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Biomedical subjects

S Kelly

Publications and source records attributed to S Kelly.

At least 19 recordsLinked to original sources

Transplantation of hNT neurons into the ischemic cortex: cell survival and effect on sensorimotor behavior.

Cell transplantation offers a potential new treatment for stroke. Animal studies using models that produce ischemic damage in both the striatum and the frontal cortex have shown beneficial effects when hNT cells (postmitotic immature neurons) were transplanted into the ischemic striatum. In this study, we investigated the effect of hNT cells in a model of stroke in which the striatum remains intact and damage is restricted to the cortex. hNT cells were transplanted into the ischemic cortex 1 week after stroke induced by distal middle cerebral artery occlusion (dMCAo). The cells exhibited robust survival at 4 weeks posttransplant even at the lesion border. hNT cells did not migrate, but they did extend long neurites into the surrounding parenchyma mainly through the white matter. Neurite extension was predominantly toward the lesion in ischemic animals but was bidirectional in uninjured animals. Extension of neurites through the cortex toward the lesion was also seen when there was some surviving cortical tissue between the graft and the infarct. Prolonged deficits were obtained in four tests of sensory-motor function. hNT-transplanted animals showed a significant improvement in functional recovery on one motor test, but there was no effect on the other three tests relative to control animals. Thus, despite clear evidence of graft survival and neurite extension, the functional benefit of hNT cells after ischemia is not guaranteed. Functional benefit could depend on other variables, such as infarct location, whether the cells mature, the behavioral tests employed, rehabilitation training, or as yet unidentified factors.

Analysis of Variance↗

Impact of the 1998 Gobi dust event on hospital admissions in the Lower Fraser Valley, British Columbia.

The adverse public health impacts of anthropogenically derived particulate matter have been well documented, with measurable increases in both morbidity and mortality rates associated with high particulate matter pollution events. Most current research has focussed on the health impacts of anthropogenically derived particulate matter, and there is a distinct scarcity of literature that examines the role of naturally derived particulate matter and adverse health impacts in the urban context. This study of a Gobi desert dust event in the Greater Vancouver region of British Columbia, Canada, in spring of 1998 provided a unique opportunity to identify the adverse health effects related to naturally derived particulate matter in a large urban setting. Respiratory and cardiac hospitalizations were examined for a three-year period (January 1997 to December 1999), with the Gobi dust event occurring in late April 1998. A meteorological analogue was identified for spring 1997 in order to identify the public health impacts associated with anthropogenically derived particulate matter and those impacts associated with the presence of the Gobi desert dust. Results indicate that this Gobi dust event was not associated with an excess of hospitalizations in the Greater Vancouver region. Peak particulate matter concentrations of Gobi desert dust in the airshed were only associated with an additional one or two hospitalizations per 100,000 population for respiratory and cardiac illnesses, and these increases were not distinguishable from the 'normal' variability in hospitalization rates. Despite high particulate matter concentrations, fine particle size, presence of heavy metals in the dust and extended exposure periods, it appears that the Gobi desert dust event was not associated with significant risk to public health in Greater Vancouver, British Columbia. Therefore it is concluded that naturally derived particulate matter is more benign than particulate matter of anthropogenic origin, and thus poses a low risk to health for the general public.

Air Pollutants↗

Characterization and differential nuclear localization of Nopp140 and a novel Nopp140-like protein in trypanosomes.

Trypanosomatids possess two homologues of Nopp140: a canonical Nopp140 and a Nopp140-like protein (TbNoLP) in which a GAR domain replaces the C-terminal SRP40 domain. Both are phosphorylated and coimmunoprecipitate with RNA polymerase I. Each paralogue has a distinct subnuclear localization, and depletion of TbNoLP produces an enlarged nucleolus in which TbNopp140-containing regions disperse. The restricted occurrence pattern of NoLP proteins reflects an intriguing convergence in evolution, suggestive of a function in nucleoplasmic small nucleolar ribonucleoprotein shuttling.

