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Biomedical subjects

M O'Reilly

Publications and source records attributed to M O'Reilly.

At least 19 recordsLinked to original sources
PubMed2006

Screening for Chlamydia trachomatis in asymptomatic women attending outpatient clinics in a large maternity hospital in Dublin, Ireland.

BACKGROUND: Chlamydia trachomatis can cause a sexually transmitted infection, which, untreated, may result in considerable morbidity. METHODS: A prevalence study was conducted for C trachomatis using nucleic acid amplification technology in asymptomatic women, and certain risk factors that may be used to direct future screening strategies were assessed. RESULTS: The study population comprised 945 asymptomatic women, of whom 783 were attending antenatal clinics, 91 were attending infertility clinics and 71 were attending family planning clinics. An overall C trachomatis prevalence of 3.7% (35/945) was found, with the highest prevalence of 11.2% (22/196) in Irish single women aged <25 years. Logistic regression analysis showed that single status and age <25 years were independent, statistically significant predictors of C trachomatis infection. CONCLUSION: These results support routine screening of asymptomatic women who are sexually active and aged <25 years. An opportunist active screening of all sexually active women independent of age should be additionally considered if resources permit.

Adult↗
PubMed2006

Investigation of avian influenza (H5N1) outbreak in humans--Thailand, 2004.

INTRODUCTION: Beginning in late 2003, a substantial outbreak of influenza A (H5N1) virus spread among poultry in Thailand. On January 23, 2004, the Ministry of Public Health (MPH) detected the first confirmed human case of H5N1 infection in humans. METHODS: During February-November 2004, the MPH's Bureau of Epidemiology and provincial health offices worked together to investigate the H5N1 outbreak in humans. Two studies were conducted: a descriptive study to describe clinical manifestations and epidemiologic characteristic of the cases and a matched case-control study to determine risk factors for persons who might subsequently become ill with H5N1. RESULTS: A total of 16 patients with confirmed H5N1 were identified for the case-control study. Fever and respiratory symptoms predominated. Leucopenia and thrombocytopenia were present respectively in nine (100%) and four (44%) persons aged <15 years. Direct touching of unexpectedly dead poultry was the most significant risk factor (odds ratio = 29.0; 95% confidence interval = 2.7-308.2). Overall mortality was 75%; mortality for persons aged <15 years was 90%, compared with 57% for persons aged > or =15 years. CONCLUSION: Avian influenza was more severe in children, who should avoid handling dead poultry during epizootics. Early avian influenza in children resembled the more common dengue fever, but presence of cough and absence of hemoconcentration distinguished avian influenza, which often progressed rapidly to acute respiratory distress syndrome, requiring intensive care.

Adolescent↗
PubMed2005

Effect of triclosan on the development of bacterial biofilms by urinary tract pathogens on urinary catheters.

OBJECTIVES: To examine (i) the effect of triclosan on the formation of catheter biofilms by urinary tract pathogens and (ii) the diffusion of triclosan through the retention balloons of urinary catheters. METHODS: Models of the catheterized bladder were infected with eight different urinary tract pathogens and the effect of triclosan on biofilm formation was assessed by determining the numbers of viable cells colonizing the catheters and by scanning electron microscopy. HPLC was used to determine the triclosan concentration in urine draining from models that had been fitted with triclosan-inflated silicone catheters. RESULTS: When catheters were inflated with triclosan (10 g/L) the formation of catheter biofilm by Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Proteus mirabilis was prevented. The numbers of Enterococcus faecalis and Providencia stuartii cells colonizing catheters were also significantly reduced (P<0.05). Serratia marcescens, Morganella morganii and Pseudomonas aeruginosa, however, were able to produce extensive catheter biofilms in the presence of triclosan. Only P. mirabilis produced alkaline urine and encrusted the catheters. Concentrations of 0.02-0.16 mg/L of the biocide were detected in urine draining from the model over the 48 h experimental period. CONCLUSIONS: Triclosan diffused through silicone catheter balloons and produced urinary concentrations that prevented catheter encrustation by P. mirabilis and biofilm formation by several other common pathogens of the catheterized urinary tract. It had little effect on urease-producing P. aeruginosa, S. marcescens or M. morganii but these species did not produce alkaline urine or crystalline biofilms.

Anti-Infective Agents, Local↗
PubMed2005

Sensory peptide neurotransmitters mediating mucosal and distension evoked neural vasodilator reflexes in guinea pig ileum.

