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J Duncan

Publications and source records attributed to J Duncan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural product occurring in grapes and various other plants with medicinal properties. The phenolic antioxidant has been identified as a potential cancer chemopreventative agent and its presence in red wine has been suggested to be linked to the low incidence of heart disease in some regions of France. Recently, however, resveratrol was reported to promote DNA fragmentation in the presence of copper ions (K. Fukuhara and N. Miyata, 1998, Bioorg. Med. Chem. Lett. 8, 3187-3192), prompting us to investigate this phenomenon in mechanistic detail. By acting as a reducing agent, resveratrol was found to promote hydroxyl-radical (*OH) formation by DNA-bound Cu(H) ions. However, in the presence of either ascorbic acid or glutathione (i.e., under more physiological conditions), the phenolic lost this property and behaved as an antioxidant. In the ascorbate system, resveratrol had no effect on the rate of *OH formation, but protected DNA from damage by acting as a radical-scavenging antioxidant. In contrast, in the glutathione system, resveratrol inhibited *OH formation via a novel mechanism involving the inhibition of glutathione disulfide formation. We have concluded, therefore, that the DNA-damaging properties of resveratrol, identified recently by Fukuhara and Miyata, will be of no significance under physiological conditions. To the contrary, we have demonstrated that the phenolic behaves as a powerful antioxidant, both via classical, hydroxyl-radical scavenging and via a novel, glutathione-sparing mechanism.

Antioxidants↗
PubMed2000

A neural basis for general intelligence.

Universal positive correlations between different cognitive tests motivate the concept of "general intelligence" or Spearman's g. Here the neural basis for g is investigated by means of positron emission tomography. Spatial, verbal, and perceptuo-motor tasks with high-g involvement are compared with matched low-g control tasks. In contrast to the common view that g reflects a broad sample of major cognitive functions, high-g tasks do not show diffuse recruitment of multiple brain regions. Instead they are associated with selective recruitment of lateral frontal cortex in one or both hemispheres. Despite very different task content in the three high-g-low-g contrasts, lateral frontal recruitment is markedly similar in each case. Many previous experiments have shown these same frontal regions to be recruited by a broad range of different cognitive demands. The results suggest that "general intelligence" derives from a specific frontal system important in the control of diverse forms of behavior.

Adult↗
PubMed2000

Common regions of the human frontal lobe recruited by diverse cognitive demands.

Though many neuroscientific methods have been brought to bear in the search for functional specializations within prefrontal cortex, little consensus has emerged. To assess the contribution of functional neuroimaging, this article reviews patterns of frontal-lobe activation associated with a broad range of different cognitive demands, including aspects of perception, response selection, executive control, working memory, episodic memory and problem solving. The results show a striking regularity: for many demands, there is a similar recruitment of mid-dorsolateral, mid-ventrolateral and dorsal anterior cingulate cortex. Much of the remainder of frontal cortex, including most of the medial and orbital surfaces, is largely insensitive to these demands. Undoubtedly, these results provide strong evidence for regional specialization of function within prefrontal cortex. This specialization, however, takes an unexpected form: a specific frontal-lobe network that is consistently recruited for solution of diverse cognitive problems.

Animals↗
PubMed2000

The use of cognitive context in schizophrenia: an investigation.

BACKGROUND: Cognitive deficits in schizophrenia have recently been ascribed to impaired representation and use of cognitive context. Context is defined as relevant information held temporarily in mind to mediate appropriate but often non-habitual responses. METHODS: Parallel studies in a variety of cognitive domains were designed in order to explore the generality of any schizophrenic deficit in context use. In all of the tasks (a Stroop task, a Continuous Performance Task and a cued spatial location task), we examined how performance was affected by the time for which contextual information must be held in mind, and by whether context or task demands were consistent or varying between trials. It was predicted that manipulation of these variables would produce tests especially sensitive to schizophrenic attentional problems. RESULTS: Predictions were partially confirmed. Although increasing contextual demands failed in most cases to produce disproportionate slowing of performance in patients, error data were largely in line with predictions. At the same time, the data did not suggest a simple unitary context deficit. Instead, different aspects of context--the time over which contextual information must be held in mind and the consistency of context--were differentially important in different tasks. CONCLUSIONS: The cognitive impairments of schizophrenic patients cannot be simply characterized as a generalized context deficit. A more differentiated, if not task specific, picture of schizophrenic deficits is suggested.

Adult↗
PubMed2000

Rehabilitation of executive functioning: an experimental-clinical validation of goal management training.

