Biomedical subjects

M Donini

Publications and source records attributed to M Donini.

28 records · Page 2Linked to original sources

PubMed1994

Tyrosine phosphorylation and activation of NADPH oxidase in human neutrophils: a possible role for MAP kinases and for a 75 kDa protein.

Challenge of neutrophils with concanavalin A (ConA), formyl-methionyl-leucyl-phenylalanine (FMLP), and phorbol 12-myristate 13-acetate (PMA) induced the tyrosine phosphorylation of several proteins. Among these proteins we have identified two mitogen-activated protein kinase (MAPK) isoforms of 43 kDa (p43 MAPK) and 45 kDa (p45 MAPK) molecular mass. Moreover here we show that: (1) FMLP induced the tyrosine phosphorylation of the p43 MAPK, and ConA that of p45 MAPK, while PMA induced the tyrosine phosphorylation of both p43 and p45 MAPK; all these agonists induced the tyrosine phosphorylation of a 75 kDa protein (p75). (2) With FMLP or ConA as agonists, tyrosine phosphorylations of MAPK and p75 can be involved in the process of NADPH oxidase activation. On the contrary, PMA can activate the respiratory burst independently of these phosphorylations. (3) In Ca(2+)-depleted neutrophils, where phospholipid hydrolysis did not take place, ConA or FMLP did not activate the respiratory burst, but while ConA induced the tyrosine phosphorylation of p45 MAPK and p75, FMLP was not able to phosphorylate p43 MAPK and p75. (4) As previously observed in our laboratory, a double stimulation of Ca(2+)-depleted neutrophils with ConA plus FMLP induced a respiratory burst in the absence of activation of second messengers derived from phospholipase C, D and A2 activity. This respiratory burst was accompanied by tyrosine phosphorylation of both p43 and p45 MAPKs. These results indicate that when FMLP is the agonist, both the tyrosine phosphorylation of p43 MAPK and p75, and the activation of NADPH oxidase, are coupled to Ca(2+)-dependent mechanisms. On the contrary, ConA can induce the tyrosine phosphorylation of p45 MAPK and p75 independently of calcium, but an unknown Ca(2+)-dependent mechanism is necessary for the activation of NADPH oxidase by this agonist. This mechanism could be substituted by the induction of tyrosine phosphorylation of both p43 MAPK and p45 MAPK when Ca(2+)-depleted neutrophils are stimulated with ConA plus FMLP.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1994

Tyrosine phosphorylation of phospholipase C-gamma 2 is involved in the activation of phosphoinositide hydrolysis by Fc receptors in human neutrophils.

The stimulation of phosphoinositide hydrolysis by a number of agonists (phosphoinositide response) is a ubiquitous transmembrane signalling process for the regulation of several cell functions. Two mechanisms of activation have been identified that involve different phospholipases C: one regulated by G-proteins and another regulated by receptors having an intrinsic tyrosine kinase domain or that stimulate intracellular tyrosine kinase activity. This last mechanism is activated in several immunological cells, including lymphocytes, mastocytes, NK cells and monocytes, in response to agonists that bind antigen receptors, and receptors for IgE and IgG. In the present study, we have investigated the role of tyrosine phosphorylation in the stimulation of phosphoinositide hydrolysis mediated by Fc gamma Rs in human neutrophils. The results demonstrated that: 1) the activation of Fc gamma Rs with insoluble immune complexes (IIC) induced a tyrosine phosphorylation of several proteins that was dose-dependently inhibited by the tyrosine kinase inhibitor, genistein; 2) the activation of Fc gamma Rs caused a stimulation of phosphoinositide hydrolysis measured as [3H]inositol phosphates formation; 3) genistein depressed the activation of phosphoinositide hydrolysis; 4) among the several proteins that became tyrosine phosphorylated upon Fc gamma Rs activation by IIC, one 145 kDa protein was identified as PLC-gamma 2, using a specific antiserum. The phosphorylation of PLC-gamma 2 was completely inhibited by genistein. These results demonstrate that the phosphoinositide response to activation of Fc gamma Rs involves the tyrosine phosphorylation of PLC-gamma 2.

