Showing papers by "Emory University published in 2000"

Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress

Abstract: Accumulating evidence suggests that oxidant stress alters many functions of the endothelium, including modulation of vasomotor tone. Inactivation of nitric oxide (NO(.)) by superoxide and other reactive oxygen species (ROS) seems to occur in conditions such as hypertension, hypercholesterolemia, diabetes, and cigarette smoking. Loss of NO(.) associated with these traditional risk factors may in part explain why they predispose to atherosclerosis. Among many enzymatic systems that are capable of producing ROS, xanthine oxidase, NADH/NADPH oxidase, and uncoupled endothelial nitric oxide synthase have been extensively studied in vascular cells. As the role of these various enzyme sources of ROS become clear, it will perhaps be possible to use more specific therapies to prevent their production and ultimately correct endothelial dysfunction.

Chronic systemic pesticide exposure reproduces features of Parkinson's disease

Abstract: The cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity. Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.

NAD(P)H Oxidase: Role in Cardiovascular Biology and Disease

Abstract: Reactive oxygen species have emerged as important molecules in cardiovascular function. Recent work has shown that NAD(P)H oxidases are major sources of superoxide in vascular cells and myocytes. The biochemical characterization, activation paradigms, structure, and function of this enzyme are now partly understood. Vascular NAD(P)H oxidases share some, but not all, characteristics of the neutrophil enzyme. In response to growth factors and cytokines, they produce superoxide, which is metabolized to hydrogen peroxide, and both of these reactive oxygen species serve as second messengers to activate multiple intracellular signaling pathways. The vascular NAD(P)H oxidases have been found to be essential in the physiological response of vascular cells, including growth, migration, and modification of the extracellular matrix. They have also been linked to hypertension and to pathological states associated with uncontrolled growth and inflammation, such as atherosclerosis.

Ecological Resilience—In Theory and Application

Abstract: ▪ Abstract In 1973, C. S. Holling introduced the word resilience into the ecological literature as a way of helping to understand the non-linear dynamics observed in ecosystems. Ecological resilience was defined as the amount of disturbance that an ecosystem could withstand without changing self-organized processes and structures (defined as alternative stable states). Other authors consider resilience as a return time to a stable state following a perturbation. A new term, adaptive capacity, is introduced to describe the processes that modify ecological resilience. Two definitions recognize the presence of multiple stable states (or stability domains), and hence resilience is the property that mediates transition among these states. Transitions among stable states have been described for many ecosystems, including semi-arid rangelands, lakes, coral reefs, and forests. In these systems, ecological resilience is maintained by keystone structuring processes across a number of scales, sources of renewal and ...

Pituitary-Adrenal and Autonomic Responses to Stress in Women After Sexual and Physical Abuse in Childhood

Abstract: ContextEvidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association.ObjectiveTo determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions.Design and SettingProspective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga.ParticipantsForty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse).Main Outcome MeasuresAdrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups.ResultsWomen with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60.4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001).ConclusionsOur findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress.

Indoor air pollution in developing countries: a major environmental and public health challenge

Abstract: Around 50% of people, almost all in developing countries, rely on coal and biomass in the form of wood, dung and crop residues for domestic energy. These materials are typically burnt in simple stoves with very incomplete combustion. Consequently, women and young children are exposed to high levels of indoor air pollution every day. There is consistent evidence that indoor air pollution increases the risk of chronic obstructive pulmonary disease and of acute respiratory infections in childhood, the most important cause of death among children under 5 years of age in developing countries. Evidence also exists of associations with low birth weight, increased infant and perinatal mortality, pulmonary tuberculosis, nasopharyngeal and laryngeal cancer, cataract, and, specifically in respect of the use of coal, with lung cancer. Conflicting evidence exists with regard to asthma. All studies are observational and very few have measured exposure directly, while a substantial proportion have not dealt with confounding. As a result, risk estimates are poorly quantified and may be biased. Exposure to indoor air pollution may be responsible for nearly 2 million excess deaths in developing countries and for some 4% of the global burden of disease. Indoor air pollution is a major global public health threat requiring greatly increased efforts in the areas of research and policy-making. Research on its health effects should be strengthened, particularly in relation to tuberculosis and acute lower respiratory infections. A more systematic approach to the development and evaluation of interventions is desirable, with clearer recognition of the interrelationships between poverty and dependence on polluting fuels.

