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Biomedical subjects

R Testi

Publications and source records attributed to R Testi.

At least 91 records · Page 5Linked to original sources

Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol.

Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.

Adolescent↗

Old and new in chest physiotherapy.

Some "old" chest physiotherapy techniques, such as postural drainage of bronchial secretions, breathing control, relaxation, pre- and post-surgical treatments and exercise training have survived until today because of their unquestionable and persistent validity. This does not mean that in this field of rehabilitation medicine nothing new exists. Chest physiotherapy has now completely overcome the empirical phase that characterized every branch of medicine during its early development. We now employ mainly respiratory pathophysiology techniques for objective evaluation of physiotherapy efficacy. For example we use transcutaneous monitoring of blood gas variations during therapy. Among new chest physiotherapy techniques, biofeedback training may lead to better relaxation in a shorter time, and it is now widely used in breathing control. Jet-ventilation and percussion-ventilation seem likely to mark a further improvement in bronchial secretion drainage. Concerning the future of chest physiotherapy, the recent advances in the physiology and pathophysiology of respiratory muscles are disclosing important practical implications, e.g. in defining criteria for respiratory muscle training and rest in chronic respiratory failure.

Breathing Exercises↗

Constitutive expression of a phosphorylated activation antigen (Leu 23) by CD3bright human thymocytes.

Leu 23 is a human cell surface differentiation Ag expressed very early during lymphoid cell activation. Resting T lymphocytes do not express Leu 23. However, expression of Leu 23 glycoprotein can be induced on the Jurkat T leukemia cell line within a few hours after stimulation with soluble anti-CD3 mAb or Con A. After removal of the stimulus Leu 23 is expressed for greater than 30 h. A total of 20 to 30% of resting human thymocytes was unexpectedly stained by anti-Leu 23 mAb. Biochemical analysis revealed that the Leu 23 Ag expressed on thymocytes is a phosphorylated disulfide-linked dimer composed of 28- and 32-kDa subunits. Within the thymus, Leu 23 is preferentially expressed on the CD3bright, mostly CD4+ CD8- or CD4- CD8+ subpopulations. By contrast, CD3dim CD4+CD8+ thymocytes expressed only very low levels of Leu 23, and CD7+ CD3- CD4- CD8- thymocytes were Leu 23-. However, Leu 23 was induced on the CD3dim thymocytes by in vitro culture of thymocytes with anti-CD3-conjugated Sepharose. The transition from CD3dim to CD3bright within the thymus may be an important differentiation stage and influence selection of the antigenic repertoire. Therefore, the ability to detect subpopulations within the thymus that express Leu 23 Ag may help to identify thymocytes activated in vivo, possibly by the functional engagement of their CD3/TCR.

Antigens, CD↗

Proliferative effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophores on human large granular lymphocytes (LGL).

The proliferative responses of natural killer (NK) cells to 12-O-tetradecanoylphorbol-13-acetate (TPA), which directly activates protein kinase c(PKC), and to the Ca2+ ionophores A23817 and ionomycin, known to enhance the intracellular calcium, have been investigated. Highly purified large granular lymphocytes (LGL) were cultured for 12-30 hr in the presence of TPA, ionomycin, or A23817. TPA alone (1-20 ng/ml) triggered rapid LGL proliferation, whereas the calcium ionophores were ineffective. The addition of either calcium ionophore to suboptimal doses or TPA (0.1-0.5 ng/ml) resulted in a synergistic effect on LGL proliferation. Under these conditions high levels of IL-2 activity were released by the LGL. Phenotypic analysis revealed the rapid loss of the Fc gamma receptors (CD16) on LGL and the induction of the expression of IL-2 (CD25) and transferrin receptors and of HLA-DR, but not of CD3. Removal of extracellular Ca2+ by addition of EGTA at the beginning of the culture greatly depressed LGL proliferation and IL-2 production, and blocked phenotypic changes, such as the expression of Tac antigen. Finally, progression to the proliferative phase of LGL, activated by TPA alone or with ionomycin, was completely abrogated by a hyperimmune anti-IL-2 antiserum.