Genistein↗

PubMed1994

In human neutrophils the binding to immunocomplexes induces the tyrosine phosphorylation of Fc gamma RII but this phosphorylation is not an essential signal for Fc-mediated phagocytosis.

It has been recently suggested that protein tyrosine phosphorylation is involved in Fc gamma Rs-mediated signalling. In this paper we have investigated if in human neutrophils a tyrosine phosphorylation of Fc gamma RII takes places after the binding with immunocomplexes and if this phosphorylation plays a role in phagocytic signal. The immunoprecipitation with mAb anti-Fc gamma RII of lysates of neutrophils challenged in suspension with insoluble immunocomplexes (IIC) or sheep erythrocytes opsonized with IgG (E-IgG), followed by immunoblotting with anti-phosphotyrosine antibody, demonstrated that Fc gamma RII was tyrosine phosphorylated. When neutrophils were pretreated with different doses of tyrosine kinase inhibitors, genistein or erbstatin, the phosphorylation of Fc gamma RII induced by IIC or E-IgG was dose dependently inhibited. In these conditions both genistein and erbstatin failed to inhibit the phagocytosis of E-IgG. These results demonstrated that in human neutrophils in suspension the binding to Fc of IgG induces a tyrosine phosphorylation of Fc gamma RII but this phosphorylation is not an essential signal for phagocytosis of IgG-opsonized particles.

Antigen-Antibody Complex↗

PubMed1993

Acute anti-inflammatory activity and gastrointestinal tolerability of diclofenac and nitrofenac.

Diclofenac and its derivative nitrofenac were compared to test their anti-inflammatory efficacy and gastrointestinal toxicity in rats. A similar good anti-inflammatory activity of the two drugs was observed in carrageenan oedema and a marked gastrointestinal toxicity was induced by diclofenac, while nitrofenac failed to produce gastric damage even with very high doses (50 and 100 mg/kg). The lack of the gastric ulcers in rats treated with nitrofenac could be due to the absorption of the drug as an inactive inhibitor of PG synthesis and/or to the fact that probably nitric oxide is released in the intestine and plays an important protective role in maintaining the tissue integrity.

Animals↗

PubMed1992

Influence of radiotherapy on intestinal microflora in cancer patients.

We investigated in 15 patients with carcinoma of the uterine cervix or endometrium, who were undergoing postoperative radiation therapy, the effects of different fractionated radiation exposures on counts of fecal bacteria, on the growth of Clostridium difficile and Clostridium perfringens enterotoxin production. We observed a generally significant decrease in intestinal microflora after the first radiation exposure, whereas at the end of radiotherapy all bacteria increased and reached basal values except Enterococcus faecium 1, lactobacilli and total anaerobes. In some patients we observed an overgrowth of some Clostridium spp. which were potential pathogens associated with clinical symptoms. We did not observe an influence of multiple radiations on C. perfringens enterotoxin fecal contents. We conclude that patients receiving radiotherapy may benefit from the intake of oral bacteriotherapy, i.e. live beneficial bacteria such as Bacillus subtilis at the beginning of the irradiation exposure.

Aged↗

PubMedDate not supplied

Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats.

The gastrointestinal effects of single and repeated administration of ferrous sulphate was evaluated measuring faecal flora modifications and histology of stomach and duodenum of the rat. The acute experiments showed reversible histopathological lesions of stomach and duodenum with iron deposition and increase in faecal Cl. perfringens toxin after treatment with a high dose of FeSO4. The chronic experiment at lower doses showed no relevant histological damage, some iron deposition and strong alterations in faecal flora. A strong impact of oral FeSO4 on gastrointestinal environment was demonstrated.

Animals↗

PubMedDate not supplied

Effects on intestinal microflora, gastrointestinal tolerability and antiinflammatory efficacy of diclofenac and nitrofenac in adjuvant arthritic rats.

