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Biomedical subjects

J Donahue

Publications and source records attributed to J Donahue.

At least 19 recordsLinked to original sources
PubMed2000

G6PD deficient cells and the bioreduction of disulfides: effects of DHEA, GSH depletion and phenylarsine oxide.

We used Glucose 6 phosphate dehydrogenase (G6PD) minus cells (89 cells) and G6PD containing cells (K1) to understand the mechanisms of bioreduction of disulfide and the redox regulation of protein and non protein thiols in mammalian cells. The 89 cells reduce hydroxyethyldisulfide (HEDS) to mercaptoethanol (ME) at a slower rate than K1 cells. HEDS reduction results in loss of nonprotein thiols (NPSH) and a decrease in protein thiols (PSH) in 89 cells. The effects are less dramatic with K1 cells. However, the loss of NPSH and PSH in K1 cells are increased in the absence of glucose. Glutathione-depletion with L-BSO partially blocks HEDS reduction in K1 and 89 cells. Treatment with the vicinal thiol reagent phenyl arsenic oxide (PAO) blocks reduction of HEDS in both cells. Surprisingly, dehydroepiandrosterone (DHEA), a known inhibitor of G6PD, inhibits the growth and blocks the reduction of HEDS both in 89 and K1 cells suggesting that its mechanism for inhibition of growth is not G6PD related.

Animals↗
PubMed2000

A method for measuring disulfide reduction by cultured mammalian cells: relative contributions of glutathione-dependent and glutathione-independent mechanisms.

A method is described for measuring bioreduction of hydroxyethyl disulfide (HEDS) or alpha-lipoate by human A549 lung, MCF7 mammary, and DU145 prostate carcinomas as well as rodent tumor cells in vitro. Reduction of HEDS or alpha-lipoate was measured by removing aliquots of the glucose-containing media and measuring the reduced thiol with DTNB (Ellman's reagent). Addition of DTNB to cells followed by disulfide addition directly measures the formation of newly reduced thiol. A549 cells exhibit the highest capacity to reduce alpha-lipoate, while Q7 rat hepatoma cells show the highest rate of HEDS reduction. Millimolar quantities of reduced thiol are produced for both substrates. Oxidized dithiothreitol and cystamine were reduced to a lesser degree. DTNB, glutathione disulfide, and cystine were only marginally reduced by the cell cultures. Glucose-6-phosphate deficient CHO cells (E89) do not reduce alpha-lipoate and reduce HEDS at a much slower rate compared to wild-type CHO-K1 cells. Depletion of glutathione prevents the reduction of HEDS. The depletion of glutathione inhibited reduction of alpha-lipoate by 25% and HEDS by 50% in A549 cells, while GSH depletion did not inhibit alpha-lipoate reduction in Q7 cells but completely blocked HEDS reduction. These data suggest that the relative participation of the thioltransferase (glutaredoxin) and thioredoxin systems in overall cellular disulfide reduction is cell line specific. The effects of various inhibitors of the thiol-disulfide oxidoreductase enzymes (1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), arsenite, and phenylarsine oxide) support this conclusion.

Animals↗
PubMed1999

Implementing a latex safe environment in a hospital setting. Case study.

1. Change is a difficult process. Using a change model as a guide to implementing change can make the process easier. 2. Hospitals work well using the team approach to accomplishing change. Representation from all key areas of the hospital is essential. 3. It is important to educate resisters regarding the benefit and need for change. The strongest opponents can become the strongest leaders in the change process. 4. Education cannot be underestimated. It is essential to use formal and informal means to educate all personnel.

Hospitals, Community↗
PubMed1998

An in vitro model fails to demonstrate aerosolization of tumor cells.

