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C B Davis

Publications and source records attributed to C B Davis.

54 records · Page 3Linked to original sources
PubMed1989

Topology of the yeast plasma membrane proton-translocating ATPase.

Four proteases have been used to assess the topology of the H+-ATPase from Saccharomyces cerevisiae reconstituted into phosphatidylserine vesicles. Limited proteolysis by trypsin and alpha-chymotrypsin inactivates the enzyme and produces stable, membrane-bound fragments. Sequence analyses of these peptides have located the peptide bonds hydrolyzed. The labile bonds are on opposite sides of a central hydrophilic domain containing consensus sequences for the site of phosphorylation and fluorescein isothiocyanate binding of several related ATPases. Limited proteolysis of the ATPase by elastase cuts approximately 50 amino acids from the C terminus, leaving the remaining membrane-bound fragments active. Proteolysis by carboxypeptidase Y in the presence and absence of detergent suggests that the C terminus is on the inside of the vesicle in this reconstitution. A model for the transmembrane arrangement of the polypeptide is proposed. In this model, the C terminus is on the inside of the vesicle, the N terminus is on the outside, the ATP binding region is on the outside, and the polypeptide passes through the membrane a minimum of five times.

Amino Acid Sequence↗
PubMed1989

Activity of aromatic substituted phenylpiperazines lacking affinity for dopamine binding sites in a preclinical test of antipsychotic efficacy.

Generally, antipsychotic agents are dopamine receptor blocking agents that also block conditioned avoidance responding (CAR) in the rat. Recently, however, both (Q-methoxyphenyl)piperazine (OMPP, 1h) and (m-chlorophenyl)piperazine (MCPP, 1o) have been reported to block conditioned avoidance responding in the rat although neither has dopamine receptor blocking properties. The present paper examines the behavioral and biochemical profile of a number of additional substituted phenylpiperazines. None of the phenylpiperazines tested demonstrated high affinity for either dopamine D-1 or D-2 receptor sites, yet many were effective in blocking CAR. The results suggest that the phenylpiperazines may be effective antipsychotic agents without blocking dopamine receptors. Moreover, the active compounds did demonstrate activity in displacing ligand binding to serotonin receptors. Receptor binding profiles were determined for 5-HT-1A and 5-HT-1B binding sites as well as for 5-HT-2 sites. The data from this preclinical test suggest these phenylpiperazines might be effective antipsychotic agents acting via a nondopaminergic mechanism of action.

Animals↗
PubMed1989

A donor-age-dependent change in the activity of alpha-mannosidase in human cultured RPE cells.

Six acidic glycosidase activities in cultured human retinal pigment epithelium (RPE) cells from donors of different ages (19 to 80 years) were studied with regard to pH optimum, Km, Vmax and specific activity. For alpha-mannosidase we found significant age-dependent decreases in specific activity and Vmax but not in Km. The other glycosidases and acid phosphatase, lactate dehydrogenase (LDH) and citrate synthase showed no change in these parameters with donor age. The alpha mannosidase activity of older donor cells could be activated almost 2-fold by the addition of zinc. This is the first report of age-dependent change in a human RPE lysosomal enzyme. Since alpha-mannosidase is probably required for the degradation of rhodopsin in the phagolysosomal system of the RPE, decrease in this enzyme activity may lead to accumulation of undigested rod outer segments (ROS) and drusen, both of which are associated with age-related macular degeneration (AMD).

Adult↗
PubMed1988

Effects of respiratory alkalosis on thromboxane-induced pulmonary hypertension in piglets.

Acute hypoxic pulmonary vasoconstriction is attenuated by respiratory alkalosis. It is unknown if alkalosis similarly reduces pulmonary vasoconstriction produced by thromboxane A2. Respiratory alkalosis does not always attenuate persistent pulmonary hypertension in newborns, some of whom have elevated serum thromboxane B2 levels. We hypothesized that alkalosis attenuates thromboxane-induced pulmonary vasoconstriction less than it does hypoxic pulmonary vasoconstriction in infants. Hemodynamic responses to respiratory alkalosis during pulmonary vasoconstriction produced in random order by breathing 12% inspired oxygen and by infusing 0.1 micrograms/kg/min of the thromboxane-mimetic U46,619 were compared in eight 2-wk-old piglets. Hypoxia increased mean pulmonary artery pressure from 12 +/- 3 to 29 +/- 2 mm Hg and pulmonary vascular resistance (PVR) from 11 +/- 4 to 25 +/- 8 mmHg/L/min; U46,619 increased pulmonary artery pressure from 16 +/- 5 to 37 +/- 6 mm Hg and PVR from 14 +/- 5 to 51 +/- 17 mm Hg/liter/min. U46,619 also decreased cardiac output accounting in part for the greater increase in PVR compared to hypoxia-induced vasoconstriction. Respiratory alkalosis decreased PVR to 14 +/- 6 mm Hg/liter/min during exposure to hypoxia and to 28 +/- 9 mm Hg/liter/min during infusion of U46,619. In six additional piglets with U46,619-induced pulmonary vasoconstriction, the effects of lung stretch and hypocapnic alkalosis were separated by doubling tidal volume and then adding inspired CO2 to return PaCO2 to prehyperventilation levels. Respiratory alkalosis decreased PVR from 52 +/- 36 to 35 +/- 21 mm Hg/liter/min. Despite the increased tidal volume, PVR increased to 53 +/- 35 Hg/liter/min when PaCO2 returned to 44 +/- 5 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkalosis, Respiratory↗
PubMed1986

