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Biomedical subjects

R C Dunn

Publications and source records attributed to R C Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of a transposable element insertion on alcohol dehydrogenase expression in Drosophila melanogaster.

Variation in the DNA sequence and level of alcohol dehydrogenase (Adh) gene expression in Drosophila melanogaster have been studied to determine what types of DNA polymorphisms contribute to phenotypic variation in natural populations. The Adh gene, like many others, shows a high level of variability in both DNA sequence and quantitative level of expression. A number of transposable element insertions occur in the Adh region and one of these, a copia insertion in the 5' flanking region, is associated with unusually low Adh expression. To determine whether this insertion (called R142) causes the low expression level, the insertion was excised from the cloned R142 Adh gene and the effect was assessed by P-element transformation. Removal of this insertion causes a threefold increase in the level of ADH, clearly showing that it contributes to the naturally occurring variation in expression at this locus. Removal of all but one LTR also causes a threefold increase, indicating that the mechanism is not a simple sequence disruption. Furthermore, this copia insertion, which is located between the two Adh promoters and their upstream enhancer sequences, has differential effects on the levels of proximal and distal transcripts. Finally, a test for the possible modifying effects of two suppressor loci, su(wa) and su(f), on this insertional mutation was negative, in contrast to a previous report in the literature.

Alcohol Dehydrogenase↗
PubMed1995

Short-term Lupron or danazol therapy for pelvic endometriosis.

OBJECTIVE: To compare the efficacy of a 3-month trial of leuprolide acetate (LA; Lupron; TAP Pharmaceuticals, Deerfield, IL) versus danazol (Danocrine; Scenofi Winthrup Pharmaceuticals, New York, NY) therapy on laparoscopically proven endometriosis. DESIGN: Endometriosis severity was assessed at the time of laparoscopy and patients were randomized to receive 0.1 mg SC LA (n = 22) or 800 mg danazol orally (n = 18) daily for 3 months. A second laparoscopy and/or laparotomy was performed to assess the change in the extent of endometriosis and for surgical therapy. SETTING: Private practice at a university-affiliated hospital. PATIENTS: Forty patients with mild, moderate, or severe endometriosis. Ten patients were excluded. INTERVENTION: Three-month treatment randomly assigned to either LA or danazol. MAIN OUTCOME MEASURES: Prospective measurement of American Fertility Society endometriosis scores and size of ovarian endometriomata before and after therapy via laparoscopy. RESULTS: The mean endometriosis score including adhesions decreased significantly from 36 +/- 4.9 to 29 +/- 5.0 (mean +/- SEM) with LA and from 34 +/- 6.4 to 29 +/- 6.5 with danazol. The mean laparoscopic endometriosis score not including adhesions decreased from 27 +/- 3.5 to 22 +/- 3.4 with LA and 22 +/- 3.5 to 19 +/- 3.1 with danazol. Seven of 18 (39%) endometriomata responded to LA and 6 of 15 (40%) endometriomata responded to danazol. CONCLUSION: We conclude that both danazol and LA will reduce endometriosis scores after a 3-month course of therapy. Larger clinical trials are needed to compare short courses of therapy with the more established 6-month trials. A 3-month versus a 6-month course of therapy offers obvious benefits including decreased cost and decreased side effects.

Danazol↗
PubMed1994

Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention.

The aim of this study was to optimize the properties of a lubricious bioerodible hydrogel barrier for the prevention of postoperative adhesions. Water-soluble macromers based on block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) or poly(glycolic acid) with terminal acrylate groups were used, and these macromers were gelled in vivo by exposure to long wavelength ultraviolet light. The precursor was photopolymerized from buffered saline solution while in contact with the tissues. This resulted in the conformal coating of the tissue with an adherent hydrogel film, while forming a nonadhesive barrier at the free surface, on the treated wound site. The hydrogels were evaluated in two animal models of postsurgical adhesions, first in a rat cecum abrasion model and then in a rabbit uterine horn ischemia model. In the rat cecum model, six of seven animals treated with a hydrogel, with glycolide in the precursor as the comonomer, showed no adhesions; untreated animals and animals treated with precursor, but not gelled with light, showed consistent dense adhesions. In the rabbit uterine horn ischemia model, using hydrogels with lactide in the precursor as the comonomer, and PEG of molecular weight from 6,000 to 18,500 Da, adhesions were dramatically reduced, with occurrence in none of seven animals treated with a gel containing PEG 10,000. By contrast, the seven animals in the control group demonstrated a mean of 35% involvement of the horn length in dense, fibrous adhesions. These materials, photopolymerized in vivo in direct contact with the tissues, appear to form an adherent hydrogel barrier that is highly effective in reducing postoperative adhesions in the models used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Efficacy of a resorbable hydrogel barrier, oxidized regenerated cellulose, and hyaluronic acid in the prevention of ovarian adhesions in a rabbit model.