BACKGROUND: We investigated the ability of pressurized CO2 gas to aerosolize B16 melanoma (B16) tumor cells in an in vitro model. METHODS: The experimental apparatus consisted of an 18.9-L plastic cylindrical vessel and a compliant latex pouch was attached to the top. Two 5-mm ports penetrated the vessel; insufflation and desufflation were carried out through them. A culture dish containing 20 million B16 cells in liquid culture media was placed at the base within the container. In the first experiment, the vessel was insufflated with CO2 gas to a static pressure of 15 or 30 mm Hg with the outflow port closed. After 10 min, the outflow port was opened and the gas was desufflated through a collecting device containing sterile culture medium. In a second experiment, a continuous flow of CO2 through the vessel was maintained after a pressure of 15 or 30 mm Hg was established. A total of 10 L CO2 was cycled through the vessel. In both experiments, 24 determinations were carried out at each pressure. Each experimental culture dish was microscopically scanned for 2 weeks for the presence of tumor cells. The third and fourth experiments tested for the presence of aerosolized nonviable tumor cells in the expelled gas. Using the model described above, after 10 mins of 30 mm Hg static pressure, the CO2 gas was expelled directly onto a glass slide and cytofixed. Alternately, after 10 mins at 30 mm Hg static pressure, the gas was expelled through a saline-filled Soluset (Abbott Laboratories), centrifuged, and the residue cytofixed onto a glass slide. Each of the five slides per experiment were examined microscopically for the presence of cells. RESULTS: In the first and second experiments, no cells or growth were observed in any of the 96 experimental dishes. In experiments three and four, no cells were detected on any of the slides. CONCLUSIONS: It was not possible with this model to aerosolize tumor cells in a pressurized CO2 environment. Our results suggest that aerosolization of tumor cells is not the mechanism of port site recurrences after laparoscopic surgery for malignant disease.

Aerosols↗
PubMed1998

Wound tensile strength and contraction rate are not affected by laparotomy or pneumoperitoneum.

BACKGROUND: Many cellular elements responsible for wound healing are affected by laparotomy. The aim of this study was to evaluate the effects of laparotomy and CO2 pneumoperitoneum on wound healing. METHODS: Male Sprague Dawley rats were randomly assigned to one of three experimental groups. Anesthesia control rats underwent no procedure. Pneumoperitoneum group rats were insufflated with CO2 gas. Laparotomy group rats underwent a 7-cm midline laparotomy incision. The interventions were 30 min long. For the incisional study (n = 30), a 4-cm dorsal full-thickness skin incision was made on each rat and then closed with staples. On postoperative days 7 and 14, an equal number of rats were sacrificed from each group, and wound tensile strength measurements were performed. For the excisional study (n = 45), each group of 15 rats underwent a 2-cm diameter circular dorsal full-thickness skin excision. Blinded measurements of wound area were performed every other day until wounds closed. RESULTS: Wound tensile strength values were not significantly different among experimental groups at either time point. The study had a power of 80% to find a 30% difference at POD 7 and a power of 80% to find a 23% difference at POD 14 to a confidence level of p < 0.05. Wound contraction data from the excisional model were analyzed with the Generalized Estimation Equations statistical approach. When we modeled the treatment group as a covariate, no statistical difference was found between groups, demonstrating equal slopes across time. CONCLUSIONS: From the results of these studies, we conclude that wound healing in this model is not significantly diminished following laparotomy or peritoneal insufflation, as compared to anesthesia control.

Animals↗
PubMed1997

Changing relations between phonological processing abilities and word-level reading as children develop from beginning to skilled readers: a 5-year longitudinal study.

Relations between phonological processing abilities and word-level reading skills were examined in a longitudinal correlational study of 216 children. Phonological processing abilities, word-level reading skills, and vocabulary were assessed annually from kindergarten through 4th grade, as the children developed from beginning to skilled readers. Individual differences in phonological awareness were related to subsequent individual differences in word-level reading for every time period examined. Individual differences in serial naming and vocabulary were related to subsequent individual differences in word-level reading initially, but these relations faded with development. Individual differences in letter-name knowledge were related to subsequent individual differences in phonological awareness and serial naming, but there were no relations between individual differences in word-level reading and any subsequent phonological processing ability.

Aptitude↗
PubMed1994

Inhibition of x-ray induced transformation and effect on myc and fos gene expression by the nucleotide analog, 2-aminopurine.

Ionizing radiation is a carcinogen that is known to induce malignant transformation of C3H/10T1/2 fibroblasts in vitro. Radiation is also known to induce c-myc expression and protease inhibitors that suppress radiation transformation reduce myc and fos gene expression. The antiproliferative protein kinase inhibitor 2-aminopurine has been shown to selectively inhibit serum induced c-fos and c-myc expression in human hemopoetic cells. The myc and fos oncogenes are thought to play a role in the regulation of cell proliferation and may be involved in early stages of carcinogenesis. We determined the ability of 2-aminopurine to affect x-ray-induced transformation in C3H/10T1/2 cells in vitro and its effect on myc and fos gene expression in these cells. Treatment with 2-aminopurine (5 x 10(-4) M) resulted in a 50-100% reduction in transformation yield when C3H/10T1/2 cells were irradiated with 6 Gy of x-irradiation. The 2-aminopurine had to be present during the post-confluent stage of cell growth in order to exert its inhibitory effect. Treatment of cells with 2-aminopurine significantly reduced the level of myc gene expression; the inhibitory effect of 2-aminopurine on fos gene expression in these cells was not statistically significant.

