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Biomedical subjects

J O'Reilly

Publications and source records attributed to J O'Reilly.

At least 19 recordsLinked to original sources

Assessing the burden of respiratory disease in the UK.

This review explores the health and social burden of some of the main respiratory diseases (asthma, chronic obstructive pulmonary disease, cryptogenic fibrosing alveolitis, cystic fibrosis, lung cancer, mesothelioma, obstructive sleep apnoea and tuberculosis) in order to increase awareness of these diseases and highlight areas where improvements in care are required. The overall impact of respiratory diseases in the U.K. in terms of prevalence, mortality, morbidity and economic costs, with particular reference to secondary care has been considered and comparisons made with the rest of Europe where data are available. Respiratory diseases are responsible for a significant proportion of serious morbidity and premature death among the population of the U.K. and they will continue to present a growing challenge; special support is needed to tackle this burden.

Adolescent↗

Differential increase in cerebral cortical glucose oxidative metabolism during rat postnatal development is greater in vivo than in vitro.

The steady-state rate of glucose oxidation through the mitochondrial TCA cycle (V(TCA)) was measured in acid extracts of 10- and 30-day-old cerebral cortex of rats receiving [1-13C]glucose intravenously and in neocortical slices superfused in vitro with the same isotope. TCA cycle flux was determined for each age group based on metabolic modeling analysis of the isotopic turnover of cortical glutamate and lactate. The sensitivity of the calculated rates to assumed parameters in the model were also assessed. Between 10 and 30 postnatal days, V(TCA) increased by 4.3-fold (from 0.46 to 2.0 micromol g(-1) min(-1)) in the cortex in vivo, whereas only a 2-fold (from 0.17 to 0.34 micromol g(-1) min(-1)) increase was observed in neocortical slices. The much greater increase in glucose oxidative metabolism of the cortex measured in vivo over that measured in vitro as the cortex matures suggests that function-related energy demands increase during development, a process that is deficient in the slice as a result of deafferentiation and other mechanisms.

Aging↗

Long-term visual results following primary trabeculectomy for infantile glaucoma.

PURPOSE: To report the long-term visual outcome of eyes that underwent primary trabeculectomy for infantile glaucoma and to evaluate factors that affect visual prognosis. METHODS: Thirty-five eyes of 22 consecutive patients presenting between 1980 and 1995 were included. Visual acuity, visual fields and refractive status were assessed and patient records reviewed. RESULTS: Nineteen of 22 patients (86.3%) achieved 6/12 or better, (21 of 35 eyes; 60%). Reasons for decreased vision included amblyopia (5 eyes), field loss (4 eyes), corneal opacification (2 eyes), and uncontrolled IOP (1 eye). Primary glaucoma had a better outcome than secondary glaucoma. Vision was frequently unequal despite controlled pressure, clear media and full fields in both eyes. This was associated with myopic anisometropia and apparent amblyopia. Ten patients responded to patching. Eyes with field defects were unresponsive to patching. CONCLUSIONS: Field defects, corneal scarring, marked anisometropia and severe astigmatism result in poor vision. Anisometropic amblyopia is frequently present and responds well to patching. Visual outcome is dependent on early and sustained control of intraocular pressure and aggressive treatment of amblyopia.

Adolescent↗

Prokaryote multidrug efflux proteins of the major facilitator superfamily: amplified expression, purification and characterisation.

In bacterial genomes 3-12% of open reading frames are predicted to encode membrane transport proteins. These proteins can be vital for antibiotic efflux, protein/ toxin secretion, cell nutrition, environmental sensing, ATP synthesis, and other functions. Some, such as the multidrug efflux proteins, are potential targets for the development of new antibacterials and also for applications in biotechnology. In general membrane transport proteins are poorly understood, because of the technical difficulties involved in isolating sufficient protein for elucidation of their structure-activity relationships. We describe a general strategy for the amplified expression, purification and characterisation of prokaryotic multidrug efflux proteins of the 'Major facilitator superfamily' of transport proteins, using the Bacillus subtilis multidrug resistance protein, 'Bmr', as example.

Amino Acid Sequence↗

Software essentials for lab success.

"Look around before you make a decision," Whelan said. "Take the time for a hands-on trial of different systems. Ask other labs using the system what they think of it. After all, this is an important decision for the long-term health of your business and one you will live with for a long time."

Computer User Training↗

Retention behaviour of strong acid anions in ion-exclusion chromatography on sulfonate and carboxylate stationary phases.

