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Biomedical subjects

G C Brown

Publications and source records attributed to G C Brown.

At least 19 recordsLinked to original sources
PubMed2006

Interactions between nitric oxide, oxygen, reactive oxygen species and reactive nitrogen species.

ROS (reactive oxygen species) and RNS (reactive nitrogen species) are central to the innate immunity that protects us from infection, but also contribute to degenerative diseases and possibly aging. However, ROS and RNS are increasingly recognized to contribute to physiological signalling. This review briefly describes the main interactions between ROS and RNS and shows how their origins, chemistry, metabolism and biological actions are intimately linked.

Cell Death↗
PubMed2005

European corn borer (Lepidoptera: Crambidae) effects on qualitative traits of high oil content corn grown in Kentucky.

The European corn borer, Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae), is one of the most important pests of corn, Zea mays L., because it consistently causes high loss of yield. A study was conducted in 2000-2002 at field sites in central and western Kentucky to investigate whether infestation by O. nubilalis differentially affects the production of high-oil corn compared with traditional field corn. Statistical differences in grain weight and percentage of oil content between the five infestation levels were significant at both locations and for all years. Average grain yield was reduced by 0.40% and average oil concentration by 0.011% for each 1% of damaged plants, and there was a strong correlation (0.76) between leaf damage ratings (i.e., Guthrie scale) and yield reduction. In general, corn planted at the early planting date tended to have a higher yield (grain weight) and oil content.

Animals↗
PubMed2004

Nitric oxide, hypoxia and brain inflammation.

NO (nitric oxide) acutely and potently inhibits mitochondrial cytochrome oxidase in competition with oxygen, thereby raising the apparent K(M) for oxygen of mitochondria and neurons into the physiological or pathological range. We find that NO from an NO donor or glial inducible NOS (nitric oxide synthase) highly sensitizes neurons to hypoxia-induced death, probably via the NO-oxygen competition at cytochrome oxidase. Thus the NO from neuronal NOS during excitotoxicity or the NO from inducible NOS during inflammation may sensitize the brain to hypoxic/ischaemic damage.

Animals↗
PubMed2004

Neuropsychological and information processing performance and its relationship to white matter changes following moderate and severe traumatic brain injury: a preliminary study.

Reductions in information processing speed have frequently been reported following moderate and severe traumatic brain injuries (TBIs), consistent with the effects of diffuse white matter damage. Although the corpus callosum (CC) is a common site for diffuse damage following TBI, the effects of this damage on information processing speed have not been adequately examined. This study assessed a TBI group and a matched control group on tests of attention, memory, fluency, and set shifting ability, together with reaction time (RT) tasks requiring the inter- and intrahemispheric processing of visual and tactile information. The RT tasks were designed to target the cognitive functions that are likely to be affected by diffuse white matter damage, including damage to the CC. The TBI group demonstrated deficits in verbal and visual fluency and verbal memory. They were also slower on the visual and tactile RT tasks, were more affected by task complexity, and slower on RT tasks requiring the interhemispheric transfer of information. In fact, one of the interhemispheric tactile RT tasks proved to be the most discriminating of all the cognitive and RT measures. MRIs completed on a subset of TBI participants indicated that the mean CC measurements were 5% to 19% smaller than a normative control group, with the most atrophied areas being the isthmus and anterior midbody. Although white matter atrophy was moderately related to visual and tactile RT performance, and total hippocampal volume related to memory performance, CC area was not related to many of the tasks that were designed to tap interhemispheric processing. None of the standard cognitive tests correlated with outcome in the TBI group, but 1 of the tactile RT measures was significantly related to 2 measures of outcome.

Adolescent↗
PubMed2003

Quality of life with macular degeneration: perceptions of patients, clinicians, and community members.

