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Biomedical subjects

Michael O'Donnell

Publications and source records attributed to Michael O'Donnell.

At least 19 recordsLinked to original sources
PubMed2006

Functional analysis of Sox8 during neural crest development in Xenopus.

Among the families of transcription factors expressed at the neural plate border, Sox proteins have been shown to regulate multiple aspects of neural crest development. Sox8, Sox9 and Sox10, exhibit overlapping expression domains in neural crest progenitors, and studies in mouse suggest that Sox8 functions redundantly with Sox9 and Sox10 during neural crest development. Here, we show that in Xenopus, Sox8 accumulates at the lateral edges of the neural plate at the mid-gastrula stage; in contrast to its mouse and chick orthologs, Sox8 expression precedes that of Sox9 and Sox10 in neural crest progenitors. Later in development, Sox8 expression persists in migrating cranial crest cells as they populate the pharyngeal arches and in trunk neural crest cells, in a pattern that recapitulates both Sox9 and Sox10 expression domains. Although morpholino-mediated knockdown of Sox8 protein did not prevent the formation of neural crest progenitors, the timing of their induction was severely affected. This delay in neural crest specification had dramatic consequences on the development of multiple lineages of the neural crest. We demonstrate that these defects are due to the inability of neural crest cells to migrate into the periphery, rather than to a deficiency in neural crest progenitors specification and survival. These results indicate that the control of Sox8 expression at the neural plate border is a key process in initiating neural crest formation in Xenopus, and highlight species-specific differences in the relative importance of SoxE proteins during neural crest development.

Animals↗
PubMed2006

Kermit 2/XGIPC, an IGF1 receptor interacting protein, is required for IGF signaling in Xenopus eye development.

GIPC is a PDZ-domain-containing protein identified in vertebrate and invertebrate organisms through its interaction with a variety of binding partners including many membrane proteins. Despite the multiple reports identifying GIPC, its endogenous function and the physiological significance of these interactions are much less studied. We have previously identified the Xenopus GIPC homolog kermit as a frizzled 3 interacting protein that is required for frizzled 3 induction of neural crest in ectodermal explants. We identified a second Xenopus GIPC homolog, named kermit 2 (also recently described as an IGF receptor interacting protein and named XGIPC). Despite its high amino acid similarity with kermit, kermit 2/XGIPC has a distinct function in Xenopus embryos. Loss-of-function analysis indicates that kermit 2/XGIPC is specifically required for Xenopus eye development. Kermit 2/XGIPC functions downstream of IGF in eye formation and is required for maintaining IGF-induced AKT activation. A constitutively active PI3 kinase partially rescues the Kermit 2/XGIPC loss-of-function phenotype. Our results provide the first in vivo loss of function analysis of GIPC in embryonic development and also indicate that kermit 2/XGIPC is a novel component of the IGF pathway, potentially functioning through modulation of the IGF1 receptor.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Association of a continuous quality improvement initiative with practice and outcome variations of contemporary percutaneous coronary interventions.

BACKGROUND: The objective of this study was to evaluate the association of a continuous quality improvement program with practice and outcome variations of percutaneous coronary intervention (PCI). METHODS AND RESULTS: Data on consecutive PCI were collected in a consortium of 5 hospitals; 3731 PCIs reflected care provided at baseline (January 1, 1998, to December 31, 1998), and 5901 PCIs reflected care provided after implementation of a continuous quality improvement intervention (January 1, 2002, to December 31, 2002). The intervention included feedback on outcomes, working group meetings, site visits, selection of quality indicators, and use of bedside tools for quality improvement and risk assessment. Postintervention data were compared with baseline and with 10,287 PCIs from 7 hospitals added to the consortium in 2002. Quality indicators included use of preprocedural aspirin or clopidogrel, use of glycoprotein IIb/IIIa receptor blockers and postprocedural heparin, and amount of contrast media per case. Outcomes selected included emergency CABG, contrast nephropathy, myocardial infarction, stroke, transfusion, and in-hospital death. Compared with baseline and the control group, the intervention group at follow-up had higher use of preprocedural aspirin and glycoprotein IIb/IIIa blockers, lower use of postprocedural heparin, and a lower amount of contrast media per case (P<0.05). These changes were associated with lower rates of transfusions, vascular complications, contrast nephropathy, stroke, transient ischemic attack, and combined end points (all P<0.05). CONCLUSIONS: Our nonrandomized, observational data suggest that implementation of a regional continuous quality improvement program appears to be associated with enhanced adherence to quality indicators and improved outcomes of PCI. A randomized clinical trial is needed to determine whether this is a "causal" or a "casual" relationship.

