PubMed Health⌕ Search

Biomedical subjects

M Piccoli

Publications and source records attributed to M Piccoli.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Sexually transmitted diseases in adolescence].

BACKGROUND: Sexually transmitted diseases (STD) have their most incidence in adolescence. We conducted an observational study on the symptomatic patients of our STD's office to evaluate epidemiological distribution, behavioral patterns and diffusion of genital infections in teen-agers in respect of the adult population. METHODS: From april 1996 to april 1999 we studied two groups of patients: 54 teen-agers (13-19 years) and 917 women in fertile age (20-40 years). All the patients underwent to a clinical and microbiological examination of vaginal secretions (Gram slide, wet mount, cultures for bacteria, yeasts, eventually Chlamydia trachomatis, Mycoplasma spp, Neisseria gonorrhoeae, Herpes simplex virus--HSV--) and to an anamnestic and socio-epidemiological questionnaire. RESULTS: The more frequent genital infections among adolescents was vulvovaginal candidiasis (35% vs. 23.9% of adult people). HSV was found in 1.8% of teen-agers (vs. 0.6%) and when requested, Chlamydia trachomatis and mycoplasmas was found respectively in 16.6% (vs. 1.1%) and 50% (vs. 28%) in adolescents. We observed a high percentage of pregnancy (22.2%) of voluntary pregnancy interruption (41.6%) and a specific sexual behavior among teenagers. CONCLUSIONS: Our data show a particular behavioral risk pattern in the adolescence population and indicate the necessity of a serious program of prevention and sexual education that allow young people to live with more consciousness and safety their sexuality.

Adolescent↗
PubMed1999

Alterations of T cell distribution and functions in prenatally cypermethrin-exposed rats: possible involvement of catecholamines.

The synthetic pyrethroid insecticide, cypermethrin (50 mg/Kg) was given during gestation to pregnant rats by gavage in corn oil. Prenatal cypermethrin-exposure induces a marked and long-lasting increase of adrenaline (A) and noradrenaline (NA) plasma concentrations. The enhancement of plasma catecholamine levels was accompanied by a marked increase of CD5+, CD4+, and CD8+ total T cell numbers in the peripheral blood, while in the spleen a reduction of all T cell subsets was observed. In addition, peripheral blood lymphocytes (PBL) from rats prenatally exposed to cypermethrin showed an enhanced capability to proliferate in response to different doses of Concanavalin A (ConA), or human recombinant interleukin-2 (hrIL-2), whereas an impaired proliferative response was observed in the spleen. The percent increase of NA, but not A plasma concentrations paralleles the immunomodulatory effects induced by cypermethrin neonatal exposure on T cell distribution and mitogen-induced proliferation in the peripheral blood and spleen. Collectively, our results suggest that the changes in mitogen-induced proliferative responses in the peripheral blood and spleen of prenatally cypermethrin-exposed rats may be attributable to pesticide-induced catecholamine release, which causes an increased output of CD5+, CD4+, and CD8+ T cells from the spleen to the peripheral blood, and a consequent lymphocytosis.

Adjuvants, Immunologic↗
PubMed1999

CD94/NKG2-A inhibitory complex blocks CD16-triggered Syk and extracellular regulated kinase activation, leading to cytotoxic function of human NK cells.

The CD94/NKG2-A complex is the inhibitory receptor for the nonclassical MHC class I molecule HLA-E on human NK cells. Here we studied the molecular mechanisms underlying the inhibitory activity of CD94/NKG2-A on NK cell functions by analyzing its interference on CD16-initiated signaling pathways involved in the control of cytolytic activity. Both tyrosine phosphorylation and activation of Syk kinase together with tyrosine phosphorylation of CD16 receptor zeta subunit are markedly inhibited by the coengagement of CD94/NKG2-A complex. As a downstream consequence, CD94/NKG2-A cross-linking impairs the CD16-induced activation of extracellular regulated kinases (ERKs), a pathway involved in NK cytotoxic function. The block of ERK activation is exerted at an early, PTK-dependent stage in the events leading to p21ras activation, as the CD16-induced tyrosine phosphorylation of Shc adaptor protein and the formation of Shc/Grb-2 complex are abrogated by CD94/NKG2-A simultaneous engagement. Our observations indicate that CD94/NKG2-A inhibits the CD16-triggered activation of two signaling pathways involved in the cytotoxic activity of NK cells. They thus provide molecular evidence to explain the inhibitory function of CD94/NKG2-A receptor on NK effector functions.

