Ethanol-specific impairment of T-lymphocyte activation is caused by a transitory block in signal-transduction pathways.

BACKGROUND: Immune system derangement is characteristic of alcoholic liver cirrhosis. However, in vitro studies have never clarified the alcohol-induced T-lymphocyte dysfunction. The aim of this study was to examine any discrete phenotypical and functional abnormalities and possible impairment in transmembrane signal-transduction pathways that, if present on lymphocytes of patients with alcoholic cirrhosis, would also be reproducible after in vitro ethanol exposure of normal T cells. METHODS: Lymphocytes from 25 patients were analyzed for their in vitro proliferative functions, intracellular Ca2+ fluxes, and inositol 1,4,5-triphosphate (IP3) generation. The same procedures were applied to normal T cells exposed in vitro to ethanol. RESULTS: Lymphocytes failed to respond to anti-CD3 and anti-CD2 after in vitro stimulation, with decreased intracellular Ca2+ mobilization and IP3 generation but showed normal proliferative response to phytohemagglutinin. In vitro ethanol incubation of normal T lymphocytes resulted in rearrangement of the membrane CD45 antigen, favoring the expression of high-molecular-weight isoforms, and showed a poor blastogenic response to anti-CD3 and anti-CD2 with a decrease in intracellular Ca2+ mobilization and IP3 production. After a 6-month period of ethanol withdrawal, some patients had normalization of phenotypic and functional alterations. CONCLUSIONS: The T-lymphocyte response to specific polyclonal activators may be severely impaired in alcohol abusers. However, it seems reversible after a period of controlled ethanol withdrawal.

Regulation of CA 125 production by amnion and WISH cells in culture.

Amnion and human amnion-derived WISH cells release CA 125 antigen into culture medium. CA 125 output was higher in WISH cells than in amnion cells. In this study we showed that release of the antigen is regulated, with both amnion and WISH cells responding in a similar manner to the tested agents. Release of CA 125 decreased in the presence of dexamethasone (10(-6) mol/L) or cycloheximide (0.1 micrograms/ml) and increased when colchicine (0.01 micrograms/ml) was added to the culture medium. Stimulatory and inhibitory effects were more apparent after 3 days in culture. The precise mechanisms by which some of these agents (colchicine and dexamethasone) affect CA 125 release remain unknown. We propose that amnion and WISH cells in culture represent a useful model to investigate some regulatory aspects of the production of CA 125 in normal tissues.

[Immunotherapy in allergic diseases. Evaluation of short-term efficacy of aluminum hydroxide-absorbed slow-release preparations]. / L'immunoterapia nelle malattie allergiche. Valutazione dell'efficacia a breve termine di preparati ritardo assorbiti su idrossido di alluminio.

Clinical and immunological changes after immunotherapy (ITS) for respiratory allergy were evaluated in 29 subjects during a one year follow up period. No adverse effects were noted with alum-absorbed allergen extracts. However, only patients receiving ITS for grass pollens demonstrated clinical improvement and blocking IgG increase as compared with those with multiple allergen sensitivity.

[The determination of specific IgE in allergy diagnosis. The clinical significance of specific IgE in drug allergies]. / Il dosaggio delle IgE-specifiche nella diagnostica allergica. Significato clinico delle IgE-specifiche nelle allergie a farmaci.

IgE-mediated allergic reactions to drugs may be diagnosed on the basis of anamnestic criteria, clinico-pathological manifestations as well as by the measurement of allergen-specific IgE. The concordance of these diagnostic procedures was investigated in 50 patients with a history of sensitivity to penicillin (12), sulphamethoxazole (9) or both (14), aspirin (2) and pyrazolones (13). All subjects displayed chronic urticaria/angioedema syndrome. Optimal concordance values were observed for penicillin and sulphamethoxazole, while no specific IgE were detected in the ASA-sensitive group. False positive results were noted in pyrazolone-sensitive patients with high total IgE levels. Based on these results, serological methods that detect drug-specific IgE may be carefully used as complementary diagnostic procedure only in those patients in whom an adverse reaction to antibiotics is suspected.

Immunochemical and immunohistochemical evaluation of lung permeability in ventilated newborn rabbits.

These experiments were designed to quantify the vascular-to-alveolar leakage albumin in the neonatal lung and to analyze the distribution of leaking airspaces in the lung parenchyma. Immediately after delivery, newborn rabbits with gestational age 27-29 days received an intravenous injection of human albumin as a marker and were ventilated for 15 min with standardized tidal volume (10 ml/kg). After the period of ventilation the lungs were either lavaged via the airways or fixed for histological studies. The median amount of albumin in lung lavage fluid, determined by immunodiffusion, was 4.8% of the injected dose after 27 days, 1.3% after 28 days, and 0.4% after 29 days of gestation; it was inversely correlated with the compliance of the respiratory system (r = -0.78; p less than .001). Immunohistochemical examination of lung section revealed that the leak was not diffuse; even in animals with gestational age 27 days it involved only a median of 48% of total alveoli. The median amount of alveoli containing the label fell to 6% after 28 days and to 0% after 29 days gestation, correlating inversely with the compliance of the respiratory system (r = -0.53; p less than 0.01). We suggest that our experimental model is useful for histological demonstration of serum proteins leaking into the airpaces under experimental conditions and for evaluating the effect of therapeutic regiments on neonatal lung permeability.

CA 125 is released by human amnion cells in culture.

CA 125 was measured in the medium of human amnion cells in primary culture after confluence. The antigen accumulated as a function of time with a median value of 1897 U/mg protein after 7 days in culture. CA 125 was detectable by immunoperoxidase staining in the cells, which supports the possibility that amnion cells play a role as a source of the CA 125 found in the amniotic fluid.

Helper inducer T cells in the lungs of sarcoidosis patients. Analysis of their pathogenic and clinical significance.

Phenotypic analysis of helper CD4+TQ1- cell population, the major helper T-cell subset for B-cell responses, was carried out in BAL fluid of sarcoidosis patients. Most of the BAL CD4+ cells lacked TQ1 membrane antigen. A correlation between the number of helper CD4+TQ1- cells and IgM and IgA levels was observed in 27 sarcoidosis patients' BAL. A role of CD4+TQ1- cells in modulating lung B-cell immunoglobulin secretion in sarcoidosis was confirmed by the fact that BAL IgG level and helper T-cell number correlated well in patients with low-intensity alveolitis. Results showed an inverse correlation between symptom duration and BAL IgM levels and CD4+TQ1- cell number. The number of helper cells was above normal in patients who had symptoms for less than 12 months and within normal range in those who had symptoms for more than that. The pathogenic and clinical relevance of these data is discussed.

Analysis of CD4-positive T cell subpopulation in sarcoidosis.

Double-labelling immunofluorescence analysis within the CD4+ cell subset was carried out in 27 bronchoalveolar lavage fluids and 11 peripheral blood samples of sarcoidosis patients with anti-TQ1, anti-2H4 and anti-4B4 monoclonal antibodies. Helper/inducer CD4+TQ1-/4B4+ cells were strongly increased in the lung and slightly, but significantly, decreased in the blood of sarcoidosis patients with respect to normal controls. No differences were found in the number of both lung and blood CD4+2H4+ cells between sarcoidosis patients and controls. The findings are further evidence for a compartmentalization of T cell subsets in sarcoidosis.