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Biomedical subjects

S C Tucker

Publications and source records attributed to S C Tucker.

9 recordsLinked to original sources

Unusual skin ulceration in an HIV-positive patient who had cutaneous syphilis and neurosyphilis.

We present a case of a patient coinfected with syphilis and the human immunodeficiency virus (HIV) who had unusual and severe cutaneous ulceration. The profound immune defects associated with HIV may lead to an altered clinical presentation and a more aggressive course in patients infected with Treponema pallidum. Despite non-confirmatory histological findings, we feel our patient's cutaneous ulcers probably represent superficial gummata, which have failed to resolve completely following currently accepted high-dose antisyphilis chemotherapy.

Adult

Beta-L-thymidine 5'-triphosphate analogs as DNA polymerase substrates.

beta-L-3'-Deoxythymidine 5'-triphosphate (L-ddTTP) and beta-L-3'-deoxy-2',3'-didehydrothymidine 5'-triphosphate (L-d4TTP) were substrates for human immunodeficiency virus reverse transcriptase, Escherichia coli DNA polymerase I (Klenow), and Sequenase (modified T7 DNA polymerase). The beta-D- and beta-L-enantiomers of 5-methyluridine 5'-triphosphate (rTTP) were inhibitors but not substrates of reverse transcriptase. The steady-state Km values for L-ddTTP and L-d4TTP, with all three enzymes, were 12-70-fold larger than the Km values for the corresponding D-enantiomers. The Km value of reverse transcriptase for L-ddTTP was 50-fold larger than that for D-ddTTP because the Kd for L-ddTTP was 5-fold larger than that for D-ddTTP, and the first-order rate constant for incorporation of L-ddTMP into the template-primer was 10% that of the D-enantiomer. The D- and L-enantiomers had kcat values with reverse transcriptase and Sequenase that were similar to kcat for the natural substrate, thymidine 5'-triphosphate (dTTP). Thus, the rate determining step appeared to be dissociation of the enzyme-chain-terminated template-primer complex. In contrast, kcat values for the L-enantiomers with Klenow were only 0.1% that of dTTP, and the kcat values for the D-enantiomers were 15% the kcat for dTTP. The reduced kcat values were due to a change in rate determining step from dissociation of the Klenow-chain-terminated template-primer complex to an earlier step in the reaction mechanism, presumably catalysis. Thus, these DNA polymerases did not stereospecifically recognize D-nucleoside 5'-triphosphate analogs as substrates.

Bacteriophage T7

Temperature regulation of Shigella virulence: identification of the repressor gene virR, an analogue of hns, and partial complementation by tyrosyl transfer RNA (tRNA1(Tyr)).

virR is the central regulatory locus required for coordinate temperature-regulated virulence gene expression in the human enteric pathogens of Shigella species. Detailed characterization of VirR+ clones revealed that virR consisted of a 411 bp open reading frame (ORF) that mapped to a chromosomally located 1.8kb EcoRI-AccI DNA fragment from Shigella flexneri. Insertional inactivation of the virR ORF at a unique HpaI restriction site resulted in a loss of VirR+ activity. The virR ORF nucleotide sequence was virtually identical to the Escherichia coli hns gene, which encodes the histone-like protein, H-NS. Based on the predicted amino acid sequence of E. coli H-NS, only a single conservative base-pair change was identified in the virR gene. An additional clone, designated VirRP, which only partially complemented the virR mutation, was also characterized and determined by Southern hybridization and nucleotide sequence analysis to be unique from virR. Subclone mapping of this clone indicated that the VirRP phenotype was a result of the multiple copy expression of the S. flexneri gene for tRNA(Tyr). These data constitute the first direct genetic evidence that virR is an analogue of the E. coli hns gene, and suggest a model for temperature regulation of Shigella species virulence via the bacterial translational machinery.

Bacterial Outer Membrane Proteins

Multiple lead ECG submaximal treadmill exercise tests in angiographically documented coronary heart disease.

One hundred patients underwent submaximal exercise tolerance testing and coronary cineangiography. Sixty-six percent of the exercise tests were diagnostic including 48 positive and 18 negative tests; 34 patients had indeterminate test results. The occurrence of exercise induced ventricular premature beats was not related to significant coronary artery disease. Ventricular asynergy was significantly more frequent in patients with positive exercise tests (p less than .0001). Application of the age-adjusted target heart rate criterion recommended from Scandinavia and Myrtle Beach to patients with indeterminate results due to failure to reach target heart rate resulted in six false negative tests and lowered sensitivity. The number of positive diagnostic responses achieved using a multiple electrocardiographic lead system was compared with positive diagnostic responses detected in a single lead (V5) and the number of positive tests identified by the additional leads was highly significant (p less than .0001). A high incidence of indeterminate test results due to failure to achieve target heart rate is noted.

Adolescent