Some factors influencing the retention of strong-acid anions on ion-exclusion columns were investigated using columns with sulfonate and carboxylate functional groups. The nature of the functional group on the resin, the eluent pH and the eluent ionic strength all significantly affected the retention and separation of these analytes. Retention was observed for all strong-acid anions over the eluent pH range 2.2-5.7 and increased with both decreasing eluent pH and increasing eluent ionic strength. Some separation of strong-acid anions was possible when using a resin with carboxylate functional groups. It has also been demonstrated that strong-acid anions are poor markers of column void volume for ion-exclusion chromatography. A more accurate value was obtained using the neutral polymeric material dextran blue. When using eluents of low ionic strength, poor or fronted peak shapes were observed. A mechanism for these observations is proposed that relates the shape to ionic strength changes across the peak. A system peak was encountered under most experimental conditions. The properties of this peak are discussed and a cause for the system peak postulated.

Acids↗

A unique structural abnormality of chromosome 16 resulting in a CBF beta-MYH11 fusion transcript in a patient with acute myeloid leukemia, FAB M4.

A 43-year-old female with a peripheral white cell count of 118.0 x 10(9)/L and 96% blasts was diagnosed with acute myeloid leukemia (AML), FAB M4. Cytogenetics, performed on a bone marrow sample, revealed the following abnormal karyotype: 46,XX,ins(16)(q22p13.1p13. 3). Fluorescence in situ hybridization (FISH) confirmed the inter-arm insertion using a probe for 16p. The result of this structural rearrangement was the fusion of CBF beta to MYH11 seen commonly in inv(16)(p13q22). The patient commenced high-dose intensive combination chemotherapy (big ICE; Idarubicin, Cytarabine, and Etopiside). Five days post chemotherapy, she developed febrile neutropenia. Despite broad spectrum intravenous antibiotics and antifungal therapy, the patient died at day nine post chemotherapy. This case demonstrates a previously unreported structural abnormality of chromosome 16 in a patient with AML M4, which represents a third mechanism to inv(16)(p13q22) and t(16;16)(p13q22) in producing the CBF beta-MYH11 fusion. CBF beta-MYH11 fusions masked by cryptic translocations at the cytogenetic level have been detected by FISH and PCR techniques. Due to the improved prognosis associated with CBF beta-MYH11 fusions compared to the standard risk group for AML, its detection remains important.

Adult↗

The steady-state levels of oxidative DNA damage and of lipid peroxidation (F2-isoprostanes) are not correlated in healthy human subjects.

Oxidative damage to DNA in human tissues can be determined by measuring multiple products of oxidative damage to the purine and pyrimidine bases using gas chromatography-mass spectrometry (GC-MS). Oxidative damage to lipids (lipid peroxidation) can be quantitated by the mass spectrometry-based determination of F2-isoprostanes, specific end-products of the peroxidation of arachidonic acid residues in lipids. For both DNA base damage products and 8-epi prostaglandin F2alpha (PGF2alpha), there is a wide variation in levels between different healthy human subjects. We measured multiple products of oxidative damage to DNA bases in white cells, and 8-epi PGF2alpha in plasma, from blood samples obtained from healthy human subjects in the UK and in Portugal. No correlation of 8-epi PGF2alpha levels with levels of any modified DNA base (including 8-hydroxyguanine) was observed. We conclude that no single parameter can be measured as an index of "oxidative stress" or "oxidative damage" in vivo.

Adult↗

Effects of time intervals and tone durations on auditory stream segregation.

Adult listeners rated the difficulty of hearing a single coherent stream in a sequence of high (H) and low (L) tones that alternated in a repetitive galloping pattern (HLH-HLH-HLH...). They could hear the gallop when the sequence was perceived as a single stream, but when it segregated into two substreams, they heard H-H- ... in one stream and L-L- ... in the other. The onset-to-onset time of the tones, their duration, the interstimulus interval (ISI) between tones of the same frequency, and the frequency separation between H and L tones were varied. Subjects' ratings on a 7-point scale showed that the well-known effect of speed's increasing stream segregation is primarily due to its effect on the ISI between tones in the same frequency region. This has implications for several theories of streaming.

Adult↗

Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE).

