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M O'Brien

Publications and source records attributed to M O'Brien.

At least 91 records · Page 5Linked to original sources
PubMed1999

Fertilization and wounding of the style induce the expression of a highly conserved plant gene homologous to a Plasmodium falciparum surface antigen in the wild potato Solanum chacoense Bitt.

Pistil tissues are actively involved in pollen tube growth and respond to the presence of the growing pollen tubes by modulating the expression of specific genes. Once fertilization has occurred, complex developmental programs lead to embryogenesis, ovary maturation, and seed set. In order to understand the early events that follow pollination and fertilization we have used a subtractive hybridization approach to characterize genes which are related to pollination and fertilization events. One cDNA clone isolated and named SPP30 (Solanum pollinated pistil) was found to share significant sequence identities with a Plasmodium falciparum (malaria parasite) surface antigen and a yeast gene of unknown function. Searches in recent EST databases also revealed that SPP30 homologues are found in both monocot and dicot species. The presence of this conserved gene in evolutionarily distant organisms such as yeast, Plasmodium, and plants suggests that it codes for an essential cellular function. This is also strengthened by its extremely high sequence conservation in both monocots and dicots where virtually all substitutions tolerated are conservative.

Amino Acid Sequence↗
PubMed1999

Pollination, wounding and jasmonate treatments induce the expression of a developmentally regulated pistil dioxygenase at a distance, in the ovary, in the wild potato Solanum chacoense Bitt.

Pollination and fertilization trigger unique developmental programs leading to embryogenesis, ovary maturation and seed set. Pistil tissues are actively involved in pollen tube growth and respond to the presence of the growing pollen tubes by modulating the expression of specific genes. Using subtractive hybridization to isolate genes involved in pollen-pistil interactions and fertilization, we have isolated a pollination- and fertilization-induced dioxygenase which is predominantly expressed in the pistil. In situ hybridization analyses revealed that the SPP2 dioxygenase (Solanum pollinated pistil) from the self-incompatible wild potato Solanum chacoense Bitt. is also developmentally regulated, with mRNA levels gradually regressing from the tip of the style towards the ovary during pistil development. At maturity, the upper limit of SPP2 transcript distribution coincided with the abscission zone of the style and SPP2 dioxygenase expression in ovaries coincided with the fertilization receptivity period of the flower. Pollination, as well as wounding of the style, induced an increase in SPP2 mRNA steady-state levels at a distance, in the ovary. Treatments with stress hormones including methyl jasmonate, jasmonic acid and salicylic acid mimicked the wound response and also induced SPP2 transcripts in the ovary. The SPP2 dioxygenase could be involved in the biosynthesis of deterrent alkaloids in reproductive tissues or in generating chemical signals involved in pollen tube guidance.

Acetates↗
PubMed1999

Postpartum affect and depressive symptoms in mothers and fathers.

In a study of the postpartum affective experiences of couples, mothers and fathers completed questionnaires on coping, marital satisfaction, stress, positive and negative affect, and depression one month pre- and then one month postpartum. More than one-fourth of both mothers and fathers reported elevated depressive symptoms, which correlated significantly between parents. Prepartum coping, stress, and affect significantly predicted postpartum affect. Research and clinical applications of the findings are discussed.

Adaptation, Psychological↗
PubMed1999

A comparison of physiological responses to rowing on friction-loaded and air-braked ergometers.

The physiological responses of 10 trained rowers to a progressive incremental rowing protocol to exhaustion were investigated on Gjessing, Rowperfect fixed-mechanism and Rowperfect free-mechanism rowing ergometers. Heart rate, oxygen uptake (VO2), ventilation (VE) and blood lactate were determined at matched power values for each ergometer. The mean power and heart rate at the lactate anaerobic threshold were determined by graphical interpolation of data for each ergometer. Analysis of variance and linear regression showed differing responses at matched power and an approximate 40-50 W difference in power at the lactate anaerobic threshold when comparing the friction-loaded Gjessing with the air-braked Rowperfect fixed and Rowperfect free ergometers (P<0.01). No significant differences were noted when comparing the air-braked Rowperfect fixed and Rowperfect free ergometers. However, comparisons of VO2, VE and blood lactate at given heart rates and of heart rate at the lactate anaerobic threshold showed no significant differences between ergometers. Our results indicate similar physiological profiles for all ergometers tested when compared at equivalent heart rates, but differences when compared at matched power. A direct comparison of the data from Gjessing (friction-loaded) with Rowperfect fixed and Rowperfect free (air-braked) ergometers would therefore require a correction factor for inter-ergometer variation in displayed power data.

