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Showing papers by "University of Louisville published in 2005"


Journal ArticleDOI
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

4,258 citations


Journal ArticleDOI
15 Sep 2005-Spine
TL;DR: This study shows that although even mildly positive sagittal balance is somewhat detrimental, severity of symptoms increases in a linear fashion with progressive sagittal imbalance, and shows that kyphosis is more favorable in the upper thoracic region but very poorly tolerated in the lumbar spine.
Abstract: Study Design.This study is a retrospective review of 752 patients with adult spinal deformity enrolled in a multicenter prospective database in 2002 and 2003. Patients with positive sagittal balance (N = 352) were further evaluated regarding radiographic parameters and health status measures, includ

1,531 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examined the dynamic interplay among teacher identity, agency, and context as these affect how secondary teachers report experiencing professional vulnerability, particularly in terms of their abilities to achieve their primary purposes in teaching students.

1,143 citations


Journal ArticleDOI
15 Mar 2005-Spine
TL;DR: This study suggests that restoration of a more normal sagittal balance is the critical goal for any reconstructive spine surgery and suggests that magnitude of coronal deformity and extent of Coronal correction are less critical parameters.
Abstract: Study design This study is a retrospective review of the initial enrollment data from a prospective multicentered study of adult spinal deformity. Objectives The purpose of this study is to correlate radiographic measures of deformity with patient-based outcome measures in adult scoliosis. Summary of background data Prior studies of adult scoliosis have attempted to correlate radiographic appearance and clinical symptoms, but it has proven difficult to predict health status based on radiographic measures of deformity alone. The ability to correlate radiographic measures of deformity with symptoms would be useful for decision-making and surgical planning. Methods The study correlates radiographic measures of deformity with scores on the Short Form-12, Scoliosis Research Society-29, and Oswestry profiles. Radiographic evaluation was performed according to an established positioning protocol for anteroposterior and lateral 36-inch standing radiographs. Radiographic parameters studied were curve type, curve location, curve magnitude, coronal balance, sagittal balance, apical rotation, and rotatory subluxation. Results The 298 patients studied include 172 with no prior surgery and 126 who had undergone prior spine fusion. Positive sagittal balance was the most reliable predictor of clinical symptoms in both patient groups. Thoracolumbar and lumbar curves generated less favorable scores than thoracic curves in both patient groups. Significant coronal imbalance of greater than 4 cm was associated with deterioration in pain and function scores for unoperated patients but not in patients with previous surgery. Conclusions This study suggests that restoration of a more normal sagittal balance is the critical goal for any reconstructive spine surgery. The study suggests that magnitude of coronal deformity and extent of coronal correction are less critical parameters.

1,040 citations


Journal ArticleDOI
TL;DR: Ability to adapt to changing cytokine environments has significant in vivo relevance, as evidenced by the demonstration that macrophage functional phenotypes established in vivo in aged or tumor-bearing mice can be altered by changing their microenvironment.
Abstract: Recent studies have described the development of distinct functional subsets of macrophages in association with cancer, autoimmune disease, and chronic infections. Based on the ability of Th1 vs Th2 cytokines to promote opposing activities in macrophages, it has been proposed that macrophages develop into either type 1 inflammatory or type 2 anti-inflammatory subsets. As an alternative to the concept of subset development, we propose that macrophages, in response to changes in their tissue environment, can reversibly and progressively change the pattern of functions that they express. As demonstrated herein, macrophages can reversibly shift their functional phenotype through a multitude of patterns in response to changes in cytokine environment. Macrophages display distinct functional patterns after treatment with IFN-gamma, IL-12, IL-4, or IL-10 and additional functional patterns are displayed depending on whether the cytokine is present alone or with other cytokines and whether the cytokines are added before or concomitantly with the activating stimulus (LPS). Sequential treatment of macrophages with multiple cytokines results in a progression through multiple functional phenotypes. This ability to adapt to changing cytokine environments has significant in vivo relevance, as evidenced by the demonstration that macrophage functional phenotypes established in vivo in aged or tumor-bearing mice can be altered by changing their microenvironment. A concept of functional adaptivity is proposed that has important implications for therapeutic targeting of macrophages in chronic diseases that result in the dominance of particular functional phenotypes of macrophages that play a significant role in disease pathology.