Amino Acid Sequence↗

Influence of mechanical stress and surface interaction on the aggregation of Aspergillus niger conidia.

Productivity of fungal cultures is closely linked with their morphologic development. Morphogenesis of coagulating filamentous fungi, like Aspergillus niger, starts with aggregation of conidia, also denominated as spores. Several parameters are presumed to control this event, but little is known about their mode of action. Rational process optimization requires models that mirror the underlying reaction mechanisms. An approach in this regard is suggested and supported by experimental data. Aggregation kinetics was examined for the first 15 h of cultivation under different cultivation conditions. Mechanical stress was considered as well as pH-dependent surface interaction. Deliberations were based on a two-step aggregation mechanism. The first aggregation step is only affected by the pH-value, not by the fluid dynamic conditions in the bioreactor. The second aggregation step, in contrast, depends on the pH-value as well as on agitation and aeration induced power input. For the given experimental set-up, agitation had much more influence than aeration. In addition, hyphal growth rate was determined to be the driving force for the second aggregation step.

Aspergillus niger↗

Morphology and productivity of filamentous fungi.

Cultivation processes involving filamentous fungi have been optimised for decades to obtain high product yields. Several bulk chemicals like citric acid and penicillin are produced this way. A simple adaptation of cultivation parameters for new production processes is not possible though. Models explaining the correlation between process-dependent growth behaviour and productivity are therefore necessary to prevent long-lasting empiric test series. Yet, filamentous growth consists of a complex microscopic differentiation process from conidia to hyphae resulting in various macroscopically visible appearances. Early approaches to model this morphologic development are recapitulated in this review to explain current trends in this area of research. Tailoring morphology by adjusting process parameters is one side of the coin, but an ideal morphology has not even been found. This article reviews several reasons for this fact starting with nutrient supply in a fungal culture and presents recent advances in the investigation of fungal metabolism. It illustrates the challenge to unfold the relationship between morphology and productivity.

Acremonium↗

Interventions for preventing obesity in children.

BACKGROUND: Obesity prevention is an international public health priority. The prevalence of obesity and overweight is increasing in child populations throughout the world, impacting on short and long-term health. Obesity prevention strategies for children can change behaviour but efficacy in terms of preventing obesity remains poorly understood. OBJECTIVES: To assess the effectiveness of interventions designed to prevent obesity in childhood through diet, physical activity and/or lifestyle and social support. SEARCH STRATEGY: MEDLINE, PsycINFO, EMBASE, CINAHL and CENTRAL were searched from 1990 to February 2005. Non-English language papers were included and experts contacted. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials with minimum duration twelve weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Twenty-two studies were included; ten long-term (at least 12 months) and twelve short-term (12 weeks to 12 months). Nineteen were school/preschool-based interventions, one was a community-based intervention targeting low-income families, and two were family-based interventions targeting non-obese children of obese or overweight parents. Six of the ten long-term studies combined dietary education and physical activity interventions; five resulted in no difference in overweight status between groups and one resulted in improvements for girls receiving the intervention, but not boys. Two studies focused on physical activity alone. Of these, a multi-media approach appeared to be effective in preventing obesity. Two studies focused on nutrition education alone, but neither were effective in preventing obesity. Four of the twelve short-term studies focused on interventions to increase physical activity levels, and two of these studies resulted in minor reductions in overweight status in favour of the intervention. The other eight studies combined advice on diet and physical activity, but none had a significant impact. The studies were heterogeneous in terms of study design, quality, target population, theoretical underpinning, and outcome measures, making it impossible to combine study findings using statistical methods. There was an absence of cost-effectiveness data. AUTHORS' CONCLUSIONS: The majority of studies were short-term. Studies that focused on combining dietary and physical activity approaches did not significantly improve BMI, but some studies that focused on dietary or physical activity approaches showed a small but positive impact on BMI status. Nearly all studies included resulted in some improvement in diet or physical activity. Appropriateness of development, design, duration and intensity of interventions to prevent obesity in childhood needs to be reconsidered alongside comprehensive reporting of the intervention scope and process.