The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation, and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat-sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64% by the CGRP 8-37 and 37% by NK3 (SR 142801) antagonists. When the two antagonists were combined with hexamethonium, only a small vasodilation persisted. Balloon distension-evoked vasodilations were inhibited by NK3 antagonists (66%) but were not altered by CGRP 8-37. In preparations in which myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8-37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distension-evoked responses were significantly blocked by NK3 antagonists, suggesting that stretch activation of myenteric sensory neurons release tachykinins that activate NK3 receptors on myenteric vasodilator pathways.

Animals↗
PubMed2005

Three-year follow-up of a family support service cohort of children with behavioural problems and their parents.

Abstract Background The aim of this study was to establish the medium-term (three-year) psychosocial outcome of children with behavioural problems and their parents, who had received an intervention from a family support service. Methods Forty families were traced at the three-year follow-up and agreed to participate. Pre- and post-intervention and follow-up measures were the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) and the Strengths and Difficulties Questionnaire (SDQ). Results The primary HoNOSCA outcome items (i.e. those initially targeted by the parenting intervention) of aggression/antisocial behaviour and family relationships were not found to have changed significantly from the baseline (but had not sustained the sort-term improvement following the intervention). Deterioration was found in other HoNOSCA items such as overactivity, self-harm, scholastic/language skills, emotional, and poor school attendance. When we compared pre-intervention with follow-up SDQ scores, there was no significant change on any scales, i.e. these had returned to the level reported at the time of the original referral to the family support service. Conclusions Following the intervention from a family support service, children and families reported a significant improvement in most outcome measures, predominantly child behaviour and family relationships. However, these improvements were either not sustained or there were additional difficulties at three-year follow-up. These could be related to various external and developmental factors. This lack of sustainable treatment effects for children with behavioural problems is consistent with previous research findings on parenting programmes.

Adolescent↗
PubMed2003

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗
PubMed2003

Acute lateral dislocation of the patella: correlation of ultrasound scanning with operative findings.

Acute lateral dislocation of the patella has been associated with disruption of the medial restraints of the patella. Following non-operative management there is a re-dislocation rate of up to 44%. The purpose of this study was to test whether sonography is a reliable method of assessing the medial retinaculum after acute dislocation of the patella. Ten patients following acute patellar dislocation had an ultrasound scan (USS) performed by an experienced musculoskeletal radiologist. Each patient subsequently had an examination under anaesthetic, arthroscopy, and repair of the ruptured structures. The ultrasound reports were compared to the surgical findings to determine the accuracy of this investigation. USS located deficiencies in the ligamentous attachments to the medial border of the patella and the presence of avulsed bony fragments, all of which were confirmed at operation. The sonographic diagnosis of haematoma or torn fibres in the vastus medialis obliquus (VMO) corresponded with our operative findings. The most significant findings were the correlation of free fluid around the medial collateral ligament (MCL) with avulsion of the femoral attachment of the medial patellofemoral ligament (MPFL) and the presence of avulsed fragments of bone from the medial border of the patella.

Adolescent↗
PubMed2003

Physician knowledge of the diagnosis and management of Rocky Mountain spotted fever: Mississippi, 2002.

Rocky Mountain spotted fever (RMSF), a tick-borne illness that has its highest incidence in the south central and southeastern United States, is often a diagnostic challenge, as patients frequently present with nonspecific symptoms during the early stages of illness. RMSF has a high case fatality rate among untreated individuals, and the median time from onset of symptoms to death is only eight days, making early recognition and treatment of RMSF crucial. In two Mississippi public health districts, 148 primary care physicians were randomly selected and mailed surveys regarding RMSF diagnosis, treatment, and prevention. Eighty-four of the 148 (57%) physicians responded. Responses from different specialties and different health districts were compared using chi square statistics. Almost all (99%) physicians correctly identified doxycycline as the antibiotic agent of choice for treating adults and adolescents. However, only 21% of family practice physicians, and 25% of emergency medicine physicians correctly identified the antibiotic of choice for treating children with RMSF. Twenty-three percent of physicians responded that waiting for the development of a rash before prescribing antibiotics is an appropriate treatment strategy. The current standard of care-doxycycline as the agent of choice among children 8 years of age or younger with suspected RMSF-has not been effectively communicated to all physicians caring for children. Also, many physicians are not familiar with the rationale underlying initiation of antibiotic therapy prior to the development of rash in patients with suspected RMSF. Continuing education efforts should focus on antibiotic selection in pediatric patients and initiation of therapy prior to the onset of rash in appropriate patients.