898 citations


Journal ArticleDOI
TL;DR: It is suggested that strategies aimed at modulating the SDF‐1–CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.
Abstract: The alpha-chemokine stromal-derived factor (SDF)-1 and the G-protein-coupled seven-span transmembrane receptor CXCR4 axis regulates the trafficking of various cell types. In this review, we present the concept that the SDF-1-CXCR4 axis is a master regulator of trafficking of both normal and cancer stem cells. Supporting this is growing evidence that SDF-1 plays a pivotal role in the regulation of trafficking of normal hematopoietic stem cells (HSCs) and their homing/retention in bone marrow. Moreover, functional CXCR4 is also expressed on nonhematopoietic tissue-committed stem/progenitor cells (TCSCs); hence, the SDF-1-CXCR4 axis emerges as a pivotal regulator of trafficking of various types of stem cells in the body. Furthermore, because most if not all malignancies originate in the stem/progenitor cell compartment, cancer stem cells also express CXCR4 on their surface and, as a result, the SDF-1-CXCR4 axis is also involved in directing their trafficking/metastasis to organs that highly express SDF-1 (e.g., lymph nodes, lungs, liver, and bones). Hence, we postulate that the metastasis of cancer stem cells and trafficking of normal stem cells involve similar mechanisms, and we discuss here the common molecular mechanisms involved in these processes. Finally, the responsiveness of CXCR4+ normal and malignant stem cells to an SDF-1 gradient may be regulated positively/primed by several small molecules related to inflammation which enhance incorporation of CXCR4 into membrane lipid rafts, or may be inhibited/blocked by small CXCR4 antagonist peptides. Consequently, strategies aimed at modulating the SDF-1-CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.

769 citations


Journal ArticleDOI
TL;DR: It is suggested that PMV play an important role in tumor progression/metastasis and angiogenesis in lung cancer.
Abstract: The role of platelets in tumor progression and metastasis has been recognized but the mechanism of their action remains unclear. Five human lung cancer cell lines (A549, CRL 2066, CRL 2062, HTB 183, HTB 177) and a murine Lewis lung carcinoma (LCC) cell line (for an in vivo model of metastasis) were used to investigate how platelet-derived microvesicles (PMV), which are circular fragments shed from the surface membranes of activated platelets, and exosomes released from platelet alpha-granules, could contribute to metastatic spread. We found that PMV transferred the platelet-derived integrin CD41 to most of the lung cancer cell lines tested and stimulated the phosphorylation of mitogen-activated protein kinase p42/44 and serine/threonine kinase as well as the expression of membrane type 1-matrix metalloproteinase (MT1-MMP). PMV chemoattracted 4 of the 5 cell lines, with the highly metastatic A549 cells exhibiting the strongest response. In A549 cells, PMV were shown to stimulate proliferation, upregulate cyclin D2 expression and increase trans-Matrigel chemoinvasion. Furthermore, in these cells, PMV stimulated mRNA expression for angiogenic factors such as MMP-9, vascular endothelial growth factor, interleukin-8 and hepatocyte growth factor, as well as adhesion to fibrinogen and human umbilical vein endothelial cells. Intravenous injection of murine PMV-covered LLC cells into syngeneic mice resulted in significantly more metastatic foci in their lungs and LLC cells in bone marrow than in control animals injected with LCC cells not covered with PMV. Based on these findings, we suggest that PMV play an important role in tumor progression/metastasis and angiogenesis in lung cancer.

712 citations



Journal ArticleDOI
TL;DR: A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia and is prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain-facilitator process.
Abstract: Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that smalldose ketamine prevents this hyperalgesia. Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 g kg 1 min 1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 g kg 1 min 1 (largedose remifentanil); or (3) intraoperative remifentanil at 0.40 g kg 1 min 1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 g kg 1 min 1 until skin closure and then 2 g kg 1 min 1 for 48 h (large-dose remifentanil‐ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h. Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects. Conclusion: A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia was prevented by small-dose ketamine, implicating an N-methyl-D-aspartate pain-facilitator process.