Adolescent↗

Evaluation of endometrial receptivity during in-vitro fertilization using three-dimensional power Doppler ultrasound.

OBJECTIVE: To compare sonographic endometrial characteristics in in-vitro fertilization (IVF) cycles between women who conceive and those who do not. METHODS: Thirty-five women undergoing IVF treatment participated in the study. Using three-dimensional (3D) power Doppler ultrasound, we assessed endometrial patterns, volume and vascularization, after follicle stimulating hormone (FSH) stimulation but before human chorionic gonadotropin (hCG) administration (referred to hereafter as 'after FSH stimulation') and again on the day of oocyte retrieval. RESULTS: The pregnancy rate was 37% (13/35). After FSH stimulation, 29 of the 35 women had a triple-line endometrial pattern, compared with five out of 35 on the day of oocyte retrieval. In those who had a triple-line pattern after FSH stimulation the pregnancy rate was 44.8% (13/29) and it was 0% (0/6) in those with a homogeneous pattern (chi-square test, P = 0.039). If a triple-line pattern was present on the day of oocyte retrieval the pregnancy rate was 80.0% (4/5), whereas if the pattern was homogeneous the pregnancy rate was 30.0% (9/30) (P = 0.032). There were no differences between those who conceived and those who did not in endometrial thickness, volume or vascularization on either day examined. Endometrial volume decreased significantly after hCG injection in women who conceived, but not in those who did not conceive. In both groups endometrial and subendometrial vascularization decreased after hCG injection, while the endometrial thickness remained unchanged. CONCLUSIONS: The existence of a homogeneous endometrial pattern after FSH stimulation seems to be a prognostic sign of an adverse outcome in IVF, while a triple-line pattern after FSH stimulation and a decrease in endometrial volume appear to be associated with conception.

Adult↗

An in silico analysis of trypanosomatid RNA polymerases: insights into their unusual transcription.

African trypanosomes employ both Pol I (RNA polymerase I) and Pol II to transcribe protein-coding genes in large polycistronic units of up to 50 genes. Subsequent processing produces mature capped mRNAs. Evidence suggests that regulation of gene expression is primarily exerted post-transcriptionally. Here, we use the recently completed genome sequences of three trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, in an in silico analysis of their fundamental RNA polymerase complexes. The core complement of Pol II subunits, including those that are shared with Pol I and Pol III are present. However, both Pol I and Pol III complexes are missing members of the rpoE-rpoF subunit groups. Out of the five shared subunits, both RPB5 and RPB6 have two isoforms in the three trypanosomes. One represents the canonical polymerase subunit and the other differs by insertion or deletion of stretches of charged residues. We propose that these alternative isoforms function in distinct polymerase complexes, and may influence recruitment of the trypanosome RPB4-RPB7 heterodimer.

Animals↗

Low glycaemic index diets for coronary heart disease.