Antigens, Surface↗

Structural and serological heterogeneity of gamma/delta T cell antigen receptor expression in thymus and peripheral blood.

Monoclonal antibodies (mAb) reactive against the gamma/delta T cell antigen receptor (TcR) have been used to characterize the distribution and structural properties of gamma/delta TcR-bearing lymphocytes in blood and thymus. Consistent with prior reports the TcR gamma/delta-1 and delta-1 mAb react with all gamma/delta TcR+ T lymphocytes in blood and thymus. By contrast the TCS-delta mAb was found only to react with a subset of the gamma/delta TcR-bearing T cell population. Several lines of evidence suggest that this reagent preferentially reacts with the V delta 1 gene product. Using these reagents, it was observed that gamma/delta TcR+ T lymphocytes comprise 4.6 +/- 3.5% (range 1.0-16.3%) of peripheral blood lymphocytes. However, analysis of peripheral blood from normal adult donors revealed that in 29 of 32 the TCS-delta (possibly V delta 1)-bearing cells comprised less than 30% of the total gamma/delta-TcR+ population. Biochemical analysis demonstrated that the predominant form of the gamma/delta TcR in adult peripheral blood is a disulfide-linked heterodimer, indicating preferential use of the C gamma 1 gene. The delta TcR chain from these TcR-gamma/delta-1+/TCS-delta- T cells was remarkably basic in charge, as analyzed by nonequilibrium pH gradient electrophoresis. By contrast with peripheral blood the majority of freshly isolated and interleukin 2-cultured gamma/delta TcR+ thymocytes were predominantly TcR-gamma/delta-1+/TCS-delta +, and preferentially expressed V delta 1. Moreover, both disulfide-bonded and nondisulfide-bonded gamma/delta TcR heterodimers were expressed in all thymuses examined and both forms were contained within the TCS-delta + thymic subset. Similar to recent findings in the mouse, these studies suggest a possible bias in the structural form of gamma/delta TcR based on tissue location.

Antibodies, Monoclonal↗

Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects.

To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 micrograms bid), high dose beclomethasone aerosol (1000 micrograms bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV1) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (+/- SE) value of FEV1 4 h after exposure to TDI was 2.6 +/- 0.17 L, which went to 3.3 +/- 0.12 after low dose beclomethasone, and to 3.5 +/- 0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV1 in the 8 h after exposure to TDI, between treatments: F = 9.87, (P less than 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD20 decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD20 decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Effect of ranitidine on the absorption of aspirin.

Six healthy male volunteers received 1 week's pretreatment with ranitidine, 150 mg twice daily, and placebo in a double-blind cross-over trial. On the 8th day, each volunteer received 1 g of aspirin in order to study the pharmacokinetics of this nonsteroidal anti-inflammatory drug. The results of this study suggest that ranitidine does not induce clinically significant alterations to the kinetics of a single dose of aspirin in healthy males.

Adult↗

Sequential metabolic events and morphological changes during in vivo large granular lymphocyte activation and proliferation.