14-3-3 Proteins: Structure, Function, and Regulation

Abstract: The 14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. A striking feature of the 14-3-3 proteins is their ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. This plethora of interacting proteins allows 14-3-3 to play important roles in a wide range of vital regulatory processes, such as mitogenic signal transduction, apoptotic cell death, and cell cycle control. In this review, we examine the structural basis for 14-3-3-ligand interactions, proposed functions of 14-3-3 in various signaling pathways, and emerging views of mechanisms that regulate 14-3-3 actions.

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.

Abstract: Background Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. Methods We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments. Results Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response ...

Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer : The Prostate Cancer Outcomes Study

Abstract: ContextPatients with prostate cancer and their physicians need knowledge of treatment options and their potential complications, but limited data on complications are available in unselected population-based cohorts of patients.ObjectiveTo measure changes in urinary and sexual function in men who have undergone radical prostatectomy for clinically localized prostate cancer.DesignThe Prostate Cancer Outcomes Study, a population-based longitudinal cohort study with up to 24 months of follow-up.SettingPopulation-based cancer registries in 6 geographic regions of the United States.ParticipantsA total of 1291 black, white, and Hispanic men aged 39 to 79 years who were diagnosed as having primary prostate cancer between October 1, 1994, and October 31, 1995, and who underwent radical prostatectomy within 6 months of diagnosis for clinically localized disease.Main Outcome MeasuresDistribution of and change in urinary and sexual function measures reported by patients at baseline and 6, 12, and 24 months after diagnosis.ResultsAt 18 or more months following radical prostatectomy, 8.4% of men were incontinent and 59.9% were impotent. Among men who were potent before surgery, the proportion of men reporting impotence at 18 or more months after surgery varied according to whether the procedure was nerve sparing (65.6% of non–nerve-sparing, 58.6% of unilateral, and 56.0% of bilateral nerve–sparing). At 18 or more months after surgery, 41.9% reported that their sexual performance was a moderate-to-large problem. Both sexual and urinary function varied by age (39.0% of men aged <60 years vs 15.3%-21.7% of older men were potent at ≥18 months [P<.001]; 13.8% of men aged 75-79 years vs 0.7%-3.6% of younger men experienced the highest level of incontinence at ≥18 months [P = .03]), and sexual function also varied by race (38.4% of black men reported firm erections at ≥18 months vs 25.9% of Hispanic and 21.3% of white men; P = .001).ConclusionsOur study suggests that radical prostatectomy is associated with significant erectile dysfunction and some decline in urinary function. These results may be particularly helpful to community-based physicians and their patients with prostate cancer who face difficult treatment decisions.

Neurodevelopmental and Functional Outcomes of Extremely Low Birth Weight Infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994

Abstract: Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401–1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. Study Design. A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months9 corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. Results. Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 ± 135 g, mean gestation (best obstetric dates) 26 ± 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index Conclusion. ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months9 corrected age.

Relationship Marketing Activities, Commitment, and Membership Behaviors in Professional Associations:

Abstract: The authors conceptualize and empirically examine professional associations’ relationship-building efforts (core services performance, rewards for contributions, dissemination of organizational knowledge, member interdependence enhancement activities, and reliance on external membership requirements) that are theorized to enhance their membership’s commitment to the relationship as well as the membership’s relationship behaviors. Three components of commitment—affective, continuance, and normative—are theorized to mediate differentially the correlation between the associations’ relationship-building efforts and their members’ relationship behaviors (membership retention, exchange-based participation, and cooperatively based coproduction). Confirmatory factor analysis validates the commitment measures, and structural equations analysis indicates that normative and affective commitment partially mediate the effects of selected relationship-building efforts on coproduction and member participation. ...

Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease.

Abstract: Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment. Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction. As caspase-1 and nitric oxide seem to play a role in Huntington disease, we evaluated the therapeutic efficacy of minocycline in the R6/2 mouse model of Huntington disease. We report that minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA upregulation, and decreases inducible nitric oxide synthetase activity. In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. This is the first demonstration of caspase-1 and caspase-3 transcriptional regulation in a Huntington disease model.

