Structure-function studies of the SERPIN plasminogen activator inhibitor type 1. Analysis of chimeric strained loop mutants.

Three chimeric mutants of plasminogen activator inhibitor 1 (PAI-1) have been constructed where the strained loop of wild type PAI-1 (wtPAI-1) has been replaced with a 19-amino acid region from either plasminogen activator inhibitor 2 (PAI-2), antithrombin III, or with an artificial serine protease inhibitor superfamily consensus strained loop. The inhibitors were expressed in Escherichia coli, and the purified proteins had specific activities toward urokinase-type plasminogen activator (uPA) or the single- and two-chain forms of tissue type plasminogen activator (tPA) that were similar to wtPAI-1. Experiments suggest that the strained loop of PAI-1 is not responsible for the transition between the latent and the active conformations or for binding to vitronectin.

Role of tRNA modification in translational fidelity.

In transfer RNA many different modified nucleosides are found, especially in the anticodon region. In this region, pseudouridine (psi) is found in positions 38, 39 or 40 in a subset of tRNA species, 2-methylthio-6-hydroxyisopentenyladenosine (ms2io6A) is found in position 37 in tRNAs that read codons starting with U and 1-methylguanosine (m1G) is found in position 37 in tRNAs reading codons of the UCCNG type. We have used the mutants hisT, miaA and miaB and trmD, which are deficient in the biosynthesis of psi, ms2io6A, and m1G, respectively, to study the functional aspects of the respective modified nucleosides.

Effect of dose on serum pharmacokinetics of intravenous ciprofloxacin with identification and characterization of extravascular compartments using noncompartmental and compartmental pharmacokinetic models.

The effect of dose on the pharmacokinetics of ciprofloxacin in serum and urine following single intravenous doses of 100, 150, and 200 mg was studied in nine healthy volunteers. Mean peak levels in serum were 1.4, 2.

Pharmacokinetics and pharmacodynamics of intravenous ciprofloxacin. Studies in vivo and in an in vitro dynamic model.

The pharmacokinetics and pharmacodynamics of a 200-mg intravenous dose of ciprofloxacin were studied in normal volunteers and in an in vitro dynamic model that exposes bacteria to changing concentrations of the drug in a neutropenic setting. Peak ciprofloxacin concentrations in vivo averaged 3.2 micrograms/ml.

Lead in ancient human bones and its relevance to historical developments of social problems with lead.

Concentrations of metabolic lead in buried ancient bones are obscured by replacement of calcium in apatite by excessive amounts of soil moisture Pb. Concentrations of metabolic barium in bones are affected in a similar way. Added soil Pb and Ba, expressed as log(Pb/Ca) versus log(Ba/Ca) among various bones at a given burial site, are positively covariant, with about 5-fold more soil Pb added for each unit of added soil Ba.

Pleiotropic effects induced by modification deficiency next to the anticodon of tRNA from Salmonella typhimurium LT2.

A strain of Salmonella typhimurium LT2 was isolated, which harbors a mutation acting as an antisuppressor toward an amber suppressor derivative, supF30, of tRNATyr1. The mutant is deficient in cis-2-methylthioribosylzeatin[N6-(4-hydroxyisopentenyl)-2-me thylthioadenosine, ms2io6A], which is a modification normally present next to the anticodon (position 37) in tRNA reading codons starting with uridine. The gene miaA, defective in the mutant, is located close to and counterclockwise of the purA gene at 96 min on the chromosomal map of S.

High-performance liquid chromatographic quantitation of trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole in body fluids.

We describe a rapid, precise and simple procedure for the quantitative determination of trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole in body fluids by reversed-phase high-performance liquid chromatography. This method utilizes antipyrine as an internal standard with the compounds detected by dual-wavelength monitoring at 225 nm and 254 nm after a single-step extraction. Precision, sensitivity, and accuracy of this assay are within the range of clinical utility; the coefficient of variation is less than or equal to 3%, sensitivity less than 0.

Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole in children and adults with normal and impaired renal function.

Thirty-seven children and adults aged 0.2-82 years were treated intravenously with 150 mg of trimethoprim (TMP) and 750 mg of sulfamethoxazole (SMZ)/m2 every 8 hr, usually for known or suspected pneumocystis pneumonia; when necessary dosage was adjusted to maintain peak TMP levels of 5-10 micrograms/ml. On day 2 of treatment, mean peak levels of TMP-SMZ were 7.

Stability of trimethoprim-sulfamethoxazole injection in two infusion fluids.

The concentrations over time of trimethoprim (TMP) and sulfamethoxazole (SMZ) in solution after preparations of admixtures of TMP-SMZ in 5% dextrose injection (D5W) and in 0.9% sodium chloride injection (NS) were measured. Admixtures (50 ml) containing three TMP concentrations (0.

Skeletal concentrations of lead in ancient Peruvians.

The level of biologic lead (expressed as the ratio of atomic lead to atomic calcium) in bones of Peruvians buried 1600 years ago was found to be 3 x 10(-8), as compared to 2100 to 3500 x 10(-8) in the bones of present-day residents of England and the United States. The ratio of barium to calcium was 2 to 3 x 10(-6) in bones of ancient Peruvians and present-day Americans. Barium and lead have similar morphologic distributions in organisms, so this discrepancy for lead must result from overexposure of present-day people to industrial lead and not from natural variations.