Animals↗
PubMed2001

Quantification of red blood cells using atomic force microscopy.

For humans the sizes and shapes of their red blood cells are important indicators of well being. In this study, the feasibility of using the atomic force microscope (AFM) to provide the sizes and shapes of red blood cells has been investigated. An immobilisation procedure has been developed that enabled red blood cells to be reliably imaged by contact AFM in air. The shapes of the red blood cells were readily apparent in the AFM images. Various cell quantification parameters were investigated, including thickness, width, surface area and volume. Excellent correlation was found between the AFM-derived immobilised mean cell volume (IMCV) parameter and the mean cell volume (MCV) parameter used in current haematological practice. The correlation between MCV and IMCV values has validated the immobilisation procedure by demonstrating that the significant cell shrinkage that occurs during immobilisation and drying does not introduce quantification artifacts. Reliable IMCV values were obtained by quantifying 100 red blood cells and this typically required 3-5 AFM images of 100 microm x 100 microm area. This work has demonstrated that the AFM can provide in a single test the red blood cell size and shape data needed in the assessment of human health.

Anemia, Macrocytic↗
PubMed2001

New family of regulators in the environmental signaling pathway which activates the general stress transcription factor sigma(B) of Bacillus subtilis.

Expression of the general stress regulon of Bacillus subtilis is controlled by the alternative transcription factor sigma(B), which is activated when cells encounter growth-limiting energy or environmental stresses. The RsbT serine-threonine kinase is required to convey environmental stress signals to sigma(B), and this kinase activity is magnified in vitro by the RsbR protein, a positive regulator important for full in vivo response to salt or heat stress. Previous genetic analysis suggested that RsbR function is redundant with other unidentified regulators. A search of the translated B. subtilis genome found six paralogous proteins with significant similarity to RsbR: YetI, YezB, YkoB, YojH, YqhA, and YtvA. Their possible regulatory roles were investigated using three different approaches. First, genetic analysis found that null mutations in four of the six paralogous genes have marked effects on the sigma(B) environmental signaling pathway, either singly or in combination. The two exceptions were yetI and yezB, adjacent genes which appear to encode a split paralog. Second, biochemical analysis found that YkoB, YojH, and YqhA are specifically phosphorylated in vitro by the RsbT environmental signaling kinase, as had been previously shown for RsbR, which is phosphorylated on two threonine residues in its C-terminal region. Both residues are conserved in the three phosphorylated paralogs but are absent in the ones that were not substrates of RsbT: YetI and YezB, each of which bears only one of the conserved residues; and YtvA, which lacks both residues and instead possesses an N-terminal PAS domain. Third, analysis in the yeast two-hybrid system suggested that all six paralogs interact with each other and with the RsbR and RsbS environmental regulators. Our data indicate that (i) RsbR, YkoB, YojH, YqhA, and YtvA function in the environmental stress signaling pathway; (ii) YtvA acts as a positive regulator; and (iii) RsbR, YkoB, YojH, and YqhA collectively act as potent negative regulators whose loss increases sigma(B) activity more than 400-fold in unstressed cells.

Bacillus subtilis↗
PubMed2000

How the multifunctional yeast Rap1p discriminates between DNA target sites: a crystallographic analysis.

Rap1p from Saccharomyces cerevisiae is a multifunctional, sequence-specific, DNA-binding protein involved in diverse cellular processes such as transcriptional activation and silencing, and is an essential factor for telomere length regulation and maintenance. In order to understand how Rap1p discriminates between its different DNA-binding sites, we have determined the crystal structure of the DNA-binding domain of the Rap1p (Rap1pDBD) in complex with two different DNA-binding sites. The first DNA sequence is the HMRE binding site found at silencers, which contains four base-pair substitutions in comparison to the telomeric binding site present in our earlier crystal structure of the Rap1pDBD-TeloA complex. The second complex contains an alternative telomeric binding site, TeloS, in which two half-sites are spaced closer together than in the TeloA complex. The determination of these structures was complicated by the presence of merohedral twinning in the crystals. Through identification of the twinning operator and determination of the twin fraction of the crystals, we were able to deconvolute the twinned intensities into their untwinned components, and to calculate electron density maps for both complexes. The structural information shows that the two domains present in the Rap1pDBD bind to these two biologically relevant binding sites through subtle side-chain movements at the protein-DNA interface, rather than through global domain rearrangements.

