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C J Schmeichel

Publications and source records attributed to C J Schmeichel.

5 recordsLinked to original sources
PubMed1992

Human gene therapy: a role for the primary care physician.

Human gene therapy, once thought to be the unique province of specialized clinical centers, will be diffusing rapidly into primary care medicine. More than 10 medical centers in the United States and several centers world-wide are beginning to use this potentially curative therapy. Eleven trials of protocols are under way, nine are about to begin, and more than 12 protocols are nearing completion of the approval process. The diseases being treated are not the rare disorders found only in one in 100,000 patients, but instead include various types of cancer, diseases of the cardiovascular and pulmonary systems, and inborn errors of metabolism. Combined, these diseases affect more than half of the American population.

Clinical Protocols↗
PubMed1991

Oxidant-induced restriction polymorphism maps to kinase region of c-abl oncogene.

Reactive oxygen species generated by activated human phagocytes can cause a variety of genetic injuries and produce malignant transformation in target cells. We previously reported that DNA extracted from phagocyte-transformed 10T1/2 mouse fibroblasts contained Msp I-dependent restriction fragment length polymorphisms in the c-abl oncogene. The data suggested that the oxidant-induced RFLP resulted from an alteration in the methylation pattern in c-abl. We have now mapped one of these RFLP to a specific 'CCGG' tetramer found within the tyrosine kinase region of the gene. The polymorphic 'CCGG' site has been localized to the intron between exon 2 and 3a. Restriction analysis indicates that a repetitive sequence exists within this intron and that the RFLP is associated with this repeat.

Animals↗
PubMed1987

Methylxanthine bronchodilators potentiate multiple human neutrophil functions.

Methylxanthines, including the bronchodilators theophylline and aminophylline, in high concentrations (greater than 10(-4) M) inhibit cyclic nucleotide phosphodiesterase activity and in low, clinically relevant concentrations (10(-5) to 10(-4) M) are antagonists of extracellular adenosine receptors. The effect of therapeutic concentrations of methylxanthines on human neutrophil functions stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was examined. Preincubation of cytochalasin B-treated neutrophils with 10(-5) M to 3 X 10(-3) M methylxanthine resulted in a biphasic, concentration-dependent effect on neutrophil aggregation, lysosomal enzyme release, and superoxide anion formation. At 10(-5) to 10(-4) M, theophylline and aminophylline potentiated neutrophil aggregation, lysosomal enzyme release (30 to 50%, p less than 0.005), and superoxide anion formation (30 to 60%, p less than 0.005). 1-Methyl-3-isobutylxanthine at these same concentrations potentiated only neutrophil aggregation and lysosomal enzyme release (30 to 40%, p less than 0.005). The three methylxanthines inhibited each response up to 90% at concentrations greater than 10(-4) M. 8-Phenyltheophylline, which does not inhibit phosphodiesterase activity, produced only potentiation. Preincubation of neutrophils with adenosine deaminase mimicked the methylxanthine potentiation, whereas addition of adenosine (3 X 10(-8) to 3 X 10(-7) M) reversed the methylxanthine-induced potentiation in a concentration-dependent manner. These results indicate that therapeutic concentrations of methylxanthines may potentiate neutrophil activation in vivo by competing with circulating adenosine for neutrophil adenosine receptors.

1-Methyl-3-isobutylxanthine↗