Adult↗
PubMed1999

Production of an S RNase with dual specificity suggests a novel hypothesis for the generation of new S alleles.

Gametophytic self-incompatibility in plants involves rejection of pollen when pistil and pollen share the same allele at the S locus. This locus is highly multiallelic, but the mechanism by which new functional S alleles are generated in nature has not been determined and remains one of the most intriguing conceptual barriers to a full understanding of self-incompatibility. The S(11) and S(13) RNases of Solanum chacoense differ by only 10 amino acids, but they are phenotypically distinct (i.e., they reject either S(11) or S(13) pollen, respectively). These RNases are thus ideally suited for a dissection of the elements involved in recognition specificity. We have previously found that the modification of four amino acid residues in the S(11) RNase to match those in the S(13) RNase was sufficient to completely replace the S(11) phenotype with the S(13) phenotype. We now show that an S(11) RNase in which only three amino acid residues were modified to match those in the S(13) RNase displays the unprecedented property of dual specificity (i.e., the simultaneous rejection of both S(11) and S(13) pollen). Thus, S(12)S(14) plants expressing this hybrid S RNase rejected S(11), S(12), S(13), and S(14) pollen yet allowed S(15) pollen to pass freely. Surprisingly, only a single base pair differs between the dual-specific S allele and a monospecific S(13) allele. Dual-specific S RNases represent a previously unsuspected category of S alleles. We propose that dual-specific alleles play a critical role in establishing novel S alleles, because the plants harboring them could maintain their old recognition phenotype while acquiring a new one.

Alleles↗
PubMed1999

Use of human intravenous immunoglobulin in lower motor neuron syndromes.

OBJECTIVE: To determine whether patients with the clinical phenotype of multifocal motor neuropathy but without the electrophysiological criteria for conduction block would respond to intravenous immunoglobulin (IVIg). METHODS: Ten patients were selected with a slowly progressive, asymmetric, lower motor neuron disorder, and were treated prospectively with IVIg at a dose of 2g/kg over 5 days. All subjects had neurophysiological testing to look for evidence of conduction block before treatment. Muscle strength was assessed by MRC grades and hand held myometry, measuring pinch and grip strength. A 20% increase in both pinch and grip myometry was considered a positive response. RESULTS: In no patient was conduction block detected. Four of the 10 patients showed a positive response to IVIg, with the best response occurring in two patients who presented with weakness but without severe muscle wasting. Three of the four responders have continued to receive IVIg for a mean period of 17 months (range 15-24 months), with continued effect. The response to IVIg was not related to the presence of anti-GM1 antiganglioside antibodies, but responders had a selective pattern of muscle weakness and normal (>90% predicted) vital capacity. CONCLUSION: The findings suggest that a course of IVIg should be considered in patients with the clinical phenotype of multifocal motor neuropathy but without neurophysiological evidence of conduction block.

Adult↗
PubMed1999

Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial.

Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase I trial was designed to determine the maximum tolerated dose, the dose-limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v. infusion for 1 h every 21 days with a starting dose of 150 mg/m2 and an escalation to 185 mg/m2 and 235 mg/m2 in subsequent patient cohorts. G-CSF (5 microg/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the post-nadir neutrophil count reached 10,000/microl. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m2. Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/1microl) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/microl), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis, back pain, asthenia, and neuropathy. One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G-CSF support in children is 185 mg/m2, which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85 % higher than the recommended adult dose.

Adolescent↗
PubMed1999

Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine.

Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase.

Aldehyde Oxidase↗
PubMed1998

SRS travelling fellowship.

