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D DiSilvestre

Publications and source records attributed to D DiSilvestre.

8 recordsLinked to original sources
PubMed1997

Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice.

Exposures to the common air pollutant ozone (O3) cause decrements in pulmonary function and induce airway inflammation that is characterized by infiltration of polymorphonuclear neutrophils (PMNs; refs 1-4). Because of the impact that O3 may have on public health, it is critical to identify susceptibility factors. Highly reproducible, significant inter-individual variations in human pulmonary function responses to O3 support the hypothesis that genetic background is an important determinant. Initial analysis of PMN responses to O3 exposure in segregant populations derived from inflammation-prone (susceptible) C57BL/6J (B6) and inflammation-resistant C3H/HeJ (C3) inbred mice indicated that susceptibility was controlled by a locus we termed Inf2 (ref. 7). Subsequent analyses with recombinant inbred strains suggested that a more complex interaction of genes is involved. In this report, we identify a quantitative trait locus (QTL) for O3 susceptibility on chromosome 17. Candidate genes for the locus include Tnf, the gene encoding the pro-inflammatory cytokine tumour necrosis factor-alpha (Tnf). Antibody neutralization of the protein product of this putative candidate gene significantly protected against O3 injury in susceptible mice. These results strongly support linkage of O3 susceptibility to a QTL on chromosome 17 and Tnf as a candidate gene.

Animals↗
PubMed1995

Structure and DNA sequence of the mouse MnSOD gene.

Oxidative damage to the cell has been implicated in the pathogenesis of a number of disorders, including chronic inflammation, aging, and cancer. Manganese superoxide dismutase (Mn-SOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxide radicals and other excited oxygen species. In this report we describe the genomic organization and DNA sequence of the murine MnSOD gene. This gene is interrupted by four introns. The coding sequence of this gene was examined in C57BL/6J and C3H/HeJ mice that are SUSCEPTIBLE AND RESISTANT, respectively, to the pulmonary injuries induced by the inhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the size or steady-state level of this transcript, biologic variability in the pulmonary inflammatory response to ozone and hyperoxia does not arise from an altered gene structure. Examination of the noncoding sequence revealed a dC.dA polymorphism in intron 2 and a StyI RFLV in intron 4 of the MnSOD gene. These sequence and mapping data provide the basis for continued study of biologic variability in the MnSOD gene as a cause of disease.

Amino Acid Sequence↗
PubMed1992

Regulation of the Escherichia coli uncH gene by mRNA secondary structure and translational coupling.

The uncH gene is one of the most poorly-expressed genes of the proton-translocating ATPase (unc) operon of Escherichia coli. We constructed in-frame lacZ fusions to uncH and used site-directed mutagenesis to decrease the stability of the putative mRNA secondary structure in the Shine and Dalgarno region for this gene. These mutations significantly increased the expression of uncH. We also used the unc-lac fusions to show that the insertion of stop codons and a frameshift mutation in uncF, the gene preceding uncH, caused a 10-fold reduction in uncH expression. Hybridization of total cellular RNA with a lacZ-specific probe indicated that transcriptional polarity could not account for the observed decrease in gene expression. These results demonstrate that uncH expression is controlled by mRNA sequences around the translational initiation region, and is translationally coupled to uncF, even in cases where the putative mRNA secondary structure is weakened or eliminated.

Bacterial Proteins↗
PubMed1989

Nucleotide sequence of human papillomavirus type 31: a cervical neoplasia-associated virus.

The nucleotide sequence of human papillomavirus (HPV) 31 DNA (7912 bp) was determined and used to deduce the genomic organization of this cervical cancer-associated virus. Based on comparisons of the HPV 31 DNA sequence to other sequenced HPVs, HPV 31 is a typical papillomavirus most related to HPV 16 (70% identical nucleotides). The E6 and E7 open reading frames (ORF) of HPV 31 contain several potential DNA binding motifs (Cys-X-X-Cys), the locations of which are conserved in all HPVs. The E6 ORF also has the potential to code for an E6* protein. The E7 ORF of HPV31 encodes a polypeptide motif which appears to distinguish HPVs associated with cervical cancer, such as types 16, 18, 31, and 33, from HPVs found primarily in benign lesions, such as types 6 and 11.

Base Sequence↗