PubMed Health⌕ Search

Biomedical subjects

M Gillespie

Publications and source records attributed to M Gillespie.

At least 19 recordsLinked to original sources
PubMed2005

Reactome: a knowledgebase of biological pathways.

Reactome, located at http://www.reactome.org is a curated, peer-reviewed resource of human biological processes. Given the genetic makeup of an organism, the complete set of possible reactions constitutes its reactome. The basic unit of the Reactome database is a reaction; reactions are then grouped into causal chains to form pathways. The Reactome data model allows us to represent many diverse processes in the human system, including the pathways of intermediary metabolism, regulatory pathways, and signal transduction, and high-level processes, such as the cell cycle. Reactome provides a qualitative framework, on which quantitative data can be superimposed. Tools have been developed to facilitate custom data entry and annotation by expert biologists, and to allow visualization and exploration of the finished dataset as an interactive process map. Although our primary curational domain is pathways from Homo sapiens, we regularly create electronic projections of human pathways onto other organisms via putative orthologs, thus making Reactome relevant to model organism research communities. The database is publicly available under open source terms, which allows both its content and its software infrastructure to be freely used and redistributed.

Animals↗
PubMed2005

Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study.

OBJECTIVE: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). METHODS: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). RESULTS: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. CONCLUSIONS: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

Aged↗
PubMed2005

Mortality of geese as a result of collision with the ground.

Two incidents are reported in which groups of migrating wild geese were found dead in agricultural fields in southern Manitoba during spring. In each case, the birds died overnight and poisoning was suspected; however, the birds had lesions of severe traumatic injury. The first incident, in 1985, involved about 150 lesser snow geese (Anser caerulescens caerulescens); the second, in 2003, involved 62 Canada geese (Branta canadensis). Both incidents occurred on dark, moonless nights. One possible explanation is that the birds became disoriented in a manner analogous to spatial disorientation described in aircraft pilots and flew as a flock directly into the earth. In the first incident, geese might have been frightened by sonic booms from aircraft; in the second, there was a thunderstorm with strong gusty winds in the area.

Animals↗
PubMed2003

Adenosine A(2A) receptor antagonist treatment of Parkinson's disease.

BACKGROUND: Observations in animal models suggest that A(2A) antagonists confer benefit by modulating dopaminergic effects on the striatal dysfunction associated with motor disability. This double-blind, placebo-controlled, proof-of-principle study evaluated the pathogenic contribution and therapeutic potential of adenosine A(2A) receptor-mediated mechanisms in Parkinson disease (PD) and levodopa-induced motor complications. METHODS: Fifteen patients with moderate to advanced PD consented to participate. All were randomized to either the selective A(2A) antagonist KW-6002 or matching placebo capsules in a 6-week dose-rising design (40 and 80 mg/day). Motor function was rated on the Unified PD Rating Scale. RESULTS: KW-6002 alone or in combination with a steady-state IV infusion of each patient's optimal levodopa dose had no effect on parkinsonian severity. At a low dose of levodopa, however, KW-6002 (80 mg) potentiated the antiparkinsonian response by 36% (p < 0.02), but with 45% less dyskinesia compared with that induced by optimal dose levodopa alone (p < 0.05). All cardinal parkinsonian signs improved, especially resting tremor. In addition, KW-6002 prolonged the efficacy half-time of levodopa by an average of 47 minutes (76%; p < 0.05). No medically important drug toxicity occurred. CONCLUSIONS: The results support the hypothesis that A(2A) receptor mechanisms contribute to symptom production in PD and that drugs able to selectively block these receptors may help palliate symptoms in levodopa-treated patients with this disorder.

Adenosine A2 Receptor Antagonists↗
PubMed2002

Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.