Two studies assessed the effects of a training procedure (Goal Management Training, GMT), derived from Duncan's theory of goal neglect, on disorganized behavior following TBI. In Study 1, patients with traumatic brain injury (TBI) were randomly assigned to brief trials of GMT or motor skills training. GMT, but not motor skills training, was associated with significant gains on everyday paper-and-pencil tasks designed to mimic tasks that are problematic for patients with goal neglect. In Study 2, GMT was applied in a postencephalitic patient seeking to improve her meal-preparation abilities. Both naturalistic observation and self-report measures revealed improved meal preparation performance following GMT. These studies provide both experimental and clinical support for the efficacy of GMT toward the treatment of executive functioning deficits that compromise independence in patients with brain damage.

Adult↗
PubMed2000

Prolonged somatosensory evoked potential depression following a brief exposure to low concentrations of inhalation anaesthetic in a 3-year-old child.

A 3-year-old child was brought to the operating room for removal of a brainstem juvenile pilocytic astrocytoma. Following inhalation induction and intubation, he was maintained on 0.5% isoflurane. Somatosensory evoked potentials (SSEPs) were recorded but unobtainable initially and up to 90 min after all inhalation agents were discontinued. The operation was cancelled and the patient was transported to the paediatric intensive care unit (PICU). Subsequent PICU testing revealed a depression of amplitude with propofol and absence of potentials with 0.5% isoflurane. He returned to the operating room, was induced with propofol, and maintained with a propofol: nitrous oxide:fentanyl technique. This anaesthetic technique allowed adequate tumour resection with appropriate monitoring of SSEPs. These findings suggest that a total intravenous anaesthetic technique may be preferable for resection of spinal cord tumours where SSEPs are monitored.

Anesthetics, Inhalation↗
PubMed2000

Maintaining and shifting attention within left or right hemifield.

Positron emission tomography (PET) was used to examine two questions: (i) which structures of the intact human brain change their activity with the direction of attention to left or right visual field; and (ii) how does activity in these structures, and in parietal cortex in particular, depend on the frequency of attentional shifts? Subjects were required to discriminate the orientation of peripheral gratings. The two main experimental variables were the attended hemifield (left or right) and the proportion of trials requiring a shift within that hemifield (20% or 80%). A detection control condition was also included. Behaviourally, subjects were less accurate and significantly slower when a trial required a shift than when it did not. Ventral and lateral occipital areas showed significantly higher blood flow levels contralateral to the direction of attention. Replicating previous work, there was also a significant main effect of the direction of attention in left lateral prefrontal cortex: blood flow levels were higher during leftward attention in comparison both to baseline and to rightward attention. This left frontal effect reached significance in single subjects in whom several activation sites could be distinguished within left middle and inferior frontal gyrus. Right and left parietal cortex were activated during both left- and right-field attention conditions, with a tendency for higher activity levels when attention was directed contralaterally. Contrary to the experimental hypothesis, however, parietal regions were not activated differentially by high versus low numbers of attentional shifts. The current experiment confirms that left frontal convexity is sensitive to manipulations of the direction of visuospatial attention. The results do not indicate a specific role of parietal cortex in attentional shifting.

Adult↗
PubMed2000

Oxidase activity in lignifying xylem of a taxonomically diverse range of trees: identification of a conifer laccase.

In a diverse taxonomic range of tree species, including representative species of ancient families of angiosperms (Magnolia x soulangiana Soul.-Bod.) and gymnosperms (Ginkgo biloba L.), oxidase activity was associated with cell walls of developing xylem and was enriched in extracts of cell wall-associated glycoproteins. In all species where oxidase activity was detected histochemically, it was expressed in cell walls of lignifying, differentiating xylem cells and was absent from old wood, cambium and phloem, suggesting that oxidases have a conservative role in lignification of tree xylem. An oxidase from the developing xylem of Picea sitchensis (Bong) Carr. (Sitka spruce) was partially purified by a combination of lectin affinity and immobilized metal ion affinity chromatography. A portion of the total oxidase activity had high affinity for immobilized zinc ions and this feature allowed it to be separated from the bulk of oxidase activity. Two polypeptides that could have been responsible for the bound oxidase activity were enriched by this procedure. The smaller polypeptide of Mr approximately 73 kDa yielded an N-terminal amino-acid sequence that was homologous to laccase-like polyphenol oxidases (E.C. 1.10.3.2) from loblolly pine (Pinus taeda L.), poplar (Populus euramericana (Dode) Guinier) and Arabidopsis. The larger polypeptide (Mr approximately 77 kDa) yielded an N-terminal amino-acid sequence that was homologous with a range of plant subtilisin-like serine proteinases. The roles of oxidase and proteinase activities in developing xylem are discussed.

