Idiotypic modulation of autoimmunity by therapeutic human immunoglobulin preparations (IVIg).
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Autoantibodies↗
Biomedical subjects
F Rossi
Publications and source records attributed to F Rossi.
Extraarticular manifestations of rheumatoid arthritis and HLA antigens in northern Italy.
We performed retrospective analysis of 141 Northern Italian patients with rheumatoid arthritis (RA). This series represents all the patients seen as in and/or outpatients at the rheumatologic unit of Reggio Emilia Hospital during a 2 year period (1987-88). We observed a low frequency of nodules (16%) and vasculitis (2.1%). Thus, RA seems to be milder in our population compared to Caucasian patients with RA originating from North America or England. We observed a weak association with DR4 (RR = 2.4) in the total group of patients with RA. A low frequency of DR4 was observed in patients and controls (29 vs 14.5%, p = 0.001). When compared with controls the frequency of DR4 was significantly higher in seropositive (p = 0.001), but not in seronegative patients. We found that DR4 was significantly associated with nodules (RR = 6.4), with extraarticular features (EAF) (RR = 4) and with erosions (RR = 3) compared with controls. The subgroups with nodules and EAF had a DR4 frequency (respectively, of 52 and 40%) which was significantly higher than that observed in remaining patients (respectively, 25 and 24%). No significant difference was observed in the DR4 frequency between the patients with erosions and those without (34 vs 18%). Thus, DR4 in our population seems to be predominantly associated with a subgroup of patients characterized by seropositivity and EAF.
Aged↗
Interferon-gamma transcriptionally modulates the expression of the genes for the high affinity IgG-Fc receptor and the 47-kDa cytosolic component of NADPH oxidase in human polymorphonuclear leukocytes.
We examined the mechanisms responsible for the regulation by interferon-gamma (IFN-gamma) of the expression of the genes encoding the high affinity IgG-Fc receptor (Fc gamma R-I, CD64) and the NADPH oxidase 47-kDa cytosolic factor (p47-phox) in human polymorphonuclear leukocytes (PMN). Nuclear run-on transcriptional assays demonstrated that the Fc gamma R-I gene transcription is undetectable in untreated PMN but is significantly induced by IFN-gamma. Unlike Fc gamma R-I, p47-phox gene transcription is constitutively active in resting PMN and is down-regulated by a 2-h treatment of these cells with IFN-gamma. The transcriptional modulation by IFN-gamma of Fc gamma R-I and p47-phox genes is not influenced by the protein synthesis inhibitor cycloheximide. Moreover, Northern blot analysis revealed that cycloheximide superinduces p47-phox mRNA expression by increasing its half-life and without affecting p47-phox gene transcription. These findings indicate that human PMN can regulate gene expression by transcriptional and posttranscriptional events.
Antigens, Differentiation↗
Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII:C inhibitors.
Intravenous immunoglobulin (IV Ig) is useful in most patients with spontaneous factor VIII:C (FVIII:C) inhibitors, but some complete failures also are observed. Among patients responding to this therapy, decreases in FVIII:C autoantibody titer occurs within 24-48 hours and may lead to suppression of inhibitor activity. The prolonged response observed in some cases suggest an effect on autoantibody synthesis. The immediate decrease in FVIII:C inhibitory activity after IV Ig infusion indicates a direct interaction between IV Ig and the autoantibody. This effect is reproducible in vitro by mixing the patient's plasma and Ig at an appropriate molar ratio, which differs in each patient. Similarly, incubation of Ig with F(ab)'2 fragments of a patient's IgG and Ig reproduces inhibition, and this result indicates that the interaction is mediated by antigen binding sites (epitopes) on the immunoglobulins. The suggestion is that an idiotype- anti-idiotype mechanism must be at work. The origin of such anti-idiotypes in Ig prepared from pooled plasma of several thousand blood donors is unclear. The F(ab)'2 fragments were prepared from individual blood donors and tested in similar experiments with F(ab)'2 fragments of three distinct spontaneous FVIII:C inhibitors. The plasma level of anti-idiotypic antibodies reacting with FVIII:C inhibitors varied according to age and gender.
Antibodies, Anti-Idiotypic↗
Source and role of diacylglycerol formed during phagocytosis of opsonized yeast particles and associated respiratory burst in human neutrophils.