Aged↗
PubMed2005

The doublesex-related gene, XDmrt4, is required for neurogenesis in the olfactory system.

The Dmrt genes encode a large family of transcription factors whose function in sexual development has been well studied. However, their expression pattern is not restricted to the gonad, suggesting that Dmrt genes might regulate other developmental processes. Here, we report the expression and functional analysis of one member of this family: Xenopus Dmrt4 (XDmrt4). XDmrt4 is initially expressed in the anterior neural ridge and then becomes progressively restricted to part of the telencephalon and the olfactory placode/epithelium. XDmrt4 is induced at the anterior neural plate by a balance of neural inducers and caudalizing factors. Interference with XDmrt4 function by injection of a morpholino oligonucleotide or an inhibitory mutant resulted in a similar phenotype, the specific disruption of the olfactory placode expression of Xebf2 without affecting the expression of other placodal markers. Xebf2 belongs to a family of helix-loop-helix transcription factors implicated in neuronal differentiation, and later in embryogenesis XDmrt4-deficient embryos show impaired neurogenesis in the olfactory epithelium. Consistent with this finding, XDmrt4 is sufficient to activate neurogenin, Xebf2, and neural cell adhesion molecule expression in animal explants and is required for Noggin-mediated neuralization. Altogether, these results indicate that XDmrt4 is an important regulator of neurogenesis in the olfactory system upstream of neurogenin and Xebf2.

Animals↗
PubMed2005

Public reporting and case selection for percutaneous coronary interventions: an analysis from two large multicenter percutaneous coronary intervention databases.

OBJECTIVES: The purpose of this research was to determine the potential effect of public reporting on case selection for percutaneous coronary intervention (PCI). BACKGROUND: Previous studies have suggested that public reporting of coronary artery bypass graft surgery (CABG) mortality might result in case selection bias and in denial of care to or out migration of high-risk patients. The potential effect of public reporting on case selection for PCI is unknown. METHODS: We compared demographics, indications, and outcomes of 11,374 patients included in a multicenter (eight hospitals) PCI database in Michigan where no public reporting is present, with 69,048 patients in a statewide (34 hospitals) PCI database in New York, where public reporting is present. The primary end point was in-hospital mortality. RESULTS: Patients in Michigan more frequently underwent PCI for acute myocardial infarction (14.4% vs. 8.7%, p < 0.0001) and cardiogenic shock (2.56% vs. 0.38%, p < 0.0001) than those in New York. The Michigan cohort also had a higher prevalence of congestive heart failure and extracardiac vascular disease. The unadjusted in-hospital mortality rate was significantly lower in New York than in Michigan (0.83% vs. 1.54%, p < 0.0001; odds ratio [OR] 0.54, 95% confidence interval [CI] 0.45 to 0.63). However, after adjustment for comorbidities, there was no significant difference in mortality between the two groups (adjusted OR 1.05, 95% CI 0.84 to 1.31, p = 0.70, c-statistic 0.88). CONCLUSIONS: There are significant differences in case mix between patients undergoing PCI in Michigan and New York that result in marked differences in unadjusted mortality rates. A propensity in New York toward not intervening on higher-risk patients because of fear of public reporting of high mortality rates is a possible explanation for these differences.

Angioplasty, Balloon, Coronary↗
PubMed2005

Proteomic and genomic characterization of chromatin complexes at a boundary.

We have dissected specialized assemblies on the Saccharomyces cerevisiae genome that help define and preserve the boundaries that separate silent and active chromatin. These assemblies contain characteristic stretches of DNA that flank particular regions of silent chromatin, as well as five distinctively modified histones and a set of protein complexes. The complexes consist of at least 15 chromatin-associated proteins, including DNA pol epsilon, the Isw2-Itc1 and Top2 chromatin remodeling proteins, the Sas3-Spt16 chromatin modifying complex, and Yta7, a bromodomain-containing AAA ATPase. We show that these complexes are important for the faithful maintenance of an established boundary, as disruption of the complexes results in specific, anomalous alterations of the silent and active epigenetic states.

Chromatin↗
PubMed2005

Management of stage T1 tumors of the bladder: International Consensus Panel.

The International Consensus Panel on T1 bladder tumors markers reviewed the subject from a clinical perspective. From diagnosis to treatment decisions, what are the important issues in the management of a new patient? The assessment of prognostic factors for progression requires optimal resection and documentation. The role of immediate adjuvant intravesical chemotherapy after resection remains controversial. How often should the upper tract be assessed for tumor recurrence? The decision on whether to attempt bladder conservation with intravesical therapy or to perform a cystectomy is the most difficult issue in the management of superficial bladder cancer today. Finally, what therapies exist if initial intravesical bacille Calmette-Guérin fails to eradicate the disease or prevent recurrence? The panel thoroughly explored all these subjects and has made recommendations with supporting evidence.