BACKGROUND/AIMS: Age related macular degeneration (ARMD) is a common ophthalmological disorder that can significantly impair a patient's ability to function independently and potentially have a dramatic impact on health related quality of life. The aim of this study is to evaluate the quality of life of patients with ARMD, through the use of utility evaluation, and assess whether clinicians and healthy volunteers appreciate the impact of ARMD on health related quality of life. METHODS: A standardised questionnaire using the time-tradeoff method of utility analysis was created to assess health related quality of life. This questionnaire was distributed to 115 patients with ARMD. A similar questionnaire was distributed to 142 healthy volunteers and 62 clinicians who were asked to assume that they had ARMD. Comparisons were made among the responses from the members of the three groups. RESULTS: There was a significant difference in the utility scores among respondents with mild, moderate, and severe ARMD when compared to members of the general public and clinicians who were asked to assume they had each severity of ARMD. For mild ARMD the mean utility scores were 0.932, 0.960, and 0.832, for the general public, clinicians, and patients respectively (F = 21.7; p <0.001). No significant difference was found between the community members and clinicians (p <0.166); however, the patient group differed significantly from the general public (p<0.001) and clinician (p <0.001) groups. The utility scores for moderate ARMD for the general public, clinicians, and patients were 0.918, 0.877, and 0.732, respectively. (F = 34.6, p <0.001). There was no significant difference between the general public and clinicians (p <0.143); however, the patient group differed significantly compared with the general public (p <0.001) and clinician (p <0.001) groups. The utility scores for people with severe ARMD in the general public, clinician, and patient groups were 0.857, 0.821, and 0.566, respectively (F = 45.5; p <0.001). No significant difference was shown between the community members and clinicians (p <0.386); however, a significant difference was seen when comparing the patient group with the community member and clinician (p<0.001) groups. CONCLUSION: Clinicians and community members may greatly underestimate the impact of mild, moderate, and severe ARMD on health related quality of life.

Adolescent↗
PubMed2003

Utilities associated with diabetic retinopathy: results from a Canadian sample.

BACKGROUND/AIMS: To report patient based utilities, using the time trade-off technique, associated with visual loss secondary to diabetic retinopathy in a sample of Canadian patients. In addition, to compare these utility values with a sample collected in a similar manner in a tertiary care practice in the United States. METHODS: A cross sectional study of eligible patients with diabetic retinopathy presenting to a tertiary facility was performed. Demographic and clinical variables (including Snellen visual acuity), and utilities were collected both through chart review and standardised interviews with diabetic patients. RESULTS: 221 patients with diabetic retinopathy were eligible for this study and completed the interview. The mean age was 63.5 (SD 12.5) years, and 48.4% were female. Over 35% of the sample had visual acuity in the affected eye of 6/60 or worse. The mean utility for the sample was 0.79 (SD 0.23). The mean utility from this sample did not differ significantly from that obtained from a series of patients with diabetic retinopathy who were referred to a tertiary facility in the United States (mean 0.77, SD 0.21, p=0.313). Our cross border comparison had a power of 95% to detect a difference in utility of 0.1 between the two groups. CONCLUSION: On average, Canadian patients with diabetic retinopathy were willing to trade off over 20% of their remaining lifespan in order to eliminate their ocular disease. The mean utility obtained from our sample of Canadian patients with diabetic retinopathy was not statistically different from that obtained from a similar sample of American patients.

Adolescent↗
PubMed2003

Bionomics of Scymnus (Pullus) louisianae J. Chapin (Coleoptera: Coccinellidae) as a predator of the soybean aphid, Aphis glycines Matsumura (Homoptera: Aphididae).