Interferon (IFN) and IFN inducers are known to boost natural killer (NK) activity in vivo and in vitro. In vivo enhancement of NK activity results from activation of preexisting NK cells as well as from an increased number of large granular lymphocytes (LGL), with a portion of them undergoing cell division. Our study was addressed to analyze the sequence of metabolic events occurring within the LGL population of Fischer rats treated with poly(I:C), as an IFN inducer. The increase in cytotoxic activity and LGL number in the peripheral blood already reached maximal levels by 12 hr after poly(I:C) injection, remained on a plateau 24 to 48 hr later, then slightly decreased on Day 4, and returned to control levels by Day 6. A similar kinetics was observed for RNA synthesis. In contrast DNA synthesis first increased at 24 hr, peaked at 48 hr, then decreased on Day 4, and was not detectable on Day 6. Percoll fractionation resulted in 92-97% of LGL in fraction 1, and cells in this fraction accounted for the increase of cytotoxicity as well as for newly synthesized RNA and DNA. However, LGL recovered on Day 1 or 2 after poly(I:C) stimulation displayed quite heterogeneous morphology, and a number of mitotic configurations were seen on Day 2 within the LGL population. Our results indicate that the boosting of NK activity by poly(I:C) is always associated with an increase in LGL numbers, the enhanced lytic capacity is associated in vivo with new RNA synthesis by the NK cells, and only in a later phase NK cell proliferation may account for the increase in LGL numbers.

Animals↗

Salbutamol plus beclomethasone dipropionate versus theophylline for the prevention of methacholine-induced bronchospasm in patients with chronic bronchitis.

Forty patients suffering from chronic bronchitis with basal forced expiratory volume in one second (FEV1) values at least 20% below ECSC (European Community Steel and Coal) predicted values were treated with a combination of salbutamol plus beclomethasone dipropionate or with theophylline for a period of 4 weeks. Methacholine bronchial inhalation challenges were performed before and after treatment. Both treatments produced significant increases in FEV1, forced vital capacity (FVC) and FEV1 100/FVC, while only the salbutamol plus beclomethasone dipropionate combination significantly reduced the decrease in FEV1 values after bronchial inhalation challenge.

Adult↗

In vitro enhancement of bone marrow natural killer cells after incubation with thymopoietin32-36 (TP-5).

Natural killer (NK) activity and interferon (IFN) production of spleen and bone-marrow lymphocytes were investigated in 8 to 10-wk-old C3HeB/FeJ/Cne mice, before and after in vitro exposure to the synthetic pentapeptide corresponding to positions 32-36 of the sequence of thymopoietin (TP-5). NK activity was studied against the 51Cr-radiolabelled Moloney virus-induced lymphoid cell line YAC 1, while IFN titres were determined by the inhibition of cytopathology of vesicular stomatitis virus on L929 cells, scored for CPE after 24 h from viral infection. A part of the lymphocytes from the spleen and bone marrow were incubated with different preselected doses (0.1, 1 and 10 micrograms/ml) of TP-5 for 1 h at 37 degrees C, and a part were left unincubated. At the end of the incubation time they were tested, without being washed, for NK activity and IFN production. TP-5 was able to significantly enhance (P less than 0.001 chi 2 test with Yate's correction) bone-marrow NK activity at a dose of 1 microgram/ml, while it was ineffective on spleen cells. A decrease of NK activity, seemingly due to a toxic effect, was observed both in bone-marrow and spleen lymphocytes, after incubation with a dose of 10 micrograms/ml. IFN production was not enhanced after exposure to TP-5. In all, our experiments suggest that TP-5 may enhance bone-marrow NK cells, perhaps by permitting the maturation of their precursors, as already known for T-cell-mediated cytotoxicity. Its effect is independent on IFN production and might be able to induce the rearrangement of certain surface specific receptors.

Animals↗

[Behavior of some enzymes of nucleoside catabolism in circulating lymphocytes during paraproteinemia].

The circulating lymphocytes of 16 normal subjects and of 18 patients with paraproteinemia have been characterized by measuring the levels of ADA, AMPA, PNPase, CDA. The results obtained reveal a highly significant increase in PNPase of subjects affected by paraproteinemia as compared to that of normal subjects (p less than 0.005). The fact that the increased enzymatic levels are found mainly in patients not affected by Bence-Jones proteinuria seems to indicate that the evolution of the paraproteinemia disease is in some way related to the intralymphocyte levels of PNPase.

AMP Deaminase↗

Short-term treatment with a low dose of inhaled fluticasone propionate decreases the number of CD1a+ dendritic cells in asthmatic airways.