The potential role of oestrogenic agents, antioxidants and intestinal glucose-uptake inhibitors in the treatment of diabetes is briefly reviewed. Reports in the literature suggest that oestrogen replacement therapy may favourably modulate glucose homeostasis. A soya phytochemical extract (SPE) containing the isoflavone phytoestrogens genistein and daidzein (mostly in their glycone forms as genistin and daidzin) was investigated as an antioxidant and modulator of intestinal glucose-transport. In the present study, SPE was found to protect against glucose-induced oxidation of human low density lipoproteins (LDL) in vitro. Equol (a gut bacterial metabolite of daidzein) was a more effective antioxidant than daidzein or genistein in this system and was of similar antioxidant potency to the dietary flavonols quercetin and kaempferol and to the endogenous antioxidant 17beta-oestradiol. SPE was found to be an inhibitor of glucose uptake into rabbit intestinal brush border membrane vesicles in vitro, though of weaker potency than the classical sodium dependent glucose transporter (SGLT) inhibitor, phlorizin. Thus SPE displays a range of properties which may be of benefit in diabetes, namely as an oestrogenic agent, an inhibitor of intestinal glucose-uptake and a preventive agent for glucose-induced lipid peroxidation.

Animals↗

Congenital ptosis: longterm results using stored fascia lata.

PURPOSE: Frontalis brow suspension, using stored donor fascia lata, allows early correction of severe congenital ptosis. We report longterm results of 18 patients, (29 ptotic eyelids). METHODS: Patient records were retrospectively reviewed. Lid position at the first and subsequent post-operative visits was recorded, as was the time when ptosis recurred. RESULTS: The mean follow-up period was 42.9 months (range 7 to 84 months). All patients achieved a Good initial result. Partial ptosis recurrence was noted in 7 patients (10 eyelids), within 18 months of surgery. One of these patients required reoperation. Lid position did not change after the first 18 months. No late failures were encountered. CONCLUSION: Longterm lid position is remarkably stable after early surgical correction of severe congenital ptosis using stored fascia lata.

Blepharoptosis↗

Expression of delayed toxicity and lethal mutations in the progeny of human cells surviving exposure to radiation and other environmental mutagens.

PURPOSE: Delayed expression of lethal mutations in the progeny of cells which survived a toxic insult was first shown for ionizing radiation and is one of the signs of induced genomic instability. The effect appears to be related to DNA strand breakage or repair but not to the physical break itself. To investigate this and the relationship of lethal mutations or delayed death to other instability endpoints, cultures of immortal but non-transformed human keratinocytes were exposed to a range of environmental mutagens or cytotoxic compounds with different DNA damaging properties. METHODS: Delayed expression of damage was assessed by scoring a number of endpoints in the progeny of cells which survived exposure and underwent at least 15 population doublings. Endpoints included delayed apoptosis, cloning efficiency of cells in 'healthy' colonies and expression of the apoptosis regulatory proteins bcl-2 and BAX. RESULTS: The results clearly linked expression of delayed lethal mutations with substances that induced DNA strand breaks. All these substances are known also to induce oxidative stress. The occurrence of delayed damage required a threshold level of toxicity in the initially exposed population, which was remarkably similar for all the effective substances except cadmium. Alkylating agents or microtubule poisons that do not permit repair of DNA damage did not cause any delayed death. CONCLUSION: It is concluded that delayed cell death may be caused by widespread radical damage to DNA which is either signalled, thereby inducing an apoptotic response, or (mis-)repaired yielding a weak or unstable genome. It is likely that the process may be an important factor in determining the long-term response of populations to 'sublethal' levels of environmental mutagens whose mechanism of action includes DNA strand breakage and repair.

Antineoplastic Agents↗

Longer-term visual outcome of eyes with retinopathy of prematurity treated with cryotherapy or diode laser.

AIMS: Visual outcome of 66 eyes in 37 patients who had undergone treatment with either cryotherapy or diode laser for threshold retinopathy of prematurity was assessed. METHODS: 17 patients, representing 30 eyes treated with cryotherapy, were examined at between 56 and 98 months corrected age (median 68 months). 20 patients representing 36 eyes treated with diode laser, were examined at between 30 and 66 months corrected age (median 51 months). Structural outcome was categorised as: optimal--flat posterior pole; suboptimal--macular ectopia, optic nerve hypoplasia, retinal fold involving the macula, and retinal detachment involving the macula. RESULTS: Optimal structural outcome was, in the absence of amblyopia, associated with optimal visual acuity (of 6/12 or better) in all cases, with most eyes achieving a visual acuity of 6/9 or 6/6. Suboptimal structural outcome was invariably associated with suboptimal visual acuity. Amblyopia was present in eight out of 20 cryotherapy treated eyes and in five out of 26 laser treated eyes with an optimal structural outcome. Refractive errors were significantly less in laser treated eyes as was the incidence of anisometropic amblyopia. CONCLUSION: Eyes treated with either cryotherapy or diode laser for threshold retinopathy of prematurity with optimal structural outcome are associated with development of optimal visual acuity--that is, 6/12 or better. Treatment with either cryotherapy or laser does not in itself reduce the visual potential of these eyes.

Amblyopia↗