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Biomedical subjects

Brian O'Connell

Publications and source records attributed to Brian O'Connell.

12 recordsLinked to original sources
PubMed2006

A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes.

Adult mesenchymal stem cells have the proclivity to differentiate along multiple lineages giving rise to new bone, cartilage, muscle, or fat. Collagen, a normal constituent of bone, provides strength and structural stability and is therefore a potential candidate for use as a substrate on which to engineer bone and cartilage from their respective mesenchymal-derived precursors. In this study, a collagen- glycosaminoglycan scaffold was used to provide a suitable three-dimensional (3-D) environment on which to culture adult rat mesenchymal stem cells and induce differentiation along the osteogenic and chondrogenic lineages. The results demonstrate that adult rat mesenchymal stem cells can undergo osteogenesis when grown on the collagen-glycosaminoglycan scaffold and stimulated with osteogenic factors (dexamethasone, ascorbic acid, beta-glycerophosphate), as evaluated by the temporal induction of the bone-specific proteins, collagen I and osteocalcin, and subsequent matrix mineralization. The osteogenic factors were coupled to activation of the extracellular-regulated protein kinase (ERK), and this kinase was found to play a role in the osteogenic process. As well as supporting osteogenesis, when the cell-seeded scaffold was exposed to chondrogenic factors (dexamethasone and TGF-1beta), collagen II immunoreactivity was increased, providing evidence that the scaffold can also provide a suitable 3-D environment that supports chondrogenesis.

Animals↗
PubMed2006

The occurrence of severe sepsis and septic shock are related to distinct patterns of cytokine gene expression.

Patient response to acute bacterial infection is highly variable. Differing outcomes in this setting may be related to variations in the immune response to an infectious insult. Using quantitative real-time polymerase chain reaction, we quantified gene expression of the tumor necrosis factor alpha(TNFalpha), interferon gamma (IFNgamma), and interleukin 10 (IL10), IL12p35, and IL4 genes in 3 patient groups. These groups consisted of an intensive care unit (ICU) cohort who presented with severe sepsis or septic shock, a group of noncritically ill ward patients with documented Gram-negative bacteremia, and a group of healthy controls. Greater interleukin 10 messenger RNA (mRNA) levels were detected in the ICU group in comparison with both the bacteremic and control groups (P < 0.0001). More TNF-alpha mRNA was detected in the ICU group when compared with the control group (P < 0.0001). However, TNF-alpha mRNA was most abundant in the bacteremic group (P = 0.0007). Lesser IFN-gamma mRNA levels were detected in the ICU group when compared with both the bacteremic and control groups (P < 0.0003). Cytokine mRNA levels were not associated with the occurrence of shock upon admission to ICU. On the seventh day of ICU stay, the presence of shock was associated with lesser IFN-gamma mRNA (P = 0.0004) and lesser TNF-alpha mRNA (P = 0.001). Survivors had greater TNF-alpha mRNA copy numbers on day 7 of ICU stay than nonsurvivors (P = 0.002). We conclude that a proinflammatory response is the appropriate response in the setting of infection and is associated with lesser requirements for inotropes and lesser mortality. Quantitative real-time polymerase chain reaction can be used to predict infection outcome in clinically relevant situations where enzyme-linked immunosorbent assay testing has proved disappointing.

Adult↗
PubMed2006

Multiple dental fractures following tongue barbell placement: a case report.

The number of adolescents and young adults undergoing intra-oral piercing, is increasing worldwide. There have been several case reports documenting oral and systemic complications of this practice. These include damage to the dentition, gingivae, infection, speech impediments and nerve damage. The case presented here draws attention to the possibility of multiple tooth fracture as a result of trauma incurred from a barbell inserted into the tongue.

Adolescent↗
PubMed2005

First reported case of endocarditis caused by Candida dubliniensis.

Candida dubliniensis is an uncommon cause of bloodstream infection. We describe the first reported case of endocarditis caused by C. dubliniensis and the use of a rapid and novel real-time PCR assay based on the internal transcribed spacer 2 variable region of the rRNA operon that was used to identify this organism.

Adult↗
PubMed2004

High-density lipoproteins: multifunctional vanguards of the cardiovascular system.

The plasma level of high-density lipoprotein (HDL)-cholesterol is inversely correlated with coronary artery disease, the leading cause of death worldwide. HDL particles are thought to mediate the uptake of peripheral cholesterol and, through exchange of core lipids with other lipoproteins or selective uptake by specific receptors, return this cholesterol to the liver for bile acid secretion or hormone synthesis in steroidogenic tissues. HDL particles also act on vascular processes by modulating vasomotor function, thrombosis, cell-adhesion molecule expression, platelet function, nitric oxide release, endothelial cell apoptosis and proliferation. Many of these effects involve signal transduction pathways and gene transcription. Several genetic disorders of HDLs have been characterized at the molecular level. The study of naturally occurring mutations has considerably enhanced understanding of the role of HDL particles. Some mutations causing HDL deficiency are associated with premature coronary artery disease, while others, paradoxically, may be associated with longevity. Modulation of HDL metabolism for therapeutic purposes must take into account, not only the cholesterol content of a particle but its lipid (especially phospholipid) composition, apolipoprotein content, size and charge. Current therapeutic strategies include the use of peroxisome proliferating activator receptor-alpha agonists (fibrates) that increase apolipoprotein AI production and increase lipoprotein lipase activity, statins that have a small effect on HDL-cholesterol but markedly reduce low-density lipoprotein-cholesterol, the cholesterol/HDL-cholesterol ratio and niacin that increases HDL-cholesterol. Potential therapeutic targets include inhibition of cholesteryl ester transfer protein, modulating the ATP-binding cassette A1 transporter, and decreasing HDL uptake by scavenger receptor-B1. Novel therapies include injection of purified apolipoprotien AI and short peptides taken orally, mimicking some of the biological effects of apolipoprotein AI.

