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Biomedical subjects

W J Ryan

Publications and source records attributed to W J Ryan.

At least 19 recordsLinked to original sources
PubMed1994

Bullatacin--in vivo and in vitro experience in an ovarian cancer model.

The cytotoxicity and antitumor effects of the acetogenin Bullatacin were evaluated in vitro in multiple ovarian cancer cell lines and in vivo in a murine ovarian teratocarcinoma (MOT) model in C3HeB/FeJ mice. The in vitro cytotoxicity of Bullatacin against four human ovarian epithelial tumor cell lines (OC-194, OC-222, OVCAR-3, and A-2780) was assessed in 48- and 72-h tetrazolium-dye (MTT) cytotoxicity assays. The percentage of cytotoxicity was determined on the basis of the mean optical density of the respective untreated cells and the dose effective against 50% of the cells (ED50) was calculated for each cell line. In vivo experiments were performed on adult female C3HeB/FeJ mice, which were injected i.p. with 10(5) MOT cells and varying amounts of Bullatacin given either in a single dose or in 5 subsequent doses over 72 h. All mice were observed for survival relative to that of the control groups, which were injected either with 10(5) MOT cells with or without serial injections of vehicle or with vehicle only. All four epithelial ovarian cancer cell lines displayed sensitivity to Bullatacin. The relative cytotoxic effects were very heterogeneous, with the ED50 value ranging between 10(-7) micrograms/ml for OC-194 and 4 micrograms/ml for the cisplatin-resistant cell line OVCAR-3 in a 72-h MTT cytotoxicity assay. All mice that had been injected i.p. with 10(5) MOT cells and 1.4 mg/kg or more of Bullatacin died within the first 24 h after injection, whereas all mice that had received 600 micrograms/kg of Bullatacin or less survived equally as long as the controls that had been injected with MOT only (21.1 +/- 0.9 days). Mice that had received Bullatacin at a dose ranging from 600 micrograms/kg to 1.4 mg/kg either died during the 1st day postinjection or survived, but not longer than the MOT control group. Serial i.p. injections of Bullatacin again either led to death of the mice within 24-48 h of the last dose of Bullatacin or did not have any effect on the survival of the mice as compared with the respective control groups, which had been injected with the tumor and serial injections of vehicle (22.5 +/- 2.2 days). In summary, Bullatacin showed no effect on MOT-caused animal death in C3HeB/FeJ mice at nonlethal dose ranges, whether it was given as a single i.p. dose or serially over 72 h. In vitro, however, it proved to be a very potent cytotoxic agent in a variety of ovarian cancer cell lines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Characterization of a human alpha 1-antitrypsin null allele involving aberrant mRNA splicing.

alpha 1-Antitrypsin (alpha 1AT) is a major protease inhibitor present in high concentrations in the plasma. Inheritance of alpha 1AT deficiency or null alleles (alleles associated with no detectable serum alpha 1AT) is associated with an increased risk for emphysema. In contrast to beta zero-thalassemia variants in which RNA splicing and promoter mutations constitute more than 40% of beta zero-thalassemia variants, all nine alpha 1AT null variants identified are the result of mutations involving the protein coding region of the alpha 1AT gene. During routine screening of individuals applying for enrollment in the USA alpha 1AT Deficiency Registry we identified an individual with emphysema and a Protease Inhibitor (PI*) type heterozygous for a novel alpha 1AT null allele. Direct DNA sequencing of this individual's alpha 1AT alleles demonstrated one normal and one novel allele, designated PI*QOwest, characterized by a single G-->T base substitution at position 1 of intron II, a highly conserved nucleotide position in vertebrate splice donor sites. Metabolic labeling of NIH-3T3 cells transfected with a plasmid vector containing an alpha 1AT minigene with the QOwest mutation demonstrated an absence of detectable immunoprecipitable alpha 1AT confirming that the G-->T mutation is responsible for the observed null phenotype. QOwest alpha 1AT minigene transfected cells expressed 25-100 fold less alpha 1AT mRNA than a normal control. DNA sequencing of polymerase chain reaction amplified mRNA obtained from transfected cells demonstrated the use of a cryptic splice site 84 bases upstream from the normal splice site.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1992

Comparative anti-inflammatory efficacy of topical corticosteroids with low glaucoma-inducing potential.

