Post-traumatic fatal <Emphasis Type="Italic">Nattrassia mangiferae</Emphasis> orbital infection

Nattrassia mangiferae orbital infection is a very rare disease that is usually curable. We report the first case of a fatal N. mangiferae orbital infection following a thorn penetration injury in a patient who also had diabetes mellitus, heart failure, and cirrhosis.     

Mechanism of action of a novel "combi-triazene" engineered to possess a polar functional group on the alkylating moiety: evidence for enhancement of potency

Previous studies showed that SMA41, a 3-methyltriazene termed "combi-molecules" possessing a dual epidermal growth factor receptor (EGFR)/DNA targeting properties induced potent antiproliferative activity against alkylating-agent-resistant cells expressing EGFR in vitro. However, despite its marked potency, its antitumour activity in vivo was significantly hampered by its poor hydrosolubility and the moderate reactivity of its alkylating moiety. To circumvent this problem, we designed the quinazolinotriazene ZRBA1 to contain a N,N-dimethylaminoethyl group grafted to the 3-position of the triazene chain where it could serve both as a water soluble and a more potent alkylating moiety. ZRBA1 exhibited five-fold stronger EGFR tyrosine kinase (TK) inhibitory activity (IC(50)=37nM) than SMA41, decomposed into a 6-amino-quinazoline FD105 (IC(50)=200nM) and preferentially blocked EGF- over platelet-derived growth factor (PDGF)-or serum-induced cell growth. ZRBA1 induced DNA damage, concomitantly blocked EGF-stimulated EGFR phosphorylation by a partially irreversible mechanism in MDA-MB-468 breast cancer cells, and induced partially irreversible antiproliferative activity. It also prevented EGFR-mediated MAP kinase activation and, in contrast to FD105 and SMA41, induced high levels of apoptosis. Furthermore, ZRBA1 showed significantly greater antitumor activity (p<0.05) than SMA41 in the human MDA-MB-468 breast cancer xenograft model. The results in toto indicate that the appendage of N,N-dimethylaminoethyl to combi-triazenes may be an alternative to the reduced hydrosolubility and also to the lack of potency of monofunctional combi-triazenes against resistant tumours.     

Intranasal exposure to Stachybotrys chartarum enhances airway inflammation in allergic mice

RATIONALE: Exposure to building dampness, often associated with growth of microbes such as Stachybotrys chartarum, has been linked to respiratory symptoms. We have shown previously in a murine model that exposure to S. chartarum can induce lung inflammation characterized by infiltration of neutrophils and lymphocytes; this process is regulated by proinflammatory cytokines and leucocyte-attracting chemokines. OBJECTIVES: Because an atopic predisposition may influence the response to microbes, we examined the effects of S. chartarum on allergic mice in an experimental model. BALB/c mice were sensitized to ovalbumin by intraperitoneal injections and exposed for 3 wk to spores of S. chartarum. MEASUREMENTS AND MAIN RESULTS: Numbers of eosinophils and neutrophils were drastically increased in bronchoalveolar fluid from these mice as compared with the ovalbumin-sensitized/challenged mice or those exposed to S. chartarum without ovalbumin sensitization. Histologic sections showed severe granulomatous inflammatory cell infiltrates in all compartments of the lung, including peribronchial, perivascular, and alveolar spaces. The mRNA levels of proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha and the chemokine CCL3/MIP-1alpha were also markedly increased in the lungs. Despite the enhancement of the pulmonary inflammatory reaction, exposure to S. chartarum spores significantly down-regulated airway hyperresponsiveness and showed a tendency to decrease levels of Th2 cytokines in the lung. CONCLUSION: Exposure to S. chartarum modulates the inflammatory reaction and airway hyperresponsiveness, depending on the allergic status of the exposed mice.     

Cladosporium herbarum and Pityrosporum ovale allergen extracts share cross-reacting glycoproteins

BACKGROUND: Patients sensitized to airborne fungi such as Alternaria alternata and Cladosporium herbarum often also show positive skin prick test results and specific serum IgE antibodies to a yeast, Pityrosporum ovale. We examined whether part of the IgE binding to these fungi is explained by cross-reacting mould and yeast allergens. METHODS: Serum samples from 36 patients with positive skin prick test to A. alternata or C. herbarum were analyzed for IgE antibodies to fungal extracts by ELISA and immunoblot analysis. Cross-reactivity between mould and yeast extracts was studied by ELISA and immunoblot inhibition assays. In further analysis, the mannan-containing glycoproteins were removed from the yeast extract by concanavalin A-Sepharose chromatography, and the IgE binding properties of the extracts were compared. RESULTS: Serum IgE reactivity to P. ovale was found in 40% of the mould-sensitized patients. The IgE antibody binding to A. alternata and C. herbarum moulds was partially inhibited by the yeast P. ovale in ELISA and immunoblot inhibition assays. When the glycoproteins were removed from the extract, cross-reactivity was markedly reduced. CONCLUSION: Part of the IgE binding to mould and yeast allergen extracts is due to cross-reacting glycoproteins. False-positive IgE and skin prick test results should be taken into account in the diagnosis of mould allergy.     

Limits of medical research – some considerations

Objective. To study the association of milk-IgE antibodies in serum to milk-related gastrointestinal symptoms in adults in primary care. Design. Open clinical study. Setting. Five outpatient clinics in primary care in Southern Finland. Subjects. A total of 756 subjects who reported milk-related gastrointestinal symptoms in primary care and as controls 101 subjects with no such symptoms. Methods. IgE values for specific food antigens were measured (Pharmacia CAP System) in a total of 857 subjects. All food screen-positive samples (>0.35 IU/l) were analysed further for IgE for untreated skimmed milk (milk-IgE) and for boiled milk. Those found positive for milk-IgE were invited for an open milk challenge test. Results. Some 5.4% (46/857) of all subjects had a positive IgE antibody screen for food antigens. Of those with a positive food screen, 28% (13/46) had milk-IgE antibodies comprising 1.5% of the total group screened. The prevalence of milk-IgE was not statistically different between those with milk-related symptoms and those with no such symptoms. IgE antibodies for boiled milk were rare. All specific IgE antibody levels were low. Bloating was the only observed symptom in milk challenge tests. Conclusion. IgE antibodies to cow's milk were relatively rare in the adult population and were not indicative of milk protein allergy. The observed IgE levels were low and did not correlate with subjective milk-related symptoms. The measurement of milk-specific IgE in adults should be discouraged in outpatient clinics.