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M Mahoney

Publications and source records attributed to M Mahoney.

At least 19 recordsLinked to original sources
PubMed2006

Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris, or just "witnesses of disease"?

Pemphigus vulgaris (PV) is fascinating to dermatologists, epithelial biologists and immunologists alike, as its pathogenesis has been clarified to a much greater extent than that of most other organ-specific autoimmune diseases, and as it has provided abundant novel insights into desmoglein biology and pathology along the way. Historically, the most influential PV pathogenesis concept is that of Stanley and Amagai. This concept holds that autoantibodies against desmogleins are both essential and sufficient for epidermal blister formation (acantholysis) by impeding the normal functioning of these major adhesion proteins. However, as with most good theories, this landmark concept has left a number of intriguing and important questions open (or at least has not managed to answer these to everyone's satisfaction). Moreover, selected dissenting voices in the literature have increasingly called attention to what may or may not be construed as inconsistencies in this dominant PV pathogenesis paradigm of the recent past. The present debate feature therefore bravely rises to the challenge of re-examining the entire currently available evidence, as rationally and as undogmatically as possible, by provocatively asking a carefully selected congregation of experts (who have never before jointly published on this controversial topic!) to discuss how essential anti-desmoglein autoantibodies really are in the immunopathogenesis of PV. Not surprisingly, some of our expert "witnesses" in this animated debate propose diametrically opposed answers to this question. While doing so, incisive additional questions are raised that relate to the central one posed, and our attention is called to facts that may deserve more careful consideration than they have received so far. Together with the intriguing (often still very speculative) complementary or alternative pathogenesis scenarios proposed in the following pages, this offers welcome "food for thought" as well as very specific suggestions for important future research directions--within and beyond the camp of PV aficionados. The editors trust that this attempt at a rational public debate of the full evidence that is currently at hand will constructively contribute to further dissecting the exciting--and clinically very relevant!--immunopathogenesis of PV in all its complexity.

Animals↗
PubMed2005

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York.

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35-134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

Adult↗
PubMed2004

Sport safety policies and practices in two rural Victorian communities.

Australian football and netball are the predominant sports played in rural Victoria, Australia. This exploratory study is the first to report the sport safety policies and practices adopted by junior Australian football and netball clubs in small rural communities. Eleven informants from four clubs completed a semi-structured interview and survey. Whilst the clubs performed a range of injury prevention activities, they did not have formal sports safety policies. Generally, netball informants reported fewer safety practices than football informants. Crucial factors influencing safety policies and practices were the reliance on volunteers and a lack of senior players. Barriers towards the adoption of safety policies and practices appeared to be related to rural population declines, a lack of qualified people and attitudes to injury in rural areas. Future research needs to identify how widespread this lack of sport safety policies and practices is across rural Australia and to identify strategies to overcome barriers to implementing them.

Athletic Injuries↗
PubMed2003

The effect of processed meat and meat starter cultures on gastrointestinal colonization and virulence of Listeria monocytogenes in mice.

Listeria monocytogenes is a foodborne pathogen of major concern to the food industry in general and the meat industry in particular. The aim of this study was firstly to identify a strain of Listeria that was virulent in SPF BALB/c mice. Secondly, to investigate if a traditional meat starter culture (FloraCarn) and nontraditional meat starter (NTMS) cultures of dairy product and human origin (Lactobacillus and bifidobacteria) inhibit this pathogen in vivo. In addition, the inhibition of Listeria was investigated in vitro. In vitro inhibition was investigated using an agar inhibition assay, where soft agar containing the pathogen was laid over colonies of NTMS cultures, and inhibition expressed as the zones of inhibition developing around the colonies. For assessment of virulence, mice were intragastrically challenged with broth cultures of five strains of Listeria. For assessment of anti-listeria effect in vivo, the Listeria strain proven to be most pathogenic (LM3) was given to mice in salami batter containing no other added cultures (control) or batter inoculated with either (1) FloraCarn, (2) a NTMS culture, or (3) a combination of FloraCarn and a NTMS culture. The batter was given to mice after a 3-day fermentation and faecal levels of pathogen and body weight were monitored. Intragastric challenge with LM3, but no other strains, resulted in a significant weight loss (p<0.05) and up to 10(6) colony forming units (cfu) of LM3 per gram faeces. No weight loss was observed in animals fed with salami batter containing LM3. Consumption of salami batter fermented by a combination of NTMS culture (Lactobacillus acidophilus LAFTI(R) L10) and FloraCarn reduced faecal levels of the pathogen by 2.5 log units compared to the control. Consumption of salami batter fermented with FloraCarn and LAFTI(R) L10 (L10) alone reduced faecal levels by 0.5-1 and 1.5 log units, respectively. Of the NTMS cultures investigated here, L10 displayed the greatest inhibition of LM3 in vitro. These results indicate that the ability of pathogenic Listeria to cause listeriosis is dependent on the nature of the food in which the pathogen is present, and that a traditional meat starter culture (FloraCarn) and some NTMS cultures, particularly L10, inhibit growth of the pathogen during passage through the gastrointestinal tract.