Cycadopsida↗
PubMed2000

Evidence that herpes simplex virus VP16 is required for viral egress downstream of the initial envelopment event.

During infection with herpes simplex virus type 1 (HSV-1), VP16 serves multiple functions, including transcriptional activation of viral immediate early genes and downregulation of the virion host shutoff protein vhs. Furthermore, VP16 has been shown to be involved in some aspect of virus assembly and/or maturation. Experiments with a VP16 null virus, 8MA, suggested that VP16 plays a direct role in virion assembly, since removal of VP16 from the HSV-1 genome results in reduced levels of encapsidated DNA and a failure to produce extracellular enveloped particles. However, VP16 null mutants display a severe translational arrest due to unrestrained vhs activity, thus complicating interpretation of these data. We examine here the role of VP16 in virion assembly and egress in the context of a vhs null background, using the virus 8MA/DeltaSma (VP16(-) vhs(-)). Comparison of 8MA and 8MA/DeltaSma with respect to viral DNA accumulation and encapsidation and accumulation of the major capsid protein, VP5, revealed that the 8MA lethal phenotype is only partially due to uncontrolled vhs activity, indicating that VP16 is required in HSV-1 virion formation. Electron microscopy confirmed these results and further showed that VP16 is required for HSV-1 egress beyond the perinuclear space. In addition, we describe the isolation and characterization of an 8MA derivative capable of propagation on Vero cells, due to second site mutations in the vhs and UL53 (gK) genes. Taken together, these results show that VP16 is required for viral egress downstream of the initial envelopment step and further underscore the importance of VP16 in controlling vhs activity within an infected cell.

Animals↗
PubMed2000

BRU59-21, a second-generation 99mTc-labeled 2-nitroimidazole for imaging hypoxia in tumors.

UNLABELLED: Hypoxia in tumors is believed to be an important cause of local failure of radiotherapy in certain types of cancer. BRU59-21 (BMS194796) is a second-generation 99mTc-labeled 2-nitroimidazole that has been shown to offer improved characteristics for imaging myocardial ischemia. It has now been evaluated in models of tumor hypoxia. METHODS: Accumulation of BRU59-21 was compared with that of BMS181321 in Chinese hamster ovary cells incubated under aerobic or hypoxic conditions. The effects of competition with unlabeled nitroimidazoles and oxygen were studied. Biodistribution studies were performed in mice bearing transplanted KHT-C tumors in the leg. RESULTS: Within 5 min, BRU59-21 partitioned into aerobic cells in vitro at a level 10 times higher than external medium with no further increase over time. In hypoxic cells this initial partitioning was followed by selective accumulation to levels 5 times higher than in aerobic cells by 4 h. Low levels of oxygen (approximately 40 ppm) inhibited the maximal accumulation rate by 50%. Unlabeled misonidazole, a 2-nitroimidazole, inhibited accumulation of radioactivity, whereas tinidazole, a 5-nitroimidazole, enhanced accumulation; similar effects had been reported with BMS181321. Biodistribution studies in mice showed rapid clearance of radioactivity from the blood, resulting in enhanced tumor-to-blood ratios compared with BMS181321. Increasing the hypoxic fraction in the tumor by injection of nitro-L-arginine resulted in increased retention of tracer in the tumor without affecting other tissues. CONCLUSION: These results suggest that BRU59-21 warrants further investigation as an agent for imaging tumor hypoxia in the clinic.

Animals↗
PubMed1999

Human cyclophilin has a significantly higher affinity for HIV-1 recombinant p55 than p24.

The ability of cyclophilin to bind a panel of recombinant HIV-gag proteins was assessed using sensitive, quantitative, sandwich enzyme-linked immunosorbant assays (ELISAs). Significantly higher binding to cyclophilin was observed when recombinants contained at least 12 carboxy-terminal amino acids of p17 in addition to p24 sequences. These results indicate that the carboxy-terminus of p17 is important for optimal binding of cyclophilin to p24 and support the theory that cyclophilin acts on the uncleaved HIV-1 gag (p17-p24) precursor.

Gene Products, gag↗
PubMed1999

A minimax entropy registration framework for patient setup verification in radiotherapy.

In external beam radiotherapy (EBRT), patient setup verification over the entire course of fractionated treatment is necessary for accurate delivery of a specified dose to the tumor. We are working on the development of a minimax entropy registration framework for patient setup verification using dual portal images and the treatment planning 3D CT dataset. In this paper, we present an overview of our registration framework, where an iteratively and automatically estimated segmentation of the portal image is utilized to more accurately and robustly register the portal image to the 3D treatment-planning CT data. In addition, we describe initial testing of this approach. We note that, due to low resolution and low contrast of the portal images, this registration presents a difficult problem. We also note that the registration of the images in our proposed method is guided by the bony structure visible in the portal and the 3D CT images. However, since the prostate can move with respect to the pelvic bone, we propose using ultrasound images to quantify this movement.