Social amnesia in mice lacking the oxytocin gene.

Abstract: The development of social familiarity in rodents depends predominantly on olfactory cues and can critically influence reproductive success. Researchers have operationally defined this memory by a reliable decrease in olfactory investigation in repeated or prolonged encounters with a conspecific. Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding. Pharmacological studies indicate that AVP administration may enhance social memory, whereas OT administration may either inhibit or facilitate social memory depending on dose, route or paradigm. We found that male mice mutant for the oxytocin gene (Oxt-/-) failed to develop social memory, whereas wild-type (Oxt+/+) mice showed intact social memory. Measurement of both olfactory foraging and olfactory habituation tasks indicated that olfactory detection of non-social stimuli is intact in Oxt-/- mice. Spatial memory and behavioural inhibition measured in a Morris water-maze, Y-maze, or habituation of an acoustic startle also seemed intact. Treatment with OT but not AVP rescued social memory in Oxt-/- mice, and treatment with an OT antagonist produced a social amnesia-like effect in Oxt+/+ mice. Our data indicate that OT is necessary for the normal development of social memory in mice and support the hypothesis that social memory has a neural basis distinct from other forms of memory.

A meta-analytic review of sex differences in facial expression processing and their development in infants, children, and adolescents

Abstract: Quantitative and qualitative reviews of the literature on sex differences in facial expression processing (FEP) have yielded conflicting findings regarding children. This study was designed to review quantitatively the literature on sex differences in FEP from infancy through adolescence and to evaluate consistency between the course of FEP development and predictions derived from preliminary theoretical models. Results, which indicate a female advantage at FEP, are consistent with predictions derived from an integrated neurobehavioral/social constructivist model. These findings suggest a need for research examining both neurological maturation and socialization as important factors in the development of sex differences in FEP and related skills. Possible directions for future study are discussed, with emphasis on the need to integrate the infant literature with research focused on older children and adults.

Application of the Theory of Gender and Power to Examine HIV-Related Exposures, Risk Factors, and Effective Interventions for Women

Abstract: Developed by Robert Connell, the theory of gender and power is a social structural theory based on existing philosophical writings of sexual inequality and gender and power imbalance. According to the theory of gender and power, there are three major social structures that characterize the gendered relationships between men and women: the sexual division of labor, the sexual division of power, and the structure of cathexis. The aim of this article is to apply an extended version of the theory of gender and power to examine the exposures, social/behavioral risk factors, and biological properties that increase women's vulnerability for acquiring HIV. Subsequently, the authors review several public health level HIV interventions aimed at reducing women's HIV risk. Employing the theory of gender and power among women marshals new kinds of data, asks new and broader questions with regard to women and their risk of HIV, and, most important, creates new options for prevention.

Modulation of Protein Kinase Activity and Gene Expression by Reactive Oxygen Species and Their Role in Vascular Physiology and Pathophysiology

Abstract: Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

Abstract: A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness

Abstract: The hepatitis B virus (HBV) genotype was determined in a total of 121 plasma samples collected in France and the US from patients chronically infected with HBV HBV genotype A was predominant in this collection, appearing in 66 samples (54%), while genotypes B, C, D, E and F occurred in 4 (3%), 14 (12%), 23 (19%), 1 (1%) and 0 (0%) of samples, respectively However, the genotype of a total of 13 (11%) samples (2 from France, 11 from the US) could not be determined with the methodology used Sequence analysis, and subsequent phylogenetic analysis of the complete genome and the individual open reading frames, showed that the virus isolate from these samples was 3248 bp long and, phylogenetically, did not cluster with any of the known genotypes This strain was provisionally called HBV genotype G Virus isolates that were obtained from geographically separated regions like France and the US were closely related to each other All virus strains analysed contained some characteristic differences when compared to genotype A: a translational stop codon at aa 2 and 28 of the preCore region; a 36 nt (12 aa) insert in the amino-terminal part of the Core antigen (HBcAg); a 2 aa deletion in the carboxy-terminal part of HBcAg; and a 1 aa deletion in the preS1 open reading frame The deduced amino acid sequence of HBsAg suggests that this newly discovered genotype G strain belongs to serological group adw2

Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders.

