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Biomedical subjects

E Maggi

Publications and source records attributed to E Maggi.

At least 19 recordsLinked to original sources
PubMed2006

Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-gamma- and interleukin-10-production.

BACKGROUND: The clinical efficacy and safety of sublingual immunotherapy (SLIT) for aeroallergens has been demonstrated in several trials, whereas the immunological changes induced by this treatment, which may account for the clinical improvement, are still unclear. OBJECTIVE: To investigate the effects of a successful SLIT on the in vitro allergen-driven T cell response and cytokine secretion as well as on the serum levels of chemokines and of IgE, IgG1 and IgG4 antibodies (Abs). MATERIALS AND METHODS: Twenty-five Dermatophagoides pteronyssinus (Dp)-sensitive patients with perennial rhinitic and/or rhinitic and asthmatic symptoms were randomized into two groups (13 untreated (UT) and 12 SLIT-treated) for a 1 year and half study. The proliferative response of peripheral blood mononuclear cell (PBMC) to purified Der p1 allergen, their cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta) production and serum levels of chemokines associated with T helper type 1 (Th1) (CXCL10) or T helper type 2 (Th2) (CCL22) responses and of Dp-specific IgE, IgG1 and IgG4 Abs were evaluated before and after 6 months of treatment. RESULTS: SLIT induced a significant reduction of symptom medication scores after 6, 12 and 18 months of treatment in comparison with UT patients. SLIT-treated patients showed a significant decrease in serum levels of DP-specific IgE Abs, whereas total IgE, and specific IgG1 and IgG4 Abs remained unchanged. The proliferative response of allergen-specific T cells to Der p1 in vitro after 6 months of treatment was reduced, while no effect was observed on T cell proliferation to recall antigen (streptokinase). Moreover, Der p1-driven IFN-gamma and IL-10 were significantly increased in culture supernatants of PBMC from 6 month-treated patients in comparison with those detected at the beginning of therapy. CONCLUSIONS: These data suggest that the allergen-driven enhancement of IL-10- and IFN-gamma-producing T cells precedes and associates with SLIT-induced down-regulation of specific IgE, thus providing a rationale to explain the clinical benefit of SLIT in allergic patients.

Administration, Sublingual↗
PubMed2005

CXCR3 and alphaEbeta7 integrin identify a subset of CD8+ mature thymocytes that share phenotypic and functional properties with CD8+ gut intraepithelial lymphocytes.

BACKGROUND: We previously demonstrated the existence of two distinct subsets of T cell receptor (TCR)alphabeta+CD8alphabeta+ single positive (SP) cells in human postnatal thymus which express the chemokine receptor CCR7 or CXCR3 and migrate in vitro in response to their specific ligands. AIM: To investigate whether these two CD8+ thymocyte subsets had distinct peripheral colonisation. METHODS: TCRalphabeta+CD8+ SP cells were obtained from normal postnatal thymus, mesenteric lymph node (LNs), small bowel, and peripheral blood (PB) specimens. Cells were then evaluated for expression of surface molecules, cytolytic potential, telomere length, and profile of cytokine production. RESULTS: CD8+CCR7+CXCR3- thymocytes exhibited CD62L, in common with those which localise to LNs. In contrast, CD8+CCR7-CXCR3+ thymocytes lacked CD62L but exhibited CD103, similar to intraepithelial lymphocytes (IELs) present in the gut mucosa where the CXCR3 ligand, CXCL10, and the CD103 ligand, E-cadherin, are highly and consistently expressed. In addition, thymocytes and gut CD8+CXCR3+CD103+ cells showed comparable telomere length, which was higher than that of PB CXCR3+CD8+ T cells. However, both of these populations contained perforin and granzyme A, and displayed the ability to produce interferon gamma and interleukin 2. Of note, CXCR3 deficient, in comparison with wild-type C57Black/6, mice showed decreased proportions of CD3+CD8alphabeta+ and increased proportions of CD3+CD8alphaalpha+ lymphocytes at gut level. Moreover, adoptive transfer of CD3+CD8alphabeta+ thymocytes from wild-type into CXCR3 deficient mice resulted in a significant increase in CD3+CD8alphabeta+ T cells in the gut mucosa but not in other tissues. CONCLUSIONS: The results of this study demonstrate the existence of a previously unrecognised subset of TCRalphabeta+CD8alphabeta+ SP CXCR3+CD103+ thymocytes which share phenotypic and functional features with CD8+ IELs, thus suggesting the possibility of their direct colonisation of the gut mucosa.

Adoptive Transfer↗
PubMed2005

Autologous chondrocyte implantation (ACI) for aged patients: development of the proper cell expansion conditions for possible therapeutic applications.