OBJECTIVE: To compare the efficacy of a resorbable hydrogel material with oxidized regenerated cellulose and hyaluronic acid in an ovarian adhesion model. DESIGN: Controlled, blinded, and randomized study involving female rabbits. SETTING: Academic research environment. INTERVENTIONS: A water-soluble hydrogen precursor was applied to the ovary as a liquid and converted to a hydrogel by exposure to long wavelength ultraviolet light, a 0.4% solution of hyaluronic acid was applied to the ovary, or an oxidized regenerated cellulose patch was applied to the ovary after wedge resectioning. MAIN OUTCOME MEASURES: Extent and severity of adhesion formation. RESULTS: Application of the hydrogel reduced adhesion formation by 88%. Neither oxidized regenerated cellulose nor hyaluronic acid reduced adhesion formation. CONCLUSION: The photopolymerized, resorbable hydrogel material is highly effective for the reduction of periovarian adhesions in this model.

Animals↗
PubMed1994

Prevention of postoperative adhesions in the rat by in situ photopolymerization of bioresorbable hydrogel barriers.

OBJECTIVE: To assess the efficacy of a novel resorbable hydrogel barrier for preventing postoperative adhesions in animals. METHODS: A hydrogel barrier was formed in situ by photopolymerizing a solution of a macromolecular prepolymer in buffered saline using long-wavelength ultraviolet light. Two models in the rat were evaluated. In a primary adhesion model, devascularization and serosal injury were performed on the uterine horns using bipolar electrocautery. The prepolymer solution was applied to the horns and illuminated to form the barrier. On the seventh postoperative day, the fraction of the length of the horns involved in adhesions was scored, as was the quality of the adhesions. In a readhesion model, adhesions were formed as described and were surgically lysed on the seventh day, then were treated subsequently with the barrier and scored after 7 additional days. Each group in both models consisted of seven animals per treatment condition. Four prepolymer concentrations were examined in the primary adhesion model, and the optimal one was examined in the readhesion model. RESULTS: A conformal hydrogel barrier coating was formed upon in situ photopolymerization and adhered to the treated tissues. No residual hydrogel barrier was observed 7 days after application of the optimal gel concentrations. In the primary adhesion model, the mean fraction of the horns involved in adhesions was reduced significantly, from 76% in controls to 10% (P < .0001), and treatment with a 10% solution of prepolymer was determined to be optimal (P = .025). In the readhesion model, surgical lysis of adhesions alone did not reduce adhesions significantly (from 86% to 79%; P = .3), whereas lysis with barrier treatment did (79% to 28%; P = .002). CONCLUSIONS: In situ photopolymerization allowed the formation of adherent, conformal barriers, which demonstrated high efficacy in the prevention of adhesion formation and reformation in animals. This efficacy and ease of use warrant clinical evaluation.

Animals↗
PubMed1994

Growth factor effects on endometrial epithelial cell differentiation and protein synthesis in vitro.

