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Biomedical subjects

P Hawley

Publications and source records attributed to P Hawley.

At least 19 recordsLinked to original sources
PubMed2000

Reductionism in the pursuit of nursing science: (in)congruent with nursing's core values?

Within nursing scholarship a critique has developed around the philosophy and approaches of traditional science. The central theme of this critique is that the approaches of traditional science are antithetical to nursing's commitment to a humanistic philosophy, as reflected in the premise that reductionism is incongruent with nursing's core values. Several nurse scholars, believing that nursing's humanistic philosophy should guide the research efforts of the discipline, have advocated abandonment of the reductionistic approaches of traditional science. The authors contend that adoption of such a position will have serious consequences for knowledge development in nursing and subsequently will be detrimental to the advancement of nursing practice and the discipline of nursing. They refute the premise that reductionism is incongruent with nursing's core values, argue for reductionism in nursing science, and conclude that without the pursuit of epistemological holism, the actualization of nursing's core values is in jeopardy.

Humans↗
PubMed1999

Comparison of binding of N3'-->P5' phosphoramidate and phosphorothioate oligonucleotides to cell surface proteins of cultured cells.

The binding of uniformly modified N3'-->P5' phosphoramidate and stereorandom and stereopure phosphorothioate oligonucleotides (ODN) to cell surface proteins was studied, using both a fibroblast and an epithelial cell line, to assess the effect of different analog backbone types and base composition on cell surface protein binding. Marked differences were observed, both quantitative and qualitative, in the proteins to which individual ODN bound. One phosphoramidate, antisense to the insulin-like growth factor-1 (IGF-1) receptor (IGF-1R), bound to different proteins than did either a 6-base mismatch phosphoramidate IGF-1R sequence or a sense N-ras sequence. The latter bound poorly to the fibroblast line and predominantly to a 46 kDa protein in the epithelial line, as did many of the other ODN. This binding was not so marked as that of the isosequential end-capped phosphodiester N-ras sequence, which bound to this protein in both cell lines. Stereopure and stereorandom phosphorothioates containing a G-quartet (shown in other studies to form high-order tetrad structures), antisense to c-myc, exhibited considerable nonspecific binding to many proteins, as did the isosequential phosphoramidate. In particular, this ODN sequence gave notable binding to high molecular weight proteins. In general, binding of the c-myc ODN to proteins of 28-30, 46, 67, and 70-90 kDa was found in this study.

3T3 Cells↗
PubMed1998

Hypersensitivity pneumonitis in a machinist.

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a patchy, interstitial lung disease that involves an immunologic reaction of the lung to repeated inhalation of foreign antigens. In this report, we describe a machinist with exposure to metalworking fluids (MWFs) and biopsy-confirmed HP. Return to work, which could be equated with a retrospective workplace-specific bronchoprovocation test, proved that working within an environment in which MWFs were used was associated with clinical deterioration in the patient's pulmonary status and with clinical improvement after removal from exposure.

Aerosols↗
PubMed1997

Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy.

Female carriers of Duchenne muscular dystrophy (DMD) may demonstrate elevated serum creatine kinase (CK) and reduction of muscle dystrophin in all muscle types. We hypothesized that decreased dystrophin in uterine or pelvic girdle musculature might affect the obstetrical performance of females heterozygous for a dystrophin mutation. We reviewed the outcome of 34 deliveries resulting in 35 children from 13 women who were mothers of males attending a muscular dystrophy clinic. Obstetrical performance was examined retrospectively by chart review and patient contact. Of 35 children, 6 (17%) were delivered in the breech position, which is a fivefold increase above the national standards for term pregnancies. Of the six infants with breech presentation, two were males affected with DMD, one was a female heterozygote, one was a male who died perinatally, and the carrier status of the other two females is unknown. Most DMD affected males (12/14) were delivered in the vertex position. Thus, it is likely that maternal, rather than fetal, muscle weakness was the significant factor in determination of fetal position at term. We speculate that subtle changes in uterine or pelvic girdle muscle tone may contribute to a higher rate of fetal breech position in carriers of the DMD gene.

Breech Presentation↗
PubMed1996

Interaction of oligodeoxynucleotides with mammalian cells.

