Reduction in superoxide dismutase expression in the epithelial mucosa of eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Eosinophils generate large amounts of oxidant species. The eosinophil-dominant type of chronic rhinosinusitis (CRS) with nasal polyps is related to more extensive disease and a decreased likelihood of surgical success. Superoxide dismutase (SOD) is the first-line and only antioxidant enzyme that converts superoxide to hydrogen peroxide. METHODS: The patients with CRS with nasal polyps were divided into eosinophilic and noneosinophilic groups. The expression of three isoforms of SOD, intracellular copper-zinc SOD (CuZnSOD), mitochondrial manganese SOD (MnSOD) and extracellular SOD (ECSOD), were examined by enzyme activity assay, immunohistochemistry and quantitative real-time RT-PCR sampled by laser capture microdissection. RESULTS: SOD activity in the eosinophilic and noneosinophilic groups was significantly reduced compared to that of the control groups. Immunostaining of both CuZnSOD and MnSOD in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. CuZnSOD mRNA of the eosinophilic group was significantly decreased compared with that of the control group, whereas MnSOD mRNA in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. Neither immunoreactivity nor mRNA of ECSOD was different among the three groups. The degree of epithelial damage and disease severity were inversely correlated with CuZnSOD and MnSOD immunoreactivity. CONCLUSIONS: The reduction in SOD activity and the downregulation of the SOD message are suggested to be related to eosinophil recruitment and epithelial damage of CRS with nasal polyps.

E-Cell 2: multi-platform E-Cell simulation system.

A new version of the E-Cell simulation system,which runs on Windows as well as Linux, has been released as free software under the terms of the GNU General Public License.

Characterization of reactive oxygen species generated from the mixture of NaClO and H2O2 used as root canal irrigants.

Characterization of a mixed solution of sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2), which have been used as root canal irrigants, was investigated using electron spin resonance spectroscopy combined with a spin-trapping technique. In the solution, two kinds of reactive oxygen species, the superoxide anion radical (O2-.) and the hydroxyl radical (.OH), were detected. The pH changes and dissolved oxygen values in the NaClO-H2O2 reaction mixture were investigated. The pH influenced the generation of O2-. and .OH, and O2 was generated from H2O2. It is suggested that root canal irrigation with NaClO and H2O2 induces biological effects, such as tissue irritation (from the chemical reactions of O2-. and .OH) and physical effects, such as O2 bubbling.

Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus.

We examined bcl-2 expression as well as p53 expression and mutation in human uterine smooth muscle tumours to determine the influence of bcl-2 expression on prognosis in patients with uterine leiomyosarcomas. bcl-2 protein was expressed in nearly all benign smooth muscle tumours but in only 57% of leiomyosarcomas. Benign smooth muscle tumours were usually negative for p53 protein, but 16 out of 21 (76%) leiomyosarcomas were positive. A p53 gene mutation was detected in nine of the 16 leiomyosarcomas that showed p53-positive staining. A significant positive correlation was observed between p53 mutation and p53 expression, between the number of mitoses and the Ki-67 labelling index, and between clinical stage and p53 mutation. A significant negative correlation was observed between bcl-2 expression and p53 mutation, and between bcl-2 expression and p53 overexpression. Univariate survival analysis revealed that bcl-2 expression, p53 mutation and clinical stage (stage 1 vs stages 2-4) all showed a significant correlation with prognosis. In a multivariate stepwise regression analysis, positive bcl-2 expression and stage 1 disease were the independent predictors of a favourable prognosis. Our results suggest that bcl-2 is frequently expressed in human uterine smooth muscle tumours, and that its expression may correlate with a favourable prognosis in patients with uterine leiomyosarcoma.

Effect of nonsteroidal anti-inflammatory drugs on lipid peroxidation by hydroxyl radical.

1. Effects of acetaminophen and sodium salicylate on hydoxyl radical elimination were studied using an electron-spin-resonance spin-trapping method. The effects of these agents on lipid peroxidation of the human erythrocyte membrane were also investigated by the thiobarbituric acid method. 2. Acetaminophen and sodium salicylate depressed hydroxyl radical generated by Cu2+/H2O2. 3. Acetaminophen inhibited Cu2+/H2O2-dependent lipid peroxidation; however, sodium salicylate enhanced Cu2+/H2O2-dependent lipid peroxidation.

Forskolin derivatives. I. Synthesis, and cardiovascular and adenylate cyclase-stimulating activities of water-soluble forskolins.

Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl, a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were prepared, and their positive inotropic as well as vasodilative activities were evaluated in anesthetized dogs. 7-Deacetylforskolin (2) and 7-deacetyl-1-silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7-deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6-position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7-deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d). Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and 6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and vasodilative activities comparable to those of forskolin (1). The activities of 13b and 13d were approximately ten times more potent than those of 7-aminoacyl- and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6-Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c) were less potent than 1. The effects of the soluble forskolins on adenylate cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d) exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.

[Bilateral renal cell carcinoma associated with von Hippel-Lindau disease].

A 52-year-old man was referred to the department of neurosurgery of our hospital for evaluation of left occipital pain on September 27, 1982. Brain CT and arteriography showed midcerebellar tumor and an operation was performed on October 7, 1982. Histopathologically, the tumor was hemangioblastoma (solid type). His whole-body CT showed bilateral multiple renal tumors but no angioma retinae were found. Angiography revealed that the lesions were bilateral multiple (more than 20) renal tumors, bilateral adrenal tumors and left retroaortic renal vein. The patient underwent bilateral radical nephrectomy and lymphadenectomy on December 15, 1982. Renal cell carcinoma (grade II greater than III) with adrenal and left renal vein involvement were noted on the pathologic specimen. Postoperatively, he received supplement therapy with hydrocortisone and hemodialysis, but died of bleeding from the recurrent hemangioblastoma on July 7, 1983.