Animals↗
PubMed2003

Too hot to trot? Exploring potential links between climate change, physical activity and health.

Based on an analysis of existing literature, this paper explores the links between climate change, physical activity and health. It highlights the importance of physical activity for health, explores current understandings of factors influencing participation in sport and physical activity, and develops some hypotheses about the ways in which climate change may impact on the factors influencing physical activity and thereby on the level of participation in physical activity. The paper argues that climate change has the potential to be a barrier to participation in physical activity, particularly in areas where temperatures are already relatively high, and that a reduction in physical activity across the population is likely to have detrimental health impacts. The need for research to clarify the nature and extent of the threat posed to physical activity participation is highlighted, as is the need to take into account the direct and indirect costs of any changes or reductions in physical activity in any assessment of the costs of climate change and/or its mitigation.

Australia↗
PubMed2002

Playing their part: the role of physical activity and sport in sustaining the health and well being of small rural communities.

It is widely recognised that the health of rural Australians is poor in comparison with their urban counterparts. Similarly, the role played by physical activity in maintaining health has been well researched and is well documented. However, little appears to have been published in recent years about the links between physical activity and health in rural communities. The objective of this article was to begin to address that gap. To achieve this, the article drew on research conducted in two small rural communities in Victoria Australia, and highlighted the role that physical activity and sport played in sustaining the health and wellbeing of individuals and communities in rural areas. Taking the World Health Organisation's definition of health (a state of complete physical, mental and social well-being and not merely the absence of disease) as its measure, the paper highlighted the many ways in which physical activity and sport in rural communities contribute to physical health, mental wellbeing and social cohesiveness. Based this finding, the authors suggest that physical activity and sport make a significant contribution to the health and wellbeing of rural people and their communities and suggest that further research is necessary to better define this apparent contribution.

Journal Article↗
PubMed2002

Microanatomical changes in alveolar type II cells in juvenile mice intratracheally exposed to Stachybotrys chartarum spores and toxin.

Stachybotrys chartarum is an important environmental fungus. We have shown recently that alveolar type II cells are sensitive to exposure to Stachybotrys chartarum spores and to the trichothecene, isosatratoxin-F, both in vitro and in vivo, in a juvenile mouse model. This sensitivity is manifest as significant changes in the composition and normal metabolic processing of pulmonary surfactant. This study evaluated the effects of a single intratracheal exposure of S. chartarum spores and toxin on ultrastructure and dimensions of alveolar type II cells from juvenile mice. This was to determine whether there are concurrent morphological and dimensional changes in the alveolar type II cell that reflect the metabolic alterations in pulmonary surfactant that we observed in the treated mice. Marked ultrastructural changes were associated with alveolar type II cells in both S. chartarum and isosatratoxin-F treated animals compared to untreated, saline, and Cladosporium cladosporioides spore treated animals. These ultrastructural changes included condensed mitochondria with separated cristae, scattered chromatin and poorly defined nucleolus, cytoplasmic rarefaction, and distended lamellar bodies with irregularly arranged lamellae. Point count stereological analysis revealed a significant increase (p < 0.05) in lamellar body volume density in S. chartarum and isosatratoxin-treated animals after 48 h exposure. Mitochondria volume density was significantly lower in the isosatratoxin-F (48 h exposure) and S. chartarum treated (24 and 48 h exposure) animals compared to those in the other treatment groups. These results reveal that exposure to S. chartarum spores and toxin elicit cellular responses in vivo differently from those associated with exposure to spores of a nontoxigenic mold species. They also indicate that accumulation of newly secreted pulmonary surfactant in the alveolar space of S. chartarum and isosatratoxin-F treated animals might be a consequence of cellular trauma resulting in lamellar body volume density changes leading to increased release of pulmonary surfactant into the alveolar space.