560 citations


Journal ArticleDOI
TL;DR: Intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function, and establishes C SCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.
Abstract: The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

508 citations


Journal ArticleDOI
TL;DR: Free-living amoebae are important predators that control microbial communities that have been isolated from various natural sources such as soil, freshwater, salt water, dust, and air.
Abstract: Free-living amoebae are important predators that control microbial communities. They are ubiquitous and have been isolated from various natural sources such as soil, freshwater, salt water, dust, and air. Although their abundance in soil is only limited, they have been implicated in the stimulation

Journal ArticleDOI
TL;DR: Treatment with AR inhibitors prevents vascular smooth muscle cell growth and endothelial cell apoptosis in culture and inflammation and restenosis in vivo, and additional studies indicate that the antioxidant and signaling roles of AR are interlinked and that AR regulates protein kinase C and nuclear factor-kappaB via redox-sensitive mechanisms.
Abstract: Aldose reductase (AR) is widely expressed aldehyde-metabolizing enzyme. The reduction of glucose by the AR-catalyzed polyol pathway has been linked to the development of secondary diabetic complications. Although treatment with AR inhibitors has been shown to prevent tissue injury in animal models of diabetes, the clinical efficacy of these drugs remains to be established. Recent studies suggest that glucose may be an incidental substrate of AR, which appears to be more adept in catalyzing the reduction of a wide range of aldehydes generated from lipid peroxidation. Moreover, inhibition of the enzyme has been shown to increase inflammation-induced vascular oxidative stress and prevent myocardial protection associated with the late phase of ischemic preconditioning. On the basis of these studies, several investigators have ascribed an important antioxidant role to the enzyme. Additionally, ongoing work indicates that AR is a critical component of intracellular signaling, and inhibition of the enzyme preven...

Journal ArticleDOI
TL;DR: Tobacco smoking has widespread systemic effects, many of which may provide mechanisms for the increased susceptibility to periodontitis and the poorer response to treatment.
Abstract: Aim: To review the potential biological mechanisms underlying the effects of tobacco smoking on periodontitis. Main findings: Smoking has major effects on the host response, but there are also a number of studies that show some microbiological differences between smokers and non-smokers. Smoking has a long-term chronic effect on many important aspects of the inflammatory and immune responses. Histological studies have shown alterations in the vasculature of the periodontal tissues in smokers. Smoking induces a significant systemic neutrophilia, but neutrophil transmigration across the periodontal microvasculature is impeded. The suppression of neutrophil cell spreading, chemokinesis, chemotaxis and phagocytosis have been described. Protease release from neutrophils may be an important mechanism in tissue destruction. Tobacco smoke has been found to affect both cell-mediated immunity and humoral immunity. Research on gingival crevicular fluid has demonstrated that there are lower levels of cytokines, enzymes and possibly polymorphonuclear cells in smokers. In vitro studies have shown detrimental effects of nicotine and some other tobacco compounds on fibroblast function, including fibroblast proliferation, adhesion to root surfaces and cytotoxicity. Conclusion: Tobacco smoking has widespread systemic effects, many of which may provide mechanisms for the increased susceptibility to periodontitis and the poorer response to treatment.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the collateral consequences of sex offender registration from the perspective of the offender and found that social stigmatization, loss of relationships, employment, and housing, and both verbal and physical assaults are experienced by a significant minority of registered sex offenders.
Abstract: Sex offender registrationwas widely implemented in the 1990s as a means of enhancingcommunity awareness of sex offenders to promote community safety. This study is one of the first examinations of the collateral consequences of sex offender registration from the perspective of the offender. Drawing on data from 121 registered sex offenders in Kentucky, this research shows that social stigmatization, loss of relationships, employment, and housing, and both verbal and physical assaults are experienced by a significant minority of registered sex offenders.