The results presented in this paper demonstrate that in human neutrophils phagocytosis of C3b/bi and IgG-opsonized yeast particles is associated with activation of phospholipase D and that this reaction is the main source of diglycerides. The demonstration is based upon the following findings: 1) the challenge of neutrophils with these opsonized particles was followed by a rapid formation of [3H]alkyl-phosphatidic acid [( 3H]alkyl-PA) and [3H]alkyl-diglyceride [( 3H]alkyl-DG) in cells labeled with [3H]alkyl-lyso-phosphatidylcholine; 2) in the presence of ethanol [3H]alkyl-phosphatidylethanol was formed, and accumulation of [3H]alkyl-PA and [3H]alkyl-DG was depressed; 3) propranolol, by inhibiting the dephosphorylation of [3H]alkyl-PA, completely inhibited the accumulation of [3H]alkyl-DG and depressed by about 75% the formation of diglyceride mass. Evidence is also presented that phagocytosis of C3b/bi and IgG-opsonized yeast particles and associated respiratory burst can take place independently of diglyceride formation and of the activity of this second messenger on protein kinase C. In fact: a) propranolol while completely inhibited the formation of diglyceride mass did not modify either the phagocytosis or respiratory burst; b) these two processes were insensitive to staurosporine.
Alkaloids↗
Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses.
Cerebellar climbing fibres react by collateral sprouting after subtotal lesions of the inferior olive, and the newly formed branches are able to reinnervate neighbouring denervated Purkinje cells. In the present paper, we used the Phaseolus vulgaris leucoagglutinin (PHA-L) tracing technique to label the climbing fibres and study their plasticity in detail at the light microscopical level. The specific objectives were to study the time course and morphological aspects of their sprouting, to estimate their extent of growth, and to compare the newly formed terminal plexuses with normal climbing fibres. Intraperitoneal injection of 3-acetylpyridine induced degeneration of the majority of the olivary neurones, which terminate as climbing fibres in the cerebellar cortex. Regularly, small numbers of neurones survived in the inferior olive. In the cerebellar cortex scattered surviving climbing fibres were found, which were devoid of any sign of injury. Already 3 days after the lesion, surviving climbing fibres had emitted collateral branches, which elongated for some distance through the molecular layer and ended with a number of varicosities and very fine branchlets. By 7 days, it was possible to recognize new developing arbours which grew in the molecular layer with the same orientation as normal climbing fibres. At longer survival times, extensive terminal arbours had developed and double labelling experiments confirmed that they terminated around the proximal dendrites of Purkinje cells. The newly formed terminal plexuses resembled, in all essential aspects, normal climbing fibres. In addition, from 1 month onward, it was evident that every surviving climbing fibre was able to form several new terminal plexuses reinnervating a number of neighbouring Purkinje cells. The result of this process was the formation of large clusters of newly formed plexuses around the parental arborization. Quantitative estimates indicated that the domain of innervation of single surviving climbing fibres could be increased by more than six times. It is concluded that climbing fibres surviving a subtotal olivary lesion are capable of extensive sprouting, axonal growth, and formation of new terminal plexuses, which resemble normal climbing fibres. Previous electrophysiological evidence indicates that this reinnervation is functional. The high specificity with which sprouting olivary axons reinnervate the proximal Purkinje cell dendrites suggests the existence of precise interactions between the growing fibres and their target. This example of "homotypic" collateral sprouting and reinnervation may thus provide a useful model for the study of nerve-target interactions.
Animals↗
Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. II. Synaptic organization on reinnervated Purkinje cells.
