Dysfunctional schemas and psychopathology in referred obese adolescents

Objective: Referred obese adolescents often display psychological problems. The present study aimed at investigating whether Young's schema theory constitutes a comprehensive framework to understand psychopathology in youth in general and in referred obese adolescents in particular. Methods: 91 youngsters referred for obesity treatment and 91 normal weight controls (all between 12 and 18 years of age) filled out the Young Schema Questionnaire and the Youth Self‐Report. Parents were asked to complete the Child Behavior Checklist. Results: The obese youngsters displayed an overall greater severity of dysfunctional schemas than normal weight controls. The obese group scored significantly higher for the schemas Emotional Deprivation, Social Isolation/Alienation, Defectiveness/Shame, Failure to Achieve, Dependence/Incompetence and Subjugation. Social Isolation/Alienation and Vulnerability to Harm/Illness were highly predictive for internalizing symptoms in youth. The schemas Entitlement and Dependence/Incompetence were predictive for externalizing symptoms in youth. Conclusion: Referred obese individuals display high levels of maladaptive schemas and these are generally related to internalizing and externalizing symptoms. Copyright © 2007 John Wiley & Sons, Ltd.     

The rational design of TAP inhibitors using peptide substrate modifications and peptidomimetics

The major histocompatibility complex (MHC)-encoded transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum. This step precedes the binding of peptides to MHC class I molecules and is essential for cell surface expression of the MHC class I/peptide complex. TAP has a broad sequence specificity and a preference for peptides of around 9 amino acids. To synthesize inhibitors for TAP, we studied various alterations of the peptide substrate. The results indicate that TAP is stereospecific and that peptide bonds engineered into isosteric structures can improve translocation of the peptide. Furthermore, TAP is able to translocate peptides with large side chains that correspond to a peptide of ～ 21 amino acids in extended conformation. Peptides with longer side chains compete for the peptide binding site of TAP but fail to be translocated. Therefore, they represent the first rationally designed inhibitors of TAP.     

Phenotypic analysis of peripheral blood gammadelta T lymphocytes and their targeting by human immunodeficiency virus type 1 in vivo

There is increasing evidence that a wider range of lymphoid cell types other than CD4(+) T helper lymphocytes are infected with HIV-1 in vivo, including CD8 lymphocytes, natural killer cells, and reticulodendritic cells. Each potentially contributes to the reservoir of infected cells that resist antiviral treatment and to the impairment of immune responses in AIDS. By quantitative PCR for HIV proviral sequences we have now obtained evidence for substantial infection of gammadelta lymphocytes, contributing 3-45% of the proviral load in peripheral blood. A large proportion of gammadelta lymphocytes constitutively expressed the chemokine receptors CCR5 and CXCR4, with evidence for marked up-regulation of CD8 in samples from HIV-infected individuals, corresponding to an activated phenotype. That gammadelta lymphocytes might be susceptible to HIV infection was investigated using in vitro infectivity assays of recombinant HIV-expressing green fluorescent protein, followed by flow cytometry. gammadelta, CD4, and CD8 lymphocytes were each productively infected, with gammadelta lymphocytes showing the greatest susceptibility. For each cell type, blocking assays with an anti-CD4 monoclonal antibody indicated that entry was CD4-dependent.     

Association between bone mineral density (DXA), body structure,and body composition in middle‐aged men

The association between bone mass, body structure, and body composition was explored in 156 men, 40 years of AGE . Bone mineral density (total body, lumbar spine, left arm, and left leg) was obtained by dual‐energy X‐ray absorptiometry (DXA; Hologic QDR 4500A). Body structure was determined from a battery of anthropometric dimensions with a principal components analysis. Body composition was estimated with DXA. From the 24 anthropometric dimensions, three components were extracted and identified as muscle, fat, and skeletal length. Significant correlations between the muscle component and all BMD measurements (r = 0.28–0.44) were obtained. Except for BMD of the left arm, which correlated significantly, but negatively, with the fat component (r = ?0.16), no significant relations were found between the fat component and BMD. There were significant correlations between lean mass, fat mass, and BMD measurements. The correlations were higher between lean mass and BMD (r = 0.22–0.44) than between fat mass and BMD (r = 0.08–0.24). The multiple regression analysis revealed that except for BMD of the left arm only lean mass or the muscle component, and not fat mass or the fat component, were independent predictors of BMD. It is concluded that the principal anthropometric determinant of BMD in middle‐aged men is lean mass or muscle. Am. J. Hum. Biol. 14:735–742, 2002. © 2002 Wiley‐Liss, Inc.     

Randomized, double-blind, placebo-controlled study of montelukast for treating perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) is a persistent allergic inflammation of the upper respiratory tract due to year-round allergen exposure. OBJECTIVE: To evaluate the leukotriene receptor antagonist montelukast for the treatment of PAR. METHODS: Protocol 265 was a 2-arm study performed during the winter. After a placebo run-in period, adults with perennial allergen sensitivity and active symptoms of PAR were randomized to receive 10 mg of montelukast (n=1002) or placebo (n=990) once daily during a 6-week, double-blind, active-treatment period. The primary end point was the daytime nasal symptoms score, defined as the average of scores for nasal congestion, rhinorrhea, and sneezing rated daily by patients. RESULTS: Statistically significant improvements in PAR symptoms were seen in patients treated with montelukast. Their daytime nasal symptoms scores were reduced during treatment compared with those of the placebo group: the difference between treatments in least squares mean change from baseline was -0.08 (95% confidence interval [CI], -0.12 to -0.04; P < .001). Montelukast treatment also improved global evaluations of allergic rhinitis by patients and Rhinoconjunctivitis Quality of Life Questionnaire scores: differences vs the placebo group were -0.15 (95% CI, -0.27 to -0.04; P < .01) and -0.15 (95% CI, -0.24 to -0.06; P < .001), respectively. Other end points that showed statistically significant improvement with montelukast treatment were nighttime symptoms and each of the 4 nasal symptoms (congestion, rhinorrhea, sneezing, and itching). The treatment effects of montelukast were stable and persistent during the entire 6 weeks of treatment. CONCLUSION: Montelukast provided statistically significant relief of PAR symptoms during 6 weeks of treatment.     

Adoptive immunotherapy for posttransplantation viral infections.

Viral diseases are a major cause of morbidity and mortality after hemopoietic stem cell transplantation. Because viral complications in these patients are clearly associated with the lack of recovery of virus-specific cellular immune responses, reconstitution of the host with in vitro expanded cytotoxic T lymphocytes is a potential approach to prevent and treat these diseases. Initial clinical studies of cytomegalovirus and Epstein-Barr virus in human stem cell transplant patients have shown that adoptively transferred donor-derived virus-specific T cells may restore protective immunity and control established infections. Preclinical studies are evaluating this approach for other viruses while strategies for generating T cells specific for multiple viruses to provide broader protection are being evaluated in clinical trials. The use of genetically modified T cells or the use of newer suicide genes may result in improved safety and efficacy.