Algorithms↗
PubMed1999

Misregulation of connexin43 gap junction channels and congenital heart defects.

Although there is general agreement that gap junction channels formed by the connexin43 (Cx43; alpha 1) protein most likely have important roles during heart development, evidence to support this view has been equivocal. Lacking this information, it is difficult to understand the basis of heart malformations found in the Cx43 knockout mice and in children with a severe form of visceroatrial heterotaxia that coincides with missense mutations of the Cx43 gene. To address this issue we used a combination of western blots to follow the emergence of Cx43 in heart, and in vitro and in vivo phosphorylation to assess the effect of mutation on Cx43 phosphorylation. We evaluated the activity ratios of cAMP-dependent protein kinase and protein kinase C in hearts of 8.5-day-old mouse embryos through to birth. The results demonstrate that Cx43 is present in the native phosphorylated species in day 8.5 hearts and thereafter. Further, the activities of cAMP-dependent protein kinase and protein kinase C are mirror images of each other during the 8.5-10.5 days of early heart development. From these results we conclude that Cx43 gap junction channels are present and capable of being regulated by day 8.5 of embryonic heart development.

Amino Acid Sequence↗
PubMed1999

Systematic analysis of deficits in visual attention.

A variety of impairments in visual attention can follow damage to the brain. The authors develop systematic methods for analyzing such impairments in terms of C. Bundesen's (1990) Theory of Visual Attention and apply these in a group of 9 patients with parietal lobe lesions and variable spatial neglect. In whole report, patients report letters from brief, vertical arrays in left or right visual field. The results show substantial, largely bilateral impairments in processing capacity, implying a major nonlateralized aspect to neglect. In partial report, arrays contain 1 or 2 letters in red and/or green. The task is to report only those letters in a specified target color. In addition to the expected bias against left-sided letters, patients show striking, bilateral preservation of top-down control, or attentional priority for targets. The results show how differentiation of attentional impairments can be informed by a theory of normal function.

Aged↗
PubMed1999

Vascular surgical society of great britain and ireland: scottish audit of surgical mortality, 1997

BACKGROUND: A national audit of surgical deaths can be seen as the final step in what has been termed the 'journey of care' for both the individual patient and for the population as a whole. METHODS: The Scottish Audit of Surgical Mortality (SASM) examines all hospital deaths in Scotland occurring while under the care of a surgical specialist and all deaths within 30 days of an operation. RESULTS: Compliance for the completion of forms relating to vascular deaths during the first 4 years of the SASM (1994-1997) has remained over 92 per cent. In 1997 the compliance was 97 per cent. These figures compare favourably with the other surgical specialties where the overall compliance for 1997 was 92 per cent. Some 14 per cent of the 4408 deaths reported in 1997 occurred in patients admitted with vascular disease, the majority (83 per cent) being emergency admissions. Of these 507 vascular deaths, 293 were postoperative; the remaining 214 patients did not undergo operation. This represents an improvement over the years 1994-1996 when vascular deaths numbered 554, 573 and 524 respectively. The mean age of the patients who died from vascular disease in 1997 was 73 (range 19-92) years. A consultant surgeon made the decision to operate in 98 per cent of the patients with vascular disease who died at operation and was the principal surgeon in 70 per cent of cases. Vascular consultants carried out a higher percentage of operations than their counterparts in other surgical specialties (general surgery, 63 per cent; mean for other subspecialties, 60 per cent). In the non-operative group of vascular deaths in 1997, a vascular consultant was in charge in 66 per cent of cases; the figure for operated cases was 87 per cent. Adverse factors were believed to contribute to death in 10 per cent of cases, but were considered a direct cause of death in fewer than 1 per cent. CONCLUSION: These figures reflect the high quality of vascular services in Scotland, where there is a considerable consultant presence in the management of high-risk patients. This consultant involvement is higher than in other subspecialties and, bearing in mind the high percentage of emergencies, has significant resource implications for the delivery of vascular services.

Journal Article↗
PubMed1999

Best practice guidelines for the management of women with epilepsy. The Women with Epilepsy Guidelines Development Group.

Clinical guidelines for the treatment of epilepsy have been published. A statement on management issues for women with epilepsy has recently been produced by the American Academy of Neurology which has raised awareness of the issues facing women with epilepsy. The communication presented here aims to review current literature on specific issues relating to women with epilepsy, and proposes graded recommendations for its management within a UK health care framework.

Abnormalities, Drug-Induced↗