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Ian Miller

Publications and source records attributed to Ian Miller.

13 recordsLinked to original sources
PubMed2006

Molecular basis of cell-biomaterial interaction: insights gained from transcriptomic and proteomic studies.

With the growing interest in clinical interventions that involve medical devices, the role for new biomaterials in modern medicine is currently expanding at a phenomenal rate. Failure of most implant materials stems from an inability to predict and control biological phenomena, such as protein adsorption and cell interaction, resulting in an inappropriate host response to the materials. Contemporary advances in biological investigation are starting to shift focus in the biomaterials field, in particular with the advent of high-throughput methodologies for gene and protein expression profiling. Here, we examine the role that emerging transcriptomic and proteomic technologies could play in relation to biomaterial development and usage. Moreover, a number of studies are highlighted which have utilized such approaches in order to try to create a deeper understanding of cell-biomaterial interactions and, hence, improve our ability to predict and control the biocompatibility of new materials.

Biocompatible Materials↗
PubMed2006

Novel method to prepare morphologically rich polymeric surfaces for biomedical applications via phase separation and arrest of microgel particles.

We outline here a simple method to prepare polymeric surfaces of controlled surface topography on the micrometer scale, via assembly and arrest of microgel particles, for use in a range of biological applications to modify cell adhesion and spreading. In previous work by other groups, it has transpired that topography on the nanoscale is unlikely to be useful for this purpose, as roughness on this scale is often covered or coated by serum derived proteins during the early stages of cell adhesion and cells can easily bridge nanoscale roughness. Therefore, in our work, we have focused on roughness or topographic variations on the micrometer length scale. The basic idea is to modify the interactions between particles, thereby causing the microgel particles to phase separate into particle-dense and particle-dilute domains and to arrest these domains on the surface. The result is the creation of surfaces with controlled topography. By changing the particle size, it is possible to alter the size of the pores formed and their distribution in the film. Preliminary results show that the system can readily be arrested into a homologous series of such structures (formed from microgel particles of the same size and same chemical structure) with biological implications. At the extremes of this series, large phenotypic differences are observed between cells, ranging (at one end) from localization of the cells in the pores to (at the other end) cells that avoid such localization, and remain extended, growing along the ridges between the pores. This constitutes a sort of cell localization transition on a surface with identical chemical components, where only the morphology has been adjusted.

Acrylamides↗
PubMed2006

Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury.

RATIONALE: Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. OBJECTIVE: To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. METHODS: Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction. MEASUREMENTS AND MAIN RESULTS: In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. CONCLUSIONS: These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.

Animals↗
PubMed2006

Minimal incision for open thyroidectomy.

OBJECTIVES: To establish the incision length for thyroid surgery that optimizes access and cosmesis. STUDY DESIGN AND SETTING: Prospective study from January 2003 to June 2004. All thyroidectomies were included. Exclusion criteria were concomitant neck dissections, previous surgery, and those performed endoscopically. The first 40 cases were attempted through a 5 cm incision and the second 40 through a 4 cm incision. METHODS: In both groups, the size of the incision was compared with the thyroid's weight and histology. RESULTS: Two subtotal, 22 total, and 56 hemithyroidectomies were performed. In the first group, median gland weight was 39.5 gm and 62.5% of these were removed through a 5 cm incision. In the second group, median gland weight was 34 gm and 75% were removed through a 4 cm incision. CONCLUSION: A 4 cm incision provides adequate access for the majority of thyroidectomies in our cohort. SIGNIFICANCE: The minimal incision thyroidectomy is a useful addition to the thyroid surgeon's armamentarium. EBM RATING: B-3b.

Adult↗
PubMed2005

Assessing contributory risk using economic input-output life-cycle analysis.

The contribution of consumer purchases of non-essential products to environmental pollution is characterized. Purchase decisions by consumers induce a complex sequence of economy-wide production interactions that influence the production and consumption of chemicals and subsequent exposure and possible public health risks. An economic input-output life-cycle analysis (EIO-LCA) was used to link resource consumption and production by manufacturers to corresponding environmental impacts. Using the US Department of Commerce's input-output tables together with the US Environmental Protection Agency's Toxics Release Inventory and AIRData databases, the economy-wide air discharges resulting from purchases of household appliances, motor homes, and games and toys were quantified. The economic and environmental impacts generated from a hypothetical 10,000 US dollar purchase for selected consumer items were estimated. The analysis shows how purchases of seemingly benign consumer products increase the output of air pollutants along the supply chain and contribute to the potential risks associated with environmental chemical exposures to both consumers and non-consumers alike.

