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T A Shapiro

Publications and source records attributed to T A Shapiro.

44 records · Page 3Linked to original sources

A knotted free minicircle in kinetoplast DNA.

Kinetoplast DNA, the mitochondrial DNA of trypanosomes, is a network containing thousands of minicircles that are topologically interlocked. The minicircle replication intermediates are free molecules that have been released from the network. We report here that one form of free minicircles is a trefoil knot. Identification of this knotted structure is based on its electrophoretic and sedimentation properties, its response to treatments with restriction enzymes or topoisomerase II, and its appearance by electron microscopy. Except for its topology, the knotted minicircle closely resembles a previously described replication intermediate with a unique gap in the newly synthesized L strand.

Animals↗

Ribonucleotides associated with a gap in newly replicated kinetoplast DNA minicircles from Trypanosoma equiperdum.

In Trypanosoma equiperdum, some newly replicated kinetoplast DNA minicircles contain a single gap at a unique location in their newly synthesized strand (Ntambi, J. M., and Englund, P. T. (1985) J. Biol. Chem. 260, 5574-5579). We now report that ribonucleotides are associated with this gap, with one or two covalently attached to the 5' terminus of the newly synthesized strand. There appear to be two possible RNA/DNA junctions at adjacent positions in the sequence. The ribonucleotides may be remnants of a replication primer, and their presence strongly implies that the gap is at the site of a replication origin.

Animals↗

Clinical evaluation of amoscanate in healthy male volunteers.

Single oral doses of amoscanate (4-isothiocyanato-4'-nitrodiphenylamine), an experimental antiparasitic agent, are highly effective in animals against the four major species of schistosomes which infect humans. Two prospective, randomized, double blinded, placebo controlled Phase I studies were designed to evaluate the tolerance and safety of the 5% aqueous suspension of 2-mu particles of amoscanate administered to healthy male volunteers. In addition to routine safety monitoring, particular attention was directed toward detecting hepatic, neurological, cardiovascular or ocular toxicity. Three of four men who received 3.5 mg/kg of amoscanate developed mild, reversible hepatotoxicity, which could not be unequivocably attributed to the drug. In the second study, of 1 mg/kg amoscanate, there was no statistically significant evidence of hepatotoxicity, although 1 of 12 drug recipients developed transient liver chemistry changes. Despite intensive monitoring, there was no evidence in either study of significant symptomatic complaints, or of neurological, cardiovascular or ocular toxicity. No mutagenic activity attributable to amoscanate was detectable in the urine. These results suggest that this formulation of amoscanate, at 1 mg/kg, is sufficiently well tolerated and safe to justify evaluation for efficacy in patients with schistosomiasis.

Adult↗

Diagnostic testing of cardiac function.

The electrocardiogram's value in detecting atrial abnormalities, ventricular hypertrophy, and myocardial injury is described, with attention to ambulatory monitoring and exercise stress testing. Perfusion imaging, assessment of resting cardiac function with echocardiography, and other techniques also are addressed.

Cardiovascular Diseases↗