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Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 541 records · Page 30Linked to original sources
PubMed1989

Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig.

We observed that pooled normal polyspecific human IgG for therapeutic use (IVIg) inhibited the binding of antithyroglobulin, anti-DNA and antiintrinsic factor antibodies to their autoantigens in vitro. The inhibitory effect of IVIg was dependent on interactions between the variable regions of IVIg and variable regions of the autoantibodies. Affinity chromatography of F(ab')2 fragments or of IgG containing anti-TG, anti-DNA, or anti-IF autoantibody activity on Sepharose-bound F(ab')2 from IVIg resulted in the specific retention of autoantibody activity, indicating that IVIg contain antiidiotypic antibodies against human autoantibodies. Inhibition of autoantibody activity by anti-Id in IVIg in vitro is dose dependent with maximal inhibition occurring at a specific molar ratio between patient's IgG and IVIg and shows a prozone phenomenon. The relative content in anti-Id against a particular autoantibody may differ between IVIg preparations. Affinity chromatography of IVIg on Sepharose-bound F(ab')2 fragments from IVIg also resulted in specific retention of anti-TG and anti-DNA activities that were found to be present in pooled normal immunoglobulins. The presence in IVIg of anti-Id against autoantibodies from patients and from normal individuals may provide a mechanism for the suppressive effect of IVIg in human autoimmune diseases and supports the concept of a functional idiotypic network regulating autoimmune responses in man.

Antibodies, Anti-Idiotypic↗
PubMed1989

Studies on the NADPH oxidase of phagocytes. Production of a monoclonal antibody which blocks the enzymatic activity of pig neutrophil NADPH oxidase.

We describe in this paper a monoclonal antibody to pig NADPH oxidase which inhibits enzymatic activity. This antibody, designated 1H8.2, was selected from a group of monoclonal antibodies produced against active preparations of purified NADPH oxidase and which showed selectivity of binding. 1H8.2 is an IgM restricted in binding to pig NADPH oxidase and showing higher binding to NADPH oxidase purified from phorbol myristate acetate-stimulated than from resting neutrophils. The antibody inhibits by about 90% the oxidase activity at 20-50 micrograms/ml. Inhibition is due to a decrease of the Vmax of the oxidase, and the Km is not affected. Incubation of the NADPH oxidase with 1H8.2 in the presence of concentrations of NADPH up to 25-fold the Km does not prevent the inhibition. Together with the evidence that the antibody does not inhibit the neutrophil superoxide dismutase-insensitive NADPH cytochrome c reductase and the liver NADPH-cytochrome c reductase this observation indicates that the 1H8.2 does not bind to an epitope belonging to the NADPH-binding site. Experiments of immunoprecipitation of iodinated membrane proteins and of immunoaffinity purification showed that 1H8.2 recognizes a heterodimer of apparent molecular mass of 16/18 and 14 kDa. These polypeptides can be involved in the NADPH oxidase activity or represent still unrecognized molecules able to modulate its function.

Animals↗
PubMed1989

Studies on molecular regulation of phagocytosis in neutrophils. Con A-mediated ingestion and associated respiratory burst independent of phosphoinositide turnover, rise in [Ca2+]i, and arachidonic acid release.

The role of the activation of phosphoinositide turnover and of the increase in cytosolic free calcium, [Ca2+]i, in the phagocytosis and associated activation of the respiratory burst was investigated. We report the results obtained on the phagocytosis of yeast cells mediated by Con A in normal and in Ca2+-depleted human neutrophils. In normal neutrophils the phagocytosis was associated with a respiratory burst, a stimulation in the formation of [3H] inositol phosphates and [32P]phosphatidic acid, the release of [3H]arachidonic acid, and a rise in [Ca2+]i. Ca2+-depleted neutrophils are able to perform the phagocytosis of yeast cells mediated by Con A and to activate the respiratory burst without stimulation of [3H]inositol phosphates and [32P]phosphatidic acid formation, [3H]arachidonic acid release, and rise in [Ca2+]i. In both normal and Ca2+-depleted neutrophils the phagocytosis and the associated respiratory burst, 1) were inhibited by cytochalasin B; 2) were insensitive to H-7, an inhibitor of protein kinase C; and 3) did not involve GTP-binding protein sensitive to pertussis toxin. These findings indicate that the activation of phosphoinositide turnover, the liberation of arachidonic acid, the rise in [Ca2+]i, and the activity of protein kinase C are not necessarily required for ingestion of Con A-opsonized particles and for associated activation of the NADPH oxidase, the enzyme responsible for the respiratory burst. The molecular mechanisms of these phosphoinositide and Ca2+-independent responses are discussed.

Arachidonic Acids↗
PubMed1989

Ala analogues of the cyclolinopeptide A.