OBJECTIVE: To examine the acute effects of the NMDA receptor antagonist amantadine on motor and cognitive function in Huntington's disease (HD). BACKGROUND: Chorea in HD and in the levodopa-induced dyskinesias of PD may be clinically indistinguishable. In PD, hyperphosphorylation of NMDA receptors expressed on striatal medium spiny neurons contributes to peak-dose dyskinesias, and drugs that block these receptors can diminish chorea severity. Because these spiny neurons are the primary target of the neurodegenerative process in HD, sensitization of NMDA receptors on residual striatal neurons might also participate in the generation of motor dysfunction in HD. METHODS: To evaluate this possibility, 24 patients with HD entered a double-blind placebo-controlled crossover study of amantadine with two 2-week arms. RESULTS: Chorea scores were lower with amantadine (usually 400 mg/d) than placebo, with a median reduction in extremity chorea at rest of 36% (p = 0.04) for all 22 evaluable patients and of 56% in the 10 individuals with the highest plasma drug levels. Improvement correlated with plasma amantadine concentrations (p = 0.01) but not CAG repeat length. Parkinsonian rating scores did not worsen and there was no consistent change in cognitive measures. Adverse event profile was benign. CONCLUSIONS: Results suggest that NMDA receptor supersensitivity may contribute to the clinical expression of choreiform dyskinesias in HD and that selective antagonists at that site can safely confer palliative benefit.

Adult↗
PubMed2001

Bupropion overdose: a potential problem with the new 'miracle' anti-smoking drug.

Bupropion (Zyban) has recently been launched in the UK as an aid to smoking cessation. As a result of the considerable publicity, there has been unprecedented demand for this new drug in primary care. Within a few weeks of its launch, four patients presented to our A&E department having taken bupropion as an intentional overdose. Three recovered with simple supportive measures; one one was critically ill and required admission to the intensive care unit. There are several case reports on bupropion overdose in the US but none so far in the UK.

Adolescent↗
PubMed2000

Chronic intermittent stimulation of the thyroarytenoid muscle maintains dynamic control of glottal adduction.

Patients with laryngeal motor control disorders need improved dynamic glottal closure for speech and swallowing. To evaluate the functional outcome of intermittent chronic thyroarytenoid muscle stimulation in an animal model, 6 canines were implanted with bilateral Medtronic Xtrel systems containing Peterson-type electrodes in the inferior and superior portions of the thyroarytenoid muscle. Stimulation was on one side only at 60 Hz, for 5 s on and 5 s off, over 8 h, 5 days per week, up to 8 months. Monthly videorecordings were done under anesthesia to measure the voltage threshold for detectable movement on each side, and vocal fold displacement and velocity during maximal stimulation of each side. Movement thresholds were lower in the inferior portion of the thyroarytenoid muscle (P </= 0.0005). Movement velocity was greater on the stimulated than on the nonstimulated side after 3 to 8 months (P = 0.039). No differences in the percentage distribution of different myosin heavy chain types were found between the stimulated and nonstimulated muscle samples. Sustained dynamic glottal adduction with no alteration in thyroarytenoid muscle function or fiber type was achieved with intermittent stimulation over 8 months. The results suggest that chronic intermittent thyroarytenoid stimulation has good potential for improving airway protection in dysphagia.

Animals↗
PubMed2000

Role of hypertension, diabetes, obesity, and race in the development of symptomatic myocardial dysfunction in a predominantly minority population with normal coronary arteries.

BACKGROUND: Hypertension, diabetes, and obesity have been reported as risk factors for both vascular and myocardial disease. Myocardial disease may be manifest as systolic or diastolic dysfunction. The development of coronary artery disease frequently obscures or confounds the myocardial disease. Our purpose was to study the effect of these risk factors and race on the frequency and severity of myocardial disease in the absence of coronary artery disease. METHODS AND RESULTS: We studied patients referred to the cardiac catheterization laboratory. We selected 233 patients with normal coronary arteries and excluded patients with other structural cardiac disorders and other causes of myocardial disease. Systolic function and diastolic function were determined. We gathered demographic, risk factor, clinical, and hemodynamic data on each patient. A multivariate analysis was performed to determine factors important to the development of myocardial disease in the absence of coronary artery disease. Diastolic dysfunction (44%) and systolic dysfunction (25%) were common findings. The 3 risk factors were found most often in black and Hispanic patients, but hypertension and obesity were most severe (P <.001) in black patients. Multivariate analysis indicated that a prior diagnosis of hypertension, level of systolic blood pressure, and severe obesity were the 3 factors independently associated with myocardial disease. CONCLUSIONS: Systolic dysfunction and diastolic dysfunction are common in patients with normal coronary arteries who have hypertension, diabetes, and/or obesity. Because these risk factors are so frequent and severe in the black population, myocardial disease is significantly more common in this segment of the population.

