Heat stability of chaetoglobosins A and C.

Chaetomium globosum is commonly found in water-damaged buildings and produces the mycotoxins chaetoglobosin A and chaetoglobosin C (Ch-A and Ch-C, respectively). While attempting to purify Ch-A and Ch-C, we observed that these mycotoxins were broken down after heating. The objective of this study was to determine the temperature and the amount of time necessary to break down Ch-A and Ch-C. We demonstrated that the amounts of Ch-A were significantly reduced when exposed to 75 degrees C for 24 h and 100 degrees C for 90, 120, or 150 min. Under the same conditions, the levels of Ch-C were also lower (although not significantly). At 175 degrees C, no Ch-A was detected after 15 min and Ch-C was significantly reduced after 30 min. Our findings will aid other researchers who work with these mycotoxins in the future.

Towards progress on DNA vaccines for cancer.

Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response while also targeting tumor evasion mechanisms.

SV40 association with human malignancies and mechanisms of tumor immunity by large tumor antigen.

SV40 was discovered as a contaminate of poliovirus vaccine lots distributed to millions of individuals in the United States between 1955 and 1963 while contaminated vaccine batches were later circulated worldwide. After SV40 was observed to cause in vitro animal and human cell transformations and in vivo tumor formations in animals, the search for a connection between the virus and human malignancies has continued to the present day. Different molecular methods have been used to detect SV40 gene products in a variety of human cancers, though SV40 causality in these tumor types has yet to be established. These data, however, are not without controversial issues related to inconclusive SV40 serological and epidemiological evidence alongside tools and methodologies that may contribute to false-positive results in human specimens. This review will also explore how vaccination against SV40 protein products may be used to help prevent and treat individuals with SV40-expressing cancers.

A randomized trial assessing the utility of a test-dose program with taxanes.

OBJECTIVE: Taxanes are commonly used anticancer agents with a potential of producing an allergic or hypersensitivity reaction (HSR). We performed a randomized study to evaluate the value of a test dose given prior to the full dose of either paclitaxel or docetaxel. RESEARCH DESIGN AND METHODS: Patients were randomly assigned to either the administration of the full dose or to the prior administration of a 1 mg intravenous test dose of either paclitaxel or docetaxel. The primary endpoints were severity of the HSR and the cost of drug wastage due to a HSR. RESULTS: Two hundred and eighteen patients were randomized from three different treatment sites. The overall incidence of HSR was 6.5% and there was no significant difference in the incidence of HSR in either group. The mean HSR severity grade was 2.8 for patients without a test dose and 2.3 for those receiving a test dose. There was, however, a reduction in the wastage of taxane in the test dose arm. Wastage avoided in the test dose arm was $1573 per patient who had a HSR and $104 per patient treated with a taxane. CONCLUSION: Although a test dose may not reduce the severity of a HSR with the administration of a taxane, it does reduce the cost associated with drug wastage.

Effect of chlorine dioxide gas on fungi and mycotoxins associated with sick building syndrome.

The growth of indoor molds and their resulting products (e.g., spores and mycotoxins) can present health hazards for human beings. The efficacy of chlorine dioxide gas as a fumigation treatment for inactivating sick building syndrome-related fungi and their mycotoxins was evaluated. Filter papers (15 per organism) featuring growth of Stachybotrys chartarum, Chaetomium globosum, Penicillium chrysogenum, and Cladosporium cladosporioides were placed in gas chambers containing chlorine dioxide gas at either 500 or 1,000 ppm for 24 h. C. globosum was exposed to the gas both as colonies and as ascospores without asci and perithecia. After treatment, all organisms were tested for colony growth using an agar plating technique. Colonies of S. chartarum were also tested for toxicity using a yeast toxicity assay with a high specificity for trichothecene mycotoxins. Results showed that chlorine dioxide gas at both concentrations completely inactivated all organisms except for C. globosum colonies which were inactivated an average of 89%. More than 99% of ascospores of C. globosum were nonculturable. For all ascospore counts, mean test readings were lower than the controls (P < 0.001), indicating that some ascospores may also have been destroyed. Colonies of S. chartarum were still toxic after treatment. These data show that chlorine dioxide gas can be effective to a degree as a fumigant for the inactivation of certain fungal colonies, that the perithecia of C. globosum can play a slightly protective role for the ascospores and that S. chartarum, while affected by the fumigation treatment, still remains toxic.

An animal model for allergic penicilliosis induced by the intranasal instillation of viable Penicillium chrysogenum conidia.