Amino Acid Sequence↗
PubMed2000

An assessment of the aggressive potential of radiolucencies related to the mandibular molar teeth.

AIM: The purpose of this study was to outline the radiographic appearance of radiolucent lesions related to the molar teeth and to determine which features indicate aggressive lesions. PATIENTS AND METHODS: Panoramic radiographs were reviewed in 66 patients with radiolucencies related to the molar teeth. The radiographic appearances of the lesions were assessed with regard to location and size, and the relationship to the molar teeth. Radiographic evidence of aggression was assessed and pathology reviewed. RESULTS: Nineteen patients had aggressive and 47 had non-aggressive radiolucent lesions. The aggressive lesions included keratocysts, unicystic ameloblastoma, adenoid cystic carcinoma, giant cell granuloma, myxofibroma, chondroblastic osteosarcoma, mestastases and squamous cell carcinoma of the tongue invading the mandible. CONCLUSION: The differential diagnosis of radiolucent lesions in the mandible can be difficult using panoramic radiographs alone. Helpful features in determining aggression were older patients, larger lesions, Lodwick type IC tumour border, condition of the mandibular cortex, movement of adjacent teeth and the relationship of the inferior alveolar canal.

Adult↗
PubMed2000

Expression of a new operon from Bacillus subtilis, ykzB-ykoL, under the control of the TnrA and PhoP-phoR global regulators.

The ykzB and ykoL genes encode two peptides, of 51 and 60 amino acids, the functions of which are unknown. The ykzB and tnrA genes are contiguous and transcribed divergently. Expression of ykzB and ykoL is induced by glutamate and is under the control of the TnrA global regulator of nitrogen utilization. TnrA regulated its own synthesis in glutamate minimal medium. Two DNA sequences (TnrAB1 and TnrAB2) homologous to the TnrA binding site are present in the region between tnrA and ykzB. Deletion mapping indicated that the TnrAB2 binding site was involved in activation of the ykzB promoter. In addition, transcription of tnrA depends on the presence of the TnrAB1 binding site. The ykzB and ykoL genes are probably in the same transcriptional unit. A single promoter involved in transcription in the presence of glutamate was mapped by primer extension. ykoL expression was induced by phosphate limitation and depended on the PhoP-PhoR two-component regulatory system. Its promoter was mapped to the region between ykoL and ykzB. Four boxes similar to the PhoP binding site are present upstream from the ykoL promoter. These boxes are probably recognized by PhoP approximately P during the activation of transcription in phosphate limitation conditions.

Bacillus subtilis↗
PubMed2000

Ribozyme-based therapeutic approaches for autosomal dominant retinitis pigmentosa.

PURPOSE: To design, generate, and compare in vitro a range of hammerhead ribozymes targeting retinal transcripts implicated in autosomal dominant retinitis pigmentosa (adRP) and thereby identify ribozymes that may be valuable as therapeutic agents for adRP. To address mutational heterogeneity in rhodopsin and peripherin-linked adRP using mutation-independent ribozyme-based therapeutic approaches. METHODS: Ribozyme and cDNAs constructs were cloned into pcDNA3 and expressed in vitro from the T7 promoter. Cleavage reactions were separated on polyacrylamide gels, visualized by autoradiography, and quantified using an instant imager. Ribozymes targeting rhodopsin and peripherin transcripts in a mutation-independent manner (Rz9, Rz10, and Rz40) and a multimeric ribozyme (RzMM) targeting rhodopsin transcripts were evaluated for in vitro activity. Parameters such as V:(max), K:(m), k(2) and k(-1) were established for each ribozyme. RESULTS: Four ribozymes targeting retinal transcripts were evaluated. Mutation-independent ribozymes targeting degenerate sites or untranslated regions in retinal transcripts resulted in cleavage products of predicted size, whereas transcripts from modified replacement genes remained intact. Detailed kinetic evaluation of ribozymes revealed substantial differences in cleavage rates between ribozymes. CONCLUSIONS: Mutation-independent hammerhead ribozymes targeting rhodopsin and peripherin have been screened in vitro, and a number of extremely efficient ribozymes identified subsequent to detailed kinetic analyses, suggesting that these ribozymes may provide mutation-independent methods of treating adRP. These are the first ribozymes reported that potentially will provide benefit for inherited retinopathies.

Autoradiography↗