Peptide analysis,stability studies,and structural modeling explain contradictory peptide motifs and unique properties of the NOD mouse MHC class II molecule H2-A(g7)

The MHC class II molecule H2-A(g7) is the chief genetic determinant in insulin-dependent diabetes mellitus of the non-obese diabetic (NOD) mice. Poor peptide binding ability, as well as presentation of a unique subset of peptides by this molecule was suggested to promote autoimmunity in this strain. However, several laboratories have presented results in favor of an H2-A(g7) molecule that can avidly bind many different peptides. The crystal structures of H2-A(g7) in complex with two different peptides did not completely resolve this issue. To analyze the peptide binding capacity and the motif requirements of H2-A(g7), we eluted natural ligands from purified H2-A(g7) molecules isolated from the H2-A(g7)-transfected M12-C3 cells. A low peptide yield dominated by a few peptide ligands was found. Pool sequencing and alignment of individual ligands on the basis of molecular modeling revealed a peptide-binding motif with basic/aliphatic/small hydrophilic amino acids at relative position 1 (p1), aliphatic amino acids at p4, Ala at p6, and acidic amino acids and Ser/Gly at p9, as well as acidic residues at p10/11. Though weak, the binding of individual ligands, as well as the importance of an acidic C-terminal residue was confirmed by peptide binding studies to isolated H2-A(g7) molecules. Furthermore, the H2-A(g7) molecule incompletely dissociated into its constituent chains in SDS-electrophoresis under nonreducing conditions. This provides additional evidence of its weak affinity for peptides, which probably arises from the combination of beta56His/beta57Ser/beta78Ala and other unique H2-A(g7) residues in contact with the antigenic peptide. These results allow a better understanding of the role of this molecule in the development of autoimmunity and the identification of epitopes relevant to diabetes.     

Study of the carrying angle of the human elbow joint in full extension: a morphometric analysis

This study measured the carrying angle of the elbow joint in full extension in 600 students, using the supplementary angle to that between the longitudinal axis of the arm and that of the forearm. The mean carrying angle was 12.88°±5.92: 10.97°±4.27 in men and 15.07°±4.95 in women. The carrying angle changes with skeletal growth and maturity. The angle is always greater on the side of the dominant hand. We confirmed the inverse relationship between the carrying angle and the intertrochanteric diameter. Also, the type of constitution influences the value of the carrying angle, especially in women.     

A critical evaluation of current views regarding eye movement desensitization and reprocessing (EMDR): clarifying points of confusion.

EMDR is an active psychological treatment for PTSD that has received widely divergent reactions from the scientific and professional community. This article examines points of confusion in the published literature on EMDR, including the theoretical, empirical, and historical issues around EMDR and placebo effects, exposure procedures, the eye movement component, treatment fidelity issues, and outcome studies. It also examines historical information relevant to the scientific process and charges of "pseudoscience" regarding EMDR. We conclude that the confusion in the literature is due to (a) the lack of an empirically validated model capable of convincingly explaining the effects of the EMDR method, (b) inaccurate and selective reporting of research, (c) some poorly designed empirical studies, (d) inadequate treatment fidelity in some outcome research, and (e) multiple biased or inaccurate reviews by a relatively small group of authors. Reading the original research articles frequently helps to reduce the confusion arising from the research review literature.     

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.     

Adamantinoma of tibia: a case of late local recurrence along with lung metastases

Adamantinomas of long bones are rare primary low-grade malignant tumours composed of cells with epithelial and fibrous characteristics. Local recurrence, though scarce, occurs 5-15 years after the onset of diagnosis. We report a case of local recurrence of an adamantinoma localised in tibia, along with the presence of two lung metastases, 24 years after diagnosis and surgical therapy of the primary tumour. The local recurrence and the lung metastases were removed surgically. The patient remains free of the disease for 3 years.     

Expression of costimulatory molecules in peripheral blood mononuclear cells of atopic asthmatic children during virus-induced asthma exacerbations

BACKGROUND: Respiratory viruses are the most frequent triggers of acute asthma exacerbations. Herein we investigate costimulatory molecule expression on peripheral blood mononuclear cells (PBMC) during such exacerbations. METHODS: Eleven children with atopic asthma were followed prospectively and respiratory symptoms were recorded on diary cards. A blood sample and nasopharyngeal wash (NPW) were obtained at baseline and subsequently during an exacerbation. PBMC were immunophenotyped using flow cytometry. NPW samples were examined for the presence of respiratory viruses by RT-PCR. RESULTS: A virus was detected in 73% of exacerbations and none at baseline. A drop of NK cells and a marginal increase of monocytes were the only changes of cell count during the exacerbation. A significant downregulation of B7-2 on NK cells and of B7-1 on monocytes was also observed during exacerbations. CONCLUSIONS: The above observations are in contrast to in vitro findings showing an upregulation of costimulatory molecules after exposure of blood cells to viruses or allergens. It is possible that activated immune cells leave the blood stream to migrate to the inflammation site during acute asthma exacerbations.     

Detection of sheep poxvirus in skin biopsy samples by a multiplex polymerase chain reaction

The development of a multiplex polymerase chain reaction (PCR) method with amplification of capripoxvirus in a single-step procedure from skin biopsies using three primer pairs, two specific for capripoxvirus and one specific for alpha-tubulin is described. A sensitive multiplex PCR was achieved by optimization of parameters such as the primer concentrations, magnesium and dNTPs concentrations. False negative results that sometimes arise due to inhibitors of DNA amplification may be avoided by the inclusion in the assay of alpha-tubulin primers. The results reported on 42 skin biopsies from sheep suspected to have poxvirus infection, indicated that the assay could monitor simultaneously DNA extraction from skin biopsy samples and allow improved detection of capripoxvirus within 24 h of specimen receipt in the laboratory.     

Continuity, discontinuity, and coherence in attachment from infancy to late adolescence: sequelae of organization and disorganization

This longitudinal study examines continuity and discontinuity of attachment quality from infancy to late adolescence in a sample of 125 participants considered at birth to be at high-risk due to poverty. Strange Situations were conducted at 12 and 18 months; Adult Attachment Interviews were administered at age 19. Child and maternal characteristics and experiences and observational assessments of the families were explored as correlates of continuity and discontinuity in attachment. Contrary to findings of continuity from low-risk samples, analyses demonstrated no significant overall continuity in attachment security. Disorganized infants were significantly more likely than organized infants to be insecure or unresolved in late adolescence. Additionally, infant disorganization predicted unresolved abuse scores on the AAI for those participants who experienced childhood abuse. Significant correlates of continuity and change spanned a variety of age periods and included infant temperament, maternal life stress, family functioning at pre-adolescence, child maltreatment and features of the home environment. Findings are discussed as supporting the coherence of attachment over time.