2-Aminopurine↗
PubMed1994

Techniques for early diagnosis of the abnormal fetus.

The phenomenal developments in molecular genetics and technological refinements which have occurred over the past decade are revolutionizing the area of prenatal genetics. State-of-the-art care commences with comprehensive preconceptional counseling. Prenatal diagnosis is now feasible from the moment of conception onward. Imaging techniques have allowed non-invasive diagnosis while minimally invasive techniques concentrate on sampling maternal blood for fetal cells or markers of feto-placental metabolism. Invasive techniques are rapidly expanding and becoming safer, comprising of chorionic villus sampling, early amniocentesis, midtrimester amniocentesis as well as very early fetoscopy and umbilical vein sampling.

Congenital Abnormalities↗
PubMed1992

Analysis of chimeric mRNAs derived from the STE3 mRNA identifies multiple regions within yeast mRNAs that modulate mRNA decay.

In the yeast Saccharomyces cerevisiae unstable mRNAs decay 10-20 fold more rapidly than stable mRNAs. In order to examine the basis for the differences in decay rate of the unstable STE3 mRNA and the stable PGK1 and ACT1 mRNAs we have constructed and measured the decay rates of numerous chimeric mRNAs. These experiments indicate that multiple regions within yeast mRNAs are involved in modulating mRNA decay rates. Our results suggest that at least two regions within the STE3 mRNA are involved in stimulating rapid decay. One region is located within the coding region and requires sequences between codons 13 and 179. In addition, the STE3 3' UT can also function to stimulate decay. Surprisingly, the STE3 3' UT is not sufficient to accelerate the turnover of the stable PGK1 transcript unless portions of the PGK1 coding region are first deleted. These results not only identify sequences that function within yeast to stimulate mRNA turnover but also have important implications for an understanding of the basis of differences in eukaryotic mRNA decay rates.

Base Sequence↗
PubMed1992

Using the Kaminski model for evaluating philosophical thought.

A model is proposed for the evaluation of philosophical thought generated within the chiropractic profession. This model is patterned after the Kaminski et al. model used to evaluate chiropractic procedures and practices. Decisions about the knowledge status of a philosophical query are made by following a flow chart. These decisions are made based on the query items' ability to be adequately defined, philosophical plausibility and survival of philosophical "testing." The query is assigned a status as to its adequacy in terms of philosophical knowledge. The model is demonstrated using example queries. Its applications are examined and problems of implementation are discussed.

Algorithms↗
PubMed1988

High level expression of fms proto-oncogene mRNA is observed in clinically aggressive human endometrial adenocarcinomas.

Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.

Adenocarcinoma↗
PubMed1985

Pharmacokinetic analysis of a case of isopropanol intoxication.

A comatose 46-year-old woman, admitted to the emergency room, had isopropanol and acetone concentrations of 2000 and 120 mg/L, respectively, in her serum. She had no known history of acute isopropanol intoxication and was otherwise physically healthy. Pharmacokinetic analysis showed that the elimination of both isopropanol and its major metabolite acetone obeyed apparent first-order kinetics with half-lives of 6.4 and 22.4 h, respectively. These data contrast with the commonly held view that isopropanol is slowly metabolized. Concentrations of these analytes in cerebrospinal fluid 6 h after admission were similar to those in serum. This is the first report of the pharmacokinetics of both agents in a nonalcoholic person, and it gives the first data on concentrations of these substances in cerebrospinal fluid.

1-Propanol↗
PubMed1978

Effect of amitriptyline on polarography of chlordiazepoxide.

With increasing amounts of electroinactive amitriptyline, each of the three chlordiazepoxide reduction waves shifted to more cathodic half-wave potentials and decreased in limiting current. The shift was most pronounced up the 1:1 mole ratio but continued up to ratios of 200:1. This behavior was observed in several supporting electrolytes and was not due to change in pH since this factor was maintained constant as the amitriptyline concentration was increased. Shifts in E1/2 and reductions in limiting current may arise in several ways, such as complex formation between the two drugs or adsorption of the amitriptyline onto the surface of the dropping mercury electrode hindering chlordiazepoxide reduction. Most data point to adsorption as the cause.

Amitriptyline↗