Journal ArticleDOI
TL;DR: In this paper, the authors examined whether self-constructs measured at an intermediate level of specificity better correspond with the criterion variable (course grades) than general self constructions or specific constructions.
Abstract: Social cognitive theory suggests that self-constructs are better predictors when the specificity levels of self-constructs (as predictors) and the criterion variable closely correspond. In this study it was examined whether self-constructs measured at an intermediate level of specificity better correspond with the criterion variable (course grades: an intermediate level of specificity) than general self-constructs or specific self-constructs. Self-constructs in this study included self-efficacy and self-concept at varying degrees of specificity: general self-efficacy, academic self-efficacy, specific self-efficacy, academic self-concept, and specific self-concept. College students (N = 230) in general education courses voluntarily completed the three self-efficacy measures and the two self-concept measures. Results of correlation and simultaneous multiple regression analyses indicated that the closer the level of specificity of self-efficacy and self-concept, the stronger the relationship between the two constructs. Both academic self-concept and specific self-concept were significant predictors of term grades. In addition, academic self-concept was also a significant predictor, whereas neither general self-efficacy nor academic self-efficacy was significant. Measurement issues and implications of the findings are discussed. © 2005 Wiley Periodicals, Inc. Psychol Schs 42: 197–205, 2005.

Journal ArticleDOI
TL;DR: Acute, short-term hyperglycemia affects all major components of innate immunity and impairs the ability of the host to combat infection, even though certain distinctive proinflammatory alterations of the immune response can be observed under these conditions.
Abstract: Objective:To extract from the biomedical literature the reported effects of acute hyperglycemia on the major components of the innate immune system and to describe the clinical benefits of strict blood glucose control in certain patients.Data Source and Selection:A Medline/PubMed search (1966 to Jul

Journal ArticleDOI
TL;DR: Patients with heart failure experience a high level of symptoms and symptom burden, and nurses should target interventions to decrease frequency, severity, distress and overall symptom burden and improve HRQOL.
Abstract: Background: Heart failure is an escalating health problem around the world. Despite significant scientific advances, heart failure patients experience multiple physical and psychological symptoms that can impact the quality of life.Aims: To determine the (1) symptom prevalence, severity, distress and symptom burden in patients with heart failure; (2) impact of age and gender on symptom prevalence, severity, distress and symptom burden; and (3) impact of symptom prevalence and symptom burden on health-related quality of life (HRQOL) in patients with heart failure.Methods: A convenience sample of 53 heart failure patients participated in this descriptive, cross-sectional design. Symptoms and HRQOL were measured using the Memorial Symptom Assessment Scale—Heart Failure and the Minnesota Living with Heart Failure Questionnaire.Results: Patients experienced a mean of 15.1 ± 8.0 symptoms. Shortness of breath and lack of energy were the most prevalent. Difficulty sleeping was the most burdensome symptom. Lower a...

Journal ArticleDOI
TL;DR: Surgical operations induce a reversible depression of cellular immunity which precedes plasma suppressive activity in its return to pre‐operative levels, and immunostimulating agents such as interferon and the interleukins deserve evaluation as prophylactic agents pre‐operatively.
Abstract: Surgical operations have been shown to cause a variety of immunological disturbances in man both in vivo and in vitro. With few exceptions the overall picture is one of a generalized state of immunodepression in the postoperative period. The implications of these observations are that host defences may be compromised by surgical procedures, thus providing a 'fertile soil' for bacterial invasion and tumour cell metastasis at the very time when risks from invading pathogens and viable tumour cells are maximal. We have studied the effects of surgical operations on the immune system in 35 patients with benign disease. Surgical procedures were classified as either minor (n = 15) or major (n = 20). A panel of monoclonal antibodies was used to identify peripheral blood lymphocyte subpopulations and analysis was performed using flow cytometry. Simultaneous estimations of plasma alpha-1 proteinase inhibitor (alpha-1-PI), alpha-2-macroglobulin (alpha-2-M), alpha-2-pregnancy-associated glycoprotein (alpha-2-PAG) and plasma suppressive activity (PSA) on stimulated allogeneic lymphocytes were performed before operation and on postoperative days 1, 3, 7, 17 and 21. Circulating numbers of all lymphocyte subpopulations fell significantly following surgery, except for B lymphocytes which did not change. The magnitude, and duration of the reduction in cell numbers and the subpopulation affected was significantly related to the degree of surgical trauma, and returned to pre-operative values by postoperative day 7. Changes in alpha-1-PI, alpha-2-M, alpha-2-PAG and PSA were also significantly related to the degree of surgical trauma, and these plasma changes persisted longer than the cellular disturbances. Surgical operations induce a reversible depression of cellular immunity which precedes plasma suppressive activity in its return to pre-operative levels. Immunostimulating agents such as interferon and the interleukins deserve evaluation as prophylactic agents pre-operatively.