A 3-week tour of the Far East was coordinated by Dr. Ronald DeWald, senior travelling fellow appointed by the Scoliosis Research Society. Three junior fellows appointed by the Education Committee of the Scoliosis Research Society accompanied him. The purpose of this fellowship was to develop a comaraderie and exchange ideas, thoughts, and experiences in the field of spinal deformity.

Anecdotes as Topic↗
PubMed1998

Coordinate changes in expression of protective genes in drug-resistant cells.

Maintenance of cellular homeostasis is a critical survival trait when cells are exposed to electrophilic chemicals. Because conjugation and elimination of these toxins is dependent upon sequential and coordinated metabolic pathways, acquired resistance through a gradual adaptive response would rarely be expected to be the consequence of changes in one gene product. Human HT29 colon cancer cells chronically exposed to EA have acquired resistance to the drug. Commensurate with resistance, EA is more effectively conjugated to GSH and effluxed from the resistant cells. Using directed and random (differential display) approaches, a number of detoxification and/or protective gene products have been shown to be expressed at elevated levels. These include gamma-GCS (approximately 3-fold), GST-pi (approximately 3-fold), MRP (approximately 3-fold), NQO1 (approximately 3-fold), DDH (20-fold), and SSP 3521, a transcriptional regulator (approximately 3-fold). Multiple mechanisms contribute to these increases, including enhanced transcriptional rate and prolonged mRNA and protein half lives. Further indications for the involvement of transcriptional regulators is found in HL60 adriamycin-resistant cells which overexpress MRP, GST-pi and gamma-GCS and also have 15-20-fold more DNA-dependent protein kinase. It is possible that this enzyme serves as an early stress response gene which may activate downstream transcription factors. Intriguingly, the catalytic subunit of DNA-dependent protein kinase has a high avidity for [35S]azidophenacyl-GSH. High levels of GSH conjugates indicate cell stress and it would seem reasonable to speculate that DNA-dependent protein kinase may serve as a receiver and transmitter of signals which contribute to drug resistance and maintain cell viability.

Alcohol Oxidoreductases↗
PubMed1998

In vivo Bcl-2 oncogene neuronal expression in the rat spinal cord.

STUDY DESIGN: An acute mechanical rat spinal cord injury model was used to investigate in vivo Bcl-2 oncogene overexpression in neuronal tissue. OBJECTIVES: To introduce the Bcl-2 oncogene in vivo by a recombinant adenovirus vector into rat spinal cord tissue, and to investigate any potential protective effect on neural tissue in the zone of injury in a rat spinal cord model. SUMMARY OF BACKGROUND DATA: The Bcl-2 oncogene inhibits apoptotic and necrotic neural cell death in vitro by regulating an antioxidant pathway at sites of free radical generation. Thus, overexpression of the Bcl-2 oncogene may have a role in limiting the secondary injury cascade of spinal cord injury through its regulation of antioxidants. METHODS: After confirmation of Bcl-2 gene expression in vitro and in vivo in the rat spinal cord, a weight-drop spinal cord injury model was performed on seven rats with prior Bcl-2 inoculation, and on seven rats with prior B-gal inoculation (controls). RESULTS: In vivo Bcl-2 expression was documented by immunostaining. After spinal cord harvest, quantification of percentage preserved tissue at the spinal cord injury site suggested that Bcl-2 overexpression confers neuroprotection. CONCLUSIONS: In vivo Bcl-2 oncogene overexpression was successfully induced in neuronal tissue. After Bcl-2 oncogene expression in the rat spinal cord, the zone of microscopic injury was diminished. Further investigation of the Bcl-2 oncogene for potentially enhancing neuronal survival after spinal cord injury appears indicated.

Adenoviridae↗
PubMed1998

Anatomy of the proximal musculotendinous junction of the adductor longus muscle.

