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Background: Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil‐associated proteins to diagnose EoE and predict esophageal eosinophilia. Methods: Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil‐derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein‐1 (MBP‐1), galectin‐10 (CLC/GAL‐10), Eotaxin‐2 and Eotaxin‐3, and urine osteopontin (OPN) and matrix metalloproteinase‐9 (MMP‐9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed. Results: Of 183 specimens were collected from 56 EoE patients and 15 non‐EoE controls with symptoms of esophageal dysfunction; 33 EoE patients had paired pre‐ and post‐treatment specimens. Plasma (CLC/GAL‐10, ECP, EDN, Eotaxin‐3, MBP‐1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL‐10, Eotaxin‐3, ECP, EDN, MBP‐1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL‐10, ECP, and MBP‐1 were significantly decreased in patients with esophageal eosinophil counts <15/hpf in response to treatment. AEC, CLC/GAL‐10, ECP, EDN, OPN, and MBP‐1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment, and atopy; AEC combined with MBP‐1 best predicted the counts. Conclusions: We identified novel panels of eosinophil‐associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from controls and predicting esophageal eosinophil counts. [ABSTRACT FROM AUTHOR]

Background: A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1‐CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation. Objective: To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens. Methods: We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe. Results: Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen‐reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL‐GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL‐GW nanoprobe ameliorated asthma pathologies including allergen‐specific serum IgE production, allergic lung and airway inflammation and airway hyper‐responsiveness (AHR) with minimal pulmonary adverse reaction. Conclusion: The inhibition of the CSF1‐CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Ellis AK, Ackerman SJ, Crawford L, Du J, Bedi R, Denburg JA. Cord blood molecular biomarkers of eosinophilopoiesis: Kinetic analysis of GATA-1, MBP1 and IL-5Rα mRNA expression. Pediatr Allergy Immunol 2010: 21: 640–648. © 2010 John Wiley & Sons A/S Eosinophil/basophil (Eo/B) progenitor phenotype and function in cord blood (CB) are associated with atopic risk at birth and infant clinical outcomes. Molecular analyses of eosinophil–basophil differentiation events could identify clinically predictive biomarkers. To determine CB kinetic patterns of Eo/B lineage-associated gene expression (GATA-1, MBP1 and IL-5Rα) after IL-5 stimulation, CB non-adherent mononuclear cells were isolated from random fresh and frozen samples and incubated in the presence of recombinant human interleukin-5. Some underwent CD34+ positive selection using magnetic cell separation. At various time-points, mRNA expression of GATA-1, MBP1 and IL-5Rα (total transcripts) was determined utilizing multiplex quantitative polymerase chain reaction (Q-PCR). Relative expression levels of the IL-5Rα soluble vs. transmembrane isoforms were also analyzed. Stimulation of the non-adherent mononuclear cells with IL-5 resulted in early up-regulation of GATA-1, peaking at 48 h, followed by decreasing expression and down-regulation by 96 h. The CD34+ enriched population demonstrated an equivalent expression pattern ( r = 0.963, p = 0.0349). MBP1 mRNA expression [non-adherent mononuclear cells (NAMNCs) and CD34+ alike; r = 0.988, p = 0.012] was slowly up-regulated in response to IL-5, maximal at 96 h. Total IL-5Rα expression appeared stable over the time-course, mediated by differential expression of the soluble and transmembrane isoforms (i.e., initial increase in the transmembrane contribution followed by a predominance of the soluble isoform by 48–72 h). Multiplex Q-PCR analysis of mRNA from CB demonstrates expression of critical eosinophil-basophil lineage-specific events that are consistent with current understanding of eosinophil differentiation and maturation. The non-adherent mononuclear cell population provides a surrogate signal for the CD34+ progenitor population. [ABSTRACT FROM AUTHOR]

This study investigates the relationship of patient defensive functioning, therapeutic alliance and therapists' use of technical interventions in Short-Term Psychodynamic Psychotherapy (STPP; Book, 1998; Luborsky, 1984; Strupp & Binder, 1984; Wachtel, 1993). Participants in this study were 44 patients admitted for individual psychotherapy at a university based outpatient community clinic. Patient defensive functioning was assessed with the Defensive Functioning Scale (DFS) of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). Therapeutic alliance was assessed using patient ratings from the Combined Alliance Short Form (CASF; Hatcher & Barends, 1996). External raters coded videotaped sessions using the Comparative Psychotherapy Process Scale (CPPS; Hilsenroth, Blagys, Ackerman Bonge & Blais, in press) to assess the use of Psychodynamic–Interpersonal (PI) and Cognitive–Behavioral (CB) techniques early (third or fourth session) in psychotherapy. Patient Overall Defensive Functioning (ODF) was found to predict therapists' overall use of PI interventions, as well as specific PI and CB interventions. Additionally, patients who utilized fewer adaptive defenses were found to receive more PI interventions in general. The implications of these findings for treatment planning and intervention are discussed. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study investigates the facets of the alliance and their relationship with estimated effectiveness of psychotherapy using a measure called the Combined Alliance Short Form (CASF; Hatcher, 1999; Hatcher & Barends, 1996; Hatcher, Barends, Hansell, & Gutfreund, 1995). Because the CASF has both patient and therapist versions, it was possible to compare ratings of various facets of the alliance from each perspective. Data were collected from 125 patient–therapist dyads, and all participants completed the CASF as well as measures of perceived progress during therapy. Convergence was examined for each alliance subscale for the patient–therapist dyads. Both the patient and therapist Confident Collaboration factors were found to be primary predictors of perceived improvement in psychotherapy. Number of psychotherapy sessions was related to patient estimates of improvement and therapist ratings of the amount of help received by their patients as well. Confident Collaboration, a factor that reflects the level of confidence and commitment a patient experiences regarding the therapy as well as the degree to which the therapy is experienced as worthwhile, is discussed in relation to previous research. Implications regarding the presence of this factor during psychotherapy are considered in detail. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]