RelB regulation of chemokine expression modulates local inflammation.

The resolution of acute inflammation is incompletely understood but presumably requires the elimination of both inflammatory cells and production of inflammatory cytokines. In the case of recruited bone-marrow-derived inflammatory cells such as granulocytes and macrophages, their short life span helps eliminate these cells and the cytokines they produce. By contrast, resident permanent cells such as fibroblasts require other mechanisms to stop the production of chemokines generated in response to inflammatory triggers such as lipopolysaccharide. Here we demonstrate that RelB is an important regulator of chemokine expression in fibroblasts, thereby playing a key role in the resolution of acute inflammation. Activation of normal fibroblasts by lipopolysaccharide induced a transient production of chemokines, closely followed by induction of RelB expression. However, stimulated RelB-/- fibroblasts exhibited dramatic persistent induction of seven chemokines (RANTES, MIP-1 alpha, MIP-1 beta, MIP-2, IP-10, JE/MCP-1, and KC/CINC). The persistent overexpression of chemokines correlated with increased NF- kappa B binding as well as with increased p50, p65/RelA, and I kappa B alpha expression. Transfection of RelB cDNA into RelB-deficient fibroblasts reversed the lipopolysaccharide-induced chemokine overexpression. In vivo, activated RelB-/- fibroblasts dramatically increased recruitment of granulocytes into tissues. In view of the apparent role of RelB in the resolution of acute inflammation in tissues and previous work showing a requirement for RelB in the initiation of immune responses through the differentiation of antigen-presenting cells, RelB may be an important factor regulating the transition from innate to adaptive immunity.     

Effects of captopril on hemodynamics and blood gases in chronic obstructive lung disease with pulmonary hypertension

The effects of Captopril, an angiotensin-converting enzyme inhibitor, on pulmonary hemodynamics and blood gases were studied in 9 patients with chronic obstructive lung disease (COLD) and pulmonary hypertension (PA-P greater than 20 mm Hg). Hemodynamic data were recorded prior to Captopril administration (50 mg per os) and for the next 60 min. Following Captopril administration, significant reductions in mean pulmonary artery pressure (PA-P) (p less than 0.05), in mean pulmonary wedge pressure (PW-P) (p less than 0.05), and in total pulmonary resistance (TPR) were noted; significant reductions in mean brachial artery pressure (BA-P) and systemic vascular resistance (SVR) were also recorded, while cardiac output, heart rate and blood gas tensions showed no significant changes. Furthermore, the higher the hypoxemia, the greater was the reduction in BA-P (p less than 0.05). We therefore feel that Captopril, when administered to COLD patients with pulmonary hypertension, may protect the pulmonary circulation from hypoxic pulmonary vasoconstriction.     

Amoebae free-living. Report of the first Italian case of myelitis.

The AA. refer on the first Italian case of amoebae "Limax" primitive myelitis in a 25-year-old man. Microscopical observation showed amoebae free-living, but their cultivation and identification were not possible. The patient recovered because of the propriety of diagnosis and therapy with amphotericin B.     

Biological monitoring of toxic metals in urine by simultaneous inductively coupled plasma-atomic emission spectrometry

A simple and rapid method for the simultaneous determination of 11 metals (As, Be, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, and Zn) in urine by inductively coupled argon plasma-atomic emission spectrometry is presented. Acidification of the urine was the only sample preparation required. Background correction was applied to ensure accuracy. Analytical calibration was based on matrix matching using a "simulated urine" solution. Detection limits in the low mg/L range and linearity over three orders of magnitude were obtained for all 11 metals. In the Occupational Health Laboratory, this procedure has been applied for routine screening of workers for occupational exposure to toxic metals.     

The Sesto Fiorentino study: point and one-year prevalences of psychiatric disorders in an Italian community sample using clinical interviewers

BACKGROUND: It has been argued that lay interviewers' use of fully-structured interviews could lead to a diagnostic pattern different to that by treating physicians. Clinical interviewers in community samples should probably identify cases that are closer to those seen in clinical settings. The greatest advantage of using clinical interviewers consists of the immediate assessment of a possible psychopathology, i.e. the evaluation of current disorders. METHODS: Two thousand three hundred and sixty-three citizens from the community of Sesto Fiorentino, Italy, were interviewed by their own general practitioners using the Mini International Neuropsychiatric Interview (MINI). Positive cases for any lifetime psychiatric disorder as well as a random sample of the negative cases were re-interviewed by psychiatrists or trained residents in psychiatry using the Florence Psychiatric Interview (FPI). RESULTS: The point prevalence for any current disorder was 8.7%; the two disorders with the highest prevalence were generalised anxiety disorder (2.9%) and major depressive episode (2.7%). The figures increase about 50% when the sub-threshold sequelae of previous disorders are considered. Current comorbidity was generally high. The one-year prevalence of any disorder was 10.6%. Ninety-two percent of the cases sought help, 82% were being treated at the moment of interview. Social impairment was considerable. CONCLUSIONS: The period prevalence rates for most of the disorders considered were generally comparable with the range defined by previous studies conducted in other Western countries, despite using different methodologies. Conversely, the use of health facilities, the treatment received and the social impairment were much higher than those reported by the other studies, suggesting a greater similarity with the clinical samples.     

Thymic stromal cell specialization and the T-cell receptor repertoire

Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire: Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the function of the thymic medulla is discussed.