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Biomedical subjects

M Dougherty

Publications and source records attributed to M Dougherty.

At least 37 records · Page 2Linked to original sources

Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma.

In this study we examined the radiation survival response of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells (BEAS-2B) stably transfected with c-raf-1 and/or c-myc. C-raf-1 transfectants (2B-raf), and c-raf-1 and c-myc double transfectants (2B-raf/myc) were relatively radioresistant compared with c-myc (2B-myc) or control vector transfectants (2B-neo) (2B-raf, D0 = 2.445 Gy; 2B-raf/myc, D0 = 2.46 Gy; 2B-myc, D0 = 1.501 Gy; 2B-neo, D0 = 2.029 Gy). The steady state level of superoxide dismutase (SOD) mRNA was higher in radioresistant cells (2B-raf and 2B-raf/myc). In addition, 2B-raf but not 2B-raf/myc or 2B-myc transfectants revealed relatively higher number of cells in G2+M phase of the cell cycle. These findings present experimental evidence that Raf-1 expression correlates with the radiation-resistant response of 2B-raf or 2B-raf/myc transfectants and suggest a role of SOD in Raf-1-associated radiation resistance. Because 2B-raf transfectants are non-tumorigenic, and double transfectants (2B-raf/myc) are tumorigenic with some phenotypic traits found in small-cell lung carcinomas, our data imply a dissociation between the Raf-1-mediated mechanisms of radiation protection and progression of lung neoplasia.

Carcinoma, Small Cell↗

Home-based management of urinary incontinence: a pilot study with both frail and independent elders.

OBJECTIVE: The participation of older rural women and their caregivers in a pilot research study on behavioral management interventions for urinary incontinence is described. DESIGN: A quasiexperimental design was used. SETTING AND SUBJECTS: Women 55 years old and older and living in a rural county in North Florida who had episodes of urinary incontinence twice or more per week were included. Outreach was directed at two groups of elders with incontinence, those who were functioning independently and those who were frail and dependent on caregivers for assistance with activities of daily living. METHODS: Behavioral management of continence comprised three techniques for the management of urinary incontinence: self-monitoring, scheduling regimens and pelvic muscle exercise with biofeedback. MAIN OUTCOME MEASURES: The main outcome measures were episodes of urine loss and amount (In grams) of urine loss with time, determined with a weighed pad test. RESULTS: Behavioral management of continence resulted in significant decrease in urinary incontinence; decreases in frequency and volume of urine loss were found among all study participants when data were analyzed. CONCLUSIONS: Although behavioral management of continence was effective in reducing incontinence among independent, community-dwelling elderly women, there was a marked lack of response to this project by frail elders and their caregivers. The same barriers to implementing time-intensive behavioral management interventions among frail elders in long-term care facilities may operate in the home setting.

Activities of Daily Living↗

Program evaluation of a unit reengineered for patient-focused care.

A quasi-experimental research design was used to determine how successful a work redesign project based on the philosophy of patient-focused care was in meeting the established goals of increased multidisciplinary collaboration, improved satisfaction for health care clients and providers, decreased cost of care, and decreased length of stay. Results indicate that multidisciplinary collaboration decreased for all health care providers, especially the health care employee group that underwent a major role revision. Patient and health care provider satisfaction increased. The cost of care was budget neutral as a result of the shift of employee costs from centralized departments to units. Length of stay decreased.

Adolescent↗

Cutaneous leishmaniasis in Tachira State, Venezuela.

Cutaneous and mucocutaneous leishmaniases are widely spread in the mountainous Andean regions of South America. In Venezuela, these regions consist of the coffee-growing states of Trujillo, Merida and Tachira. Entomological and parasitological investigations in three geographically different climatic zones (Lomas Bajas, Delicias and La Grita) in Tachira state have shown a predominance of the sandfly species Lutzomyia spinicrassa (verrucarum group) and two Leishmania species, Leishmania mexicana and Leishmania braziliensis. Two transmission cycles appear to occur: a peridomestic cycle in Lomas Bajas and a sylvatic one in Delicias and La Grita.

Adolescent↗

Nurse practitioners, certified nurse midwives, and nurse anesthetists: changing care in acute care hospitals in New York City.

To respond to the shrinking pool of primary care physicians and to demands from managed care programs for cost containment, hospitals in New York City have increased their use of nurse practitioners, certified nurse midwives, and nurse anesthetists, creating an increased demand for these personnel. We report here on a survey of hospitals and schools of nursing in New York City and present findings on (a) current use of, and projected demand for nurse practitioners (NPs), certified nurse midwives (midwives) and nurse anesthetists (anesthetists) in hospitals in New York City; (b) the practice patterns of NPs, midwives, and anesthetists currently employed in hospitals; and (c) current and projected enrollment and curriculum in NP, midwifery, and anesthetist education programs in the New York metropolitan area.

Adult↗

Cell density regulates neuropeptide Y expression in cultured sympathetic neurons.

