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61.
Filaci G Contini P Fravega M Fenoglio D Azzarone B Julien-Giron M Fiocca R Boggio M Necchi V De Lerma Barbaro A Merlo A Rizzi M Ghio M Setti M Puppo F Zanetti M Indiveri F 《Human immunology》2003,64(1):9-20
Resident macrophages are mainly responsible for the clearance of apoptotic cells from tissue by phagocytosis. Phagocytosis of apoptotic cells is not accompanied by activation of inflammatory mechanisms, unlike what happens when necrotic phenomena occur. We analyzed the effect of phagocytosis of apoptotic bodies on macrophage cell functions. After phagocytosis of apoptotic cells macrophages were unable to present an exogenous antigen to autologous antigen-specific T-cell lines. The inhibition was mediated by different mechanisms including binding of apoptotic DNA to human leukocyte antigen (HLA) class II molecules of macrophages, decreased expression of co-stimulatory molecules and increased secretion of tumor growth factor beta (TGFbeta). When dendritic cells were cultured with macrophages phagocytosing apoptotic cells, or with their supernatant, impaired dendritic cell antigen presenting activity and reduced tumor necrosis factor alpha (TNFalpha) secretion were found. Our results suggest that: (1) the phagocytosis of apoptotic bodies inhibits macrophage antigen presentation; (2) such inhibition is mediated by the binding of apoptotic DNA to macrophage HLA class II molecules as well as by the activation of biological mechanisms that induce an anti-inflammatory functional behavior in macrophages; and (3) macrophages phagocytosing apoptotic cells inhibit antigen presentation of neighboring dendritic cells via TGFbeta secretion. These events are likely related to the preservation of healthy tissues from the onset of inflammation. 相似文献
62.
BALB/c mice immunized with multimeric DWEYSVWLSN develop IgG1 anti-DNA antibodies and glomerular immunoglobulin deposits, leading us to investigate the role of IL-4 in this model of antigen induced lupus. Splenocytes from DWEYSVWLSN immunized mice secreted IL-4 but not gamma-interferon. Following peptide immunization, IgG1 anti-peptide and anti-DNA antibodies were significantly higher in IL-4 wild type mice, while IgM and IgG3 anti-DNA levels were significantly higher in IL-4 knockout mice. Titers of IgG anti-laminin and anti-histone, but not anti-Sm/RNP and anti-cardiolipin antibodies, were significantly higher in the IL-4 wild type group. Glomerular immunoglobulin deposition was substantially decreased in IL-4 knockout mice. We conclude that while IL-4 does not materially affect the generation of some autoantibody responses associated with peptide induced autoimmunity, IL-4 deficiency inhibits kidney immunoglobulin deposition. The effect of IL-4 on humoral autoimmunity in lupus is complex, and is dependent on genetic background, the antigenic trigger and stage of disease. 相似文献
63.
64.
Anna Tesei Marco Rosetti Paola Ulivi Francesco Fabbri Laura Medri Ivan Vannini Manlio Bolla Dino Amadori Wainer Zoli 《Journal of translational medicine》2007,5(1):52
Background
Despite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs), little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, in in vitro human colon cancer models. 相似文献65.
Ilaria Ferrarotti Michele Zorzetto Roberta Scabini Paola Mazzola Ilaria Campo Maurizio Luisetti 《Diagnostic molecular pathology》2004,13(3):160-163
There is worldwide growing awareness of alpha 1-antitrypsin deficiency (AATD), a major hereditary disorder in Caucasians. The gold standard for laboratory diagnosis of AATD is thin-layer isoelectrofocusing (IEF), which is labor intensive and should be performed in reference laboratories. The aim of this study was to find an easy, fast, and cheap method for detecting alpha1-antitrypsin S and Z variants, the most frequent variants associated with AATD. The novel method herein described is based on SexAI/Hpy99I RFLP. We studied samples from 90 subjects enrolled in the Italian National Registry for AATD, previously typed by isoelectrofocusing. We found a complete agreement among our results, IEF, and genotypes obtained by standard methods. We concluded that this novel method combines efficiency, ease, swiftness, and low cost. 相似文献
66.
Rafaella Barbieri Anna Paola Rimondi Daniele Buzzoni Leone Luppi Claudio Nastruzzi Patrizia Orlando Dr Roberto Gambari 《Clinical & experimental metastasis》1989,7(4):417-426
The methylation pattern of the human HLA-DR gene was analyzed in normal breast tissues, breast primary tumors and lymphonodal metastases isolated from patients carrying breast carcinomas. In breast adenomas and also in normal tissues (including breast, muscle, brain, sperm and T- and B-lymphocytes), the HLA-DR gene is hypermethylated at the CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region is located in the 5 portion of the gene, near the promoter sequence. Further, the results indicate that the HLA-DR gene is hypomethylated in carcinomas and in the relative metastatic lymph nodes. It is suggested that hypomethylation of the human HLA-DR gene could be proposed as a molecular marker of malignant breast tumors. 相似文献
67.