Animals↗
PubMed2001

Phase response curve and light-induced fos expression in the suprachiasmatic nucleus and adjacent hypothalamus of Arvicanthis niloticus.

This article describes the phase response curve (PRC), the effect of light on Fos immunoreactivity (Fos-IR) in the suprachiasmatic nucleus (SCN), and the effect of SCN lesions on circadian rhythms in the murid rodent, Arvicanthis niloticus. In this species, all individuals are diurnal when housed without a running wheel, but running in a wheel induces a nocturnal pattern in some individuals. First, the authors characterized the PRC in animals with either the nocturnal or diurnal pattern. Both groups of animals were less affected by light during the middle of the subjective day than during the night and were phase delayed and phase advanced by pulses in the early and late subjective night, respectively. Second, the authors characterized the Fos response to light at circadian times 5, 14, or 22. Light induced an increase in Fos-IR within the SCN during the subjective night but not subjective day; this effect was especially pronounced in the ventral SCN, where retinal inputs are most concentrated, but was also evident in other regions. Both light and time influenced Fos-IR within the lower subparaventricular area. Third, SCN lesions caused animals to become arrhythmic when housed in a light-dark cycle as well as constant darkness. In summary, Arvicanthis appear to be very similar to nocturnal rodents with respect to their PRC, temporal patterns of light-induced Fos expression in the SCN, and the effects of SCN lesions on activity rhythms.

Animals↗
PubMed2000

Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry.

The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.

Adolescent↗
PubMed2000

Urine hyperglycosylated hCG plus ultrasound biometry for detection of down syndrome in the second trimester in a high-risk population.

OBJECTIVE: To evaluate measurement of levels of urine hyperglycosylated hCG, a form of hCG with abnormally branched oligosaccharide side chains, in conjunction with ultrasound biometry for Down syndrome risk prediction in an at-risk group. METHOD: We prospectively measured urine hyperglycosylated hCG levels, humeral length, and nuchal thickness in women who had second-trimester amniocentesis. Urine hyperglycosylated hCG levels were measured by a two-step enzyme-immunometric assay using monoclonal antibody beta152. Humeral length, nuchal thickness, and hyperglycosylated hCG values were expressed as multiples of the median, and the Down syndrome screening efficiency of the three analytes plus age was determined. A receiver operating characteristic (ROC) curve was generated, and the area under the curve was used to assess the Down syndrome screening performance of the algorithm. RESULTS: There were 23 cases of Down syndrome among 1016 singleton pregnancies. Mean gestational age (+/- standard deviation) was 16.1 +/- 1.2 weeks at the time of amniocentesis. Mean maternal age was 37.1 +/- 3.2 years. Biometry and measurement of hyperglycosylated hCG levels had a 91.3% detection rate at a 3.2% false-positive rate and a 100% detection rate at a 10.7% false-positive rate. The area under the ROC curve was 0.986 (P <.001), and that for measurement of hyperglycosylated hCG levels plus age was 0.941 (P <.001). The area under the curve was significantly larger with combined biochemical and biometry markers compared with measurement of hyperglycosylated hCG levels plus age alone (P <.02), proving that the former was superior to the latter. CONCLUSION: A new Down syndrome biochemical marker combined with ultrasound biometry had a high screening efficiency in a high-risk group. All cases of Down syndrome in this study population would have been detected at an amniocentesis rate of less than 10.7%. Our results appear superior to those found with other second-trimester algorithms. The combination is promising as an alternative to "automatic" genetic amniocentesis in women of advanced maternal age and other high-risk groups.

Adult↗
PubMed1997

Repression and activation of promoter-bound RNA polymerase activity by Gal repressor.

By binding to the DNA site OE at position -60.5 in the gal operon, the GalR protein activates transcription from the P2 promoter located on the opposite face of DNA (position -5) and represses transcription from the P1 promoter located on the same face (position +1). GalR increases RNA polymerase binding at P2 and inhibits isomerization at P1 by forming a GalR-DNA-RNA polymerase ternary complex in each case. The specific effect of GalR at one promoter is independent of the presence of the other promoter. The enhancement or repression is also not the intrinsic property of a promoter; the regulation can be reversed by switching the angular orientation of the promoters relative to OE. Both enhancement and repression appear to require the same interaction between RNA polymerase alpha-subunit and GalR and/or the same interaction between RNA polymerase alpha-subunit and DNA in the ternary complexes. We have discussed how GalR might exert opposite effects in the steps involved in the formation of the open complex from free RNA polymerase and DNA.