A salient feature of the cerebellar Purkinje cells is the highly ordered distribution of their excitatory afferents on the dendritic tree. Climbing fibres synapse exclusively on the proximal dendrites, whereas parallel fibres articulate with the distal branches, the so-called spiny branchlets. This input organization is lost following the removal of climbing fibres. Such denervation results in the formation of a large number of new spines on the proximal dendrites, and these become contacted by sprouting parallel fibres, which thereby extend their domain of innervation. We have previously shown that the climbing fibres surviving a subtotal lesion of the inferior olive sprout and reinnervate neighbouring Purkinje cells. In the present ultrastructural study, we have investigated the features of Purkinje cells reinnervated by sprouting climbing fibres. The objectives were to examine the fine morphology of the newly formed synapses and to determine whether the modifications of Purkinje cell morphology and afferent organization are reversed by this reinnervation. Surviving climbing fibres were labelled by the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemically visualized by means of the gold-substituted silver peroxidase technique, 2 and 6 months after 3-acetylpyridine lesions of the inferior olive in adult rats. Sprouting climbing fibres and newly formed arborizations were identified in the light microscope, isolated, and cut in serial ultrathin sections for electron microscopic analysis. The labelled boutons belonging to newly formed terminal plexuses exhibited the typical morphological features of climbing fibre terminals, i.e., a high number of round synaptic vesicles and a few small mitochondria. Most frequently they formed asymmetric synapses on stubby thorns protruding from the proximal Purkinje cell dendrites. In some instances, however, the postsynaptic element consisted of long slender spines or spines showing an atypical morphology. A number of labelled boutons was also in contact with the perikarya of reinnervated Purkinje cells, either articulating with spines or synapsing directly on the smooth somatic surface. The proximal dendrites of denervated Purkinje cells were characterized by large numbers of spines, which were frequently postsynaptic to parallel fibres. By contrast, Purkinje cells reinnervated by the sprouting climbing fibres generally showed a lower number of spines on their proximal dendrites, indicating a reversal of this morphological change. The aberrant parallel fibre input was also decreased on reinnervated dendrites or had completely disappeared. Nevertheless, some reinnervated Purkinje cells showed the persistence of some parallel fibre synapses on their proximal dendrites. On occasion, climbing fibre and parallel fibre boutons synapsed on the same spine.
Aged↗
De novo synthesis of diacylglycerol from glucose. A new pathway of signal transduction in human neutrophils stimulated during phagocytosis of beta-glucan particles.
The phagocytosis of beta-glucan particles by human neutrophils and the associated activation of NADPH O2- forming oxidase were accompanied by an increased hydrolysis of phosphoinositides by phospholipase C, hydrolysis of phosphatidylcholine by phospholipase D, accumulation of diglyceride (DG) mass, and [Ca2+]i rise. The reaction of phospholipid hydrolysis played a minor role in the formation of DG, which was mainly formed by de novo synthesis from glucose. The activation of this pathway was shown by the stimulation of the incorporation of [U-14C]glucose into DG, which occurred very rapidly after the challenge of neutrophils with beta-glucan particles. This DG derived from glucose was found almost completely as 1-acyl-2-acyl-glycerol (DAG). On the basis of the finding that phosphatidic acid was the precursor of DAG, an increase in the incorporation of [U-14C]acetate into DAG did not occur, and the [14C]radioactivity was in the glycerol backbone, the synthesis of DAG from [U-14C]glucose occurred very likely via dihydroxyacetone phosphate and glycerol 3-phosphate, stepwise acylation to phosphatidic acid, and dephosphorylation by phosphatidate phosphatase.
Calcium↗
Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8.
After phagocytosis of yeast opsonized with IgG, neutrophil leukocytes (polymorphonuclear leukocytes [PMN]) expressed high levels of neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) mRNA, which peaked after 3-5 h and were still elevated after 18 h. A similar but quantitatively less prominent effect was obtained with lipopolysaccharide (LPS). After phagocytosis, but not after exposure to LPS, the PMN progressively released considerable amounts of NAP-1/IL-8 into the culture medium (18.6-50 ng/ml in 18 h). The peptide released was biologically active, as indicated by the transient elevation of cytosolic-free calcium in PMN exposed to aliquots of the culture supernatants, and desensitization by prestimulation of the cells with recombinant NAP-1/IL-8. By producing NAP-1/IL-8 at sites where they phagocytose invading microorganisms, PMN could enhance the recruitment of new defense cells.
Calcium↗
Fluorescence line narrowing in Cr3+-doped gallium gadolinium garnet under a magnetic field.
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Journal Article↗
Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy.
We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.
Aged↗
Ion binding of cyclolinopeptide A: an NMR and CD conformational study.
CD and nmr techniques have been used to study, in acetonitrile solution, the ion-complexing capability of cyclolinopeptide A (CLA), a cyclic nonapeptide of sequence cyclo-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val) endowed with remarkable cytoprotective ability in vitro, and the conformation of the Ba(2+)/CLA complex. At room temperature, CLA in acetonitrile shows a proton nmr spectrum characteristic of the coexistence of many different conformers in intermediate exchange. The backbone contains a cis Pro-Pro bond, with all other peptide bonds in the trans conformation. CLA binds Ba2+ more tightly than the other cations studied, namely K+, Na+, Mg2+, and Ca2+; CD data are indicative of the presence of both 1:2 (sandwich) and 1:1 (equimolar) type complexes, depending on the Ba2+ ion concentration, whereas nmr data are consistent with an equimolar form. The relevant conformational features of the equimolar Ba2+/CLA complex are that the backbone contains all trans peptide bonds, a type I 6----3 beta-turn and a 3----1 gamma-turn (or a distorted 3----9 beta-turn). The global shape of the complexed peptide can be described as a bowl, with the concave (polar) side hosting Ba2+ and the convex side predominantly apolar.
