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Biomedical subjects

S E Patterson

Publications and source records attributed to S E Patterson.

8 recordsLinked to original sources
PubMed1992

The TMK1 gene from Arabidopsis codes for a protein with structural and biochemical characteristics of a receptor protein kinase.

Genomic and cDNA clones that code for a protein with structural and biochemical properties similar to the receptor protein kinases from animals were obtained from Arabidopsis. Structural features of the predicted polypeptide include an amino-terminal membrane targeting signal sequence, a region containing blocks of leucine-rich repeat elements, a single putative membrane spanning domain, and a characteristic serine/threonine-specific protein kinase domain. The gene coding for this receptor-like transmembrane kinase was designated TMK1. Portions of the TMK1 gene were expressed in Escherichia coli, and antibodies were raised against the recombinant polypeptides. These antibodies immunodecorated a 120-kD polypeptide present in crude extracts and membrane preparations. The immunodetectable band was present in extracts from leaf, stem, root, and floral tissues. The kinase domain of TMK1 was expressed as a fusion protein in E. coli, and the purified fusion protein was found capable of autophosphorylation on serine and threonine residues. The possible role of the TMK1 gene product in transmembrane signaling is discussed.

Amino Acid Sequence↗
PubMed1991

Synthesis and quantitative structure-activity relationship analysis of 2-(aryl or heteroaryl)quinolin-4-amines, a new class of anti-HIV-1 agents.

Thirty-eight 2-(aryl or heteroaryl)quinolin-4-amines, N,N-disubstituted, N-monosubstituted, and without a substituent at the amino group have been synthesized with use of novel chemistries developed by us recently. Some of these derivatives show anti-HIV-1 activity at a concentration level of 1 microM and low cell toxicity in vitro. The most active and least toxic compounds are derivatives of 2-(3-pyridyl)quinoline. The results of the quantitative structure-activity relationship analyses, including several classical, linear regression correlations and a Free-Wilson approach of de novo model, provide guidelines for the design of new active compounds of this class.

Antiviral Agents↗
PubMed1989

One-month inhalation toxicity study of tulobuterol hydrochloride in rats and dogs.

Tulobuterol hydrochloride (HCl) has beta 2-adrenergic agonist activity and is under development for use in the treatment of chronic obstructive lung disease. The purpose of this study was to determine the toxicity of inhaled tulobuterol HCl in rats and dogs. Rats were whole-body exposed to aerosol gravimetric concentrations of 0, 0.03, 0.22, or 1.1 mg/liter of tulobuterol HCl, 60 min/day for 28 days. Dogs were exposed (via insufflation) to estimated daily doses of 0, 0.2, 1.0, or 6.0 mg/kg for an equal period. Plasma levels of tulobuterol were determined following exposure on Days 1, 8, and 28 using a high-pressure liquid chromatographic method developed for this study. Results indicated that plasma tulobuterol levels were highly correlated with tulobuterol doses (p less than 0.001 for rats and dogs). No dose-related changes in body weight food consumption, hematological, or serum chemistry parameters were observed in either species. Anterior nasal cavity lesions were observed by light microscopy in rats exposed to 0.22 and 1.1 mg/liter tulobuterol HCl at an incidence of 14 and 93%, respectively. These lesions involved the nasal septum, turbinates, and/or the dorsolateral wall of the nasal cavity and consisted of suppurative rhinitis and necrosis. The corresponding mean plasma tulobuterol levels on Day 28 in mid- and high-dose rats were approximately 1000 and 15,000 ng/ml. Nasal lesions were not observed in rats allowed to recover for 2 weeks. No gross or microscopic lesions were detected in lungs or other tissues of either species.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1986

The hemodynamic and clinical responses to terazosin, a new alpha blocking agent, in congestive heart failure.