The activation of T-lymphocytes through the recognition of specific allergens is a crucial event in the development of allergic inflammation. Dendritic cells (DC) are potent accessory cells that play an important role in initiating bronchial immune responses by activation of T-lymphocytes. We investigated the distribution of CD1a+ DC in the bronchial biopsies from asthmatic patients, and evaluated the effects of a short course of low dose inhaled fluticasone propionate treatment. Twenty-three mild to moderate stable asthmatic patients and eight normal subjects were included in the study. Bronchoscopy with bronchial biopsies were performed in each subject. Eighteen of the 23 asthmatics underwent a second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 mcg bd) in a placebo-controlled double-blind study. Biopsies were embedded into glycolmethacrylate resin and analysed by immunohistochemistry methods using specific monoclonal antibodies against CD1a, which is a widely recognized marker for DC. In asthmatics, CD1a+ DC number was significantly higher in bronchial epithelium (P < 0.001) and in lamina propria (P < 0.001) when compared with normal controls. In addition, we observed that a short course of low dose inhaled fluticasone propionate treatment decreased the number of CD1a+ DC in both the bronchial epithelium (P < 0.05) and lamina propria (P < 0.01). The increased number of CD1a+ DC support the hypothesis that DC play an important role in the modulation of the immune response in chronic asthma. Short-term low dose fluticasone propionate treatment induces down-regulation of the CD1a+ DC number.

Administration, Inhalation↗

Lack of specific cell mediated immunity to cytomegalovirus in people at risk for AIDS.

Twenty apparently healthy homosexuals from Italy and five patients with lymphadenopathic syndrome (LAS) were studied for specific cell mediated immunity (CMI) to Cytomegalovirus (CMV), by means of the leukocyte migration inhibition test (LMIT). Total circulating T cells and T cell subpopulations were also investigated by the use of specific monoclonal antibodies of the OK series. An inverted OKT4/T8 ratio was also found in about 30% of subjects. CMV was recovered from the urine of three homosexuals and high specific antibody titers were found in all the people studied. In addition we found a lack of specific CMI to CMV in 18 homosexuals and in 3 patients with LAS. We think that CMV can induce a state of immune tolerance in people at risk for AIDS which may contribute to promote the disease.

Acquired Immunodeficiency Syndrome↗

Synergistic effects of alpha interferon and 1,25 dihydroxyvitamin D3: preliminary evidence suggesting that interferon induces expression of the vitamin receptor.

BACKGROUND: To active metabolite of vitamin D3-1,25(OH)2D3-is a well-known differentiation inducer. The addition of this metabolite to sensitive cell cultures inhibits proliferation and induces monocytic-macrophagic differentiation. Alpha interferon may also inhibit proliferation and increase the expression of some surface antigens in some neoplastic cells. In the present report, we describe the synergistic activity of these two drugs on U-937 and on cultured cells from a leukemic patient. METHODS: Proliferation was studied by 3H-thymidine incorporation; differentiation markers were evaluated immunologically by monoclonal antibodies and by cytochemical tests. Phagocytosis and NBT reduction test were also performed in order to confirm the differentiating properties of these drugs. Finally, the expression of the 1,25(OH)2D3 receptor was evaluated by immunochemical methods. RESULTS: After culturing these cells for 72 hours in the presence of 1,25(OH)2D3, cell proliferation was reduced and the expression of some phenotypic and functional markers suggested monocytic-macrophagic differentiation. Alpha interferon and 1,25(OH)2D3 synergistically inhibit the proliferation of U-937 cells. Alpha interferon increased the expression of the 1,25(OH)2D3 receptor in U-937 cells. CONCLUSIONS: The reported results confirm the synergistic activity of INF and 1,25(OH)2D3 on cell proliferation in monoblastic cells. The possible role of the increased expression of the vitamin receptor in cells cultured in the presence of INF is discussed.

Calcitriol↗