Black or African American↗
PubMed1999

Laryngeal long latency response conditioning in abductor spasmodic dysphonia.

Previously, we demonstrated that patients with adductor spasmodic dysphonia (ADSD) have a disinhibition of laryngeal responses to sensory input. In this study, sensorimotor responses to stimulation of the superior laryngeal nerve were compared between 10 subjects with abductor spasmodic dysphonia (ABSD) and 15 normal volunteers. The groups had similar latency and frequency characteristics of their unconditioned adductor responses (p>.05). The conditioned R1 (early) responses of the subjects with ABSD were greater and more variable in amplitude than those of the normal volunteers (p< or =.008). Similar R2 (late) conditioning effects were found in both groups, with a nonsignificant trend toward reduced inhibition of contralateral R2 responses at lower interstimulus intervals (p = .01) in the patient group. Thus, inhibitory mechanisms that modulate the R1 laryngeal sensorimotor pathway in the brain stem may be abnormal in subjects with ABSD. Abnormal modulation of laryngeal sensorimotor responses seems present in both types of spasmodic dysphonia.

Adult↗
PubMed1998

Type II SLAP lesions: three subtypes and their relationships to superior instability and rotator cuff tears.

One hundred two type II SLAP lesions without associated anterior instability, Bankart lesion, or anterior inferior labral pathology were surgically treated under arthroscopic control. There were three distinct type II SLAP lesions based on anatomic location: anterior (37%), posterior (31%), and combined anterior and posterior (31%). Preoperatively, the Speed and O'Brien tests were useful in predicting anterior lesions, whereas the Jobe relocation test was useful in predicting posterior lesions. Rotator cuff tears were present in 31% of patients and were found to be lesion-location specific. In posterior and combined anterior-posterior lesions, a drive-through sign was always present (despite absence of anterior-inferior labral pathology or a Bankart lesion) and was eliminated by repair of the posterior component of the SLAP lesion. We conclude that SLAP lesions with a posterior component develop posterior-superior instability that manifests itself by a secondary anterior-inferior pseudolaxity (drive-through sign), and that chronic superior instability leads to secondary lesion-location-specific rotator cuff tears that begin as partial thickness tears from inside the joint.

Adolescent↗
PubMed1997

Lung angiotensin receptor binding characteristics during the development of monocrotaline-induced pulmonary hypertension.

Alterations in lung angiotensin converting enzyme (ACE) activity in monocrotaline (MCT)-induced pulmonary hypertension in rats have suggested a pathophysiologic role for angiotensin II (AII) in pulmonary vascular remodeling. ACE inhibitors suppress MCT-induced pulmonary hypertension; however, losartan, an angiotensin type 1 (AT1) receptor antagonist, was without impact. The present study examined AII receptor binding characteristics by radioligand binding during the development of MCT-induced pulmonary hypertension. Saturation binding isotherms for [125I]AII binding to membrane preparations from rat lung were performed at 4, 10, and 21 days following a single injection of MCT (60 mg/kg) or saline vehicle. Right ventricular hypertrophy, an index of pulmonary hypertension, increased at 21 days post-MCT. Saturation binding isotherms revealed a single, high affinity site for [125I]AII binding in lung membranes from MCT-treated and control rats, with no change in receptor affinity or density during the development of pulmonary hypertension. Competition displacement binding demonstrated that the AT1 receptor predominates in lung membranes from control rats, with no alterations in AII receptor subtype distribution following MCT treatment. In summary, these results suggest that the AT1 receptor subtype predominates in rat lung and does not contribute to the development of MCT-induced pulmonary hypertension.

Angiotensin Receptor Antagonists↗
PubMed1996

Consumption of deoxynivalenol-contaminated wheat by mallard ducks under experimental conditions.

Captive mallards (Anas platyrhynchos) were fed wheat containing 5.8 ppm deoxynivalenol (DON, vomitoxin) from an outbreak of Fusarium graminearium head-blight that occurred on grain crops in Manitoba, Canada, during 1993. There was no evidence of taste aversion to this grain during a 10-day palatability trial. No significant differences were detected in serum protein, calcium, glucose, creatinine kinase, aspartate aminotransferase or uric acid levels, blood packed cell volume, or body or organ weight, between ducks fed contaminated wheat and those fed uncontaminated wheat during a 14-day feeding trial. No gross or microscopic lesions were detected in birds fed contaminated wheat for 14 days. Based on these results, ducks will consume grain containing moderate levels of DON and short-term exposure to this grain will not result in obvious adverse effects.