Binding Sites↗
PubMed1995

Bloodstream infections associated with a needleless intravenous infusion system in patients receiving home infusion therapy.

OBJECTIVE: To determine risk factors for bloodstream infections (BSIs) in an outbreak among patients receiving home intravenous infusion therapy. DESIGN: Case-control and retrospective cohort studies. SETTING: Home health agency. PATIENTS: Patients receiving home intravenous infusion therapy from Rhode Island Home Therapeutics (RIHT) from January through December 1993. MAIN OUTCOME MEASURE: Development of primary BSI. METHODS: We compared patients with BSI (ie, case patients) with randomly selected noninfected RIHT patients receiving intravenous therapy, conducted a cohort study of all RIHT patients receiving intravenous therapy via a central venous catheter (CVC), and conducted a culture survey of injection cap luminal fluid. RESULTS: Case patients were more likely than controls to have had therapy via a CVC (11/11 vs 14/32; odds ratio [OR] undefined; P < .001) or total parenteral nutrition and intralipid therapy (TPN/IL) (9/11 vs 3/32; OR, 43.5; 95% confidence interval [CI], 4.9 to 510.0). Among RIHT patients with CVCs, risk factors for BSI were receipt of TPN/IL (9/35 vs 2/67; rate ratio [RR], 8.6; 95% CI, 2.0 to 37.7) or use of a needleless infusion system (10/41 vs 1/61; RR, 14.9; 95% CI, 2.0 to 111.8). Only the combination of both exposures was significantly associated with development of a BSI (P < .001). Luminal fluid from injection caps of needleless devices was significantly more likely to be culture positive than fluid from protected-needle devices (5/23 vs 0/18; RR undefined; P = .04). CONCLUSIONS: Our data suggest that a needleless device used for TPN/IL was associated with increased risk of BSI when injection caps were changed every 7 days.

Case-Control Studies↗
PubMed1995

Hippocampal volumetrics differentiate patients with temporal lobe epilepsy and extratemporal lobe epilepsy.

OBJECTIVE: To determine whether the occurrence of hippocampal formation (HF) volumetric asymmetry can reliably discriminate between complex partial seizures (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a prospective study of patients with intractable CPSs (approximately 70% of patients have electrographic foci in the temporal lobe [HF volumetric asymmetry on magnetic resonance imaging scans has been shown to lateralize such foci reliably)]. DESIGN: We examined HF volumetrics on magnetic resonance imaging scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared rapid gradient echo three-dimensional sequences (producing a gapless series of high-contrast 1.25-mm images). These data were compared with ictal, interictal, invasive, and noninvasive videoelectroencephalographic monitoring data, functional imaging data, and outcome data to define each patient's type of epilepsy. SETTING AND PATIENTS: Forty-one patients were recruited from a tertiary university comprehensive epilepsy program, and 22 control subjects were recruited from the neurologically normal university community. RESULTS: Among the control subjects, the difference in HF volumetrics (right-left HF volumetrics) was + 0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the upper limit had CPSs of a temporal lobe origin. Of the patients with temporal lobe epilepsy, only three fell within normal limits. No patient with CPSs of an extratemporal lobe origin fell beyond the upper limit. CONCLUSION: The presence of significant HF volumetric asymmetry makes it highly unlikely that a patient's CPSs are of an extratemporal lobe origin.

Adolescent↗
PubMed1995

The incidence of testicular cancer in Royal Air Force personnel.

OBJECTIVES: To review the incidence of testicular cancer within the Royal Air Force (RAF) compared with the national incidence. METHODS: The medical statistics for RAF personnel (supplied by the Central Statistics Office, categorized by occupation) were reviewed for the incidence of testicular cancer and compared to the national rate. RESULTS: A significantly elevated incidence of testicular neoplasm was detected in RAF personnel, which was well above the national rate. The increased incidence appeared most marked in those personnel working directly with aircraft. CONCLUSION: The only cause of the significantly higher incidence of testicular cancer in RAF personnel is probably related to working with aircraft. This concurs with a finding that aircraft technicians in the US Navy had an increased incidence of testicular cancer, and the exposure to hydrocarbon carcinogens in the workplace was implicated.

Adult↗