Many previous studies have demonstrated that antisense oligodeoxynucleotides (ODNs) bind to surface proteins in a manner compatible with receptor-mediated endocytosis and, unless specifically modified, are internalized into endosomes with little access to the cytoplasmic structures or to the nucleus. Reports vary as to the specific proteins involved in the mechanism, and this study examines the conditions of binding, some proteins that might contribute to the process, and whether changes in binding patterns occur during differentiation. Native gel electrophoresis was used to optimize the surface binding of a phosphorothioate end-capped 16-mer to T15 mouse fibroblast cells, and comparisons are made with some human epithelial tumor cell lines. Binding to individual proteins was visualized using SDS-PAGE and autoradiography. Binding at 4 degrees C was almost exclusively to a 46 kDa protein and decreased in the presence of an excess of unlabeled ODN and heparin but not ATP. Increasing the temperature of ODN binding from 4 degrees C to 37 degrees C for 10 minutes changed the binding pattern observed. ODN binding to the total cytoplasmic and membrane proteins immobilized on a membrane showed a greater number of binding proteins, the most prominent being one of 30 kDa. Examination of the effects of serum on binding were made using the human lung carcinoma cell line COR-L23, which can be grown in serum-free conditions. Serum starvation led to an increased total binding seen on native gels coinciding with increased binding to a 46 kDa protein. Demonstration that changes in binding proteins occur when cells differentiate was made using the premacrophage cell line THP-1. Differentiation of these cells increased the total ODN binding and appeared to initiate the synthesis of some new binding proteins, although binding to a 46 kDa protein was reduced.

Animals↗
PubMed1996

The influence of polarized epithelial (Caco-2) cell differentiation on the cellular binding of phosphodiester and phosphorothioate oligonucleotides.

Cell aging and the degree of cellular differentiation are thought to be important variables governing uptake of oligonucleotides but remain poorly understood. The Caco-2 colon carcinoma cell line has the ability to spontaneously differentiate into enterocytes in vitro and serves as a useful model to further investigate the effect of differentiation on oligonucleotide binding and uptake. In this study, we report that the extent of oligonucleotide association and the expression of cell surface binding proteins are governed by the age and thus the degree of differentiation of Caco-2 epithelial cells in culture. Cellular association (normalized for cell number) of an all phosphodiester (PO), all phosphorothioate (PS), and a phosphodiester oligonucleotide containing two terminal phosphorothioate internucleotide linkages at the 3' end (EC-PO) gradually increased from day 3 to around day 17 of the culture, followed by a plateau, or slight decrease, up to day 21 of the cell aging study. Overall, a threefold to fourfold increase in binding was observed from day 3 to day 17. Oligonucleotide binding was temperature and pH dependent, but the magnitude of the effect was influenced by cell aging and the degree of differentiation. PS oligonucleotides exhibited greater binding (up to threefold) at the basolateral surface compared with the apical surface within the pH range 5-7. These findings could be directly correlated with the expression levels of cell surface oligonucleotide binding proteins during the aging study. A Caco-2 cell surface protein binding complex of around 46 kDa was identified as the major site of binding for both PO and PS oligonucleotides, although the latter also bound to several other proteins, especially at low pH.

Caco-2 Cells↗
PubMed1995

Use of educational gaming to enhance theory learning.

Using educational games in the classroom can increase enthusiasm and reinforce previously presented didactic information in an innovative way. This article presents a game format for teaching and learning components of nursing theories. A discussion of the teaching objectives, the development of the game, rules of play, and an evaluation of the experience are presented. The use of educational games in the classroom can be a positive, interactive, alternative method of teaching and information sharing. Engaging students in a game that is structured to reinforce information presented in lectures and reading assignments can help students test and apply their knowledge of key concepts.

Education, Nursing↗
PubMed1993

Sexual assault: coping with crisis.

An unexpected long-distance phone call after midnight started the day. Susan, the daughter of an old friend, had been sexually assaulted. Mother and daughter had just returned from the emergency department, where Susan had been examined and treated. Now, they felt abandoned and hopeless. "Susan feels as if she was raped again by physicians, police and you nurses," shouted her mother. "I thought professionals were helpers!"

Adaptation, Psychological↗
PubMed1992

The detection of oligodeoxynucleotide molecules following uptake into mammalian cells.

