Genomic signatures of the evolution of defence against its natural enemies in the poisonous and medicinal plant Datura stramonium (Solanaceae).

Tropane alkaloids and terpenoids are widely used in the medicine and pharmaceutic industry and evolved as chemical defenses against herbivores and pathogens in the annual herb Datura stramonium (Solanaceae). Here, we present the first draft genomes of two plants from contrasting environments of D. stramonium. Using these de novo assemblies, along with other previously published genomes from 11 Solanaceae species, we carried out comparative genomic analyses to provide insights on the genome evolution of D. stramonium within the Solanaceae family, and to elucidate adaptive genomic signatures to biotic and abiotic stresses in this plant. We also studied, in detail, the evolution of four genes of D. stramonium-Putrescine N-methyltransferase, Tropinone reductase I, Tropinone reductase II and Hyoscyamine-6S-dioxygenase-involved in the tropane alkaloid biosynthesis. Our analyses revealed that the genomes of D. stramonium show signatures of expansion, physicochemical divergence and/or positive selection on proteins related to the production of tropane alkaloids, terpenoids, and glycoalkaloids as well as on R defensive genes and other important proteins related with biotic and abiotic pressures such as defense against natural enemies and drought.

Roles of thymidylate synthase and dihydropyrimidine dehydrogenase in tumor progression and sensitivity to 5-fluorouracil in human gastric cancer.

BACKGROUND: The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated. MATERIALS AND METHODS: TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay. RESULTS: There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465). CONCLUSION: These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.

Nitinol stent for the treatment of tracheobronchial stenosis.

OBJECTIVE: The purpose of this study was to evaluate the potential utility of implantation of a nickel-titanium alloy (nitinol) stent for the treatment of malignant or benign tracheobronchial stenosis. METHODS: We evaluated 18 patients (14 men and 4 women) who received 24 nitinol stents, between November 1997 and May 2000. All 18 patients had severe dyspnea caused by tracheobronchial stenosis. The underlying condition was malignant disease in 15 patients, and benign tracheal collapse in the other 3 patients. RESULTS: Implantation of the stent was successfully performed in all patients. Seventeen patients experienced immediate clinical improvement in respiratory symptoms. The remaining 1 patient with a bronchial fistule after lobectomy did not benefit, and died of pneumonia at 16 days after the implantation. In 15 patients, the procedure was performed using a flexible bronchoscope under local anesthesia alone, while the remaining 3 patients needed intravenous sedation. There was no complication resulting from the stent implantation. Among the 3 patients with benign tracheal collapse, 2 patients were alive at 746 and at 401 days after the stent implantation, at the time of this report. One patient with cicatricial stenosis after intubation died of heart failure due to previous myocardial infarction. Among the 15 patients with malignant disease, 4 patients have survived for 177 to 305 days to date, while the other 11 patients have died of primary malignancy with a mean survival duration of 60.2 days. CONCLUSION: The nitinol stent was effective in treating malignant or benign tracheobronchial stenosis, and had some remarkable advantages compared with other tracheobronchial stents. In stenting, most procedures can be performed using flexible bronchoscope under local anesthesia.

Studies of the constituents of Gardenia species. II. Terpenoids from Gardeniae Fructus.

Four new terpenoids, gardenate A (1), 2-hydroxyethyl gardenamide A (2), (1R,7R,8S,10R)-7,8,11-trihydroxyguai-4-en-3-one 8-O-beta-D-glucopyranoside (3) and Jasminoside F (4), were isolated from Gardeniae Fructus. Their structures were established on the basis of spectral analysis.

Cutaneous late-phase reaction to environmental antigen in patients with atopic dermatitis.

Intradermal testing with 7 environmental allergens was performed on 71 patients with atopic dermatitis (AD) with respiratory atopy (RAT) and 30 pure AD patients, and the cutaneous late-phase reaction (CLPR) was observed several to 48 h after challenge. CLPR was not seen in pure AD. In AD patients with RAT, CLPR was positive in 29 of 71 patients. No macroscopic eczematous lesions appeared. All CLPR-positive patients showed RAST scores of 2 or more. We assume that CLPR can be an exacerbating factor in AD with RAT, while it is not directly involved in pure AD.