Enhancement of natural and experimental respiratory mycoplasmosis in rats by hexamethylphosphoramide. (1/14)

Hexamethylphosphoramide (HMPA) was given orally (100 mg/kg/day) to: a) conventional rats of Sprague-Dawley and Long-Evans substrains known to have indigenous Mycoplasma pulmonis infection, b) uninfected pathogen-free (PF) Fischer rats, and c) PF and axenic Fischer rats inoculated intranasally with M. pulmonis strains having a wide range of virulence. Treated rats infected with virulent M. pulmonis, either naturally or experimentally, developed severe clinical signs of murine respiratory mycoplasmosis (MRM) with mortalities of 25 to 60% compared to relatively mild MRM and no deaths in untreated, infected controls. Deaths were attributed to unusually severe lung lesions of MRM (extreme neutrophilic exudation into major bronchi and bronchiectasis) with ulceration of respiratory mucosa and hemorrhage. Rhinitis also was increased in severity by HMPA in conventional rats, but not in experimentally infected PF or axenic rats. Severity of otitis media and tracheitis was not affected by HMPA. Incidence of lesions of MRM was unchanged except for increased frequency of gross lung lesions. In the absence of M. pulmonis infection, HMPA treatment of rats caused thinning and microulceration of respiratory epithelium in major bronchi without inflammatory lung disease. Other effects induced by HMPA, with or without the infection, were destruction and fibrous replacement of olfactory epithelium, atrophy of testes, and reduced weight gains. It was concluded that HMPA markedly enhances both rate of progression and severity of the pneumonia while inconsistently potentiating the rhinitis of MRM in rats. Previous studies of HMPA are emphasized as an additional example in which the synergistic effects of an experimental chemical and an indigenous pathogen of laboratory rats have given misleading experimental results.  (+info)

Highly enantioselective alkyne additions to aldehydes in the presence of 1,1'-bi-2-naphthol and hexamethylphosphoramide. (2/14)

It is found that the addition of hexamethylphosphoramide to the solution of an alkyne, Et(2)Zn, and (S)-1,1'-bi-2-naphthol in methylene chloride allows the generation of an alkynylzinc at room temperature and shows highly enantioselective additions to aldehydes. The mild condition for the formation of the alkynylzinc reagent enables the use of functional alkynes in this asymmetric reaction with excellent enantioselectivity. It avoids the reflux of the toluene solutions of the alkynes and Et(2)Zn as previously reported.  (+info)

A reverse genetic screen in Drosophila using a deletion-inducing mutagen. (3/14)

We report the use of the cross-linking drug hexamethylphosphoramide (HMPA), which introduces small deletions, as a mutagen suitable for reverse genetics in the model organism Drosophila melanogaster. A compatible mutation-detection method based on resolution of PCR fragment-length polymorphisms on standard DNA sequencers is implemented. As the spectrum of HMPA-induced mutations is similar in a variety of organisms, it should be possible to transfer this mutagenesis and detection procedure to other model systems.  (+info)

Noninvasive monitoring of HPMA copolymer-RGDfK conjugates by magnetic resonance imaging. (4/14)

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Chromosome aberration frequency in rat peripheral lymphocytes increases with repeated dosing with hexamethylphosphoramide or cyclophosphamide. (5/14)

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Preparation and use of samarium diiodide (SmI(2)) in organic synthesis: the mechanistic role of HMPA and Ni(II) salts in the samarium Barbier reaction. (6/14)

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Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide. (7/14)

The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides. In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied. These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties. While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA. In contrast, the transformation assay found both phosphoramide and HMPA positive. This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity. Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced.  (+info)

31P-nuclear-magnetic-resonance study of muscles from Mytilus edulis. (8/14)

Phosphorus-31 nuclear magnetic resonance (NMR) spectra were recorded from freshly excised and resting anterior byssus retractor muscles of the mussel Mytilus edulis. The absolute concentrations of phosphometabolites measured by NMR compare well with the values obtained by a biochemical method. Quantitative measurements were achieved in several minutes by applying to the observed NMR signals a correction taking the saturation effects into account. The time evolution of the phosphometabolite concentrations reveals that the hydrolysis of phosphoarginine is a first-order reaction producing inorganic phosphate, whilst the adenosine triphosphate level remains constant for more than 10 h. The phosphoarginine hydrolysis rate varies as a function of the season and reaches a maximum during the reproduction period of the mussel. This increase in phosphoarginine consumption could be bound up with the higher excitability of the muscles during spring. The activation energy of the phosphoarginine hydrolysis reaction also depends on the season and the difference between the value determined in winter and that measured in spring is explained by a modification of the mode of action or of the proportions of the enzymes involved in the muscular metabolism.  (+info)

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