Terminal deletion (14)(q32.3): a new case.

A mildly dysmorphic, 2 year old girl with mental retardation was found to have a small de novo terminal deletion of the long arm of chromosome 14, del(14)(q32.3). She was found to have features in common with two previous terminal deletion cases and particularly with the well documented ring 14 syndrome, although seizures, a characteristic feature of ring 14, were notably absent.     

Soluble IL-2 receptor and CD25 cells in psoriasis: effects of cyclosporin A and PUVA therapy.

A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score.     

Cost-effectiveness analysis of budesonide aqueous nasal spray and fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis.

BACKGROUND: An economic evaluation was performed analyzing direct medical costs in Canada for the treatment of perennial allergic rhinitis (PAR) with budesonide aqueous nasal spray and fluticasone propionate nasal spray. Three hundred fourteen patients with at least a 1-year history of PAR were randomized into a double-blind, parallel-group study of 6 weeks' duration. The treatments were daily doses of budesonide 256 microg, fluticasone propionate 200 microg, or placebo. Both active treatments produced significantly lower mean scores for overall nasal symptoms compared with placebo, and both were well tolerated. Budesonide was significantly more effective than fluticasone in reducing "blocked nose." METHOD: A retrospective cost-effectiveness analysis utilizing the clinical trial data was performed on the total costs of (1) budesonide-based and (2) fluticasone-based treatment strategies, including the relative importance of the drug costs in both strategies. RESULTS: The average treatment cost per patient in Canada over 12 months in the budesonide group was CAD 389.85 which was 23.3% lower than in the fluticasone group, which was CAD 508.06, due to lower drug acquisition costs (for the year 1998). CONCLUSION: Budesonide aqueous nasal spray was shown to be more cost-effective than fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis. This result is valid in the province of Ontario, Canada and in many other settings with the same structure of relative prices. The result is mainly driven by a difference in drug cost.     

The influence of FK-506 on the thymus: an immunophenotypic and structural analysis.

The influence of the powerful new immunosuppressant FK-506 on the thymus was investigated in Sprague-Dawley rats that were immunized with sheep erythrocytes and treated with FK-506 (1 mg/kg/day i.m.) for 7 days. Suppression of humoral immunity in drug-treated animals was accompanied by reductions in circulating lymphocytes bearing activation markers (interleukin-2 receptor beta-chain and OX40, activated CD4+ cells) and by striking thymic medullary atrophy. There were, however, no significant differences in thymic weights or in thymocyte numbers between experimental and control groups during the period of FK-506 administration. Reduction of the medullary compartment was visualized immunohistochemically, by decreases in major histocompatibility complex (MHC) class I- and MHC class II-positive cells and in CD37+ (mature medullary) thymocytes. Flow cytometric analysis of thymocytes showed that FK-506 induced increases in bright, Thy-1.1+ cells and in numbers of CD4+ and CD8+ thymocytes, whilst CD37+ cells were less numerous than in controls. Percentages of MHC class I- and MHC class II-positive cells varied little throughout the course of FK-506 administration. Evidence of selective damage to medullary epithelial cells, attributable to FK-506, was found at both the light and electron microscopic levels, whilst thymic macrophages in drug-treated rats displayed features of enhanced phagocytic activity, including ingestion of damaged epithelial cells. These FK-506-induced abnormalities were reversed within 14 days of drug withdrawal. These findings suggest that, like cyclosporin A, FK-506 reversibly disrupts the thymic microenvironment and may interfere with the function/maturation of T lymphocytes.     

Identification and characterization of intestinal Peyer's patch interferon-alpha producing (plasmacytoid) dendritic cells

Recently, a subset of murine dendritic cells (DC) has been identified that resembles human plasmacytoid (pDC) the principal interferon-alpha (IFN-alpha) producing cells in blood. In this study, C57BL/10 (B10;H2b) mice were treated with fms-like tyrosine 3 kinase Ligand (Flt3L; 10 microg/d; i.p.; 10 days) that expands DC selectively in vivo. Putative pDC (CD11c+B220+) were identified in the subepithelial dome and in interfollicular regions of intestinal Peyer's patches (PP) from both normal and Flt3L-treated animals. Freshly-isolated, immunobead-purified CD11c+ DC from PP were flow-sorted to obtain lineage- (CD11b-CD19-) CD11c+ B220+ DC (purity>96%). Flow cytometric analysis revealed that these sorted PPpDC were negative for surface markers associated with myeloid DC (CD11b) and expressed only low levels of the "lymphoid-related" DC marker CD8alphaalpha+. They expressed low levels of costimulatory molecules and moderate MHC class II. They proved weak stimulators of na?ve allogeneic (C3H; H2k) T-cell proliferation. Cytospin preparations of sorted CD11c+B220+ cells revealed plasmacytoid morphology similar to that of human pDC. Immunocytochemistry and enzyme immunoassay revealed that, within 24-hour culture with Herpes simplex virus (10 p.f.u./cell), a subpopulation of stimulated (but not unstimulated) CD11c+B220+ DC produced and secreted IFN-alpha. This novel DC subset may play important roles in innate and adaptive immune responses of the gut and in the regulation of mucosal immune reactions.     

Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection

The role of intrahepatic lymphocytes in the control of hepatitis C virus (HCV) infection and the pathology associated with it is not understood; most studies of the immunology of this infection use peripheral blood lymphocyte populations. To address this further, we examined in detail the IHL from HCV-infected patients and controls, focusing on the antigen-specific CD8(+) T lymphocyte component. Individual T cells from needle liver biopsies and peripheral blood were isolated from patients with chronic HCV infection and examined directly ex vivo. We used RT-PCR spectratyping to compare the breadth of the T cell receptor usage in the liver in comparison with the peripheral blood, and applied MHC class I tetramer technology to investigate the numbers of HCV-specific CD8(+) cells in the two compartments. T cell receptor usage in the liver of HCV-infected patients was broad, comparable with that in the peripheral blood of the same patients. A much higher proportion of liver CD8(+) cells expressed receptors specific for HCV antigens compared with paired peripheral blood CD8(+) cells. A greater proportion of the liver tetramer-positive cells expressed the activation marker CD69, compared with those in the periphery or other CD8(+) cells in the liver. In the course of chronic HCV infection, HCV-specific CD8 cells, which have been recently activated, appear to accumulate specifically in the livers of infected patients but are present in much lower numbers in the peripheral circulation. Further studies are needed to determine the function of these cells and their role in protection and immunopathology.