Algorithms↗
PubMed2004

Dual functions, clamp opening and primer-template recognition, define a key clamp loader subunit.

Clamp loader proteins catalyze assembly of circular sliding clamps on DNA to enable processive DNA replication. During the reaction, the clamp loader binds primer-template DNA and positions it in the center of a clamp to form a topological link between the two. Clamp loaders are multi-protein complexes, such as the five protein Escherichia coli, Saccharomyces cerevisiae, and human clamp loaders, and the two protein Pyrococcus furiosus and Methanobacterium thermoautotrophicum clamp loaders, and thus far the site(s) responsible for binding and selecting primer-template DNA as the target for clamp assembly remain unknown. To address this issue, we analyzed the interaction between the E.coli gamma complex clamp loader and DNA using UV-induced protein-DNA cross-linking and mass spectrometry. The results show that the delta subunit in the gamma complex makes close contact with the primer-template junction. Tryptophan 279 in the delta C-terminal domain lies near the 3'-OH primer end and may play a key role in primer-template recognition. Previous studies have shown that delta also binds and opens the beta clamp (hydrophobic residues in the N-terminal domain of delta contact beta. The clamp-binding and DNA-binding sites on delta appear positioned for facile entry of primer-template into the center of the clamp and exit of the template strand from the complex. A similar analysis of the S.cerevisiae RFC complex suggests that the dual functionality observed for delta in the gamma complex may be true also for clamp loaders from other organisms.

Adenosine Triphosphate↗
PubMed2004

Economic interventions to promote physical activity: application of the SLOTH model.

Physical inactivity is responsible for major health and economic costs in the United States. Despite widespread recognition of the scope and importance of the problem of physical inactivity, only modest progress has been made in improving overall physical activity in the U.S. population. This paper applies a combined economic and public health perspective to better understand physical activity behavior and to guide a search for promising new economically oriented interventions to increase physical activity at the population level. This perspective is operationalized as the SLOTH model-a time-budget model incorporating Sleep, Leisure, Occupation, Transportation, and Home-based activities. Key economic forces that may influence individuals' choices about utilization of time and physical activity are identified. Potential interventions are proposed in response to each of the important forces and are evaluated on four criteria: (1) economic efficiency, (2) equity, (3) effectiveness, and (4) feasibility. The SLOTH model provides guidance regarding interventions that might increase physical activity in each of the four nonsleep domains. Economic intervention strategies are proposed and compared to economic and public health criteria. The results provide a starting point for selecting and evaluating potentially effective and feasible economic interventions that might be implemented as part of a larger effort to address the health crisis of inactive lifestyles and obesity.

Exercise↗
PubMed2004

Health-promotion behaviors that promote self-healing.

A large body of evidence has shown that health-promotion programs in smoking cessation, stress management, fitness, nutrition, weight control, and medical self care have been successful in helping people improve their health practices and related health conditions. However, the impact of these programs on promoting self-healing among people with acute and chronic diseases is mixed. The purpose of this paper is to identify research opportunities important to fostering a better understanding of health promotion behaviors that promote self healing. To provide context, the health-promotion concept is discussed, as is the literature on workplace health-promotion programs provided to overtly healthy people. Next, examples of the literature on health-promotion programs for people with chronic illness are provided. Finally, a research agenda and opportunities for research are presented.

Attitude to Health↗
PubMed2003

Frequency and prognosis of emergency coronary artery bypass grafting after percutaneous coronary intervention for acute myocardial infarction.

We evaluated the frequency and prognosis of emergency coronary artery bypass grafting (CABG) after percutaneous coronary intervention (PCI) for acute myocardial infarction in a large, multicenter registry of contemporary PCI. In this study, emergency CABG occurred in 2% of cases, and was associated with high in-hospital mortality (20%) and with a high incidence of stroke (8%), renal failure requiring dialysis (8.3%), and bleeding (63.3%).

Acute Disease↗
PubMed2003

Impact of extracardiac vascular disease on acute prognosis in patients who undergo percutaneous coronary interventions (data from the Blue Cross & Blue Shield of Michigan Cardiovascular Consortium [BMC2]).

Extracardiac vascular disease is associated with an increased risk of in-hospital mortality and other complications after coronary interventions, independent from other co-morbidities and baseline characteristics. The underlying cause of this significant association is unclear, but it warrants further investigation in an attempt to improve outcome in this high-risk cohort.

Aged↗