Animals↗
PubMed1999

Role for the Rac1 exchange factor Vav in the signaling pathways leading to NK cell cytotoxicity.

Here we investigate the activation of and a possible role for the hematopoietic Rac1 exchange factor, Vav, in the signaling mechanisms leading to NK cell-mediated cytotoxicity. Our data show that direct contact of NK cells with a panel of sensitive tumor targets leads to a rapid and transient tyrosine phosphorylation of Vav and to its association with tyrosine-phosphorylated Syk. Vav tyrosine phosphorylation is also observed following the activation of NK cells through the low-affinity Fc receptor for IgG (Fc gamma RIII). In addition, we demonstrate that both direct and Ab-mediated NK cell binding to target cells result in the activation of nucleotide exchange on endogenous Rac1. Furthermore, Vav antisense oligodeoxynucleotide treatment leads to an impairment of NK cytotoxicity, with Fc gamma RIII-mediated killing being more sensitive to the abrogation of Vav expression. These results provide new insight into the signaling pathways leading to cytotoxic effector function and define a role for Vav in the activation of NK cell-mediated killing.

Animals↗
PubMed1999

Beta 1 integrin cross-linking inhibits CD16-induced phospholipase D and secretory phospholipase A2 activity and granule exocytosis in human NK cells: role of phospholipase D in CD16-triggered degranulation.

Recent data indicate that integrin-generated signals can modulate different receptor-stimulated cell functions in both a positive (costimulation) and a negative (inhibition) fashion. Here we investigated the ability of beta 1 integrins, namely alpha 4 beta 1 and alpha 5 beta 1 fibronectin receptors, to modulate CD16-triggered phospholipase activation in human NK cells. beta 1 integrin simultaneous cross-linking selectively inhibited CD16-induced phospholipase D (PLD) activation, without affecting either phosphatidylinositol-phospholipase C or cytosolic phospholipase A2 (PLA2) enzymatic activity. CD16-induced secretory PLA2 (sPLA2) protein release as well as its enzymatic activity in both cell-associated and soluble forms were also found to be inhibited upon beta 1 integrin coengagement. The similar effects exerted by specific PLD pharmacological inhibitors (2,3-diphosphoglycerate, ethanol) suggest that in our experimental system, sPLA2 secretion and activation are under the control of a PLD-dependent pathway. By using pharmacological inhibitors (2,3-diphosphoglycerate, wortmannin, ethanol) we also demonstrated that PLD activation is an important step in the CD16-triggered signaling cascade that leads to NK cytotoxic granule exocytosis. Consistent with these findings, fibronectin receptor engagement, by either mAbs or natural ligands, resulted in a selective inhibition of CD16-triggered, but not of PMA/ionomycin-induced, degranulation that was reversed by the exogenous addition of purified PLD from Streptomyces chromofuscus.

Cell Degranulation↗
PubMed1999

Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats.

Substance P (SP) plays a major role in the regulation of the interaction between immune and nervous systems. SP administration stimulates Con A-induced proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 production and expression of activation antigens such as IL-2 receptor alpha chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5+ and CD4+ T lymphocytes in the peripheral blood of capsaicin-treated rats. Concomitant administration of SP with the non-peptide Neurokinin-1 receptor (NK1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 production as well as of CD4+ CD25+ and CD4+ RT1B+ T cell numbers in normal and capsaicin-treated rats. SR 140333 also blocked the increased percentage of peripheral blood CD4+ T cells induced by SP in capsaicin-treated rats.

Animals↗
PubMed1999

Laparoscopic surgery for colorectal cancer.

Despite the widespread use of laparoscopic techniques in many fields, in the realm of malignant diseases, a great concern has been raised regarding safety, efficacy, and long-term results. The authors report their experience of 163 patients operated on for colorectal malignancies by minimally invasive access. The conversion rate (20.4%), morbidity (15.1%), and null mortality compare well with other studies published worldwide. The postoperative outcome was characterized by a prompt return to activity (1.3 days) and of bowel movements (2.9 days), while length of stay and an adequate oral resumption were comparable to those of open surgery. Peritoneal lavage did not show tumor cells disseminated during the operative maneuvers. The distance of tumor from resection margins and the number of lymph nodes harvested with the operative specimen did not vary from those obtained in open surgery. Two patients (1.2%) recurred at the mini-laparotomy and port sites, but, in both cases, the traumatic manipulation of the cancer specimen was probably responsible for the event. After a mean follow-up of over 3 years, 34 patients died of neoplastic recurrence, and 17 are alive with disease relapse. The laparoscopic approach to colectomy has not yet gained an unquestioned place in the experience of the colorectal surgeon. However, if sound surgical method and judgement are used to minimize local recurrences, and if a better preservation of postoperative immune function proves to be of clinical significance in the long term, laparoscopic colectomy may prove to be a safe and less stressful approach to colon resection.

