Immunologic aspects of select agents

We are on the cusp of exciting new developments in vaccine biology. The use of DNA constructs allows virtually unlimited access to previously inaccessible organisms. Next-generation adjuvants will boost innate and acquired immunity, and will provide protection from infection with any potential biowarfare organism. We are limited only by our imaginations in the construction of a protective armamentarium.     

General practitioners' fear-avoidance beliefs influence their management of patients with low back pain

The objectives of this cross-sectional study conducted in primary care practice in France were to describe general practitioners' (GPs) fear-avoidance beliefs about low back pain (LBP), investigate the impact of these beliefs on their following guidelines for bed rest, physical activities, and sick leave, and uncover factors associated with GPs' fear-avoidance beliefs. A total of 864 GPs completed a 5-part self-administered questionnaire. Parts 1, 2, and 3 concerned demographic, professional data, and personal history of back pain, respectively. Part 4 dealt with GPs' education about LBP and practice for LBP. Part 5 assessed GPs' fear-avoidance beliefs on the Fear-Avoidance Beliefs Questionnaire (FABQ). GPs' mean age was 48.2+/-7.0 years, 80% were male, 88% had been practicing for more than 10 years, and 52% reported a previous personal episode of acute LBP. Forty-six percent had participated in an educational session on LBP during the last 3 years. Mean scores for the FABQ Phys and Work were 9.6+/-4.8 and 17.5+/-6.7, respectively. Sixteen percent of participants had high rating on the FABQ Phys (FABQ Phys score>14). FABQ Phys score was associated with recommendation of bed rest or rest during sick leave (p<0.0001) for acute LBP and less advice to maintain maximum bearable physical activities (p<0.001) for chronic LBP. FABQ Work score was associated with prescribing sick leave during painful periods (p<0.005) for acute LBP and less advice to maintain maximum bearable physical activities (p<0.001) for chronic LBP. GPs' fear-avoidance beliefs about LBP negatively influence their following guidelines concerning physical and occupational activities for patients with LBP.     

The thymus exports long-lived fully committed T cell precursors that can colonize primary lymphoid organs

Thymic export of cells is believed to be restricted to mature T cells. Here we show that the thymus also exports fully committed T cell precursors that colonize primary lymphoid organs. These precursor cells exited the thymus before T cell receptor rearrangements and colonized lymphoid organs such as the thymus and the gut. Migration of the thymic T cell-committed precursors led to permanent colonization of the gut precursor compartment, improved the capacity of gut precursors to further differentiate into T cells and was sufficient for the generation of 'euthymic like' CD8alphaalpha(+) intraepithelial lymphocytes. These data demonstrate a new function for the thymus in peripheral seeding with T cell precursors that become long lived after thymus export.     

Bonded porcelain veneers

Nowadays the porcelain laminate veneer is a frequently prescribed aesthetic restoration for anterior teeth. A substantially reduced tooth preparation is required compared to conventional aesthetic complete crown preparations, in accord with the practice philosophy of minimally invasive dentistry. The long term clinical success of porcelain veneers depends on a careful case selection and diagnostic approach, as well as accurate and appropriate tooth preparation and adhesive bonding procedures. The goal of this paper is to give a reproducible clinical method to the practitioner for the realization of reliable porcelain laminate veneers.     

Usefulness of the phage display technology for the identification of a hepatitis C virus NS4A epitope recognized early in the course of the disease

A dodecapeptide phage-displayed library was screened with the mouse monoclonal antibody (mAb) 2E3C2 which competed with human antibodies for the binding to the HCV c100 recombinant protein. Four mimotopes shared a consensus motif with the HCV 1701-1707 sequence corresponding to the carboxyl-terminal domain of the non-structural protein NS4A. However, these mimotopes reacted with 2E3C2 only, whereas the corresponding NS4 epitope defined at the sequence 1698-1709 and displayed on phage was recognized by both 2E3C2 and sera from HCV infected patients. Using the Spot method of multiple peptide synthesis and alanine replacement analysis, the respective reactivities of mAb 2E3C2 and anti-NS4A human antibodies against NS4 were shown to be directed against two slightly different overlapping minimal linear sequences and to involve different critical residues. The phage clone displaying the NS4 epitope was used to study the specific recognition of this epitope by different individual HCV positive sera as well as by two seroconversion panels of sera from HCV infected patients. Compared with the detection by RIBA of the different HCV antigens and c100 particularly, these results indicated that the antibodies directed against the NS4 (1698-1709) epitope were produced early during the course of the disease and decreased later.     

COL1A1-PDGFB fusion in a pediatric Bednar tumor with 2 copies of a der(22)t(17;22)

We present a 10-year-old girl with a pure Bednar tumor (pigmented dermatofibrosarcoma protuberans) of the right shoulder. Cytogenetic analysis demonstrated 47 chromosomes with 2 copies of a derivative chromosome 22, der(22)t(17;22)(q22;q13). Fluorescence in situ hybridization (FISH) analysis demonstrated the COL1A1-PDGFB fusion on both der(22) chromosomes. By RT-PCR and sequencing, we observed a fusion of the COL1A1 exon 41 with PDGFB exon 2. This pure pediatric Bednar tumor in a child, like childhood dermatofibrosarcoma protuberans, had a linear structural abnormality rather than a ring chromosome that is more commonly encountered in adult Bednar and dermatofibrosarcoma protuberans tumors. The underlying molecular abnormality in this pediatric Bednar tumor is the same as in dermatofibrosarcoma protuberans.     

Prolactin/growth hormone-derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis

Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical. We have previously shown that 16-kDa fragments of the human prolactin/growth hormone (PRL/GH) family members are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments possess a 14-aa sequence having the characteristics of a tilted peptide. The tilted peptides of human prolactin and human growth hormone induce endothelial cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary formation both in vitro and in vivo. These antiangiogenic effects are abolished when the peptides' hydrophobicity gradient is altered by mutation. We further demonstrate that the well known tilted peptides of simian immunodeficiency virus gp32 and Alzheimer's beta-amyloid peptide are also angiogenesis inhibitors. Taken together, these results point to a potential new role for tilted peptides in regulating angiogenesis.     

Developing a Model Psychiatric Treatment Program for Patients with Intellectual Disability in a Community Mental Health Center

The Special Needs Clinic of the Johns Hopkins Bayview Medical Center in Baltimore, Maryland provides comprehensive treatment for patients with developmental or intellectual disability and psychiatric illness. This report describes the clinical characteristics and service utilization of patients attending this clinic. Factors that support quality mental health services that are both cost-effective and accessible are identified.Florence Hackerman, Chester W. Schmidt, Charles Donald Dyson, Lisa Hovermale, and Gerard Gallucci are affiliated with Department of Psychiatry, The Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224, USA.