Injuries to the adductor longus commonly occur in the proximal part of the muscle tendon unit, close to the insertion site on the pubic bone. Ultrasonography, magnetic resonance imaging (MRI) and surgery have been helpful in localising the lesions, but the exact anatomy of the musculotendinous junction (MTJ) and insertion of the muscle remain unclear. We studied the anatomical features of the MTJ and measured the dimensions of the tendinous insertion into the pubic bone on 37 cadavers: 18 men and 19 women. The medial boundaries were the longest part of the tendon bilaterally in women, while the lateral aspect of the left muscle was greater in men. Tendinous fibres were predominantly found on the anterior surface, while the posterior surface consisted mainly of muscle tissue. The MTJ was clearly demarcated. There were several types of anomalies present which partially explains the difficulty in localising the site of injury and highlights the importance of individualized treatment.

Aged↗
PubMed1998

'Not too much, not too little, but just enough?': observations on continuing professional development in Public Health in the north of England.

Three inquiries about Public Health continuing professional development were undertaken in the Northern and Yorkshire Region of the National Health Service during 1995-96. Public Health Physicians were asked about their experience of continuing education and for their views on a regional policy for continuing professional development. Health Authority Chief Executives were asked about their reactions to Public Health Physicians continuing educational needs. The overall response rates for the Public Health Physicians were very disappointing. Most of the Chief Executives (a much smaller group) responded to the inquiry. A large minority of Public Health Physicians believed that their continuing education in the preceding two years had been adequate. Most wished their future continuing education activities to be multi-disciplinary. One finding with considerable significance for those managing Public Health education, both specialist and continuing, was that many of those with teaching responsibilities had not been trained to teach. Despite apparent concordance between the views of Chief Executives and those of Public Health Physicians; on some important points there were inconsistencies in the comments of Chief Executives, which suggested lack of understanding of both the roles of their professional colleagues and the need for their continuing education. The inquiries gave rise to a sense of apathy and under-confidence, manifested in some reluctance to accept policing of continuing education. There is a need to experiment with learning and teaching approaches in order to progress from the current traditional educational methods.

Adult↗
PubMed1998

Do inflammatory processes contribute to radiation induced erythema observed in the skin of humans?

BACKGROUND: Two prospective trials were designed to determine whether there may be a role for inflammatory mediators in human skin erythema at both high and low doses per fraction and for 'out of field' effects. METHODS: Trial 1. Effects of topical indomethacin (1%) and hydrocortisone (1%) applied before and during radiotherapy were compared for erythema induced by 20 Gy in four fractions (n = 26, 6 MV). Trial 2. Effects of topical hydrocortisone (1 %) applied before and during radiotherapy and no medication were compared for erythema induced by 1, 3, 5 and 7 Gy in five fractions (n = 21, 120 kV). Erythema was measured using reflectance spectrophotometry (RFS) and laser Doppler (LD) on a weekly basis. RESULTS: Trial 1. A bi-phasic reaction time course was suggested in two-thirds of the cases. The first phase did not appear to be influenced by hydrocortisone cream but the second was significantly attenuated. Indomethacin had no effect on either reaction phase. Erythema measured several centimetres outside of the field was reduced by hydrocortisone but not by indomethacin. Trial 2. Trial 2 confirmed the presence of measurable erythema, invisible to the eye, that coincided in its time course to the first phase of erythema noted in trial 1. This reaction was more intense than predicted by the LQ formula and was non-significantly attenuated by topical hydrocortisone. RFS readings proved to be less subject to inter- and intra-patient variations than the LD unit used. CONCLUSION: Inflammatory responses may play a role in the mediation of the erythematous response to radiation in human skin. Further studies are warranted.

Aged↗
PubMed1998

Mechanisms of peroxisome proliferation by perfluorooctanoic acid and endogenous fatty acids.