BACKGROUND: The glycaemic index (GI) is a physiological measure of the ability of a carbohydrate to affect blood glucose. Interest is growing in the low GI carbohydrate concept for the clinical management of people at risk of, or with established coronary heart disease. There is a need to review the current evidence from controlled trials in this area. OBJECTIVES: The primary objective is to review the current evidence from RCTs that assess the relationship between the consumption of low glycaemic index diets and the effects on coronary heart disease and on risk factors for coronary heart disease. SEARCH STRATEGY: We searched CENTRAL (Issue 4, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and CINAHL (1982 to 2003). We also contacted experts in the field. SELECTION CRITERIA: We selected randomised controlled trials that assessed the effects of low glycaemic index diets, over a minimum of 4 weeks, on coronary heart disease (CHD) and risk factors. Participants included were adults who carry at least one major risk factor for coronary heart disease such as abnormal lipids, diabetes or being overweight. DATA COLLECTION AND ANALYSIS: Two of our research team independently assessed trial quality and extracted data. Authors of the included studies were contacted for additional information when this was appropriate. MAIN RESULTS: Fifteen randomised controlled trials met the inclusion criteria. No studies found reported the effect of low glycaemic index diets on CHD mortality or CHD events and morbidity. All fifteen included studies report the effect of low glycaemic index diets on major risk factors for CHD. Meta-analysis detected limited and weak evidence of a relationship between low glycaemic index diets and slightly lower total cholesterol, compared with higher glycaemic index diets. There is also limited and weak evidence of a small reduction in HbA1c after 12 weeks on low glycaemic index diets but not at 4 to 5 weeks. There is no evidence that low glycaemic index diets have an effect on LDL cholesterol or HDL cholesterol, triglycerides, fasting glucose or fasting insulin levels. REVIEWERS' CONCLUSIONS: The evidence from randomised controlled trials showing that low glycaemic index diets reduces coronary heart disease and CHD risk factors is weak. Many of the trials identified were short-term, of poor quality and conducted on small sample sizes. There is a need for well designed, adequately powered, randomised controlled studies, of greater than 12 weeks duration to assess the effects of low glycaemic index diets for CHD.

Blood Glucose↗

Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex.

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances ( approximately 1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker beta-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

Animals↗

Kinetic studies on the aggregation of Aspergillus niger conidia.

Morphology has a crucial effect on productivity and the supply of substrate for cultures of filamentous fungi. However, cultivation parameters leading to the desired morphology are often chosen empirically as the mechanisms governing the processes involved are usually unknown. For coagulating microorganisms like Aspergillus niger the morphological development is considered to start with the aggregation of conidia right after inoculation. To elucidate the mechanism of this process, kinetic studies were carried out using an in-line particle size analyzer. Based on the data obtained from these experiments a model for conidial aggregation is proposed in this article. It consists of two separate aggregation steps. The first one takes place immediately after inoculation, but only leads to a small decrease of total particle concentration. Most suspended conidia aggregate after a second aggregation step triggered by germination and hyphal growth. Aggregation velocity of this second phase is linearly dependent on the particle growth rate.

Algorithms↗

L-arginine transport in the human coronary and peripheral circulation.

BACKGROUND: Nitric oxide synthase (NOS) uses arginine for the production of nitric oxide (NO). High intracellular concentrations of arginine suggest that NOS activity should be independent of plasma arginine supply. However, under certain conditions, increased plasma arginine concentrations appear to be associated with increased NOS activity. The purpose of this study was to explore arginine transport within the human coronary and peripheral circulation METHODS AND RESULTS: Mass-labeled 15N2-arginine was infused to steady state before cardiac catheterization in 31 patients. After diagnostic angiography, a catheter was placed in the coronary sinus. The transcardiac concentration gradient (aorta-coronary sinus) of 15N2-arginine was used as a measure of arginine transport at baseline and during infusions of acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA). No gradient was detected at rest. During the infusion of acetylcholine, a significant gradient was detected (2.5+/-1.2 micromol/L, P=0.01) corresponding to a fractional extraction of 11.7+/-7.5%. This is consistent with in vitro studies that suggest that stimulation of NOS induces arginine transport. During the infusion of L-NMMA, the concentration of 15N2-arginine increased in the coronary sinus, producing a gradient of -3.9+/-1.3 micromol/L (P=0.0002), corresponding to a fractional production of 20.5+/-5.0%. This is consistent with in vitro studies that suggest that L-NMMA induces the efflux of arginine from the cell to the extracellular space via transporter-mediated transstimulation. CONCLUSIONS: The use of steady-state 15N2-arginine to examine transorgan L-arginine gradients represents a novel tool for the study of L-arginine transport and the mechanisms of endothelial and NOS dysfunction.

Acetylcholine↗

The remineralizing effect of an essential oil fluoride mouthrinse in an intraoral caries test.