OBJECTIVE: To develop a baseline for projected studies of a rat endometriosis model. DESIGN: We investigated the effects of two macrophage-related growth factors, platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), on proliferation, in vitro differentiation, and protein secretion of uterine epithelial cells from immature rats. Uterine epithelial cells grown on matrix covered filters were treated with growth factors (GFs) or estrogen and/or P. Incorporation of [35S]methionine by polarized uterine epithelial cell proteins and secretion of labeled proteins into apical and basal culture medium were examined. SETTING: Department of Cell Biology, Baylor College of Medicine, Houston, Texas. MAIN OUTCOME MEASURES: Cell associated and secreted proteins were resolved by gel electrophoresis, fluorography, and immunoblotting. Proliferation was quantified by cell counts in parallel cultures by hemocytometer. RESULTS: Estrogen and P increase protein synthesis by uterine epithelium. Transforming growth factor-beta depressed protein synthesis and secretion in uterine epithelial cells. Platelet-derived growth factor appears to have no effect on epithelial protein synthesis or secretion and does not modulate the effect of TGF-beta. Estrogen and P increase complement component 3 (C3) production by epithelial cells. CONCLUSION: Macrophage-secreted GFs may play a role in the development and maintenance of ectopic endometrial tissue. Both TGF-beta and ovarian steroids may participate in the dynamic regulation of protein synthesis by ectopic uterine epithelium. These molecules may indirectly affect the macrophage-stromal axis through nonspecific modulation of C3 secretion. Platelet-derived growth factor appears to have no direct effect on uterine epithelial cells. The recognized effect of PDGF on ectopic endometrial tissue is most likely mediated via the stromal component.

Analysis of Variance↗
PubMed1993

Effect of varying days of tissue plasminogen activator therapy on the prevention of postsurgical adhesions in a rabbit model.

The depression of focal fibrinolytic activity in mesothelial or serosal tissues which results from a surgical ischemic insult can lead to the formation of permanent fibrinous adhesions. To assess the time course for the prevention of adhesion formation by recombinant tissue plasminogen activator (rt-PA), infusions of rt-PA were administered to rabbits every 12 hr for a total of 1, 2, 4, or 8 days. Animals in each rt-PA treatment group received a total cumulative dose of 16 mg. Control animals received saline with the same corresponding dosing regimens as the treated groups. Prior to dosing, all animals had a devascularizing injury to the uterine horns performed bilaterally by bipolar cauterization of the uterine mesenteric vascular arcade below the horns. A catheter was then placed from a subcutaneous port to the intraperitoneal space. rt-PA, or saline, was instilled intraperitoneally via the subcutaneous port. Adhesions were scored at the second laparotomy by assessing the percentage of the involvement of the uterine horns in adhesions. Mean score for adhesion formation in each placebo group was 35 to 40%. Mean score (+/- standard error of the mean) for rt-PA after 1 day of therapy was 13.1% +/- 3.89; after 2 days of therapy, 6.3% +/- 1.57; after 4 days of therapy, 3.8% +/- 1.57; and after 8 days of therapy, 6.9% +/- 2.3 (P < 0.01 compared to the control grouped mean for each day of treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model.

Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route.

Analysis of Variance↗
PubMed1991

Picosecond study of the near infrared absorption band of hemoglobin after photolysis of carbonmonoxyhemoglobin.

Picosecond absorption spectroscopy is used to examine the position and band shape of the near infrared absorption band of hemoglobin as a function of time after the photodissociation of CO from carbonmonoxyhemoglobin. For the earliest delay time probed, 35 ps, the peak of the transient spectrum is at 765 nm, red shifted by 6 nm from that characteristic of equilibrium deoxyhemoglobin. No evolution in either the peak position or band shape is observed for time delays up to 60 ns. In addition, the position and shape of the spectrum are independent of photolysis energies ranging from 15 microJ/pulse to 150 microJ/pulse, spanning conditions under which the photon/heme ratio is varied from 0.01 to 2.0. This indicates that the geometry in the heme group is unrelaxed and that equilibration of the surrounding protein structure occurs on a time scale longer than 60 ns.

Carboxyhemoglobin↗
PubMed1991

Subconjunctival high dose plasminogen activator in rabbit filtration surgery.

The primary cause of failure in glaucoma filtration surgery is fibroblastic proliferation and subconjunctival fibrosis at the bleb site resulting in decreased aqueous flow. We evaluated New Zealand white rabbits in a masked, placebo controlled pilot study to determine the potential reduction of episcleral fibrosis at the surgical bleb site utilizing 0.3 mls of: balanced salt solution (n = 11); an inert gel delivery vehicle (n = 13); the gel delivery vehicle with incorporated recombinant tissue plasminogen activator (tpa; n = 14), 1 mg/ml. Statistical analysis of computer assisted area measurements from multiple histologic sections demonstrated a significant decrease in episcleral fibrosis in the t-PA group as compared to the two other groups (p less than 0.05). Results from the t-PA group did not demonstrate an effect on intraocular pressure. There was no clinical evidence of toxicity or healing complications in the t-PA group.