Journal ArticleDOI
TL;DR: Results indicate that, while ‘exosomes’ express tumour antigens, leading to their proposed utility as tumour vaccines, they also can suppress T-cell signalling molecules and induce apoptosis.
Abstract: Dendritic and lymphoid ‘exosomes’ regulate immune activation. Tumours release membranous material mimicking these ‘exosomes,’ resulting in deletion of reactive lymphocytes. Tumour-derived ‘exosomes’ have recently been explored as vaccines, without analysis of their immunologic consequences. This investigation examines the composition of tumour-derived ‘exosomes’ and their effects on T lymphocytes. Membranous materials were isolated from ascites of ovarian cancer patients (n=6) and Western immunoblotting was performed for markers associated with ‘exosomes.’ Using cultured T cells, ‘exosomes’ were evaluated for suppression of CD3-ζ and JAK 3 expressions and induction of apoptosis, measured by DNA fragmentation. ‘Exosome’ components mediating suppression of CD3-ζ were isolated by continuous eluting electrophoresis and examined by Western immunoblotting. ‘Exosomes’ were shown to be identical with previously characterised shed membrane vesicles by protein staining and TSG101 expression. ‘Exosomes’ expressed class I MHC, placental alkaline phosphatase, B23/nucleophosmin, and FasL. ‘Exosomes’ suppressed expression of T-cell activation signalling components, CD3-ζ and JAK 3 and induced apoptosis. CD3-ζ suppression was mediated by two components: 26 and 42 kDa. Only the 42 kDa component reacted with anti-FasL antibody. These results indicate that, while ‘exosomes’ express tumour antigens, leading to their proposed utility as tumour vaccines, they also can suppress T-cell signalling molecules and induce apoptosis.

Journal ArticleDOI
TL;DR: The results suggest that Hcy activates PAR-4, which induces production of reactive oxygen species by increasing NADPH oxidase and decreasing thioredoxin expression and reduces NO bioavailability in cultured MVEC by 1) increasing NO2-tyrosine formation and 2) accumulating ADMA by decreasing DDAH expression.
Abstract: Hyperhomocysteinemia decreases vascular reactivity and is associated with cardiovascular morbidity and mortality. However, pathogenic mechanisms that increase oxidative stress by homocysteine (Hcy)...

Journal ArticleDOI
TL;DR: The ability of monocytes to express HLA‐DR antigen correlated directly with the clinical course in these patients and its measurement identified a group of patients at high risk of infection and death following trauma.
Abstract: Immunological assessment is important to characterize the host defence response of trauma patients as infection is the most common cause of severe morbidity and late death. Sixty trauma patients were followed serially and divided into three groups: those with an uneventful recovery (n = 17), those with recovery after major sepsis (n = 27) and those who died (n = 16). The ability of peripheral blood monocytes to express the antigen HLA-DR was measured and compared to the results from 77 asymptomatic volunteers. After initial injury, there was a significant reduction from normal in the three trauma groups. It took one week for HLA-DR antigen expression to return to the normal range in the first group, three weeks in the second group, and in the third group it never returned to normal. Monocyte HLA-DR antigen expression, after incubation with lipopolysaccharide, distinguished those patients who survived from those who died. There was no difference in HLA-DR antigen expression between a high transfusion group of 31 patients who received 10 or more units of blood and a low transfusion group of 29 patients who received less than 10 units. The ability of monocytes to express HLA-DR antigen correlated directly with the clinical course in these patients and its measurement identified a group of patients at high risk of infection and death following trauma.