The influence of ionic strength on the binding of a water soluble porphyrin to nucleic acids.

The ionic strength dependences of the binding of tetrakis (4-N-methylpyridyl)porphine (H2TMpyP) to poly(dG-dC) and calf thymus DNA have been determined. For the former system the results are typical of other intercalators, i.e., a plot of log K vs log [Na+] is linear albeit with a slope which suggests that the "effective charge" of the porphyrin is closer to two than the formal charge of +4. For calf thymus DNA, the binding profile is not completely compatible with the predictions of condensation theory. Whereas the avidity of binding does decrease with increasing [Na+] as predicted, of greater interest is the relocation of the porphyrin from GC-rich regions to AT-rich regions as the ionic strength increases.

Animals↗
PubMed1983

Flexible fiberoptic sigmoidoscopy--the Monroe Clinic experience. A prospective study of 5000 examinations.

Analysis of 5000 consecutive flexible fiberoptic sigmoidoscopies form the basis of this report. It is concluded that this method of examination of the distal large bowel is not only safe and comfortable for the patient but is a more appropriate examination than the rigid proctosigmoidoscopy because of the significant increase in pathologic material found. This examination has proven practical and acceptable in a multispecialty clinic setting and has completely replaced rigid proctosigmoidoscopy. Flexible sigmoidoscopy is now the standard "routine" examination of the rectum and distal colon. The rationale for this conclusion is presented in this timely report.

Adolescent↗
PubMed1982

The strength of microvascular anastomoses--an experimental evaluation in rats.

To determine the longitudinal strength of microvascular anastomoses during early healing, the left femoral arteries of 56 rats were divided and anastomosed with six interrupted sutures of 10-0 nylon. The right femoral arteries served as unoperated controls. The vessels were then harvested immediately, or 3, 7, 14, 21, 28, or 120-150 days after surgery. The cross-sectional surface area was measured and the force required to pull the vessels apart (burst strength) was determined with a tensiometer. Fifty-four of the 56 anastomosed vessels were patent at the time of harvest. All of the operated vessels ruptured at the site of anastomosis when the sutures pulled through the vessel wall. The mean burst strength of the anastomosed vessels was 44% of the contralateral unoperated controls immediately after surgery and did not significantly increase for four to five months. It was concluded that early mobilization of replanted parts is not limited by the strength of microarterial anastomoses.

Animals↗
PubMed1981

Evaluation of an oligomer or an oligomer plus cetyl pyridinium chloride against plaque, stain, calculus, and gingivitis.

A low molecular weight oligomer of sulfoacrylic acid (ND-2) was effective in inhibiting hydroxyapatite formation in vitro at 33 ppm from a saturated solution of calcium and phosphate. The oligomer did not damage or etch human dental enamel in vitro at pH 5.0 and 7.5. It significantly reduced calculus formation when applied topically in beagles at a concentration of 1% in a rinse. In a second study using 30 beagle dogs, the rinses containing 0.1% CPC and 0.1% CPC + 2% ND-2 significantly reduced (alpha less than 0.05) plaque and gingivitis for 12 wk when compared to a placebo rinse. One-tenth percent CPC rinse induced more discoloration of teeth than the placebo, while the rinse containing 0.1% CPC + 2% ND-2 had significantly less discoloration than CPC rinse or the placebo rinse in beagles. Thus the oligomer was effective in reducing CPC-induced discoloration in beagles.

Acrylic Resins↗
PubMedDate not supplied

Topiramate: preclinical evaluation of structurally novel anticonvulsant.