To determine the hemodynamic effects of a new alpha 1 blocker, terazosin, in congestive heart failure, six patients with this condition underwent hemodynamic testing (at rest and during exercise) before and after dosing. Doses of 2, 5, and 10 mg were examined in sequence over 3 days to define dose-response characteristics. Terazosin, in these doses, decreased pulmonary and systemic vascular resistances and right atrial and pulmonary capillary wedge pressures. Terazosin increased stroke volume and cardiac output, presumably through afterload-reduction, without altering heart rate. These aforementioned responses were apparent both at rest and during exercise. While a direct relationship existed between dose and plasma concentration, a similar relationship was not observed for dose (or plasma concentration) and hemodynamic response; no differences were noted between the hemodynamic responses to the three doses. Improvement in hemodynamics persisted and the clinical status and exercise capacity improved in the four patients chronically treated (over 2 months) with terazosin. Treating the heightened tone of the sympathetic nervous system in congestive heart failure with the alpha 1 blocker, terazosin, may be of benefit to some patients afflicted with this disorder.

Adrenergic alpha-Antagonists↗
PubMed1985

Terazosin kinetics after oral and intravenous doses.

Terazosin kinetics were followed in normal subjects after intravenous doses of 0.5, 1.0, and 2.0 mg and oral doses of 1.0 mg. Plasma and urine samples were collected for the first 48 and 24 hours. The samples were analyzed by a sensitive HPLC assay developed in our laboratory. Mean calculated peak plasma levels from the 0.5, 1.0, and 2.0 mg intravenous doses were 25.0, 44.1, and 83.3 ng/ml. After a 1 mg oral dose the mean peak level was 19.6 ng/ml. Data were fit to a two-compartment open model with mean elimination phase t1/2 values of 7.9, 8.9, and 10.1 hours for the ascending intravenous doses and 11.6 hours for the oral dose. Mean 0 to 24-hour urinary recovery after the intravenous doses was 14%, 13%, and 11%. It is concluded that terazosin kinetics are linear after oral and intravenous doses.

Administration, Oral↗
PubMed1984

Hepatic drug metabolism in rats with experimental chronic renal failure.

The activities of several hepatic microsomal, mitochondrial, and cytosolic drug-metabolizing enzymes, as well as the components of the cytochrome P-450 system, were determined in vitro for control, sham-operated, and uremic rats. Chronic renal failure (CRF) was produced by a two-stage surgical procedure. In this model, the animals were maintained for 21 days postoperatively before assay. During this time, serum urea nitrogen (SUN) levels rose from control levels of 21 mg/dl to an average of 63 mg/dl. Enzymes assayed included microsomal N-, O-, and S-demethylases, esterase, and UDP-glucuronyl transferase; monoamine oxidase; and alcohol dehydrogenase. CRF caused decreases of 24-32% in N- and O-demethylase activities, while S-demethylase, esterase, UDP-glucuronyl transferase, and monoamine oxidase activities were not altered significantly. Alcohol dehydrogenase activity was increased 71%. In addition, the functional components of the microsomal mixed-function oxidase system were assayed. CRF caused a 26% decrease in cytochrome P-450 levels, as compared to sham-operated controls, but cytochrome b5 and NADPH-cytochrome c (P-450) reductase were not altered. CRF caused an increase in hexobarbital sleeping time of more than 7-fold. In each case, alterations in enzyme activities or cytochrome P-450 correlated with the extent of renal failure, as determined by elevated SUN levels.

Animals↗
PubMed1981

Nitrofurantoin disposition.

Nitrofurantoin (50 mg) was administered in a three-way random crossover design to six healthy men. After a 45-min intravenous infusion the plasma concentration data could be described by a two-compartment open-body model with a terminal t 1/2 of 58.1 +/- 15 min. Oral availability of a tablet was 0.87 +/- 0.13 on a fasting stomach and 0.94 +/- 0.13 when taken with food. Although absorption appeared to be complete, the absorption rate profile was complex and erratic. Two subjects failed to achieve the minimum effective urine concentration of 32 micrograms/ml. After the intravenous infusion 47 +/- 13% of the dose was excreted unchanged in the urine and 1.2 +/- 0.3% was recovered as the reduced metabolite aminofurantoin.

Adult↗