Neurotransmitters and neuropeptides coexpressed by the same neuron may be regulated independently. The peptide transmitter, neuropeptide Y (NPY), has been identified in approximately 60% of rat sympathetic superior cervical ganglion (SCG) neurons, virtually all of which are catecholaminergic. However, we find that environmental signals which affect noradrenergic traits in cultured rat SCG, regulate NPY expression differently. Relatively large increases in neuronal density only slightly alter catecholaminergic properties in sympathetic neurons. However, levels of NPY were highly dependent on cell density. In pure neuronal cultures, increasing cell numbers from 8000 to 12,000 neurons per culture resulted in a 10-fold decrease in NPY. Coculture of SCG neurons with ganglion nonneuronal cells further reduced NPY levels at all neuronal densities examined. Treatment with the neuropoetic cytokine, leukemia inhibitory factor, which increased the expression of cholinergic traits and decreased noradrenergic expression, decreased NPY by 50% in cocultures. Finally, neither glucocorticoids nor the cytokine interleukin-1 beta, which regulate other transmitter systems, altered NPY expression. These observations indicate that although noradrenergic traits and NPY are often coexpressed, they are regulated independently in SCG neurons. Further, expression of NPY is highly influenced by cell-cell contact.

Animals↗

Cytokine regulation of neuronal differentiation of hippocampal progenitor cells.

The signalling mechanisms governing haematolymphopoiesis and those regulating neural development may be closely related, as indicated by similarities of higher-order structure and function of the cytokines involved, of the regional and temporal regulation of their transcription and translation, and of their bioactivity. Here we investigate this possible evolutionary connection using retroviral transduction of a temperature-sensitive mutant form of the SV40 large T antigen to develop conditionally immortalized murine embryonic hippocampal progenitor cell lines. Treatment of these cells with cytokines that are thought to participate in progressive lymphoid maturation, immunoglobulin synthesis and erythropoiesis causes progressive neuronal differentiation, as defined by morphological criteria, successive expression of increasingly mature neurofilament protein, and the generation of inward currents and action potentials. The cytokine interleukin(IL)-11 induces expression of action potentials that are insensitive to tetrodotoxin, which is indicative of developmentally immature sodium channels. By contrast, for expression of more mature action potentials (tetrodotoxin-sensitive) one of the interleukins IL-5, IL-7 or IL-9 must be applied in association with transforming growth factor-alpha after pretreatment with basic fibroblast growth factor. Our results suggest that the mechanisms regulating lineage commitment and cellular differentiation in the neural and haematopoietic systems are similar. Further, they define an in vitro model system that may facilitate molecular analysis of graded stages of mammalian neuronal differentiation.

Action Potentials↗

Cytokine-induced programmed death of cultured sympathetic neurons.

Programmed cell death (PCD) of sympathetic neurons is inhibited by nerve growth factor. However, factors that induce PCD of these cells are unknown. Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor, neuropoietic cytokines known to regulate sympathetic neuron gene expression, were examined for effects on survival of cultured sympathetic neurons. Treatment with LIF or ciliary neurotrophic factor caused neuronal death in a dose-dependent fashion. Inhibition of RNA or protein synthesis, or treatment with potassium, all of which prevent PCD after nerve growth factor deprivation, prevented LIF-induced death. The morphologic and ultrastructural characteristics of the neuronal death induced by LIF and by nerve growth factor deprivation were similar. Furthermore, LIF treatment resulted in DNA fragmentation with a characteristic "ladder" on Southern blot analysis. These observations suggest that neuron numbers may be regulated by factors which initiate PCD, as well as by factors which prevent it.

Analysis of Variance↗

Graded pelvic muscle exercise. Effect on stress urinary incontinence.

The purpose of this research was to determine the effect of pelvic muscle exercise (PME) on stress urinary incontinence in middle-aged and elderly women. The protocol required 16 weeks of exercise three times per week, for a total of 48 sessions. Measures were taken at baseline, after a 4-week control period and after 4, 8, 12 and 16 weeks of PME, corresponding to PME levels 1, 2, 3 and 4, respectively. Urine loss was evaluated using a urinary diary and 24-hour pad test at baseline, after the control period and after PME levels 2 and 4. Pelvic muscle function was evaluated every four weeks. Sixty-five parous women 35-75 years of age (mean, 51.3) with mild to moderate stress urinary incontinence were studied. No significant changes in the outcome variables were found after the control period. The results showed significant reductions in urine loss on the 24-hour pad test (t = -4.7, P < or = .0001), and episodes of urine loss decreased from 2.6 to 1.0 between the control period and PME level 4. In addition, a significant improvement occurred in pressures developed by the pelvic muscles in response to PME (t = 6.8, P < or = .0001). Significant correlations between changes in pelvic muscle pressure and in urine loss variables were not found. Women who completed the study experienced a significant reduction in the amount of urine loss as well as a significant increase in pelvic muscle characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Computer-controlled spot-scan imaging of crotoxin complex crystals with 400 keV electrons at near-atomic resolution.

400 keV electrons yield a better relative image contrast than 100 keV electrons for a beam-sensitive organic crystal when spot-scan imaging is used [J. Brink and W. Chiu, J. Microscopy 161 (1991) 279]. A FORTRAN 77 program has been written to operate the spot-scan imaging system on a computer workstation under the VMS operating system which is interfaced serially to the JEOL4000 electron microscope. We demonstrate the application of this implementation by imaging crotoxin complex crystals embedded in either vitreous ice or glucose to 2.5 A resolution. The intensity strength of the structure factors of this protein crystal are different at low (> 10 A) resolution but similar at high resolution (< 10 A) for the two embedding media as expected from their scattering contrast difference. Based on our experience as judged from the electron diffraction patterns of highly tilted crystals, flat crystals embedded in glucose can be readily obtained. Furthermore, our spot-scan imaging system also has the option of correcting the focus gradient that is present in images of tilted specimens.

Computers↗