Adolescent↗
PubMed1999

Tyrosine kinase-dependent ubiquitination of CD16 zeta subunit in human NK cells following receptor engagement.

We investigated whether aggregation of the low-affinity immunoglobulin G receptor (CD16) on human NK cells results in receptor ubiquitination. We found that the CD16 zeta subunit becomes ubiquitinated in response to receptor engagement. We then investigated whether protein tyrosine kinase (PTK) activation is required for CD16-mediated receptor ubiquitination. Pretreatment with the PTK inhibitor genistein substantially decreased ligand-induced zeta ubiquitination, suggesting a requirement for PTK activation in receptor ubiquitination. We further analyzed PTK involvement in controlling receptor ubiquitination by using the vaccinia virus expression system. Overexpression of wild-type active lck, but not a kinase-deficient mutant, enhanced both ligand-induced tyrosine phosphorylation and ubiquitination of the CD16 zeta subunit. Taken together, our data demonstrate that CD16 engagement induces zeta chain ubiquitination and strongly suggest a role for lck in regulating this modification.

Antigens, CD↗
PubMed1999

Evidence for alphavbeta3 and alphavbeta5 integrin-like vitronectin (VN) receptors in Candida albicans and their involvement in yeast cell adhesion to VN.

The expression of integrin vitronectin (VN) receptors on Candida albicans yeasts and their involvement in the adhesion to VN were investigated. By immunofluorescence and cytofluorimetric analysis, several antibodies directed against human alphav, beta3, beta5, alphavbeta3, or alphavbeta5 integrin positively stained C. albicans yeasts. Biochemical analysis on yeast lysates with anti-human alphav, beta3, or beta5 antibody revealed molecular species of 130, 110, 100, and 84 kDa. The 130-kDa band was identified as alphav, whereas the doublet of 110/100 kDa and the 84-kDa band likely correspond to the beta3 and beta5 subunits, respectively. Some 48%-54% of Candida yeasts specifically adhered to VN, and this binding was strongly inhibited by anti-human alphav, beta3, alphavbeta3, and alphavbeta5 antibodies and by RGD- but not RGE-containing peptides. In addition, VN inhibited C. albicans adherence to a human endothelial cell line. Thus, C. albicans in the yeast phase expresses VN receptors antigenically related to the vertebrate alphavbeta3 and alphavbeta5 integrins, which mediate its adhesion to VN.

Candida albicans↗
PubMed1999

Analysis of heart rate variability five minutes before the onset of paroxysmal atrial fibrillation.

BACKGROUND: Various experimental and clinical observations suggest changes in sympathetic and vagal neural regulatory mechanisms play a critical role in altering cardiac electrical properties and favor the occurrence of arrhythmic events. There is limited information about the influences of the autonomic tone on the development of episodes of paroxysmal atrial fibrillation in patients with no evidence of organic heart disease. The aim of this study was to investigate changes in sympatho-vagal balance 5 minutes before the onset of atrial fibrillation. METHODS: We evaluated 28 patients with no history of heart disease who were not undergoing pharmacological treatment and who had at least one episode of paroxysmal atrial fibrillation recorded during an 24-hour ECG Holter monitoring. We analyzed values of frequency domain heart rate variability parameters 5 minutes before the onset of atrial fibrillation (prefa period) compared to an equivalent period at least 1 hour after from atrial fibrillation (random period). RESULTS: Thirty-six episodes of atrial fibrillation were recorded and our results showed we had two types of episodes. Eighteen were classified as Type A, in which we had an increase of low frequency (LF) (79.15 +/- 10.76 in comparison with 62.64 +/- 19.55) (P = 0.004) and a decrease of high frequency (HF) (20.82 +/- 10.74 in comparison with 37.64 +/- 20.20) (P = 0.004) consistent with an increase of sympathetic tone; and 18 were classified as Type B in which there was a decrease of LF (62.82 +/- 15.38 in comparison with 85.97 +/- 8.48) (P < 0.001), and an increase of HF (36.79 +/- 14.72 compared with 14.01 +/- 8.48) (P < 0.001), consistent with an increase of parasympathetic tone. CONCLUSION: We observed abrupt changes in sympathovagal balance in the last 5 minutes preceding an episode of atrial fibrillation. This can be related to a double behavior in the neurogenic drive: in Type A episodes there is an increase of the LF spectrum, LF:HF ratio, and a decrease of the HF spectrum consistent with an increase of neurogenic sympathetic drive; in Type B episodes there is a reduction of the LF spectrum, LF/HF ratio, and an increase of HF spectrum consistent with an enhancement of the neurogenic parasympathetic drive. In some patients, we found that the two mechanisms operate during different hours of the day and that sometimes there is an increase of sympathetic tone, and in the same instances an increase of parasympathetic tone. Heart-rate variability measures fluctuation in autonomic inputs to the heart rather than the mean level of autonomic impulse; autonomic imbalance is probably more important than the vagal or sympathetic drive alone.