Animals↗
PubMed1990

Tubal pregnancy with normal hysterosalpingogram and negative serum pregnancy test.

A patient undergoing evaluation for primary infertility with regular menses had a normal hysterosalpingogram in the follicular phase and underwent diagnostic laparoscopy the next day, with the finding of a tubal pregnancy. The patient had a negative serum pregnancy test. Although a normal hysterosalpingogram and negative serum pregnancy test are each rare with a tubal pregnancy, the combination of the two occurring in a tubal pregnancy is previously unreported and did not exclude the diagnosis in this case.

Adult↗
PubMed1989

Molecular forms of acetylcholinesterase from the skeletal muscle of the ammocoete of the lamprey Petromyzon marinus.

1. We have studied the cholinesterase activity from the skeletal muscle of the ammocoete of the lamprey Petromyzon marinus. 2. On the basis of pharmacologic and kinetic criteria, we conclude that the enzyme is true acetylcholinesterase, not pseudocholinesterase. 3. The acetylcholinesterase was found to be present in both globular and asymmetric forms. 4. In contrast to muscle of adult spawning lamprey, where globular esterase is almost exclusively G4, we found that muscle from ammocoete also contains significant amounts of G1 and G2. 5. This difference may be related to the physiological states of the lamprey during the various stages of its life cycle.

Acetylcholinesterase↗
PubMed1989

Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model.

To evaluate the potential benefit of recombinant tissue plasminogen activator (rt-PA) as an agent for reducing postoperative adhesions, a rabbit uterine horn model was studied. Fifty-five rabbits underwent laparotomy, at which time the uterus was abraded with scalpel and a thermal injury was induced with electrocautery. Before abdominal closure, rt-PA was applied topically in various dosages. Adhesions were evaluated at a second laparotomy performed 2 weeks later. Treatment significantly reduced both adhesion quantity (P less than 0.001) and adhesion density (P less than 0.001). In the second phase of the study, the efficacy of rt-PA as an adjunct to surgical adhesiolysis was investigated. Again, a dose-related treatment effect was observed (P less than 0.001). No wound healing or bleeding complications were seen.

Animals↗
PubMed1988

Low-density lipoproteins increase intracellular calcium in aequorin-loaded platelets.

Low-density lipoproteins activate isolated human platelets. The mechanism of this activation is unknown, but may involve increased phosphoinositide turnover. We have examined the effect of low-density lipoproteins on intracellular calcium concentrations in platelets loaded with the photoprotein aequorin. The lipoproteins induced concentration-dependent increases in intracellular calcium, associated with shape change and aggregation. These responses could be partially inhibited by the removal of extracellular calcium and by pre-incubation with acetylsalicylic acid. They were also antagonised by agents which increase cellular concentrations of cyclic adenosine and guanosine monophosphates. It is not clear whether the platelet-lipoprotein interaction involves a 'classical' lipoprotein receptor.

Aequorin↗
PubMed1987

Changes in the secondary structure of apolipoprotein B-100 after Cu2+-catalysed oxidation of human low-density lipoproteins monitored by Fourier transform infrared spectroscopy.

Fourier transform infrared (FTIR) spectra have been obtained of human low-density lipoproteins (LDL) in H2O and 2H2O buffers. The absorption bands are assigned to vibrations of the lipid and apolipoprotein B-100 components. The analysis of second-derivative spectra allowed an assignment of individual protein bands to alpha-helical, random, coil or beta-structure and beta-turn conformations. Changes in the FTIR spectra after Cu2+-catalysed oxidation of the LDL particles indicate that the structure of apolipoprotein B-100 becomes less ordered, with some alterations of alpha-helical and beta-turn conformation. The main beta-structure absorption at 1620 cm-1 is unaffected by oxidation. Taking into account the resistance to oxidation and the slow H-2H exchange it is suggested that the beta-structure is hidden from external factors whereas other structures are mostly present on the surface of the LDL particle. Oxidation affects mainly the surface region of apolipoprotein B-100 and leads to a structural rearrangement which consequently changes the receptor specificity of the LDL.

Apolipoprotein B-100↗