A field population of Scymnus louisianae Chapin (Coccinellidae) was found attacking soybean aphids, Apis glycines Matsumura (Aphidae), a pest recently introduced into Kentucky. This coccinellid had not previously been found in Kentucky. A greenhouse population of S. louisianae was established and its predation on A. glycines studied under laboratory conditions. Total time to develop from egg to adult was about 20 d. About 70% of immatures survived to adulthood and they consumed approximately 100 aphid nymphs per beetle larva during the beetle's four larval instars. Adults lived for an average of 47 d (mated males) and 63 d (mated females) and, during their total adult lifetime, mated males consumed an average of 665 nymphs and mated females consumed 1261 nymphs. All developmental times and predation rates were comparable to those reported for other aphidophagous Scymnus spp. which, in conjunction with reports that Scymnus spp. are effective predators of cotton aphids, Aphis gossypii Glover, suggests that S. louisianae is a potentially important predator of A. glycines in the southern United States.

Animals↗
PubMed2002

Nitric oxide-dependent damage to neuronal mitochondria involves the NMDA receptor.

Cytokine-stimulated astrocytes produce nitric oxide, which can inhibit components of the mitochondrial respiratory chain. We have previously demonstrated that prolonged exposure (48 h) to rat astrocytic nitric oxide damages complexes II--III and IV of neighbouring rat neurons in coculture, resulting in neuronal death. Expanding on these observations, we have now shown that the NMDA receptor antagonist, MK-801, prevents this damage, suggesting involvement of glutamate. We postulate that astrocyte-derived nitric oxide stimulates release of neuronal glutamate. Indeed we demonstrate that neurons incubated with nitric oxide-generating astrocytes display enhanced glutamate release. Furthermore, direct exposure to the nitric oxide donor, DETA-NONOate resulted in a loss of activity of all the neuronal mitochondrial complexes, which was again prevented by MK-801. Thus, nitric oxide, generated by both cytokine-stimulated astrocytes and by a nitric oxide donor, causes activation of the NMDA receptor leading to damage to the neuronal mitochondrial respiratory chain. Glutamate exposure is known to damage the neuronal mitochondrial respiratory chain via neuronal nitric oxide synthase. Therefore, we propose that astrocyte-derived nitric oxide is capable of eliciting neuronal glutamate release, which in turn activates the neuronal NMDA receptor and stimulates further formation of reactive nitrogen species via neuronal nitric oxide synthases, leading to mitochondrial damage and neuronal death. Our findings support the hypothesis that glutamate, reactive nitrogen species and mitochondrial dysfunction may have a role in the neurodegenerative process.

Animals↗
PubMed2002

Validity of the time trade-off and standard gamble methods of utility assessment in retinal patients.

AIM: To assess the validity of the time trade-off (TTO) and standard reference gamble (SRG) techniques of utility assessment in patients with retinal disease. A cross section of eligible patients was studied and validity was determined through their relation with two logical constructs, visual acuity and scores from the Visual Function 14 (VF-14) index. METHODS: The study consisted of eligible patients presenting to a tertiary retinal facility who completed an interview. All patients had best corrected vision of 20/40 or worse in at least one eye. TTO and SRG utilities, as well as a VF-14 questionnaire, were administered through a standardised interview. Demographic and clinical (including Snellen visual acuity) information was also collected. RESULTS: 323 patients met these study criteria. Significant predictors of TTO utilities in the multivariate analysis were vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.01). Significant predictors of standard gamble utilities were also vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.05). CONCLUSION: Both the standard gamble and TTO methods demonstrate strong validity when evaluated against visual acuity in the better seeing eye and the VF-14 score.

Adolescent↗
PubMed2001

Release of mitochondrial cytochrome c and activation of cytosolic caspases induced by myocardial ischaemia.

It has previously been shown that apoptosis is increased in ischaemic/reperfused heart. However, little is known about the mechanism of induction of apoptosis in myocardium during ischaemia. We investigated whether prolonged myocardial ischaemia causes activation of caspases and whether this activation is related to cytochrome c release from mitochondria to cytosol during ischaemia. Using an in vitro model of heart ischaemia, we show that 60 min ischaemia leads to a significant accumulation of cytochrome c in the cytosol and a decrease in mitochondrial content of cytochrome c but not cytochrome a. The release of cytochrome c from mitochondria was accompanied by activation of caspase-3-like proteases (measured by cleavage of fluorogenic peptide substrate DEVD-amc) and a large increase in number of cells with DNA strand breaks (measured by TUNEL staining). Caspase-1-like proteases (measured by YVAD-amc cleavage) were not activated during ischaemia. Addition of 14 microM cytochrome c to cytosolic extracts prepared from control hearts induced ATP-dependent activation of caspase-3-like protease activity. Our data suggest that extended heart ischaemia can cause apoptosis mediated by release of cytochrome c from mitochondria and subsequent activation of caspase-3.

