No abstract

Fullerenes are a class of novel carbon allotropes that may have practical applications in biotechnology and medicine. Human mast cells (MC) and peripheral blood basophils are critical cells involved in the initiation and propagation of several inflammatory conditions, mainly type I hypersensitivity. We report an unanticipated role of fullerenes as a negative regulator of allergic mediator release that suppresses Ag-driven type I hypersensitivity. Human MC and peripheral blood basophils exhibited a significant inhibition of IgE dependent mediator release when preincubated with C60 fullerenes. Protein microarray demonstrated that inhibition of mediator release involves profound reductions in the activation of signaling molecules involved in mediator release and oxidative stress. Follow-up studies demonstrated that the tyrosine phosphorylation of Syk was dramatically inhibited in Ag-challenged cells first incubated with fullerenes. In addition, fullerene preincubation significantly inhibited IgE-induced elevation in cytoplasmic reactive oxygen species levels. Furthermore, fullerenes prevented the in vivo release of histamine and drop in core body temperature in vivo using a MC-dependent model of anaphylaxis. These findings identify a new biological function for fullerenes and may represent a novel way to control MC-dependent diseases including asthma, inflammatory arthritis, heart disease, and multiple sclerosis.

GeneticsEnhanced graphic matrix analysis of nucleic acid and protein sequences (sequence homology/transposition/secondary structure/immunoglobulin/microcomputer) JACOB V. MAIZEL, JR., AND ABSTRACT The enhanced graphic matrix procedure analyzes nucleic acid and amino acid sequences for features ofpossible biological interest and reveals the spatial patterns ofsuch features. When a sequence is compared to itselfthe technique shows regions of self-complementarity, direct repeats, and palindromic subsequences. Comparison of two different sequences, exemplified by immunoglobulin K light chain genes, by using colored graphic matrices showed domains of similarity, regions of divergence, and features explainable by transpositions. Analysis of mouse constant domain immunoglobulin sequences revealed self-complementary regions that can be used to fold the molecule into a structure consistent with electron microscopic observations. Computer translation of nucleic acid sequences into all possible amino acid sequences followed by graphic matrix analysis provides a way to detect theimost likely protein encoding regions and can predict the correct reading frames in sequences in which splicing patterns are not defined. Application ofthis technique to regions ofsimian virus 40 and polyoma virus demonstrates the frames of translation and shows the agreement of sequences determined in separate laboratories with different virus isolates. The graphic matrix technique can also be used to assemble fragmentary sequences during determination, to display local variations in base composition, to detect distant evolutionary relationships, and to display intragenic variation in rates of evolution.

No abstract

No abstract