Analogues of cyclolinopeptide A, due to the replacement of each amino acid in the Pro1-Pro2-Phe3-Phe4 sequences with an L-Ala residue, were synthesized by classical method in solution. Mixed anhydride and N,N'-dicyclohexylcarbodiimide coupling methods have been used for the synthesis of both linear and cyclic peptides. The products were characterized by Rf values and uv spectra, as well as by fast atom bombardment spectroscopy. 1H-nmr studies on [Ala2] analogues are also reported. Preliminary data in CDCl3 solution, at low temperature, seems more promising.

Alanine↗
PubMed1989

Comparison of the conformations of cyclolinopeptide A in the solid state and in solution.

Cyclolinopeptide A, a cyclic nonapeptide isolated from linseed, has lately attracted large interest for its cytoprotective activity. The recent elucidation of its solid state structure has prompted us to undertake a detailed conformational analysis in solution. Room-temperature 1H-nmr spectra in several solvents (DMSO-d6, DMSO-d6/D2O/H2O, CD3OH, (CD3)2CDOH, CDCl3) all show very broad lines, indicating the presence of chemical exchange among several conformers. It proved possible to freeze a single conformational state in CDCl3 at 214 K. Unusual chemical shifts and nuclear Overhauser enhancements are consistent with the main features of the solid state structure.

Peptides, Cyclic↗
PubMed1989

Effects of ethanol and imidazobenzodiazepine Ro 15-4513 on spontaneous saccades of the pigmented rat.

The present study was aimed at investigating the alterations of the spontaneous saccadic eye movements of pigmented rats following ethanol administration. In addition we have studied the efficacy of the imidazobenzodiazepine Ro 15-4513 in reversing the effects of alcohol on saccades. The horizontal component of spontaneous eye movements was recorded by means of the magnetic field search coil technique on 11 head-restrained, pigmented rats. After the intraperitoneal injection of ethanol (1 g/kg) spontaneous saccades showed: i) a backward post-saccadic drift, with an exponential-like time course (time constant 100-150 ms); ii) a remarkable reduction of mean saccadic amplitude, up to 37% of control; iii) a significant decrease of peak velocity, which was reduced to about 80% of control. All these effects appeared and developed within a few minutes after the administration and were still present one hour later. When Ro 15-4513 (5 mg/kg) was injected i.p., 15 min after ethanol, the post-saccadic drift amplitude was immediately reduced and the drift was completely abolished within about 30 min. Mean saccadic amplitude returned to control values within a few minutes and was then steadily maintained for the following period examined (30 min). On the contrary, peak velocity showed only a slight tendency to recover which never was significant. When the same dose of Ro 15-4513 was injected alone there was no post-saccadic drift. However, mean saccadic amplitude increased, almost immediately, up to 160% of control. Its value showed a slight constant decrease in the following 30 min. Peak velocity was only slightly increased (up to 106% of control), but never was significantly different from control. Our results show that ethanol induces a remarkable impairment in the performance of spontaneous saccades. The imidazobenzodiazepine Ro 15-4513 is able to reverse completely only some of the alcohol-induced alterations, i.e. the post-saccadic drift and the reduction of saccadic amplitude, while it fails to counter efficiently the reduction of peak velocity. Ro 15-4513 exerts an intrinsic action, which is opposite to that of ethanol, on some of the saccadic parameters we have examined.

Animals↗
PubMed1989

Clinical response to auranofin in patients with psoriatic arthritis.

Fifty-two patients with psoriatic arthritis (PA), treated with auranofin (AF), were entered into a one year prospective, open study. The total group showed a significant increase in frequency of HLA antigens A1 and B38, and a reduction of B5 when compared to healthy controls. There was a remission or an important improvement of disease in the 51% of 45 patients who completed the study. The rate of withdrawal due to side effects was low (8.8%) and the toxicity was mild in nature (diarrhoea and mucocutaneous rash). We prospectively sought predictors of response using HLA antigens, and clinical and laboratory parameters at the beginning of therapy. The only 3 factors found to be related to outcome were duration of psoriasis, physician and patient assessment of disease activity. No laboratory data or HLA specificities could be associated with substantial response to AF therapy.

Arthritis↗
PubMed1989

Neuroendocrine evidence of deranged noradrenergic activity in chronic migraine.

Migraine is a psychobiological disorder in which a recurrent failure of opioid and adrenergic systems might occur, as plasma and CSF studies suggest. In order to elucidate the relationship between noradrenergic and opioidergic functions, the plasma beta-endorphin (beta-EP) response to clonidine and the cortisol response to dexamethasone were evaluated together in 25 patients suffering from migraine without aura, and with chronic tension headache (MTH). Baseline beta-EP plasma levels and beta-EP response to clonidine were significantly lower in MTH subjects than in controls, suggesting a postsynaptic hypothalamo-pituitary impairment. Forty-four percent of the MTH subjects showed either a lack of suppression of plasma cortisol following dexamethasone administration, or basal cortisol concentrations higher than controls and suppressors, suggesting a disinhibition of the hypothalamopituitary-adrenal (HPA) axis. An inverse correlation was found between pain severity and beta-EP secretion induced by clonidine (delta max), and no relationship was found between beta-EP and mood. These data suggest a failure of central noradrenergic activity, or perhaps an impaired secretion of beta-EP not related to HPA axis hyperactivity or to affective state.