Cardiovascular System↗
PubMed2002

3.2 Ensuring research productivity in the future faculty.

The group concluded that the research productivity of a dental school depended to a large extent on the availability of resources, human and economic. Firstly it requires a group of individuals trained and educated to conduct independent research. Secondly, it requires that these individuals had time to spend on research activities. Thirdly, appropriate space and equipment in which to conduct the research were considered prerequisites. Fourthly, they require an ongoing and appropriate budget. Fifthly, it is essential to have an appropriate climate in the school that encourages and rewards research achievement.

Cultural Diversity↗
PubMed2002

Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell lines.

Activator protein-1 (AP-1) transcription factor has been linked to chemotherapeutic resistance. To assess the clinical efficacy of AP-1 inhibition toward reversing drug resistance, we have developed an adenovirus expressing a dominant negative that inhibits AP-1 DNA binding, namedAdA-FOS. We examined the consequence of AdA-FOS infection on two paired human cancer cell lines, each pair consisting of a parental cell and the drug- resistant derivative. The first pair of cells is the parental human ovarian cancer cell line A2780 and the cisplatin-resistant A2780/CP70 cell line. The second pair of cells is the parental epidermal carcinoma cell line KB8 and the multidrug-resistant (mdr) KB85 cell line. Because of an association of up-regulated AP-1 activity with their drug resistance, these cell lines were considered good targets of AdA-FOS therapy. Following infection of the drug-sensitive and drug-resistant cells, we observed a significant decrease in cell viability of KB85 and A2780/CP70 cells at drug doses normally not lethal to the cell. The parental cell lines, A2780 and KB8 cells, were not similarly affected by AdA-FOS. This decrease in viability was specific to AdA-FOS as an adenovirus control (Advector) did not reverse drug resistance. Although the efficiency of AdA- FOS in therapy would need to be further analyzed with other cisplatin-resistant and mdr cell lines, these results suggest that AP-1 is a therapeutic molecular target and that inhibition of AP-1 DNA binding may be of clinical value in treating chemotherapeutic resistance.

Adenoviridae↗
PubMedDate not supplied

Preloads generated with repeated tightening in three types of screws used in dental implant assemblies.

PURPOSE: Abutment screw loosening, especially in the case of cemented single tooth restorations, is a cause of implant restoration failure. This study compared three screws (titanium alloy, gold alloy, and gold-coated) with similar geometry by recording the preload induced when torques of 10, 20, and 35 Ncm were used for fixation. MATERIALS AND METHODS: Two abutment types were used-prefabricated preparable abutments and cast-on abutments. A custom-designed rig was used to measure preload in the abutment-screw-implant assembly with a strain gauge. Ten screws of each type were sequentially tightened to 10, 20, and 35 Ncm on ten of the two abutment types. The same screws were then loosened and re-tightened. This procedure was repeated. Thus, each screw was tightened on three occasions to the three insertion torques. A linear regression model was used to analyze the effects on preload values of screw type and abutment type for each of the three insertion torques. RESULTS: The results indicated that the gold-coated screw generated the highest preloads for all insertion torques and for each tightening episode. Further analysis focused on the effects of screw type and abutment type for each episode of tightening and for each fixation torque. The gold-coated screw, fixed to the prefabricated abutment, displayed higher preloads for the first tightening at 10, 20, and 35 Ncm. Conversely, the same screw fixed to the cast-on abutment showed higher values for the second and third tightening for all fixation torques. All screws showed decay in preload with the number of times tightened. Given the higher preloads generated using the gold-coated screw with both abutment types, it is more likely that this type of screw will maintain a secure joint when tightened for the second and third time. CONCLUSION: All screw types displayed some decay in preload with repeated tightening, irrespective of abutment type and insertion torque. The gold-coated screw showed markedly higher preloads for all insertion torques and for all instances of tightening when compared with the uncoated screws.

Analysis of Variance↗
PubMedDate not supplied

Pain and anxiety following the placement of dental implants.

PURPOSE: This study investigated pain experience and anxiety following dental implant placement using questionnaires and salivary cortisol measurements. MATERIALS AND METHODS: Patients about to undergo implant placement were instructed to keep recovery diaries to assess pain experience (limitation of activities, postoperative symptoms) and to record average pain, worst pain, and interference with daily activities on a visual analog scale (VAS). To assess anxiety, patients completed the Spielberger self-evaluation questionnaire and collected salivary samples to measure cortisol levels. Saliva was collected 1 week before surgery, the day of surgery, and 3 and 6 days postoperatively. A repeated-measure analysis of variance was used to analyze pain and anxiety data. RESULTS: Eighteen patients (12 women and 6 men) who received 30 implants were recruited for the study. Following implant placement, most patients reported mild to moderate interference with daily activities and postoperative symptoms. No patient reported high levels of any symptom. Average pain experience decreased significantly with time (F = 6.17; P < .001), from a VAS score of 24/100 on day 1 to 12 on day 3 and 9 on day 6. Worst pain (F = 7.84; P < .001) and limitation of daily activities (F= 6.26; P < .001) were also highest on the first postoperative day; they also decreased to about half the maximum level by the second or third day. State anxiety, as evaluated by the Spielberger self-evaluation scale, was highest on the day of surgery. The salivary cortisol level did not validate this, as it did not differ with the time of collection (F = 2.22; P = .075). CONCLUSIONS: Patient self-assessment indicates that implant placement is a mild to moderately painful and anxiety-provoking procedure. Some limitation of daily activities and symptoms are expected to occur, particularly during the first 3 postoperative days.

Activities of Daily Living↗