Journal ArticleDOI
Bernard Aubert1, R. Barate1, D. Boutigny1, F. Couderc1  +601 moreInstitutions (76)
TL;DR: In this article, the decay of B{bar B} events collected at the BaBar detector at the PEP-II e{sup +}e{sup -} asymmetric energy storage ring was studied.
Abstract: The authors study the decay B{sup -} {yields} J/{psi}K{sup -}{pi}{sup +}{pi}{sup -} using 117 million B{bar B} events collected at the {Upsilon}(4S) resonance with the BaBar detector at the PEP-II e{sup +}e{sup -} asymmetric-energy storage ring. They measure the branching fractions {Beta}(B{sup -} {yields} J/{psi}K{sup -} {pi}{sup +}{pi}{sup -}) = (116 {+-} 7(stat.) {+-} 9(syst.)) x 10{sup -5} and {Beta}(B{sup -} {yields} X(3872)K{sup -}) x {Beta}(X(3872) {yields} J/{psi}{pi}{sup +}{pi}{sup -}) = (1.28 {+-} 0.41) x 10{sup -5} and find the mass of the X(3872) to be 3873.4 {+-} 1.4MeV/c{sup 2}. They search for the h{sub c} narrow state in the decay B{sup -} {yields} h{sub c} K{sup -}, h{sub c} {yields} J/{psi}{pi}{sup +}{pi}{sup -} and for the decay B{sup -} {yields} J/{psi}D{sup 0}{pi}{sup -}, with D{sup 0} {yields} K{sup -}{pi}{sup +}. They set the 90% C.L. limits {Beta}(B{sup -} {yields} h{sub c}K{sup -}) x {Beta}(h{sub c} {yields} J/{psi}{pi}{sup +}{pi}{sup -}) < 3.4 x 10{sup -6} and {Beta}(B{sup -} {yields} J/{psi}D{sup 0}{pi}{sup -}) < 5.2 x 10{sup -5}.

Journal ArticleDOI
TL;DR: In this paper, the role of aP2 in macrophage biology and the molecular mechanisms underlying its actions was investigated, and it was shown that aP 2-deficient macrophages display defects in cholesterol accumulation and alterations in pro-inflammatory responsiveness, leading to elevated CD36 expression and enhanced uptake of modified low denwsity lipoprotein.

Journal ArticleDOI
TL;DR: Functional neuroimaging found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls, suggesting a genetically controlled neural circuitry for regulating human social behavior.
Abstract: Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Journal ArticleDOI
TL;DR: Observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.
Abstract: Here, we show a role for the RB1 family proteins in directing full heterochromatin formation. Mouse embryonic fibroblasts that are triply deficient for RB1 (retinoblastoma 1), RBL1 (retinoblastoma-like 1) and RBL2 (retinoblastoma-like 2) - known as TKO cells - show a marked genomic instability, which is coincidental with decreased DNA methylation, increased acetylation of histone H3 and decreased tri-methylation of histone H4 at lysine 20 (H4K20). Chromatin immunoprecipitation showed that H4K20 tri-methylation was specifically decreased at pericentric and telomeric chromatin. These defects are independent of E2F family function. Indeed, we show a direct interaction between the RB1 proteins and the H4K20 tri-methylating enzymes Suv4-20h1 and Suv4-20h2, indicating that the RB1 family has a role in controlling H4K20 tri-methylation by these histone methyltransferases. These observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.

Journal ArticleDOI
TL;DR: Books on the characteristics and possible interpretations of the event-related potential (ERP) peaks commonly identified in research are reviewed to serve as a tutorial for general readers interested in neuropsychological research and as a reference source for researchers using ERP techniques.
Abstract: This article reviews literature on the characteristics and possible interpretations of the event-related potential (ERP) peaks commonly identified in research. The description of each peak includes typical latencies, cortical distributions, and possible brain sources of observed activity as well as the evoking paradigms and underlying psychological processes. The review is intended to serve as a tutorial for general readers interested in neuropsychological research and as a reference source for researchers using ERP techniques.

Journal ArticleDOI
06 Jan 2005-Neuron
TL;DR: In this study, in vivo evidence for a late phase of Olig gene expression independent of Nkx6 and Shh gene activities is provided and a brief second wave of oligodendrogenesis in the dorsal spinal cord is revealed.