BACKGROUND: The authors conducted a two-week clinical study to determine the remineralizing effect of an experimental mouthrinse containing both fluoride and essential oils in an intraoral caries test model. METHODS: The study used an observer-blinded, randomized, controlled, 3 x 3 crossover design. The authors enrolled in the study 153 subjects, each of whom had a mandibular removable partial denture. Two partially demineralized human enamel specimens were mounted on each subject's removable partial denture. Subjects used either a fluoride mouthrinse with essential oils (the test mouthrinse), a fluoride nonessential oils mouthrinse (the positive control) or an essential oil nonfluoride mouthrinse (the negative control) twice daily for 14 days. The researchers assessed specimens for mineral content change and fluoride uptake using surface microhardness, or SMH, testing and enamel fluoride analysis, respectively. RESULTS: Of the 153 subjects enrolled in the study, 125 subjects were evaluable at the study endpoint. The results after two weeks showed that percentage of SMH recovery was 42 percent in the test group, 36 percent in the positive control group and 16 percent in the negative control group. The fluoride uptake was 19 micrograms per square centimeter, 16 microg/cm2 and 3 microg/cm2 for the test mouthrinse, positive control and negative control groups, respectively. In terms of both percentage of SMH and fluoride uptake, the test mouthrinse and positive control mouthrinse were statistically higher than the negative control mouthrinse, and the test mouthrinse was "at least as good as" the positive control mouthrinse. CONCLUSIONS: This study provides evidence that an essential oil mouthrinse with 100 parts per million fluoride is effective in promoting enamel remineralization and fluoride uptake. CLINICAL IMPLICATIONS: The combination of fluoride and essential oils in a mouthrinse may provide anticaries efficacy, in addition to essential oils' previously established antigingivitis efficacy.

Cariostatic Agents↗

Interventions for treating obesity in children.

BACKGROUND: The prevalence of overweight and obesity is increasing in child populations throughout the world. Obesity in children has significant short and long term health consequences. OBJECTIVES: To assess the effects of a range of lifestyle interventions designed to treat obesity in childhood. SEARCH STRATEGY: We searched CCTR, MEDLINE, EMBASE, CINAHL, PsychLIT, Science Citation Index, Social Science Citation Index. Each database was searched from 1985 to July 2001. We also contacted experts in child obesity treatment. SELECTION CRITERIA: We selected randomised controlled trials of lifestyle interventions for treating obesity in children with a minimum of six months duration. Examples of lifestyle interventions include dietary, physical activity and/or behavioural therapy interventions, with or without the support of associated family members. Interventions from any setting and delivered by any professional were considered. However, interventions that specifically dealt with the treatment of eating disorders were excluded. DATA COLLECTION AND ANALYSIS: Two of our research team independently assessed trial quality and extracted data. Authors of the included studies were contacted for additional information where this was appropriate. MAIN RESULTS: We included 18 randomised controlled trials with 975 participants. Many studies were run from a specialist obesity clinic within a hospital setting. Five studies (n=245 participants) investigated changes in physical activity and sedentary behaviour. Two studies (n=107 participants) compared problem-solving with usual care or behavioural therapy. Nine studies (n=399 participants) compared behavioural therapy at varying degrees of family involvement with no treatment or usual care or mastery criteria and contingent reinforcement. Two studies (n=224 participants) compared cognitive behavioural therapy with relaxation.Most of the studies included in this review were too small to have the power to detect the effects of the treatment. We did not conduct a meta-analysis since so few of the trials included the same comparisons and outcomes. Therefore, we synthesised the results in a narrative format. REVIEWER'S CONCLUSIONS: Although 18 research studies were found, most of these were very small studies drawn from homogenous, motivated groups in hospital settings and so generalisable evidence from them is limited. In conclusion, there is a limited amount of quality data on the components of programs to treat childhood obesity that favour one program over another. Further research that considers psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care is required. We conclude that no direct conclusions can be drawn from this review with confidence.

Child↗