Adult↗
PubMed1989

Antiidiotypic suppression of autoantibodies with normal polyspecific immunoglobulins.

A mechanism by which therapeutic normal polyspecific immunoglobulins (IVIg) may suppress autoimmune responses in vivo is that of antiidiotypic suppression of autoantibodies mediated by anti-idiotypes present in IVIg. In vitro incubation with IVIg of either the plasma or the IgG fraction from plasma of patients with autoantibodies against procoagulant factor VIII (VIII:C), DNA, thyroglobulin, peripheral nerve and intrinsic factor resulted in dose-dependent inhibition of autoantibody activity. The pattern of inhibition curves showed a prozone phenomenon. Maximal inhibition was achieved at a ratio of patient's IgG to IVIg which was specific for each antibody tested. Inhibition was dependent on idiotypic/antiidiotypic interactions between autoantibodies and IVIg since: 1) F(ab')2 from IVIg inhibited autoantibody activity in F(ab')2 fragments from patients' IgG; 2) IVIg contained no antigen-like activity and no antibodies against the commonest allotypes expressed in F(ab')2 fragments of human IgG; 3) autoantibody activity in F(ab')2 fragments from patients' IgG was specifically retained on affinity columns of Sepharose-bound F(ab')2 fragments from IVIg. The presence of antiidiotypes against autoantibodies in pooled normal IgG supports the concept of a functional idiotypic network regulating autoimmune responses in man.

Antibodies, Anti-Idiotypic↗
PubMed1989

A study of the cardiopressor effects of lisuride in the treatment of parkinsonism and pathological aging brain.

In this study, the hemodynamic and neurochemical effects of lisuride, a dopamine agonist with serotoninergic properties, have been evaluated in de novo parkinsonian patients and in elderly subjects with mild cognitive impairment. Blood pressure (BP), heart rate (HR), and urinary catecholamine (CA) fluctuations throughout the 24-h cycle were monitored before and during lisuride therapy along with BP, HR, and plasma CA responses to the tilt-table test. Lisuride (1.2-2.4 mg/day) administered in an open-type 15-day study was capable of decreasing the urinary CA excretion and norepinephrine plasma levels in parkinsonian patients. In some cases, the cardiovascular response to standing was impaired. Lower doses of the drug (0.15 mg/day), administered to elderly patients in a double-blind parallel group vs. placebo study, did not induce any change in cardiopressor responses but decreased the 24-h urinary excretion of epinephrine. These results suggest the importance in both conditions of detecting early stages of alterations in cardiopressor homeostatic processes before therapy with DAergic drugs is initiated.

Aged↗
PubMed1989

Anti-idiotypes against autoantibodies in normal immunoglobulins: evidence for network regulation of human autoimmune responses.

This manuscript summarizes observations indicating that anti-idiotypes against human autoantibodies may be found in sera from patients recovered from autoimmune disease and in pooled normal polyspecific immunoglobulins (IVIg). The evidence that IVIg contain anti-idiotypes against autoantibodies includes: 1) inhibition by F(ab)2 from IVIg of the binding of F(ab)2 autoantibodies to their autoantigens; 2) specific retention of autoantibodies upon affinity chromatography of F(ab)2 fragments containing autoantibody activity on Sepharose-bound F(ab)2 from IVIg; 3) lack of detection of anti-allotypes and lack of significant anti-Fc activity in IVIg; 4) specific competitive displacement by polyclonal heterologous F(ab)2 anti-idiotypes of the binding of IVIg to affinity-purified F(ab)2 autoantibodies. The high number of donors contributing to IVIg endows the preparations with anti-idiotypic specificities that may not necessarily be detectable in plasma from single healthy individuals. Our observations of the presence in IVIg of anti-idiotypes against pathogenic autoantibodies and against IgG and IgM autoantibodies found in low amounts in normal sera supports the concept of a functional network regulating expression of autoimmunity in humans. We suggest that IVIg may be efficient in selected autoimmune diseases by providing a source of anti-idiotypes with a wide range of specificities brought as interconnected antibody species that may conpensate for altered connectivity of the immune network of patients with autoimmune diseases.

Autoantibodies↗
PubMed1989

Normal reference values for regional pulmonary peripheral airspace epithelial permeability. Influence of pneumonectomy and the smoking habit.

Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smoker's lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.

Adult↗