Animals↗
PubMed2001

Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity.

Glia undergo inflammatory activation in most CNS pathologies and are capable of killing cocultured neurons. We investigated the mechanisms of this inflammatory neurodegeneration using a mixed culture of neurons, microglia, and astrocytes, either when the astrocytes were activated directly with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) or LPS/IFN-gamma-activated microglia were added to mixed neuronal cultures. In either case, activated glia caused 75-100% necrotic cell death within 48 hr, which was completely prevented by inhibitors of inducible nitric oxide synthase (iNOS) (aminoguanidine or 1400W). Activated astrocytes or microglia produced nitric oxide (NO) (steady-state level approximately 0.5 microm), which immediately inhibited the cellular respiration of cocultured neurons, as did authentic NO. NO donors also decreased ATP levels and stimulated lactate production by neurons, consistent with NO-induced respiratory inhibition. NO donors or a specific respiratory inhibitor caused rapid (<1 min) release of glutamate from neuronal and neuronal-astrocytic cultures and subsequent neuronal death that was blocked by an antagonist of NMDA receptor (MK-801). MK-801 also blocked neuronal death induced by activated glia. High oxygen also prevented NO-induced neuronal death, consistent with death being induced by NO inhibition of cytochrome c oxidation in competition with oxygen. Thus activated glia kill neurons via NO from iNOS, which inhibits neuronal respiration resulting in glutamate release and subsequent excitotoxicity. This may contribute to neuronal cell death in inflammatory, infectious, ischemic, and neurodegenerative diseases.

Adenosine Triphosphate↗
PubMed2001

Caspases are reversibly inactivated by hydrogen peroxide.

Hydrogen peroxide (H2O2) is known to both induce and inhibit apoptosis, however the mechanisms are unclear. We found that H2O2 inhibited the activity of recombinant caspase-3 and caspase-8, half-inhibition occurring at about 17 microM H2O2. This inhibition was both prevented and reversed by dithiothreitol while glutathione had little protective effect. 100-200 microM H2O2 added to macrophages after induction of caspase activation by nitric oxide or serum withdrawal substantially inhibited caspase activity. Activation of H2O2-producing NADPH oxidase in macrophages also caused catalase-sensitive inactivation of cellular caspases. The data suggest that the activity of caspases in cells can be directly but reversibly inhibited by H2O2.

Caspase 3↗
PubMed2001

Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase.

Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by a variety of means. Nanomolar concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues. Higher concentrations of NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Isolated mitochondria, cultured cells, isolated tissues and animals in vivo display respiratory inhibition by endogenously produced NO from constitutive isoforms of NO synthase (NOS), which may be largely mediated by NO inhibition of cytochrome oxidase. Cultured cells expressing the inducible isoform of NOS (iNOS) can acutely and reversibly inhibit their own cellular respiration and that of co-incubated cells due to NO inhibition of cytochrome oxidase, but after longer-term incubation result in irreversible inhibition of cellular respiration due to NO or its derivatives. Thus the NO inhibition of cytochrome oxidase may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen.

Animals↗
PubMed2001

Reliability of the time trade-off technique of utility assessment in patients with retinal disease.

