Mutagenicity of nitric oxide is not caused by deamination of cytosine or 5-methylcytosine in double-stranded DNA

Several human tumors of diverse histological origin have a high incidence of C:G to T:A transition mutations at methylated CpG sites in tumor suppressor genes. We used a sensitive genetic assay to examine the ability of nitric oxide (NO), a physiological intra- and intercellular messenger molecule, to promote these transitions by deaminating cytosine (C) or methylcytosine (5mC) in double-stranded DNA. Exposure of a test double-stranded plasmid containing C or 5mC at the target site to NO in phosphate-buffered solution at pH 7.4 followed by transformation into Escherichia coli ung- strain to avoid repair of U did not result in a significant increase in reversion frequency. In addition, exposure of E. coli transformed with the target plasmid to an NO-releasing spermine-NO complex during log-phase growth did not result in larger numbers of revertants, whereas Salmonella typhimurium strain TA1535 showed a dose-responsive increase in reversion frequency when treated in the same way. We conclude that genotoxicity of NO is not caused by deamination of C or 5mC to U or T, respectively, in double-stranded DNA. This is supported by the finding that extracts of TA1535 contained high uracil-DNA glycosylase activity, suggesting that the difference in mutagenesis between the strains is not due to a lack of uracil repair. Therefore, mutational hot-spots seen in human tumor tissues at CpG sites are probably not due to the action of NO at 5mC.     

L-type Ca2+ channel is involved in the regulation of spontaneous transmitter release at developing neuromuscular synapses

Involvement of an L-type Ca2+ channel in the regulation of spontaneous transmitter release was studied in Xenopus nerve-muscle cultures. The frequency of spontaneous synaptic currents, which reflects impulse-independent acetylcholine release from the nerve terminals, showed a marked increase in high-K+ medium or after treatment with a phorbol ester, 12-O-tetradecanoyl-phorbol 13-acetate, a drug that activates protein kinase C and depolarizes the presynaptic neuron. The potentiation effect of high K+ and 12-O-tetradecanoyl-phorbol 13-acetate requires Ca2+ influx through the L-type Ca2+ channel in the plasma membrane, since it was significantly reduced by the presence of nifedipine, verapamil or diltiazem and enhanced by Bay K 8644, an L-type Ca2+ channel agonist. It was shown recently that adenosine 5'-triphosphate markedly potentiates the spontaneous acetylcholine release at these synapses through the binding of P2-purinoceptors and the activation of protein kinase C. We found in the present study that potentiation effects of adenosine 5'-triphosphate are inhibited by L-type Ca2+ channel blockers, suggesting that the L-type Ca2+ channel is responsible for the positive regulation of spontaneous acetylcholine secretion by adenosine 5'-triphosphate at the developing neuromuscular synapses. Our data suggest that modulation of the L-type Ca2+ channel in embryonic motor nerve terminals is important for the regulation of spontaneous transmitter release.     

Orofacial manifestations of Melkersson-Rosenthal syndrome. A study of 42 patients and review of 220 cases from the literature

We investigated orofacial manifestations in 42 patients with Melkersson-Rosenthal syndrome who were examined at our institution between 1965 and 1990. Patient histories and histologic and clinical findings were reviewed in detail. These data were compared with the oral findings in 220 cases that were reported in the literature between 1965 and 1990. There were 28 females in our study. The age at onset of signs and symptoms varied widely with a mean of 33.8 years. Most frequent initial signs were labial edema, facial swelling, and Bell's palsy. During the course of the disease, 75% of all patients had labial swelling, 50% had facial edema, and 33% had Bell's palsy. Swelling, erythema, or painful erosions that affected the gingiva, buccal mucosa, palate, or tongue were common intraoral symptoms. A comparison with patients reported in the literature revealed a similar frequency of extraoral symptoms but more prevalent intraoral symptoms in our patients.     

Observations on the ageing of the metallic glass Fe80B20

The commercial binary metallic glass, Fe₈₀B₂₀, was examined using transmission electron microscopy after a variety of ageing treatments. While the material was found to be susceptible to beam-induced oxidation, some tendency to crystallization at temperatures as low as 523 K was observed. Morphologically this was different from the essentially eutectic crystallization behaviour previously observed at 573 K and above.     

Evidence for adsorption of heterospecific host immunoglobulin on the tegument of Schistosoma mansoni

Mice infected with Schistosoma mansoni were immunized against human type B Rh-positive (B+) RBC, bovine serum albumin, or horseradish peroxidase. Adult parasites, recovered by perfusion, extensively washed, and incubated in their respective antigens, selectively bound to their tegumental surfaces only those antigens to which their murine host had been immunized. All controls supported the specificity of those reactions leading to the conclusion that adult S. mansoni in mice have the ability to adsorb heterospecific antibody onto their tegumental surfaces. These surface immunoglobulins were lost within 10 min when complexed with theri antigens or within 2.5 hr when incubated at 37 degrees C. Parasites that had lost their tegumental immunoglobulins regained them when incubated in normal mouse or rat anti-human type B Rh-negative (B-) RBC serum. Those parasites that had their surface immunoglobulins reconstituted with rat anti-human B- serum specifically bound human B- RBC, suggesting the possible presence of Fc receptors on adult S. mansoni.