Abstract: There is abundant evidence for abnormalities of the norepinephrine (NE) and serotonin (5HT) neurotransmitter systems in depression and anxiety disorders. The majority of evidence supports underactivation of serotonergic function and complex dysregulation of noradrenergic function, most consistent with overactivation of this system. Treatment for these disorders requires perturbation of these systems. Reproducible increases in serotonergic function and decreases in noradrenergic function accompany treatment with antidepressants, and these alterations may be necessary for antidepressant efficacy. Dysregulation of these systems clearly mediates many symptoms of depression and anxiety. The underlying causes of these disorders, however, are less likely to be found within the NE and 5HT systems, per se. Rather their dysfunction is likely due to their role in modulating, and being modulated by, other neurobiologic systems that together mediate the symptoms of affective illness. Clarification of noradrenergic and serotonergic modulation of various brain regions may yield a greater understanding of specific symptomatology, as well as the underlying circuitry involved in euthymic and abnormal mood and anxiety states. Disrupted cortical regulation may mediate impaired concentration and memory, together with uncontrollable worry. Hypothalamic abnormalities likely contribute to altered appetite, libido, and autonomic symptoms. Thalamic and brainstem dysregulation contributes to altered sleep and arousal states. Finally, abnormal modulation of cortical-hippocampal-amygdala pathways may contribute to chronically hypersensitive stress and fear responses, possibly mediating features of anxiety, anhedonia, aggression, and affective dyscontrol. The continued appreciation of the neural circuitry mediating affective states and their modulation by neurotransmitter systems should further the understanding of the pathophysiology of affective and anxiety disorders. Depression and Anxiety, Volume 12, Supplement 1:2–19, 2000. © 2000 Wiley-Liss, Inc.

Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States.

Abstract: Background The emergence of drug-resistant strains of bacteria has complicated treatment decisions and may lead to treatment failures. Methods We examined data on invasive pneumococcal disease in patients identified from 1995 to 1998 in the Active Bacterial Core Surveillance program of the Centers for Disease Control and Prevention. Pneumococci that had a high level of resistance or had intermediate resistance according to the definitions of the National Committee for Clinical Laboratory Standards were defined as “resistant” for this analysis. Results During 1998, 4013 cases of invasive Streptococcus pneumoniae disease were reported (23 cases per 100,000 population); isolates were available for 3475 (87 percent). Overall, 24 percent of isolates from 1998 were resistant to penicillin. The proportion of isolates that were resistant to penicillin was highest in Georgia (33 percent) and Tennessee (35 percent), in children under five years of age (32 percent, vs. 21 percent for persons five or more years of ag...

Extension of life-span with superoxide dismutase/catalase mimetics

Abstract: We tested the theory that reactive oxygen species cause aging. We augmented the natural antioxidant systems of Caenorhabditis elegans with small synthetic superoxide dismutase/catalase mimetics. Treatment of wild-type worms increased their mean life-span by a mean of 44 percent, and treatment of prematurely aging worms resulted in normalization of their life-span (a 67 percent increase). It appears that oxidative stress is a major determinant of life-span and that it can be counteracted by pharmacological intervention.

Market-Driven Versus Driving Markets:

Abstract: The purpose of this article is to discuss two approaches to being market oriented—a market-driven approach and a driving-markets approach.Market driven refers to a business orientation that is based on understanding and reacting to the preferences and behaviors of players within a given market structure.Driving markets, on the other hand, implies influencing the structure of the market and/or the behavior(s) of market players in a direction that enhances the competitive position of the business. There are three generic ways of changing the structure of a market: (1) eliminating players in a market (deconstruction approach), (2) building a new or modified set of players in a market (construction approach), and (3) changing the functions performed by players (functional modification approach). Market behavior can be modified directly or, alternatively, indirectly by changing the mind-set of market players (e.g., customers, competitors, and other stakeholders).