Fluorometholone and clobetasone butyrate have been developed as ophthalmic corticosteroids because of their lesser potential to elevate intraocular pressure. Nevertheless, their primary use is the inhibition of an inflammatory response. Quantification of their anti-inflammatory effect in the rabbit cornea indicates that 0.1% fluorometholone and 0.1% clobetasone butyrate are effective, but weak, anti-inflammatory agents. An increase in concentration of fluorometholone to 0.25% failed to enhance its anti-inflammatory effectiveness significantly, while an increase in concentration of clobetasone butyrate to 0.5% did significantly increase its anti-inflammatory effect. As with all other corticosteroid bases studied to date, formulation of fluorometholone as an acetate derivative significantly increased its effectiveness, rendering it as effective as 1.0% prednisolone acetate, the most effective of commercially available ophthalmic corticosteroids.

Administration, Topical↗
PubMed1991

Quantification of stromal destruction in the inflamed cornea.

An intrastromal injection of endotoxin lipopolysaccharide (LPS) in one eye of New Zealand albino rabbits induced a prominent keratitis characterized clinically and microscopically by edema and infiltration. Polymorphonuclear leukocytes (PMNs) constituted the primary invading leukocytic element. Collagen synthesis was measured by pulsing the corneas with 3H-proline before inducing inflammation. The invasion of the cornea by leukocytes did not alter the conversion of proline to hydroxyproline significantly in the stroma during the 14-day observation period, signifying that there were only negligible changes in the rate of collagen synthesis. However, the percentage of total stromal protein represented by collagen (ie, collagen/total protein) was only 50% of that in comparable corneas receiving an injection of phosphate-buffered saline. Some animals were rendered leukopenic by intravenous nitrogen mustard before intrastromal LPS injection caused a less severe corneal inflammatory response, characterized microscopically by fewer infiltrating leukocytes. Similarly, in nonleukopenic rabbits, topical therapy with 1% prednisolone acetate markedly reduced the corneal inflammatory response which also was characterized by fewer invading leukocytes. In neither instance was there extreme collagen loss, suggesting that the loss of stromal collagen is related to PMN infiltration.

Animals↗
PubMed1990

Evaluation of the patient having cardiac surgery in the postoperative rewarming period.

Ensuring adequate oxygen delivery to the tissues with respect to oxygen demand is the treatment goal in patients undergoing coronary artery surgery (CAS). In this study we examined changes in temperature, arterial oxygen saturation (SaO2), cardiac index (CI), oxygen consumption (VO2), and mixed venous oxygen saturation (SvO2) over the initial 4-hour rewarming period in 36 patients having CAS. When patients were admitted to the intensive care unit the mean temperature was 36.27 degrees C, and it increased to 37.50 degrees C; SaO2 was 97.67% at the beginning and end of the 4-hour period; CI was 2.88 L/min/m2 and rose to 3.00 L/min/m2; VO2 was high at 0.320 L/min on admission and remained high at 0.290 L/min at the end of the 4-hour rewarming period; and SvO2 was 70.83% initially and declined to 66.53% in the same period of time. Continuous SvO2 monitoring was valuable in the ongoing assessment and management of the patients in stable, mildly hypothermic condition after CAS during the 4-hour postoperative rewarming period.

Aged↗
PubMed1990

Effects of position changes on mixed venous oxygen saturation in patients after coronary revascularization.

The purpose of this study was to investigate the effects of position changes on mixed venous oxygen saturation (SvO2) and to describe the mechanisms responsible for SvO2 changes reported to occur with position changes. The study was done from 4 to 8 hours after surgery in 34 patients after coronary artery bypass grafting. Subjects were put through a series of six position changes, including head of bed elevations and right and left lateral decubitus with return to supine between each. Each position was maintained for 30 minutes. SvO2, arterial oxygen saturation (SaO2), and oxygen consumption (VO2) were measured before and after each position change. Overall mean subject data demonstrated a decrease in SvO2 with each of the lateral position changes. The SvO2 did not drop below 60% in these mean data, and this drop returned to baseline by 5 minutes. There were no significant changes in the mean data for VO2 or SaO2. No significant correlation was found in the mean data between SvO2 and VO2 or SvO2 and SaO2 measurements. Trends were demonstrated in five specific cases that suggested a correlation between changes in SvO2 and changes in VO2 and SaO2. In conclusion, this study demonstrated that subjects were able to tolerate position changes with no clinically significant changes in SvO2, SaO2, or VO2.

Aged↗
PubMed1989

The access of relevant information for solving problems.

Two issues were investigated concerning the retrieval of recently acquired relevant information for solving riddle problems. First, although earlier research indicated that problem solvers often fail to retrieve relevant information unless they are explicitly informed of its relevance, Bowden (1985) suggested that uninformed subjects would benefit greatly from additional problem-solving time. In two experiments, we found that uninformed subjects solved more problems than did subjects who did not receive the information, but a simple model attributed this difference to these uninformed subjects "catching on" to the information's relevance after solving some problems. Second, the retrieval characteristics were examined by varying the proportion of problems for which clues were given. Informed subjects given clues for only half of the problems benefited (though perhaps not fully) from being informed, without incurring any cost from being misdirected on the unclued problems. The discussion focuses on some ways in which accessing relevant information may affect problem solving.