A mixed phosphodiester:phosphorothioate oligodeoxynucleotide was used in uptake studies with T15 mouse fibroblast cells. The presence of full-length unlabeled oligomers was identified in both cytoplasmic and nuclear extracts by a method involving gel electrophoresis and electroblotting followed by hybridization with a complementary radiolabeled probe. Detection did not depend on the presence of a label on the oligomer with the potential for its removal, often a problem in other studies. The fate of the oligonucleotides could then be followed with time for at least 3 days. This method of detection should be applicable to studies of nuclease resistance and uptake characteristics of newly developed oligonucleotide analogues.

3T3 Cells↗
PubMed1989

Prenatal diagnosis of Duchenne muscular dystrophy: prospective linkage analysis and retrospective dystrophin cDNA analysis.

The accuracy of DNA-based prenatal diagnosis of Duchenne muscular dystrophy (DMD) was determined by study of 174 families. Only 60% of families had a living affected male, and 63% had history of a single affected male. Prenatal diagnosis was declined by 47% of mothers whose DNA studies predicted a carrier risk below 2%, and none have had affected sons. Fetal risk was estimated prospectively by linkage analysis using intragenic and flanking RFLPs and retrospectively using dystrophin cDNA analysis for families whose linkage estimates lacked precision. Diagnostic accuracy was determined by comparing predictions with 40 male pregnancy outcomes. On the basis of linkage analysis, we anticipated 3.2 DMD males and observed 3.0. Retrospective cDNA analysis identified deletions in 2 of these 3 males. The combined use of linkage and cDNA deletion analysis provided a highly accurate method for prenatal diagnosis of DMD.

DNA↗
PubMed1988

Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.

We have investigated the potential for using anti-sense non-ionic methylphosphonate oligonucleotide analogues to study the relationship between oncogene expression and maintenance of the transformed phenotype in malignant cells. Our results confirmed that the methylphosphonates are resistant to biochemical degradation and are devoid of non-specific toxicity towards cultured human HT29 cells. At low temperature (less than 5 degrees C) both N-ras anti-sense and nonsense analogue 9-mers formed 1:1 complexes in solution with an N-ras sense phosphodiester oligodeoxynucleotide 20-mer, but these were largely dissociated at 25 degrees C. Only a fraction (10-20%) of the anti-sense molecules formed stable sequence specific hybrids (Tm 34 degrees C) with the 20-mer. The biological activity of the oligonucleotide analogues was tested in cell culture at 37 degrees C using T15 cells, a line of NIH 3T3 cells transfected with multiple copies of the human N-ras oncogene under control of the glucocorticoid inducible MMTV promoter. On balance the N-ras anti-sense methylphosphonate 9-mer (20-80 microM) had no effect on these cells. In only one of five experiments was an apparent reduction in dexamethasone-induced p21N-ras protein accumulation observed in the presence of the oligonucleotide analogue. Also without effect was an anti-sense 20-mer consisting of a phosphodiester sequence bounded by two methylphosphonate linkages at each end (25-50 microM in culture media; 4.8 microM by microinjection). We conclude from these experiments that, in order to achieve pronounced effects on oncogene expression, it may be necessary to use longer anti-sense methylphosphonate chains, affinity purified for their ability to hybridize with the target sequences.

Base Sequence↗
PubMed1985

The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and at lower concentration by bis(dibut.MPR)P than by bis(MPR)P. In contrast, sodium butyrate, a breakdown product of bis(dibut.MPR)P induced increases in cell size at high concentration. Bis (dibut.MPR)P was also cytotoxic to MP-resistant CH/TG cells and was approximately 300 times more effective than bis(MRP)P and MPR which exhibited similar activity against this cell line. Bis(dibut.MPR)P and dibut.MPRP were equivalent and less active than MPR in their effects on MP-sensitive L1210/0 cells where their predominant mechanism of action was via degradation to release MPR.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Hematoporphyrin-derivative and photoradiation therapy of malignant tumors.

Kodak projectors with #2418 red Corning filters were used as a light source to treat cutaneous and subcutaneous malignancies in five patients who previously had been given hematoporphyrin derivative (HpD). An argon dye laser system was used to treat malignancies in patients who also were given the HpD. These tumors included 11 melanomas of the eye, three carcinomas of the esophagus, one melanoma of the esophagus, four carcinomas of the lung, three basal cell skin cancers, and one retropharyngeal metastatic oral cancer. Clinical results and technical problems of this therapy are discussed.

Adenocarcinoma↗