OBJECTIVE: Proliferation and chondrogenic commitment of cultured articular chondrocytes are impaired when cells derive from aged donors. In those subjects the feasibility of cell-based therapies for articular surface repair is reduced. Moreover, the use of serum as medium supplement elicits non-physiological responses in cultured chondrocytes. This study was therefore undertaken to identify the expansion culture conditions needed to sustain growth and chondrogenic commitment of chondrocytes harvested from aged human subjects. DESIGN: Articular cartilage was obtained from aged (69-75 years) and from young adult subjects (27-35 years). Chondrocytes were isolated and cultured in serum-free (SF) or in serum-supplemented [fetal calf serum (FCS)] conditions. Chondrocytes were expanded in monolayer for five duplications and processed for RNA extraction and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The differentiation potential was assessed by micromass pellet cultures before and after expansion in either culture medium, or after a prolonged exposure to serum followed by a period in SF condition. RESULTS: Only SF-cultured chondrocytes reached five duplications within 25-35 days, maintaining the expression of some chondrogenic markers and without altering the levels of active matrix metalloproteinase 3 (MMP-3). Only the pellets derived from SF-expanded cultures positively stained for cartilage matrix deposition. On the contrary, exposure to serum diminished the proliferation capacities, abolished the differentiation potential in the same cells and elicited transcription of the MMP-3 gene. Shifting culture conditions from FCS to SF resumed growth rates but proper extracellular matrix deposition was only partially restored. CONCLUSIONS: The SF conditions have proven valuable to prime cell proliferation and to sustain proper commitment in chondrocytes from aged patients. This culturing approach may represent a therapeutic chance extendable to a range of patients normally excluded from clinical protocols based on autologous chondrocyte implantation (ACI).

Adult↗
PubMed2005

Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

BACKGROUND: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. PATIENTS AND METHODS: Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. RESULTS: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). CONCLUSIONS: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.

Age Factors↗
PubMed2003

Implications of spatial heterogeneity for management of marine protected areas (MPAs): examples from assemblages of rocky coasts in the northwest Mediterranean.

Marine protected areas (MPAs) are increasingly used as a management tool to preserve species and habitats. Testing hypotheses about the effectiveness of MPAs is important for their implementation and to identify informative criteria to support management decisions. This study tested the general proposition that MPAs affected assemblages of algae and invertebrates between 0.0 and 0.5 m above the mean low water level of rocky coasts on two islands in the Tuscan Archipelago (northwest Mediterranean). Protection was concentrated mainly on the west coasts of the islands, raising the possibility that neither the full range of assemblages nor the relevant scales of variation were properly represented within MPAs. This motivated the comparison of assemblages on opposite sides of islands (habitats). The effects of MPAs and habitat were assessed with a multifactorial sampling design; hypotheses were tested about differences in structure of assemblages, in mean abundance of common taxa and in univariate and multivariate measures of spatial variation. The design consisted of three replicate shores for each condition of protected and reference areas on the west side of each island and three unprotected shores on the eastern side. Assemblages were sampled independently four times on each island between June 1999 and January 2001. At each time of sampling two sites were selected randomly at each of two tidal heights to represent midshore and lowshore assemblages on each shore. Estimates of abundance were obtained using non-destructive sampling methods from five replicate 20x20 cm quadrats at each site. Results indicated differences among habitats in structure of assemblages, in mean abundance of common taxa and in univariate and multivariate measures of spatial variation at the scale of shores. Most of these patterns were inconsistent with the predicted effect of management through MPAs. The data suggest that designation of MPAs in the Tuscan Archipelago should proceed through management of multiple shores and types of habitat selected to guarantee protection to a representative sample of assemblages and to the processes responsible for maintenance of spatial patchiness at different scales. This study also shows that considerations of spatial heterogeneity are important to underpin management decisions about the number, size and location of MPAs.

Animals↗
PubMed2003

BCA-1, A B-cell chemoattractant signal, is constantly expressed in cutaneous lymphoproliferative B-cell disorders.

We analysed the immunophenotypic and molecular expression of BCA-1 (B-cell-specific chemokine) and CXCR5 (BCA-1 receptor) in normal skin and different cutaneous lymphoproliferative disorders (cutaneous T-cell lymphoma (CTCL); cutaneous B-cell lymphoma (CBCL); cutaneous B-cell pseudolymphoma (PCBCL)), with the aim of investigating their possible involvement in the pathogenesis of cutaneous B-cell disorders. BCA-1 and CXCR5 were constantly expressed in CBCL and PCBCL, but not in normal skin and CTCL. BCA-1 and CXCR5 were constantly coexpressed by CD22+ B-cells, while CD35+ follicular dendritic cells coexpressed BCA-1 in PCBCL cells only. In low grade CBCL, as compared with high grade CBCL, the intensity of CXCR5 expression on neoplastic CD22+ cells was lower than that of BCA-1. The image analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products showed a significant quantitative difference between PCBCL/low grade CBCL and high grade CBCL. The above findings, although only observed in a small series of patients, are in keeping with findings in MALT gastric and gastric MALT lymphomas, adding further evidence of the close similarities between CBCL and MALT lymphomas.

