structure. The carneic acids showed weak antibacterial and moderate antifungal activities in the serial dilution assay against selected microbial organisms. They appear to be species-specific marker molecules in H. carneum from different geographic regions, but do not constitute major metabolites of more than 100 species of Xylariaceae. Their biological and chemotaxonomic significance is discussed.

Anti-Infective Agents↗
PubMed2002

A new strategy toward the total synthesis of stachyflin, a potent anti-influenza A virus agent: concise route to the tetracyclic core structure.

[reaction: see text] A new strategy directed toward the total synthesis of stachyflin, a potent and novel anti-influenza A virus agent isolated from a microorganism, has been presented through the enantioselective synthesis of the tetracyclic core structure. The synthetic method features a BF(3) x Et(2)O-induced domino epoxide-opening/rearrangement/cyclization reaction as the key step.

Antiviral Agents↗
PubMed2001

Adult-onset asthma is associated with self-reported mold or environmental tobacco smoke exposures in the home.

BACKGROUND: In recent years, we have gained better knowledge about the influence of indoor environments on respiratory symptoms and asthma. The purpose of this study was to examine certain exposures in the home environment and the risk of adult-onset asthma. METHODS: A nested case-referent study of adult-onset asthma was performed in a random population sample (n = 15813), aged 20-50 years. Cases for the study included subjects reporting "physician-diagnosed" asthma (n= 174). The referents (n = 870) were randomly selected from the whole population sample. The case-referent sample was investigated with a comprehensive mailed questionnaire about exposures in the home environment, asthma, respiratory symptoms, smoking habits, and atopy. Odds ratios (OR) with 95% confidence intervals (CI) were calculated while controlling for age, sex, smoking, and atopy. RESULTS: Increased adjusted OR for asthma were associated with exposure to molds (OR 2.2, 95%, CI 1.4-3.5), environmental tobacco smoke (OR 2.4, 95%, CI 1.4-4.1), and the presence of a wood stove (OR 1.7, 95% CI 1.2-2.5). CONCLUSIONS: This population-based case-referent study indicates that self-reported domestic exposures to molds or environmental tobacco smoke can be associated with adult-onset asthma.

Adult↗
PubMed2003

Slight respiratory irritation but not inflammation in mice exposed to (1-->3)-beta-D-glucan aerosols.

Airway irritation effects after single and repeated inhalation exposures to aerosols of beta-glucan (grifolan) were investigated in mice. In addition, the effects on serum total immunoglobulin E (IgE) production and histopathological inflammation in the respiratory tract were studied. The beta-glucan aerosols provoked slight sensory irritation in the airways, but the response was not concentration dependent at the levels studied. Slight pulmonary irritation was observed after repeated exposures. No effect was found on the serum total IgE levels, and no signs of inflammation were seen in the airways 6 h after the final exposure. The results suggest that, irrespective of previous fungal sensitization of the animals, inhaled beta-glucan may cause symptoms of respiratory tract irritation but without apparent inflammation. Respiratory tract irritation reported after inhalation of fungi may not be entirely attributed to beta-glucan.

Aerosols↗
PubMed2004

Pathogenesis of indoor fungal diseases.

Mold growth within homes and other buildings has been associated to varying degrees with human health problems. These problems vary from allergenic disease to toxicosis. Case definitions for mold exposure have not been adequately defined to allow for a pathognomonic diagnosis of mold-caused disease following indoor exposure. Some important factors that may contribute to the pathogenesis of indoor mold induced disease include beta (1,3)-D-glucans, outer cell wall fungal hydrophobins, 1,8-dihydroxynaphthalene melanin, fungal volatile organic compounds, mycotoxins, and stachylysin. The information in this contribution was presented as the ISHAM Presidential address as a means to clarify some of the confusing surrounding indoor mold-related health issues.

Air Microbiology↗
PubMed2005

Determination of microbial volatile organic compounds adsorbed on house dust particles and gypsum board using SPME/GC-MS.

UNLABELLED: Adsorption of microbial volatile organic compounds (MVOCs) on house dust was analyzed by performing solid phase microextraction (SPME) in combination with gas chromatography-mass spectrometry (GC-MS). Settled dust samples were exposed to five selected MVOCs and to cultures of the molds Stachybotrus chartarum, Aspergillus versicolor, and Chaetomium globosum. Considerable desorption of the MVOCs adsorbed on the dust occurred spontaneously within a few hours at room temperature and within several days or weeks after storage at -20 degrees or -80 degrees C. Similar results were found for a sample of a gypsum board cultivated with A. versicolor. SPME/GC-MS analysis performed immediately after sampling revealed several of the studied MVOCs on gypsum board and settled dust collected in a house garage with visible mold growth. MVOCs adsorbed on respirable particles of house dust can be inhaled and reach deep into the respiratory system, which may partly explain health effects that have been found to be associated with the presence of low concentrations of MVOCs in air. Particle-bound MVOCs can easily be detected by SPME/GC-MS analysis, thus this technique may prove to be very useful in indoor air research for identifying factors that affect human health. PRACTICAL IMPLICATIONS: We used SPME combined with GC-MS to study the adsorption and desorption of MVOCs on house dust particles that had been exposed to cultivated molds and molds in a damp building. Adsorbed MVOCs desorb spontaneously but this process can be slowed down by storing samples at -20 degrees or -80 degrees C. This opens up a possibility to apply SPME/GC-MS to reveal mold growth in buildings and to determine MVOCs in respirable dust particles that may reach deep in the respiratory system and lead to respiratory illnesses.

Air Microbiology↗