Since it is known that nitric oxide plays an important protective role in maintaining the tissue integrity and is cytotoxic for invasive micro-organisms, diclofenac and a new original diclofenac-derivate, nitrofenac (containing the nitric oxide group), was administered at doses of 0.3 and 3 mg kg-1 per os to adjuvant arthritic rats. At the 14th, 21st and 28th days after arthritis induction, the antiinflammatory efficacy and the effects on intestinal microflora of the two drugs were evaluated; moreover, at the end of the study period, the gastrointestinal tract was examined macroscopically for any presence of lesions. Daily oral administration of diclofenac and nitrofenac at 3 mg kg-1 markedly and significantly inhibited arthritis development until the end of the study period. Some significant changes were observed in anaerobic and Gram-negative bacterial flora, particularly the total disappearance, in all treated rats, of Escherichia coli 1, also 7 days after the last drug administration. Finally, no ulcers or severe damage were observed macroscopically with either drug, even if some alterations in the mucosa and haemorrhagic effusions were more evident in rats treated with diclofenac at 3 mg kg-1. In conclusion, in this chronic model a similar therapeutic efficacy of diclofenac and nitrofenac is shown in arthritic rats. The better gastrointestinal tolerability observed in nitrofenac-treated rats could be attributed to the release of nitric oxide.

Animals↗

PubMedDate not supplied

Patterns of covariation of DSM-IV personality disorders in a mixed psychiatric sample.

The covariation patterns of DSM-IV personality disorders (PDs) were studied in 431 consecutively admitted psychiatric patients. The co-occurrence rate was greater than 50% for all DSM-IV PDs. Both bivariate association tests and loglinear models showed distinct significant covariation patterns among PDs which were stable across confounder strata. DSM-IV PD clusters were not replicated, with the exception of cluster A. Principal-component analysis (PCA) showed the presence of 3 latent dimensions, thus explaining the DSM-IV PD covariation patterns. These results seem to stress the inadequacy of the DSM-IV categorical model of PD assessment. The need for a reduction of axis II categories and the inclusion of a dimensional model in the diagnostic assessment of DSM-IV PDs are discussed.

Adult↗

PubMedDate not supplied

Contact sensitization in children.

Our study concerns contact sensitization in children, the frequency of which is still debated in the literature, even though specific reports are increasing. During a 7 year period (1988-1994) 670 patients, 6 months to 12 years of age, were patch tested with the European standard series, integrated with 24 haptens, at the same concentrations as for adults. We observed positive results in 42% of our patients. Thimerosal, nickel sulfate, Kathon CG, fragrance mix, neomycin, wool alcohols, and ammoniated mercury induced most of the positive responses. The highest sensitization rate was found in children from 0 to 3 years of age. Comments on main positive haptens are reported. Seventy-seven percent of our sensitized patients were atopics, suggesting that atopy represents a predisposing factor for contact hypersensitivity. Patch testing represents a useful diagnostic procedure for the definition of childhood eczematous dermatitis and for the identification of agents inducing contact sensitization which is frequently associated with atopic dermatitis.

Child↗

PubMedDate not supplied

The retrospective assessment of childhood attention deficit hyperactivity disorder in adults: reliability and validity of the Italian version of the Wender Utah Rating Scale.

To assess the reliability and validity of the Wender Utah Rating Scale (WURS), 759 Italian undergraduate students were administered the Italian version of the WURS. In this sample, the WURS showed good internal consistency reliability (Cronbach alpha =.888). Both 1-week (r =.981, P <.001) and 2-month (r =.924, P <.001) retest reliabilities were satisfactory. The mother/subject agreement on the WURS total score was large: intraclass r =.883, P <.001. The principal component (PC) analysis showed the presence of three positively correlated first-order PCs, and one second-order PC. This PC structure of the WURS was replicated in an independent sample of 300 consecutively admitted psychiatric inpatients and outpatients. Finally, in a sample of 132 secondary school students, the WURS showed a moderate correlation with the Conners Abbreviated Parent and Teacher Questionnaire (CAPTQ): r =.307, P <.001. In this sample, the WURS total score was negatively correlated with school performance (rho = -.460, P <.001) and conduct (rho = -.293, P <.005) indexes.

Adult↗