Amino Acid Sequence↗
Phagocytosis of opsonized yeast induces tumor necrosis factor-alpha mRNA accumulation and protein release by human polymorphonuclear leukocytes.
In this report we show that phagocytosis of yeast particles opsonized with IgG (Y-IgG) by human polymorphonuclear cells (PMN) results in the selective induction of tumor necrosis factor (TNF-alpha) messenger RNA (mRNA) and release of its mature protein. Lipopolysaccharide (LPS) was also found able to induce TNF-alpha secretion by PMN, but was a less potent stimulus compared with Y-IgG. There was no evidence of interleukin-6 (IL-6) gene expression in PMN after phagocytosis of Y-IgG or in response to LPS, whereas IL-6 mRNA expression and secretion were induced by either stimulus in monocytes. These findings demonstrate that a physiological function such as phagocytosis modulates the gene expression for a cytokine in PMN and shed new light on the understanding of the pathogenesis of the inflammatory process.
Fungal Proteins↗
Effect of flomoxef on human platelet aggregation.
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Adult↗
Studies on the gene expression of several NADPH oxidase components.
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Cell Line↗
Teicoplanin does not modify the hypoglycemic effects of phenformin or glibenclamide, nor the anticoagulant action of warfarin. Experimental study.
Eventual pharmacological interactions induced by teicoplanin administration associated with oral hypoglycemic (phenformin and glibenclamide) and oral anticoagulant (warfarin) drugs have been experimentally evaluated. The administration of teicoplanin (3-15 mg/kg/die by endoperitoneal route) to the rat for 4 days did not significantly (P greater than 0.05) modify glycemia, prothrombin and partial thromboplastin times, the hypoglycemic effect of phenformin (2.5 mg/kg/die/4 days) or glibenclamide (0.5 mg/kg/die/4 days) nor the anticoagulant effect of warfarin (0.5 mg/kg/die/4 days). In conclusion, our results document that teicoplanin does not interfere with the activity of phenformin, glibenclamide or sodium warfarin.
Administration, Oral↗
Impact of rokitamycin, a new 16-membered macrolide, on serum theophylline.
Side effects have been observed when 14-membered macrolides, erythromycin and troleandromycin, have been prescribed concurrently in patients receiving therapeutic doses of theophylline. Rokitamycin is a new 16-membered macrolide antibiotic. We have evaluated its effect on theophylline serum concentrations in 12 adult patients suffering from chronic obstructive pulmonary disease. Initially, six patients were treated for four consecutive days with theophylline as sustained-release formulation in the amount of 600 mg daily; six other patients received for four consecutive days a short term intravenous infusion of 240 mg aminophylline, given over a period of 30 min twice daily. On the last day, blood samples were taken for theophylline determination. Theophylline concentrations were measured serially for 12 hours after oral formulation and 4 hours after aminophylline by enzyme immunoassay technique. Subsequently, while theophylline and aminophylline treatments were continued at the same dosage, each patient received in addition rokitamycin tablets, 400 mg every 12 hours. After seven days of this combined medication, the serial assays of serum theophylline were repeated at the same time intervals as before. Concomitant administration of therapeutic doses of rokitamycin did not affect significantly the steady-state pharmacokinetics of oral theophylline and did not alter the (pseudo-) steady-state pharmacokinetics of intravenous aminophylline, showing that the two drugs may be coadministered without any theophylline dose adjustment.
Aged↗
Cryptochrome, phytochrome, and anthocyanin production.
Anthocyanin production in cabbage (Brassica oleracea L.) and tomato (Lycopersicon esculentum Mill.) seedlings exposed to prolonged irradiations was studied under conditions that allowed discrimination, within certain limits, between the contribution of cryptochrome and phytochrome in the photoregulation of the response. The results of the study provide confirming evidence for the involvement of cryptochrome and direct evidence for a significant contribution of cryptochrome to the fluence rate dependence of the response to blue. The results provide some preliminary, direct indication for an interaction between cryptochrome and phytochrome in the photoregulation of anthocyanin production in seedlings exposed to the prolonged irradiations required for a high level of expression of the response. The type and degree of interaction between the two photoreceptors vary significantly, depending on the species and experimental conditions.
Journal Article↗