Carlo Capelli Guglielmo Antonutto Paola Zamparo Massimo Girardis Pietro Enrico di Prampero 《European journal of applied physiology》1993,66(3):189-195
Summary The mechanical power (Wtot, W·kg–1) developed during ten revolutions of all-out periods of cycle ergometer exercise (4–9 s) was measured every 5–6 min in six subjects from rest or from a baseline of constant aerobic exercise [50%–80% of maximal oxygen uptake (VO2max)] of 20–40 min duration. The oxygen uptake [VO2 (W·kg–1, 1 ml O2 = 20.9 J)] and venous blood lactate concentration ([la]b, mM) were also measured every 15 s and 2 min, respectively. During the first all-out period, Wtot decreased linearly with the intensity of the priming exercise (Wtot = 11.9–0.25·VO2). After the first all-out period (i greater than 5–6 min), and if the exercise intensity was less than 60% VO2max, Wtot, VO2 and [la]b remained constant until the end of the exercise. For exercise intensities greater than 60% VO2max, VO2 and [la]b showed continuous upward drifts and Wtot continued decreasing. Under these conditions, the rate of decrease of Wtot was linearly related to the rate of increase of V [(d Wtot/dt) (W·kg–1·s–1) = 5.0·10–5 –0.20·(d VO2/dt) (W·kg–1·s–1)] and this was linearly related to the rate of increase of [la]b [(d VO2/dt) (W·kg–1·s–1) = 2.310–4 + 5.910–5·(d [la]b/dt) (mM·s–1)]. These findings would suggest that the decrease of Wtot during the first all-out period was due to the decay of phosphocreatine concentration in the exercising muscles occurring at the onset of exercise and the slow drifts of VO2 (upwards) and of Wtot (downwards) during intense exercise at constant Wtot could be attributed to the continuous accumulation of lactate in the blood (and in the working muscles). 相似文献
68.
Chiara Fenoglio Daniela Galimberti Laura Piccio Diego Scalabrini Paola Panina Cecilia Buonsanti Eliana Venturelli Carlo Lovati Gianluigi Forloni Claudio Mariani Nereo Bresolin Elio Scarpini 《Neuroscience letters》2007
Triggering Receptor Expressed on Myeloid cells (TREM)2 deficiency originates a genetic syndrome characterized by bone cysts and presenile dementia, named Nasu-Hakola disease (NHD). Early onset dementia and marked involvement of frontal regions are features characterizing both NHD and other kinds of neurodegenerative disorders, such as Frontotemporal Lobar Degeneration (FTLD), and, in some cases, Alzheimer's disease (AD). Three Single Nucleotide Polymorphisms (SNPs) in TREM2 coding region were screened by allelic discrimination in a population of probable AD patients as well as FTLD patients as compared with age-matched controls. In addition, mutation scanning of the coding region of TREM2 gene was carried out in 7 patients with early onset AD (EOAD), 16 FTLD, and 20 controls. None of the SNPs analyzed was present, either in patients or controls. Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms. These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes. 相似文献
69.
Lorenzo Cecchi Cecchi Lorenzo Marco Morabito Morabito Marco Maria Paola Domeneghetti Domeneghetti Maria Paola Alfonso Crisci Crisci Alfonso Marzia Onorari Onorari Marzia Simone Orlandini Orlandini Simone 《Annals of allergy, asthma & immunology》2006,96(1):86-91
BACKGROUND: Ambrosia pollen is an important allergen in North America and, as recently discovered, in some European countries. In Italy, the most affected area is the northeast, whereas ragweed has not been reported in the central and southern parts of the country. OBJECTIVE: To identify the source of ragweed pollen detected in Florence and Pistoia in central Italy. METHODS: Ragweed pollen data were collected in Florence and Pistoia for a 6-year period (1999-2004). The relationship between pollen counts and local ground prevalent wind directions was evaluated with analysis of variance and the least significant difference test. Weather conditions were also evaluated on a large-scale circulation pattern by analyzing weather maps and air mass back trajectories. RESULTS: A highly statistically significant relationship between daily prevailing wind direction and pollen count was found in the period under investigation; the ragweed pollen peaks were recorded when winds from northeast in Florence and north-northeast in Pistoia were observed. The synoptic weather situation and the path of back trajectories suggest an area around southern Hungary as a possible source of Ambrosia pollen. Furthermore, the pollen count was above the clinical threshold several times in both Florence and Pistoia. CONCLUSIONS: Several factors indicate that the detection of ragweed pollen in central Italy is due to long distance transport. Taking into consideration the high allergenicity of Ambrosia pollen, the present findings, if confirmed, suggest that the number of sensitized individuals might significantly increase in the near future. 相似文献
70.
Shen MR Furla P Chou CY Ellory JC 《Pflügers Archiv : European journal of physiology》2002,444(1-2):276-285
Hypotonicity-induced Ca2+ entry is a critical signal for the normal regulatory volume decrease in human cervical cancer cells. The aim of this study was to explore the role of myosin light chain kinase (MLCK) in the regulation of hypotonicity-induced Ca2+ signalling and Cl- channel activity. Blockade of MLCK activity by MLCK(11-19) amide, a substrate-specific peptide inhibitor, markedly attenuated hypotonicity-induced Ca2+ entry. A similar result was obtained with ML-7, a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK. More than 85% of the activity of the volume-regulated Cl- channel was suppressed when intracellular Ca2+ was buffered to near zero in the absence of extracellular Ca2+, suggesting that hypotonicity-induced Ca2+ signalling is important for the activation of the volume-regulated Cl- channel. Intracellular dialysis with MLCK(11-19) amide or ML-7 concentration-dependently reduced the amplitude and rate of activation of the volume-regulated Cl- channel. Swelling-activated taurine transport was also inhibited concentration dependently by ML-7 and MLCK(11-19) amide with IC(50) values of 6.4 and 2.0 microM, respectively. Hypotonicity induced MLC phosphorylation which was mediated totally by MLCK and depended on Ca2+ entry. However, phosphorylated MLC per se was not involved critically in the regulation of Ca2+ entry and activation of volume-sensitive organic osmolyte/anion channels (VSOAC). We propose that MLCK has a novel function in regulating the activation of VSOAC by mediating Ca2+ entry in response to hypotonicity. This function of MLCK on Ca2+ signalling does not correlate with MLC phosphorylation. 相似文献