Adult↗
PubMed1986

Effect of concurrent topical corticosteroid and NSAID therapy of experimental keratitis.

The ability of suprofen, a nonsteroidal anti-inflammatory drug, and prednisolone acetate, a corticosteroid, to suppress polymorphonuclear leukocyte invasion of the rabbit cornea during an experimental keratitis was evaluated following topical ophthalmic administration of either drug alone or both drugs concurrently. Suprofen therapy initiated immediately after induction of inflammation was ineffective. However, if suprofen therapy was begun 48 hr prior to the induction of inflammation, the drug was effective. In contrast, prednisolone acetate therapy begun after the induction of inflammation was effective; 48 hr of pretreatment with the corticosteroid produced a marked increase in its therapeutic effect. When administered according to the same regimen, concurrent therapy with suprofen and prednisolone acetate was significantly more effective than treatment with either drug alone. This result was obtained irrespective of whether concurrent therapy was initiated prior to or after the inflammatory event.

Administration, Topical↗
PubMed1986

Bioavailability and corneal anti-inflammatory effect of topical suprofen.

The bioavailability in rabbit cornea and aqueous humor of an ophthalmic formulation of suprofen, a nonsteroidal anti-inflammatory drug, was evaluated following topical administration of a single dose to the eye. The drug penetrated rapidly into the uninflamed cornea with intact epithelium; highest levels occurred during the first 30 to 45 min after instillation and decreased thereafter. The bioavailability of suprofen in cornea and aqueous humor following administration of a 1.0% concentration was twice that produced by a 0.5% concentration of the drug. Topical application of multiple doses of suprofen failed to suppress polymorphonuclear leukocyte invasion of the cornea if treatment was started after the induction of inflammation. Suprofen therapy initiated prior to the induction of corneal inflammation and maintained into the post-inflammation period did produce a significant (P less than 0.01) decrease in the numbers of PMNs that invaded the inflamed cornea. There was no significant difference (P greater than 0.05) in the corneal anti-inflammatory effect achieved by the 0.5% and 1.0% concentrations of suprofen when administered according to this regimen.

Animals↗
PubMed1985

Quantitation of herpes simplex virus in rabbit corneal epithelium.

The authors have developed an objective method for quantitation of herpes simplex virus in the corneal epithelium of rabbits. At appropriate times postinfection, full-thickness rabbit corneas were removed by trephination and subjected to one cycle of freezing and thawing. The corneal epithelium was then disrupted by sonication. The amount of infectious virus recovered from sonicated specimens was determined by an in vitro plaque assay, providing a measure of the quantity of virus present during the acute stage of herpetic keratitis. Using this technique, the authors found that the mean virus titer was reduced from 1.5 X 10(5) plaque forming units (pfu) per cornea in control rabbits to less than 200 pfu per cornea in rabbits treated topically for 2 days with 1% trifluridine. In contrast, instillation of 1% prednisolone acetate resulted in the persistence of higher levels of virus (275 pfu) than those observed in control rabbits (3 pfu) 4 days after the cessation of therapy.

Animals↗
PubMed1981

Route of antibiotic administration in bacterial keratitis.

The in vivo antibacterial effectiveness in the rabbit cornea of several antibiotics delivered by topical application, by periocular injection, and by intravenous (IV) inoculation was determined against Staphylococcus aureus and Pseudomonas aeruginosa. Topical instillation of antibiotic was highly effective in eliminating these organisms from the cornea. In contrast, despite a considerable increase in the quantity of antibiotic administered, we could demonstrate no statistically significant reduction in the number of viable staphylococcal or Pseudomonas organisms in the cornea when the antibiotic was given by periocular or by IV injection.

Administration, Topical↗
PubMed1981

Prolongation of anti-inflammatory effect of prednisolone acetate. Influence of formulation in high-viscosity gel.

Prednisolone acetate was formulated in a high-viscosity carboxypolymethylene gel at concentrations of 0.125% and 1.0%. The ability of these gel preparations to suppress inflammation in the cornea was assessed and compared with the antiinflammatory capabilities of conventional commercially available prednisolone acetate ophthalmic suspensions. When administered hourly, the gel formulations produced no greater anti-inflammatory effect than the conventional suspensions. However, the gel formulations were equal in effect to the suspensions and maintained their effects considerably longer than did the suspensions. When applied at intervals up to and including four hours, there was no falloff in effect; the gel demonstrated a level of anti-inflammatory effectiveness that could not be distinguished from hourly administration of the suspension.

Animals↗