Prokaryotic Regulation of Epithelial Responses by Inhibition of IκB-α Ubiquitination

Abstract: Epithelia of the vertebrate intestinal tract characteristically maintain an inflammatory hyporesponsiveness toward the lumenal prokaryotic microflora We report the identification of enteric organisms (nonvirulent Salmonella strains) whose direct interaction with model human epithelia attenuate synthesis of inflammatory effector molecules elicited by diverse proinflammatory stimuli This immunosuppressive effect involves inhibition of the inhibitor kappaB/nuclear factor kappaB (IkappaB/NF-kappaB) pathway by blockade of IkappaB-alpha degradation, which prevents subsequent nuclear translocation of active NF-kappaB dimer Although phosphorylation of IkappaB-alpha occurs, subsequent polyubiquitination necessary for regulated IkappaB-alpha degradation is completely abrogated These data suggest that prokaryotic determinants could be responsible for the unique tolerance of the gastrointestinal mucosa to proinflammatory stimuli

The Antecedents and Consequences of Customer-Centric Marketing:

Abstract: As we enter the twenty-first century, the marketing function remains concerned with serving customers and consumers effectively. The authors propose that just as the marketing function gradually shifted from mass marketing to segmented marketing in the twentieth century, it will increasingly move toward customer-centric marketing in the next century. In the practice of customer-centric marketing, the marketing function seeks to fulfill the needs and wants of each individual customer. The antecedents of customer-centric marketing are the increasing pressure on firms to improve marketing productivity, increasing market diversity in household and business markets, and technology applicability. On the basis of the shift toward customer-centric marketing, the authors expect increased importance of marketing as a “supply management” function, customer outsourcing, cocreation marketing, fixedcost marketing, and customer-centric organizations. This article highlights the implications of customer-centric marketing as well as the boundary conditions that will affect its adoption.

Against the Odds: Self-Efficacy Beliefs of Women in Mathematical, Scientific, and Technological Careers

Abstract: The purpose of this study was to explore the personal stories of women who selected and continue to excel at careers in areas of mathematics, science, and technology to better understand the ways in which their self-efficacy beliefs influenced their academic and career choices. Analysis of 15 narratives revealed that verbal persuasions and vicarious experiences were critical sources of the women's self-efficacy beliefs. These findings suggest that the perceived importance of these sources of self-efficacy believes may be stronger for women in male-oriented domains than for individuals operating in traditional settings. Academic and relational self efficacy perceptions resulted in the perseverance and resiliency required to overcome academic and career obstacles. Findings support and refine the theoretical tenets of A. Bandura's (1986) social cognitive theory, and they also suggest that critical tenets in this theory are consistent with the work of C. Gilligan (1982) and N. Noddings (1992).

A Standardized Method for Measuring Intracranial Arterial Stenosis

Abstract: BACKGROUND AND PURPOSE: Atherosclerosis of the major intracranial arteries is an important cause of ischemic stroke. We established measurement criteria to assess percent stenosis of a major intracranial artery (carotid, middle cerebral, vertebral, basilar) and determined the interobserver/intraobserver agreements and interclass/intraclass correlations of these measurements. METHODS: We defined percent stenosis of an intracranial artery as follows: percent stenosis = [(1 − (D stenosis /D normal ))] × 100, where D stenosis = the diameter of the artery at the site of the most severe stenosis and D normal = the diameter of the proximal normal artery. If the proximal segment was diseased, contingency sites were chosen to measure D normal : distal artery (second choice), feeding artery (third choice). Using a hand-held digital caliper, three neuroradiologists independently measured D stenosis and D normal of 24 stenotic intracranial arteries. Each observer repeated the readings 4 weeks later. We determined how frequently two observers9 measurements of percent stenosis of each of the 24 diseased arteries differed by 10% or less. RESULTS: Among the three pairs of observers, interobserver agreements were 88% (observer 1 versus observer 2), 79% (observer 1 versus observer 3), 75% (observer 2 versus observer 3) for the first reading and were 75% (observer 1 versus observer 2), 100% (observer 1 versus observer 3), and 71% (observer 2 versus observer 3) for the second reading. Intraobserver agreement for each of the observers was 88%, 83%, and 100%. Interclass correlation was 85% (first reading) and 87% (second reading). Intraclass correlation was 92% (first and second readings combined). CONCLUSION: This method shows good interobserver and intraobserver agreements for the measurement of intracranial stenosis of a major artery. If validated in subsequent studies, this method may serve as a standard for the measurement of percent stenosis of an intracranial artery.