Adult↗
PubMed1999

[Chylothorax following myocardial revascularization with the internal mammary artery].

Chylothorax is a rare but serious complication of coronary artery bypass grafting. We describe a case of double myocardial revascularization with the internal mammary artery developing the complication ten weeks after cardiac surgery. The reasons for late symptomatology of lymphatic injury are analyzed. Conservative treatment with low-fat diet, total parenteral nutrition and pleural drainage was attempted unsuccessfully; chyle leakage of around 500 ml/day and onset of nutritional deficiency made it advisable to seal the thoracic duct surgically.

Aged↗
PubMed1998

Integrin-mediated ras-extracellular regulated kinase (ERK) signaling regulates interferon gamma production in human natural killer cells.

Recent evidence indicates that integrin engagement results in the activation of biochemical signaling events important for regulating different cell functions, such as migration, adhesion, proliferation, differentiation, apoptosis, and specific gene expression. Here, we report that beta1 integrin ligation on human natural killer (NK) cells results in the activation of Ras/mitogen-activated protein kinase pathways. Formation of Shc-growth factor receptor-bound protein 2 (Grb2) and Shc-proline-rich tyrosine kinase 2-Grb2 complexes are the receptor-proximal events accompanying the beta1 integrin-mediated Ras activation. In addition, we demonstrate that ligation of beta1 integrins results in the stimulation of interferon gamma (IFN-gamma) production, which is under the control of extracellular signal-regulated kinase 2 activation. Overall, our data indicate that beta1 integrins, by delivering signals capable of triggering IFN-gamma production, may function as NK-activating receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Cypermethrin-induced alteration of thymocyte distribution and functions in prenatally-exposed rats.

The synthetic pyrethroid insecticide, cypermethrin (50 mg/kg) was given during gestation to pregnant rats by gavage in corn oil. Prenatal cypermethrin exposure induced a significant decrease in the absolute number of all thymocyte subsets during the first 30 days after birth, being the double negative CD4-CD8-, single positive CD4 and CD8 T cells preferentially affected. Later on day 60 and 90 double positive CD4+CD8+ and single positive thymocytes gradually recovered, while the total number of CD4 CD8 cells was increased. Moreover, thymocytes from rats prenatally exposed to cypermethrin showed an impaired ability to proliferate in response to different doses of Concanavalin A (ConA) and human recombinant interleukin-2 (hrIL-2) and to produce and/or release IL-2. Overall, our results indicate that cypermethrin administered during prenatal period can affect multiple steps in thymocyte differentiation pathways resulting in an altered cell subset distribution and an impairment of thymocyte functions.

Animals↗
PubMed1998

CD16-mediated activation of phosphatidylinositol-3 kinase (PI-3K) in human NK cells involves tyrosine phosphorylation of Cbl and its association with Grb2, Shc, pp36 and p85 PI-3K subunit.

Phosphatidylinositol 3-kinase (Pl-3K) plays a key role in several cellular processes, including mitogenesis, apoptosis, actin reorganization and vesicular trafficking. The molecular events involved in its activation have not been fully elucidated and several reports indicate that a key event for enzyme activation is the interaction of the SH2 domains of the p85 regulatory subunit of Pl-3K with tyrosine-phosphorylated proteins. In this study, we investigated the involvement of the product of the proto-oncogene c-Cbl in the activation of Pl-3K triggered by CD16 in human NK cells and the possible mechanisms leading to Pl-3K recruitment to the plasma membrane. Our results indicate that stimulation of NK cells through CD16 results in a rapid tyrosine phosphorylation of Cbl, which is constitutively associated with Grb2 and forms an activation-dependent complex with the p85 subunit of Pl-3K. In addition, we detected the presence of the Grb2-associated tyrosine-phosphorylated p36 and Shc proteins in anti-Cbl and anti-p85 immunoprecipitates from CD16-stimulated NK cell lysates. Upon CD16 stimulation, Pl-3K activity was found associated with Cbl and to a lesser extent with Grb2 and Shc as well as with the zeta chain of the CD16 receptor complex. Overall these results suggest that the formation of a complex containing either Shc or pp36 associated with Grb2, Cbl and the p85 subunit of Pl-3K is one of the major mechanisms which might couple CD16 to the Pl-3K pathway in NK cells.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Proline-rich tyrosine kinase-2 activation by beta 1 integrin fibronectin receptor cross-linking and association with paxillin in human natural killer cells.