Topiramate [TPM, 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] (RWJ-17021-000, formerly McN-4853) is a structurally novel antiepileptic drug (AED). The preclinical anticonvulsant profile suggests that TPM acts primarily by blocking the spread of seizures. TPM was highly effective in the maximal electroshock (MES) seizure test in rats and mice. Activity was evident < or = 0.5 h after oral administration and lasted at least 16 h. The ED50 values 4 h after oral dosing were 13.5 and 40.9 mg/kg in rats and mice, respectively. TPM blocked pentylenetetrazol (PTZ)-induced clonic seizures at high doses in mice (ED50 = 1,030 mg/kg orally, p.o.). With motor incoordination and loss of righting reflex used as indicators of neurologic impairment, the neuroprotective index (TD50/MES ED50) for TPM was equivalent or superior to that of several approved AEDs. In mice pretreated with SKF-525A (a P450 enzyme inhibitor), the anticonvulsant potency was either increased or unaffected when TPM was tested 0.5, 1, or 2 h after i.p. administration, suggesting that TPM rather than a metabolite was the active agent. In mice pretreated with reserpine or tetrabenazine, the activity of TPM in the MES test was markedly reduced. TPM was inactive in a variety of receptor binding, neurotransmitter uptake, and ion channel tests. TPM weakly inhibited erythrocyte carbonic anhydrase (CA) activity. However, the anticonvulsant activity of TPM appears to differ mechanistically from that of acetazolamide.

Animals↗
PubMedDate not supplied

Disposition of metabolically labeled recombinant soluble CD4 (sT4) in male Sprague-Dawley rats following intravenous and subcutaneous administration.

Soluble CD4 (sT4) has been metabolically labeled with [3H]leucine in Chinese hamster ovary cells and purified by S Sepharose chromatography. Over 250 microCi of high specific radioactivity [3H]sT4 (42 Ci/mmol) was prepared. The radiolabeled molecule was chemically and biologically representative of the unlabeled molecule and thus appropriate for in vivo metabolic investigations. To explore the biotransformation and disposition of a recombinant protein, this uniformly labeled [3H]sT4 was administered intravenously and subcutaneously to male Sprague-Dawley rats. Following a single dose of 0.3 mg/kg, blood samples were collected for 9 days and analyzed for total radioactivity, total plasma radioactivity, trichloroacetic acid-precipitable plasma radioactivity, sT4-related plasma radioactivity (by extraction with a Sepharose-bound polyclonal anti-sT4 antibody), and plasma sT4 concentration (by an N and C terminal-specific Leu3A/OKT4 ELISA). Excreta were analyzed for total radioactivity. The pharmacokinetic profiles of intact sT4 were as expected from the results of previous studies. sT4 was cleared rapidly from plasma with an elimination t1/2 of 7 min (intravenous), and low sT4 levels were observed following subcutaneous administration. Comparison of the kinetic profiles of total radiolabel, trichloroacetic acid-precipitable radiolabel, sT4-related radiolabel, and the isolation of plasma proteins containing tritium have led to the following conclusions. One of the major metabolic pathways for [3H]sT4 was the degradation of the polypeptide to its constituent amino acids, which were subsequently incorporated into endogenous proteins. Incorporation of tritium into blood cell proteins resulted in a prolonged radiolabel blood profile (t1/2 greater than 250 hr). Following subcutaneous administration, [3H] sT4 was significantly degraded before reaching the vascular circulation.

Amino Acid Sequence↗
PubMedDate not supplied

Disposition of growth hormone-releasing peptide (SK&F 110679) in rat and dog following intravenous or subcutaneous administration.

The disposition of growth hormone releasing peptide (SK&F 110679) has been studied in male Sprague-Dawley rats and in male and female beagle dogs following intravenous (iv) and subcutaneous (sc) administration. Mass balance/excretion of [3H]SK&F 110679 was assessed in bile duct-exteriorized rats from which radiolabeled biliary and urinary excreta were quantified and characterized. [3H]SK&F 110679 was excreted, predominantly in the bile, and to a large extent as intact peptide following either iv or sc administration. Although the extent of biliary excretion of radiolabel was similar following iv or sc administration (60-70% of the dose), the rate was significantly higher following iv administration. Using a specific plasma HPLC/fluorescence assay, the iv and sc pharmacokinetics of SK&F 110679 were investigated in both species. Following iv bolus administration, biphasic plasma concentration-time profiles were observed, and the initial phases were characterized by 2-4 min half-lives. Systemic plasma clearance was 27 ml/min/kg in the rat (0.4 mg/kg dose) and 17 ml/min/kg in the dog (0.5 mg/kg dose). High sc bioavailability (89-103%) was observed in both species; an apparent terminal half-life of 1 hr likely reflected slow absorption from the injection site.

Animals↗