BACKGROUND: A study was undertaken to determine the consequences of long term intranasal instillation of Penicillium chrysogenum propagules in a mouse model. METHODS: C57 Black/6 mice were inoculated intranasally each week for six weeks with 10(4) viable and non-viable P chrysogenum conidia. Cytokine levels and cellular responses in these animals were then measured. RESULTS: Compared with controls, mice inoculated intranasally each week for six weeks with 10(4) P chrysogenum conidia (average viability 25%) produced significantly more total serum IgE (mean difference 1823.11, lower and upper 95% confidence intervals (CI) 539.09 to 3107.13), peripheral eosinophils (mean difference 5.11, 95% CI 2.24 to 7.99), and airway eosinophilia (rank difference 11.33, 95% CI 9.0 to 20.0). With the exception of airway neutrophilia (mean difference 20.89, 95% CI 3.72 to 38.06), mice inoculated intranasally with 10(4) non-viable conidia did not show significant changes in total serum IgE, peripheral or airway eosinophils. However, when compared with controls, this group (10(4) non-viable) had a significant increase in total serum IgG(2a) (mean difference 1990.56, 95% CI 790.48 to 3190.63) and bronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-gamma (mean difference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from mice inoculated intranasally with 10(4) viable P chrysogenum conidia had significantly increased levels of interleukin (IL)-4 (mean difference 285.28, 95% CI 108.73 to 461.82) and IL-5 (mean difference 16.61, 95% CI 11.23 to 21.99). The IgG(2a)/IgE ratio and the IFN-gamma/IL-4 ratio was lower in the group of mice inoculated intranasally with 10(4) viable conidia than in the 10(4) non-viable conidia group and the controls. When proteins were extracted from P chrysogenum conidia, attached to microtitre plates and incubated with serum from the 10(4) viable group, significant increases in conidia-specific IgE and IgG(1) were observed compared with controls, while serum from the 10(4) non-viable group was similar to controls. CONCLUSIONS: These data suggest that long term inhalation of viable P chrysogenum propagules induces type 2 T helper cell mediated (Th2) inflammatory responses such as increases in total and conidia-specific serum IgE and IgG(1), together with BAL fluid levels of IL-4 and IL-5 and peripheral and airway eosinophilia, which are mediators of allergic reactions.

Correlation between the prevalence of certain fungi and sick building syndrome.

OBJECTIVE: To examine the role of fungi in the production of sick building syndrome. METHODS: A 22 month study in the United States of 48 schools (in which there had been concerns about health and indoor air quality (IAQ). Building indoor air and surface samples, as well as outdoor air samples were taken at all sites to look for the presence of fungi or their viable propagules. RESULTS: Five fungal genera were consistently found in the outdoor air and comprised over 95% of the outdoor fungi. These genera were Cladosporium (81.5%), Penicillium (5.2%), Chrysosporium (4.9%), Alternaria (2.8%), and Aspergillus (1.1%). At 20 schools, there were significantly more colony forming units per cubic metre (CFU/m3) (p < 0.0001) of propagules of Penicillium species in the air samples from complaint areas when compared with the outdoor air samples and the indoor air samples from noncomplaint areas. At five schools, there were more, although not significant (p = 0.10), Penicillium propagules in the air samples from complaint areas when compared with the outdoor air samples and the indoor air samples from noncomplaint areas. In 11 schools, the indoor air (complaint areas) fungal ratios were similar to that in the outdoor air. In these 11 schools Stachybotrys atra was isolated from swab samples of visible growth under wetted carpets, on wetted walls, or behind vinyl wall coverings. In the remaining 11 schools, the fungal ratios and CFU/m3 of air were not significantly different in different areas. Many of the schools took remedial action that resulted in an indoor air fungal profile that was similar to that outdoors. CONCLUSIONS: Propagules of Penicillium and Stachybotrys species may be associated with sick building syndrome.

4-Hydroxynonenal mimics ozone-induced modulation of macrophage function ex vivo.

Ozone is a ubiquitous pollutant that can cause acute pulmonary inflammation, cellular injury and may contribute to the development or exacerbation of chronic lung diseases. Despite much research, the effects of ozone on humans and potential cellular mechanisms of injury are still uncertain. However, ozone has been reported to increase the formation of aldehydes that could react with cellular proteins. Therefore, the purpose of these studies was to determine whether 4-hydroxynonenal (HNE), a previously unidentified aldehyde product of ozone exposure, is formed in human subjects exposed to ozone, and whether the response of human alveolar macrophages (AM) following a 1-h exposure to 0.25 ppm ozone with moderate exercise could be mimicked by in vitro incubation of AM with HNE. Western analysis demonstrated increased HNE protein adducts in airway fluid and alveolar macrophages after ozone exposure. AM were examined for endotoxin (lipopolysaccharide [LPS])-stimulated interleukin-1 beta (IL-1 beta) release and expression of heat shock protein 72 (HSP72). Immediately after ozone exposure there was no change in HSP72, but a 5-fold increase occurred 4 h after exposure. By 18 h after exposure, HSP72 levels decreased to below comparable air-exposed levels. Immediately after ozone exposure there was no effect on IL-1 beta release stimulated by LPS. However, IL-1 beta release stimulated by LPS was significantly inhibited 4 h after ozone exposure. By 18 h after ozone exposure, IL-1 beta release stimulated by LPS returned to normal. Incubation of human AM in vitro with HNE induced HSP72 and blocked LPS-stimulated IL-1 beta release possibly by inhibiting interleukin converting enzyme. Consequently, the in vitro results and demonstration of HNE protein adducts following ozone exposure are consistent with HNE being involved in this process in vivo and suggest that the cellular toxic effects of ozone could be a result of thiol reactive aldehydes produced by ozone.