Commerce↗
PubMed2004

Anorexigenic C75 alters c-Fos in mouse hypothalamic and hindbrain subnuclei.

The fatty acid synthase inhibitor C75 reduces feeding rapidly and for several days. We investigated brain sites potentially involved in actions of i.p. C75 in mice by examining c-Fos. At 3 h C75 increased numbers of c-Fos-immunoreactive cells in hindbrain feeding-related nuclei, and in the paraventricular nucleus (PVN), lateral aspects of the arcuate nucleus (ARC), and in the central amygdala. At 24 h C75 prevented fasting-induced c-Fos expression in the medial ARC and three of its targets: lateral magnocellular PVN, lateral hypothalamus, and dorsomedial hypothalamus. C75, but not fasting, increased c-Fos in parvocellular PVN. This pattern of results suggests a shift from hindbrain-initiated short-term actions to activation of hypothalamic mechanisms that could mediate the long-term anorectic responses to C75.

4-Butyrolactone↗
PubMed2004

C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase.

Energy homeostasis and feeding are regulated by the central nervous system. C75, a fatty acid synthase (FAS) inhibitor, causes weight loss and anorexia, implying a novel central nervous system pathway(s) for sensing energy balance. AMP-activated protein kinase (AMPK), a sensor of peripheral energy balance, is phosphorylated and activated when energy sources are low. Here, we identify a role for hypothalamic AMPK in the regulation of feeding behavior and in mediating the anorexic effects of C75. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an activator of AMPK, increased food intake, whereas compound C, an inhibitor of AMPK, decreased food intake. C75 rapidly reduced the level of the phosphorylated AMPK alpha subunit (pAMPKalpha) in the hypothalamus, even in fasted mice that had elevated hypothalamic pAMPKalpha levels. Furthermore, AICAR reversed both the C75-induced anorexia and the decrease in hypothalamic pAMPKalpha levels. C75 elevated hypothalamic neuronal ATP levels, which may contribute to the mechanism by which C75 decreased AMPK activity. C75 reduced the levels of pAMPKalpha and phosphorylated cAMP response element-binding protein (pCREB) in the arcuate nucleus neurons of the hypothalamus, suggesting a mechanism for the reduction in NPY expression seen with C75 treatment. These data indicate that modulation of FAS activity in the hypothalamus can alter energy perception via AMPK, which functions as a physiological energy sensor in the hypothalamus.

4-Butyrolactone↗
PubMed2004

Long-term otological outcome of hamular fracture during palatoplasty.

OBJECTIVE: It has been suggested that fracture of the hamulus during palatoplasty in children with cleft palate may lead to adverse otological sequelae, however, there is little evidence to support this. STUDY DESIGN AND SETTING: The otological records of 42 children with repaired cleft palate (excluding submucous cleft palate) aged 8 years old or older were examined. A questionnaire regarding the incidence, treatment, and outcome of middle ear problems was completed by the parents of 68 children with repaired cleft palate, aged 9 years old or older. RESULTS: There was no significant difference between children who did and did not undergo hamular fracture with regard to tympanic membrane appearance, audiometry, history of ear problems (P = 1.000), ear infections (P = 0.622), ventilation tube insertion (P = 0.532), or surgery for chronic otitis media (P = 1.000). Parents of children not undergoing hamular fracture reported a higher incidence of below normal hearing (P = 0.023).Conclusion and significance There is no evidence that hamular fracture during palatoplasty affects long-term otological outcome in cleft palate.

Adolescent↗
PubMed2004

Middle ear disease in children with congenital velopharyngeal insufficiency.

OBJECTIVE: To examine the incidence and natural history of middle ear disease in children with congenital velopharyngeal insufficiency (VPI) without cleft palate. SETTING AND SUBJECTS: Children with congenital VPI attending the combined cleft clinic at a tertiary cleft center. The diagnosis of congenital VPI in all cases was confirmed be the observation of hypernasality, nasal air escape, or both by a speech and language therapist and the demonstration of incompetence of the velopharyngeal sphincter by means of nasoendoscopy or videofluoroscopy. Children with overt cleft palate or postsurgical VPI were excluded. DESIGN: The children's medical records were reviewed, and a questionnaire regarding history of ear problems was sent to all parents. Children were divided into those with Pruzansky type I VPI (showing bifid uvula, midline diastasis of soft palate, or submucous cleft of the hard palate) and Pruzansky type II VPI (no visible stigmata). MAIN OUTCOME MEASURES: Incidence of reported ear problems, ear infections, hearing loss, and surgical intervention for middle ear disease in the whole group and in each of the subgroups. RESULTS: Seventy-one parents returned completed questionnaires. The overall incidence of middle ear disease was 63%, with 28% reported to have below-normal hearing. There was no significant difference between children with Pruzansky types I and II VPI with respect to incidence of otopathology or hearing loss. CONCLUSIONS: Irrespective of the presence of any visible palatal abnormalities, children with congenital VPI showed a substantial incidence of otopathology and should thus be closely monitored.