Journal ArticleDOI
23 Feb 2005-JAMA
TL;DR: Clinicians should use timely epidemiologic data to ascertain if influenza is circulating in their communities, then either treat patients with influenza-like illness empirically or obtain a rapid influenza test to assist with management decisions.
Abstract: ContextInfluenza vaccination lowers, but does not eliminate, the risk of influenza. Making a reliable, rapid clinical diagnosis is essential to appropriate patient management that may be especially important during shortages of antiviral agents caused by high demand.ObjectivesTo systematically review the precision and accuracy of symptoms and signs of influenza. A secondary objective was to review the operating characteristics of rapid diagnostic tests for influenza (results available in <30 min).Data SourcesStructured search strategy using MEDLINE (January 1966-September 2004) and subsequent searches of bibliographies of retrieved articles to identify articles describing primary studies dealing with the diagnosis of influenza based on clinical signs and symptoms. The MEDLINE search used the Medical Subject Headings EXP influenza or EXP influenza A virus or EXP influenza A virus human or EXP influenza B virus and the Medical Subject Headings or terms EXP sensitivity and specificity or EXP medical history taking or EXP physical examination or EXP reproducibility of results or EXP observer variation or symptoms.mp or clinical signs.mp or sensitivity.mp or specificity.mp.Study SelectionOf 915 identified articles on clinical assessment of influenza-related illness, 17 contained data on the operating characteristics of symptoms and signs using an independent criterion standard. Of these, 11 were eliminated based on 4 inclusion criteria and availability of nonduplicative primary data.Data ExtractionTwo authors independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of clinical diagnostic findings. Differences were resolved by discussion and consensus.Data SynthesisNo symptom or sign had a summary LR greater than 2 in studies that enrolled patients without regard to age. For decreasing the likelihood of influenza, the absence of fever (LR, 0.40; 95% confidence interval [CI], 0.25-0.66), cough (LR, 0.42; 95% CI, 0.31-0.57), or nasal congestion (LR, 0.49; 95% CI, 0.42-0.59) were the only findings that had summary LRs less than 0.5. In studies limited to patients aged 60 years or older, the combination of fever, cough, and acute onset (LR, 5.4; 95% CI, 3.8-7.7), fever and cough (LR, 5.0; 95% CI, 3.5-6.9), fever alone (LR, 3.8; 95% CI, 2.8-5.0), malaise (LR, 2.6; 95% CI, 2.2-3.1), and chills (LR, 2.6; 95% CI, 2.0-3.2) increased the likelihood of influenza to the greatest degree. The presence of sneezing among older patients made influenza less likely (LR, 0.47; 95% CI, 0.24-0.92).ConclusionsClinical findings identify patients with influenza-like illness but are not particularly useful for confirming or excluding the diagnosis of influenza. Clinicians should use timely epidemiologic data to ascertain if influenza is circulating in their communities, then either treat patients with influenza-like illness empirically or obtain a rapid influenza test to assist with management decisions.

Journal ArticleDOI
TL;DR: Over a wide range of RV, increasing from 0 mL to >400 mL, the frequency of regurgitation and aspiration did not change appreciably, and bowel function scores did not correlate with the incidence of aspiration or Regurgitation.
Abstract: Background and Aims:Elevated residual volumes (RV), considered a marker for the risk of aspiration, are used to regulate the delivery of enteral tube feeding. We designed this prospective study to validate such use.Methods:Critically ill patients undergoing mechanical ventilation in the medical, cor

Journal ArticleDOI
TL;DR: In this paper, a political economy model with imperfect product market competition was developed where local and foreign firms jointly lobbied the local government for a favorable pollution tax, and the effect of foreign direct investment on environmental policies was investigated.
Abstract: We suggest a novel perspective on the relationship between the stringency of environmental policies and foreign direct investment (FDI). We develop a political economy model with imperfect product market competition where local and foreign firms jointly lobby the local government for a favorable pollution tax. FDI is found to affect environmental policy, and the effect is conditional on the local government's degree of corruptibility. If the degree of corruptibility is sufficiently high (low), FDI leads to less (more) stringent environmental policy, and FDI thus contributes to (mitigates) the creation of a pollution haven. Our empirical results using panel data from 33 countries support the predictions of the model.