1. The effects of endogenous fatty acids and perfluorooctanoic acid (PFOA) and its analogs on peroxisomal acyl CoA oxidase (ACO) and microsomal laurate hydroxylase (LH) activities were evaluated in primary cultures of rat hepatocytes and activation of peroxisome proliferator-activated receptor alpha (PPARalpha) in CV-1 cells. The rank order for the stimulation of ACO activity in hepatocytes for selected compounds was PFOA >> octanoic acid>octanedioic acid, perfluorooctanol (inactive). Increases in ACO activity by PFOA, like those of ciprofibrate, were associated with a marked increase in peroxisome number and cytosolic occupancy volume. Maximal effects of ciprofibrate and PFOA on the stimulation of ACO activity were not additive, suggesting that these two compounds share a common pathway of peroxisome proliferation. 2. Saturated monocarboxylic acids of C4 to C18 chain length were inactive, and, among dicarboxylic acids, only small elevations (40-45%) in ACO activity were observed with the long-chain C12 and C16 dioic acids. Of the C18 fatty acids tested, only oleic and linoleic acids, at 1 mM, produced a two- to three-fold elevation in ACO and LH activities. In comparison with endogenous fatty acids, PFOA was more potent and exhibited a different time course and greater magnitude of stimulation of ACO and LH activities in cultured hepatocytes. 3. Addition of mitochondrial beta-oxidation inhibitors (3-mercaptopropionic and 2-bromooctanoic acids) did not alter ACO activity in the presence of octanoic acid or octanedioic acid; nor did they modify the stimulation of ACO activity by PFOA. The carnitine palmitoyltransferase I inhibitor 2-bromopalmitic acid produced a 2.5-fold increase in ACO stimulatory activity and reduced both ciprofibrate- and PFOA-mediated stimulations of ACO activity. 4. Cycloheximide treatment reduced PFOA- and ciprofibrate-induced ACO activities; however, the response to oleic acid was not blocked and increased slightly. 5. In rat and human PPARalpha transactivation assays, the rank order of activation was ciprofibrate > PFOA > oleic acid > or = octanoic acid > octanedioic acid or perfluorooctanol (inactive). PFOA, ciprofibrate and oleic acid were activators of rPPARalpha at concentrations that correlated favorably with the changes in ACO activity in cell culture. Octanoic acid did not increase ACO activity and was a weak activator of PPARalpha. 6. Our findings suggest that fatty acids such as oleic acid (endogenous fatty acids) and PFOA (a stable fatty acid) act through more than one pathway to increase ACO activity in rat hepatocytes. We conclude that the potent effects of PFOA are primarily mediated by a mechanism that includes the activation of liver PPARalpha.

Acyl-CoA Oxidase↗
PubMed1998

Immunotherapy in lung cancer.

More research and new treatment options are needed in all stages of lung cancer. To this end immunotherapy needs a revival in view of recent improved technologies and greater understanding of the underlying biology. In this review we discuss mechanisms of tumour immunotherapy, non-specific, specific and adoptive, with particular reference to a direct therapeutic action on all subtypes of lung cancer.

BCG Vaccine↗
PubMed1998

Protein-calorie malnutrition does not predict subtle vitamin K depletion in hospitalized patients.

OBJECTIVE: Recent studies suggest that subtle vitamin K depletion has far-reaching consequences. As this entity is not associated with prothrombin time elevation, it is important to determine whether alternate methods can help identify it. We investigated subtle vitamin K depletion in a hospital setting and determined whether protein calorie malnutrition predicts its presence. DESIGN, SETTING, SUBJECTS: Using a high-pressure liquid chromatography (HPLC) assay of plasma phylloquinone and a food frequency questionnaire for phylloquinone intake, we examined the phylloquinone status of 27 hospitalized patients with normal coagulation parameters, no liver disease, and no recent warfarin use. We assessed protein-calorie nutritional status with Reilly's criteria and anthropometrics. RESULTS: 51% of patients (95% CI = 31% to 70%) had evidence of subtle vitamin K depletion as defined by a subnormal plasma phylloquinone concentration. Patients whose phylloquinone intake was less than the Recommended Daily Allowance (RDA) over the preceding year had lower plasma phylloquinone concentrations when compared to other patients: median (range) 0.106 nmol/l (0.022-0.461) versus 0.301 nmol/l (0.067-3.928), respectively (P = 0.023). Plasma phylloquinone concentrations were no different, however, between well-nourished and malnourished patients: median (range) 0.245 nmol/l (0.022-0.522) versus 0.188 nmol/l (0.067-3.928), respectively (P=0.782). CONCLUSIONS: Subtle vitamin K depletion is common among hospitalized patients and protein-calorie malnutrition does not predict its presence.

Adult↗