Novel diterpenoid diacylglycerols from marine molluscs: potent morphogens and protein kinase C activators

Five novel 1,2-sn-diacylglycerols with diterpenoid acyl moieties in the sn-1 position were isolated and characterized, together with the corresponding 1,3-sn-diacylglycerols, from three species of dorid nudibranchs molluscs. Their potent activity as morphogens in vivo in the Hydra tentacle regeneration assay and their parallel activity as activators of rat brain protein kinase C (PKC) in vitro are reported here. Our findings promote the use of these compounds as useful molecular probes for both in vivo and in vitro studies on the participation of PKC in cell development.     

Giuseppe Gradenigo and his contributions to audiology

Giuseppe Gradenigo (1859-1926) was an important figure in the development of Otology. Within this paper the authors consider his background and his particular contributions to the development of various aspects of audiology.     

Multiexponential T2 relaxation in Fricke agarose gels: implications for NMR dosimetry

NMR relaxation times T1 and T2 of agarose and Fricke agarose gels have been measured in the range 17-51 MHz. The analysis of the spin echo curves indicates a multiexponential behaviour, characterized by three components, at all the examined frequencies. The relative T2 values, ranging from a few to a hundred milliseconds, can be attributed to different species of water molecules present in the gel. Two of these components are characterized by relaxation rates R2a and R2b, more sensitive than R1 to gamma irradiation, the sensitivity S being S(R1) = 0.066 s-1 Gy-1, S(R2a) = 0.088 s-1 Gy-1, S(R2b) = 0.17 s-1 Gy-1. The three T2 values decrease as a function of frequency, but no gain in dose sensitivity is obtained by changing the working frequency in the examined range. The relaxivity of agarose gels containing ferrous or ferric ions has also been measured and found to be different from those of the corresponding solutions in the absence of agarose. Thus it was possible to estimate the irradiation yield from three independent parameters, R1, R2a and R2b. No effect of the dose rate or of the source energy has been observed for any of these parameters.     

Fluconazole versus itraconazole for candida esophagitis in acquired immunodeficiency syndrome. Candida Esophagitis

BACKGROUNDS & AIMS: Contrasting opinions exist about the pharmacological treatment of esophageal candidiasis in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to assess the long-term efficacy of fluconazole and itraconazole treatment. METHODS: This study evaluated 2213 human immunodeficiency virus-positive patients at first episode of esophageal candidiasis diagnosed by endoscopy; 1105 received fluconazole and 1108 received itraconazole. The endoscopic and clinical response to treatment was assessed periodically until the end of the follow-up period (1 year). RESULTS: At week 2, endoscopic cure occurred in 81.2% of patients treated with fluconazole and in 65.6% of patients treated with itraconazole (P < 0.001). Clinical cure was observed in 81.5% of patients treated with fluconazole and in 75.2% of patients treated with itraconazole (P < 0.001). At the end of the follow-up period, endoscopic and clinical cure were observed in 96% of patients treated with fluconazole and in 95.6% of patients treated with itraconazole (P = 0.788), with similar differences by intention-to-treat analysis (93.6% vs. 93.3%; P = 0.853). Treatment failure was observed in 22.3% of fluconazole-treated patients and in 26.6% of itraconazole-treated patients (P = 0.022). CONCLUSIONS: Fluconazole and itraconazole are provided with good long-term therapeutic efficacy in the treatment of Candida esophagitis in patients with AIDS. Fluconazole is associated with a higher rate of cure than itraconazole in short-term treatment.     

基于可寻址分支分配器的CATV收费系统

给出了一种基于可寻址分支分配器的ＣＡＴＶ收费管理系统设计方案，并着重介绍了系统的工作原理及可寻址分支分配器的设计。     

A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.     

Solution conformation of the Pseudomonas syringae MSU 16H phytotoxic lipodepsipeptide Pseudomycin A determined by computer simulations using distance geometry and molecular dynamics from NMR data

Pseudomycin A is a cyclic lipodepsinonapeptide phytotoxin produced by a strain of the plant pathogenic bacterium Pseudomonas syringae. Like other members of this family of bacterial metabolites, it is characterised by a fatty acylated cyclic peptide with mixed chirality and lactonic closure. Several biological activities of Pseudomycin A are lower than those found for some of its congeners, a difference which might depend on the diverse number and distribution of charged residues in the peptide moiety. Hence, it was of interest to investigate its conformation in solution. After the complete interpretation of the two-dimensional NMR spectra, NOE data were obtained and the structure was determined by computer simulations, applying distance geometry and molecular dynamics procedures. The conformation of the large ring of Pseudomycin A in solution includes three rigid structural regions interrupted by three short flexible regions that act as hinges. The overall three-dimensional structure of the cyclic moiety is similar to that of previously studied bioactive lipodepsinonapeptides produced by other pseudomonads.     

In vitro short-term response of human erythrocytes to implant materials used in maxillo-facial rigid internal fixation

A number of retinal proteins are phosphorylated by a variety of kinases, resulting in well-known regulatory effects. The identity and role of corresponding phosphatases is less clear. We simultaneously measured the activity of serine/ threonine protein phosphatases type 1, 2A and 2C in bovine retinae. The enzymes were classified according to substrate specificity, divalent cation requirement and the effect of phosphatase subtype-specific inhibitors. The total- and specific activity of phosphatase type 2A was prevalent. Type 2C was 10-fold less abundant. 80% of type 1 and 50% of type 2A and type 2C, respectively, were soluble. An economic purification scheme was developed. We demonstrated the presence of phosphatase isozymes 2Calpha and 2Cbeta in bovine rod outer segments by enzymatic analysis as well as immunological techniques. The results suggest a yet unknown role of phosphatase type 2C in phototransduction. On the other hand, the immense amount of protein phosphatases found to be soluble - therefore not associated with rod outer segment membranes - points towards participation of these enzymes in the process of visual transduction not considered thus far.