Analysis of Variance↗
PubMed1995

Rescue of the fission yeast snRNA synthesis mutant snm1 by overexpression of the double-strand-specific Pac1 ribonuclease.

The Schizosaccharomyces pombe temperature-sensitive mutant snm1 maintains reduced steady-state quantities of the spliceosomal small nuclear RNAs (snRNAs) and the RNA subunit of the tRNA processing enzyme RNase P. We report here the isolation of the pac1+ gene as a multi-copy suppressor of snm1. The pac1+ gene was previously identified as a suppressor of the ran1 mutant and by its ability to cause sterility when overexpressed. The pac1+ gene encodes a double-strand-specific ribonuclease that is similar to RNase III, an RNA processing and turnover enzyme in Escherichia coli. To investigate the essential structural features of the Pac1 RNase, we altered the pac1+ gene by deletion and point mutation and tested the mutant constructs for their ability to complement the snm1 and ran1 mutants and to cause sterility. These experiments identified four essential amino acids in the Pac1 sequence: glycine 178, glutamic acid 251, and valines 346 and 347. These amino acids are conserved in all RNase III-like proteins. The glycine and glutamic acid residues were previously identified as essential for E. coli RNase III activity. The valines are conserved in an element found in a family of double-stranded RNA binding proteins. Our results support the hypothesis that the Pac1 RNase is an RNase III homolog and suggest a role for the Pac1 RNase in snRNA metabolism.

Amino Acid Sequence↗
PubMed1994

Cytokines and metabolic dysfunction after severe head injury.

Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect organ function, cause a systemic response to injury, and may cause secondary tissue injury. The metabolites involved in this cascade are numerous and complex. Cytokines are important cell-to-cell communication mediators during injury. It is speculated that cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and interleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular cascade of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutrophilia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, increased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokines have also been implicated in organ failure. Infusion of cytokines in basic science trials revealed that organ functions of the gut, liver, and lung are negatively altered by high-dose cytokine infusion. Infusion of certain cytokines has been shown to cause death of brain cells, increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by decreasing serum cytokine activity. We hypothesize that cytokines that are elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise.

Animals↗
PubMed1993

Molecular deletion of 9p sequences in non-small cell lung cancer and malignant mesothelioma.

Previously we have reported non-random cytogenetic abnormalities involving the short arm of chromosome 9 (9P) in the majority of primary non-small cell lung cancer (NSCLC) patient samples, which indicated loss of DNA sequences. In another lung tumor, pleural malignant mesothelioma (MM), cytogenetic changes also include apparent deletions of 9p. To define the location and extent of deletions of 9p in NSCLC and MM, Southern blot analyses on six NSCLC and five MM cell lines using molecular probes to 9p loci (IFNA, IFNB1, D9S3, and D9S19) were performed, and DNA dosage was determined by densitometry. Our data demonstrated reduced dosage of 9p sequences in three of six NSCLC and four of five MM lines. A homozygous deletion of D9S3 was found in one NSCLC and one MM cell line. The region of common loss overlapped the D9S3 locus and was flanked by the IFNB1 and D9S19 loci. IFNB as previously been localized to 9p22, and the D9S3 and D9S19 loci have been mapped in this study by in situ hybridization to 9p21 and 9p13, respectively. We hypothesize the existence of one or more tumor suppressor genes on 9p with a role in the development or progression of NSCLC and MM.

Blotting, Southern↗
PubMed1992

Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease.

Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients with Parkinson's disease. In comparison with age-matched controls, no consistent abnormality could be discerned in complex I, complex II-III, or complex IV oxygen consumption, or in the enzyme activity of these respiratory chain complexes. Neither chronic therapy with levodopa/carbidopa alone nor in combination with deprenyl significantly affected any measure of mitochondrial respiratory function. There was no discernible relationship between patient age or disease severity and any parameter of mitochondrial respiration. Moreover, blood lactate levels following glucose loading were not different in patients and controls. These results fail to support the occurrence of a generalized defect in any mitochondrial respiratory function in Parkinson's disease.

Age Factors↗