Recent evidence indicates that integrin ligation results in activation of focal adhesion kinase (pp125FAK), the prototype of a new subfamily of nonreceptor protein tyrosine kinase (PTK), including FAKB and the proline-rich tyrosine kinase 2 (PYK-2), also termed cell adhesion kinase-beta or related adhesion focal tyrosine kinase. We have previously shown that cross-linking of alpha 4 beta 1 and alpha 5 beta 1 fibronectin receptors on human NK cells stimulates tyrosine phosphorylation of two proteins migrating at 105 and 115 kDa. Here we report that cross-linking of beta 1 integrins on human NK cells stimulates tyrosine phosphorylation and PTK activity of PYK-2. PYK-2 tyrosine phosphorylation was maximal at 1 min and started to decline 20 min after stimulation. Engagement of alpha 4 beta 1 and alpha 5 beta 1 either with specific mAbs or after cell adhesion to fibronectin or its 120- and 40-kDa fragments also triggered PYK-2 tyrosine phosphorylation. Stimulation of PYK-2 tyrosine phosphorylation was inhibited by the tyrosine kinase inhibitor herbimycin A, but not by EGTA, indicating that PYK-2 tyrosine phosphorylation is PTK, but not calcium, dependent. We also demonstrate that PYK-2 is constitutively associated with paxillin, which undergoes tyrosine phosphorylation with the same kinetics of PYK-2 upon beta 1 integrin ligation.

Animals↗
PubMed1997

Selective binding of shc-SH2 domain to tyrosine-phosphorylated zeta but not gamma-chain upon CD16 ligation on human NK cells.

Fc gamma RIII (CD16) is a hetero-oligomeric receptor composed of a ligand-binding alpha subunit associated with homo- or heterodimers of the TCR zeta- and Fc epsilon RI gamma-chains. We have previously demonstrated that CD16 ligation promotes complex formation between tyrosine-phosphorylated shc and Grb2, leading to activation of ras signaling pathway in human NK cells. Here we report that CD16 engagement induces rapid shc association with the tyrosine-phosphorylated receptor complex in human NK cells. In vitro binding studies demonstrate that this interaction is mediated by the shc-SH2 domain, and immunodepletion experiments indicate that the zeta- but not the gamma-chain has the capability to mediate this association. Jurkat cell clones expressing CD16-zeta or -gamma homodimers have been used to gain more information about the mechanism of shc/CD16 association. Our data show that, while engagement of both receptors induces tyrosine phosphorylation of shc and Grb2 recruitment, shc-SH2/receptor complex association is evident only in CD16-zeta but not in CD16-gamma transfectants. Overall, our data demonstrate that the adaptor protein shc can be recruited to the activated CD16 complex by interaction with tyrosine-phosphorylated zeta-chain in a SH2-dependent manner. These results also provide further support to the notion that zeta- and gamma-chains might couple to different biochemical pathways.

Cells, Cultured↗
PubMed1997

Prenatal exposure to cypermethrin modulates rat NK cell cytotoxic functions.

The synthetic pyrethroid insecticide, cypermethrin, was given during gestation to pregnant rats by gavage in corn oil. Peripheral blood and spleen cytotoxic activity of dams and their offspring were then evaluated at different times (30, 60, 90, 120 days) after birth. Pups showed a significant increase in peripheral blood natural killer (NK) and antibody-dependent (ADCC) cytotoxic activity paralleled with a similar increase in the percentage of NK-RP1+ cells and decreased activity in the spleen. Pregnant cypermethrin-exposed dams showed no changes in peripheral blood or spleen cytotoxic function during the postnatal period. Overall, these results suggest that immunomodulation of cytotoxic activity observed in the offspring is likely attributable to a specific effect of cypermethrin administered during the prenatal period.

Animals↗