BACKGROUND: Studies in medical fields other than ophthalmology have given conflicting results regarding the reliability of the time trade-off technique of utility assessment. We performed a study to determine the test-retest reliability of the time trade-off technique for assessing utilities in patients with ocular diseases of the retina and to investigate possible factors associated with differences in utility over time. METHODS: Patients referred to the retina service of a tertiary care hospital in eastern Canada were eligible for the initial interview if they had best corrected vision of 20/30 or worse in at least one eye and were deemed competent to answer the required questions. Patients were interviewed prospectively between December 1999 and March 2000 during a normal 30-minute period needed for pharmacologic mydriasis to occur. Demographic, clinical (including Snellen visual acuity) and time trade-off utility information was collected through chart review and standardized interview. Patients who completed the interview successfully were called back 28 days later for follow-up. RESULTS: Of the 138 eligible patients 112 (81.2%) completed the initial interview. Of the 112, 96 (85.7%) completed the second interview. Half of the respondents were women, and all but one respondent were white. The mean age was 65.3 years. The primary reasons for visual loss included diabetic retinopathy (59 patients [61.4%]) and age-related macular degeneration (14 patients [14.6%]). The intraclass correlation coefficient between the initial and follow-up visual utilities was 0.7634 (95% confidence interval 0.6655-0.8355). INTERPRETATION: Our results show excellent reliability of the time trade-off technique of utility assessment in patients with ocular diseases of the retina.

Adult↗
PubMed2001

Improvement in quality of life from photodynamic therapy: a Canadian perspective.

BACKGROUND: The Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study showed that at 1 year, photodynamic therapy significantly reduced the chances of severe visual loss (15 letters or greater) compared with placebo treatment in patients with "predominantly classic" subfoveal choroidal neovascularization (CNV). We performed a study to determine the expected gain in quality of life associated with photodynamic therapy for the treatment of subfoveal CNV in a Canadian cohort of patients with age-related macular degeneration. METHODS: We created a decision analysis model to determine the incremental gain in quality-adjusted life years (QALYs) associated with photodynamic therapy over placebo over a 2-year period. The analysis was conducted using efficacy data derived from the TAP Study and patient-based utilities collected by means of the time trade-off technique. We conducted one-way and two-way sensitivity analyses to determine the robustness of our model. A Monte Carlo simulation was used to determine whether the observed gain in QALYs with photodynamic therapy was significant. RESULTS: Photodynamic therapy was associated with a relative increase in QALYs of 11.3% compared with placebo. In one-way and two-way sensitivity analyses, the relative increase in quality of life associated with photodynamic therapy ranged from 4.2% to 25.7%. The Monte Carlo simulation showed that the gain in QALYs conferred from photodynamic therapy was statistically significant (p < 0.001). INTERPRETATION: Photodynamic therapy improves the quality of life of Canadians with predominantly classic subfoveal CNV secondary to age-related macular degeneration.

Canada↗
PubMed2001

Quality of life associated with unilateral and bilateral good vision.

OBJECTIVE: To ascertain with patient preference-based methodology whether individuals with good visual acuity (20/20-20/25) in one eye have the same quality of life as individuals with good vision in both eyes. DESIGN: Cross-sectional comparative study. PARTICIPANTS: Consecutive patients seen in comprehensive ophthalmic and vitreoretinal practices with known ocular disease and good visual acuity (20/20 or 20/25) in one or both eyes. METHODS: Standardized patient interview. MAIN OUTCOME MEASURES: Time tradeoff and utility analysis values. RESULTS: The mean time tradeoff utility value in 81 patients with good visual acuity in one eye was 0.89 (standard deviation, 0.17; 95% confidence interval, 0.85-0.93), whereas the mean value in 66 patients with good vision in both eyes was 0.97 (standard deviation, 0.05; 95% confidence interval, 0.97-0.99). The difference between the means of the utility values in these two groups was significant using multiple linear regression (P = 0.001). CONCLUSIONS: From the patient preference-based point of view, individuals with ocular disease and good visual acuity in both eyes appear to have a higher time tradeoff utility value, and thus a better associated quality of life, than those with good visual acuity in only one eye.

Adult↗