We used antisera from patients with the CREST syndrome of scleroderma (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) to show that an antigenic component of the kinetochore present in metaphase chromosomes is also present in nonhistone chromosome scaffolds isolated following extensive digestion of the DNA and extraction of the bulk of chromosomal protein. All sera from 12 scleroderma CREST patients previously shown by immunofluorescence microscopy to have circulating antikinetochore antibodies recognise a protein of Mr 77,000 (CREST-77) in an immunoblotting assay. 9 of the 12 sera also recognise an antigen Of Mr 110,000 (CREST-110). These proteins are present in isolated chromosomes and nonhistone scaffolds derived from them by two different procedures . Sera of five scleroderma CREST patients who are antikinetochore negative (by immunofluorescence) bind to neither protein in immunoblots. These data suggest that CREST-77 (and possibly CREST-110) is a component of the human kinetochore, and that the kinetochore is an integral part of the mitotic chromosome scaffolding .

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. Mechanisms of the protective action of diethyldithiocarbamate-iron complex on acute cardiac allograft rejection. Am J Physiol Heart Circ Physiol 284: H1542-H1551, 2003; 10.1152/ajpheart.00913.2002.-In this study, we examined the actions of diethyldithiocarbamate-iron (DETC-Fe) complex in acute graft rejection heterotopically transplanted rat hearts. Chronic treatment with DETC-Fe inhibited the increase in plasma nitric oxide (NO) metabolites and nitrosylation of myocardial heme protein as determined by electron paramagnetic resonance (EPR) spectroscopy. Pulse injection with DETC-Fe normalized NO metabolites. We verified intragraft trapping of NO in vivo by pulse injection with DETC-Fe by the detection within allografts of an anisotropic triplet EPR signal for DETC-Fe-NO adduct with resonance positions (g tensor factors for perpendicular and parallel components, respectively gЌ ϭ 2.038 and gʈ ϭ 2.02; hyperfine coupling of 12.5 G). DETC-Fe prolonged graft survival and decreased histological rejection scores. DNA binding activity for nuclear factor (NF)-B and activator protein-1 was increased in allografts and prevented by DETC-Fe. Abrogation of the activation of NF-B by DETC-Fe was associated with increased IB␣ inhibitory protein. Western blotting and RT-PCR analysis revealed that DETC-Fe inhibited inducible NO synthase protein and gene expression. Gene expression for the proinflammatory cytokine interferon-␥ was also decreased by DETC-Fe. Thus DETC-Fe limits NF-B-dependent gene expression and possesses significant immunosuppressive properties. nitric oxide synthase; interferon-␥; electron paramagnetic resonance spectroscopy; nuclear factor-B; activator protein-1

Genetic variations in the gene coding for surfactant protein B are associated with more severe lung injury as indicated by the association of specific single nucleotide polymorphism genotypes and haplotypes with the need for mechanical ventilation in African American children with community-acquired pneumonia.