Child↗
PubMed2003

Incidence and outcome of middle ear disease in cleft lip and/or cleft palate.

OBJECTIVE: Otitis media with effusion is known to be very common among children with cleft palate, however, less is known regarding the natural history and outcome in this group. The purpose of the present study was to examine the incidence, natural history, treatment, and outcome of middle ear disease in children with clefts. METHODS: A questionnaire was sent to the parents of all children registered on the cleft lip and palate database at our institution. The medical records of all respondents were also reviewed. Statistical analysis of the results was performed using Fisher's exact test in contingency tables and binary logistic regression analyses, where appropriate. RESULTS: 397 fully completed questionnaires were returned. Ear disease was much more common in children with cleft palate, or cleft lip and palate, than in children with cleft lip. Among children with cleft palate, ear problems (infections and/or hearing loss) were most prevalent in the 4-6-year-old age group. However, ear problems persisted at a substantial level for many years after this; only after the age of 12 years did problems appear to settle. The incidence of below normal current hearing and of surgery for chronic otitis media was significantly related to history of ear infections (P=0.000 and 0.000, respectively), and to increased number of ventilation tube insertions (P=0.000 and 0.000, respectively). CONCLUSIONS: Middle ear disease is common in children with cleft palate, and, unlike the case for children without clefts, has a prolonged recovery, and a substantial incidence of late sequelae. The higher incidence of below normal hearing and surgery for chronic otitis media in children undergoing a greater number of ventilation tube insertions, although most likely reflecting an increased underlying severity of otitis media in these children, also underlines the lack of long-term benefits of ventilation tubes in this group.

Adolescent↗
PubMed2002

Atrial natriuretic peptide type C induces a cell-cycle switch from proliferation to differentiation in brain-derived neurotrophic factor- or nerve growth factor-primed olfactory receptor neurons.

With the discovery of postnatal stem cells within the brain, it has become important to understand how extracellular factors might affect the maturation of neuronal precursors in the postnatal brain. Neurotrophic factors are known to play a role in neuronal development but display pleiotrophic effects, in part because of their physiological interactions with other factors. One factor positioned to interact with neurotrophins in the brains of postnatal animals is atrial C-type natriuretic peptide (CNP). In this study, we used olfactory receptor neurons (ORNs) as a model, because their precursors demonstrate the most robust and functional postnatal neurogenesis of those systems thus far described. We examined the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and the interactions of these neurotrophins and CNP in postnatal olfactory neuronal precursors. Results obtained using mice with targeted deletion of the gene for BDNF indicated that BDNF is a neuroproliferation-inducing and survival factor for ORN precursors. These roles were confirmed in vitro using primary cultures of ORNs. NGF was found to be a proliferation-inducing factor but not a survival factor. The addition of CNP to either BDNF- or NGF-treated neuronal precursors resulted in an inhibition of proliferation and the promotion of maturation. These effects were accompanied by changes in cell-cycle proteins that suggest possible mechanisms for these effects. Thus, CNP may function in the postnatal brain to regulate the exit from the cell cycle in neuronal precursor cells.

Animals↗
PubMed2002

Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment.

We previously demonstrated that C75, a specific and potent inhibitor of fatty acid synthase (FAS), reduced food intake and decreased body weight in mice. In the present study, we determined that these effects were not due to conditioned taste aversion. To investigate the mechanism of C75 action, we examined FAS brain expression. FAS was expressed in a number of brain regions, including arcuate and paraventricular nuclei (PVN) within regions that comprise the arcuate-PVN pathway in mouse and human. Although C75 and fasting significantly downregulated liver FAS, FAS levels remained high in hypothalamus, indicating that FAS levels were regulated differently in brain from those in liver. Double fluorescence in situ for FAS and neuropeptide Y (NPY) showed that FAS co-localized with NPY in neurons in the arcuate nucleus. NPY immnuoreactivity after C75 treatment was decreased in axon terminals that innervate the PVN and lateral hypothalamus. Collectively, these results demonstrate that FAS is present and active in neurons and suggests that C75 may alter food intake via interactions within the arcuate-PVN pathway mediated by NPY.

4-Butyrolactone↗