Base Sequence↗
PubMed2002

Evaluation of different inhaled combination therapies (EDICT): a randomised, double-blind comparison of Seretide (50/250 microg bd Diskus vs. formoterol (12 microg bd) and budesonide (800 microg bd) given concurrently (both via Turbuhaler) in patients with moderate-to-severe asthma.

The aim of this study was to compare the efficacy safety and cost of Seretide (salmeterol/fluticasone propionate (Salm/FP), 50/250 microg bd) via Diskus with formoterol (Form; 12 microg bd) and budesonide (Bud; 800 microg bd) given concurrently (Form+Bud) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy. The study used a randomised, double-blind, double-dummy, parallel-group design, consisting of a 2-week run-in period on current corticosteroid therapy (1000-1600 microg/day of BDP or equivalent) and a 12-week treatment period. Symptomatic patients (n = 428) with FEV1 of 50-85% predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP (50/250 microg bd) via a single Diskus inhaleror Form+Bud (12+800 microg bd) via separate Turbuhalers. Clinic, diary card and asthma-related health-care resource utilisation data were collected. Improvement in mean morning peak expiratory flow (PEFam was similar in the Salm/FP and Form+Bud groups. Both PEFam and mean evening PEF (PEFpm) increased by a clinically significant amount (>20 L/min) from baseline in both treatment groups. The mean rate of exacerbations (mild, moderate or severe) was significantly lower in the Salm/FP group (0.472) compared with the Form+Bud group (0.735) (ratio = 0.64; P < 0.001), despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group. Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms, with a higher median percentage of symptom-free nights (P = 0.04), nights with a symptom score <2 (P = 0.03), and nights with no awakenings (P = 0.02). Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group (P<0.05). Both treatments were well tolerated, with a similar low incidence of adverse events. This study showed that in symptomatic patients with moderate-to-severe asthma, Salm/FP (50/250 microg bd), administered in a single convenient device (Diskus), was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud (800 microg bd) given concurrently with Form (12 microg bd) in terms of improvement in PEFam, and superior at reducing exacerbations and nights with symptoms or night-time awakenings. Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs.

Adolescent↗
PubMed2001

Faecal carriage of Verocytotoxin-producing Escherichia coli O157 and carcass contamination in cattle at slaughter in northern Italy.

A study on the prevalence of the faecal carriage of Verocytotoxin (VT)-producing Escherichia coli (VTEC) O157 and on the rate of carcass contamination was carried out on feedlot cattle and dairy cows at slaughter in northern Italy. Between April 1998 and January 1999, 12 sampling visits were performed on different days in seven different slaughterhouses. At each visit, 5-12 animals consecutively slaughtered were selected. From each animal, faeces were collected from the rectum immediately after slaughter and surface swabs were taken from the leg region and the diaphragmatic insertion of the carcass. All samples were examined for the presence of VTEC O157 using an immunomagnetic separation technique. A total of 100 animals coming from 60 different farms were examined. In total, VTEC O157 was isolated from the intestinal content of 17, and from the carcasses of 12 of the 100 animals examined. In particular, VTEC O157 was recovered from six (35.3%) out of the 17 carcasses from which the organism had previously been isolated from rectal content and from six (7.3%) of the 82 carcasses of the stool-negative cattle. In seven carcasses, VTEC O157 was isolated from the leg area, in two carcasses from the diaphragmatic area, and in three carcasses from both areas. Major differences in the prevalence of VTEC O157 were observed in the different groups of cattle sampled. In 7 of the 12 sampling visits, all the specimens examined were negative, while 16 of the 17 positive stool samples and 11 of the 12 positive carcass swabs were collected during three of the visits, performed in June in three different abattoirs. In these three visits, the ratios between the percentage of animals carrying VTEC O157 in the stools and the percentage of contaminated carcasses were 0.33, 0.57, and 1.66, respectively; thus, confirming that slaughter practices can largely influence the rate of carcass contamination. Phage typing and PFGE analysis of VTEC O157 isolated from samples collected at the same visit suggested that both auto- and cross-contamination occurred.

Abattoirs↗
PubMed2001

Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in human thymus.

Strong reactivity for interferon-inducible protein 10 (IP-10), monokine induced by interferon gamma (Mig), and interferon-inducible T-cell alpha chemoattractant (I-TAC) was found in epithelial cells mainly localized to the medulla of postnatal human thymus. The CXC chemokine receptor common to the 3 chemokines (CXCR3) was also preferentially expressed in medullary areas of the same thymuses and appeared to be a property of 4 distinct populations: CD3+ T-cell receptor (TCR) alphabeta+ CD8+ single-positive (SP) T cells, TCRgammadelta+ T cells, natural killer (NK)-type cells, and a small subset of CD3+(low) CD4+ CD8+ TCRalphabeta+ double-positive (DP) T cells. IP-10, Mig, and I-TAC showed chemoattractant activity for TCRalphabeta+ CD8+ SP T cells, TCRgammadelta+ T cells, and NK-type cells, suggesting their role in the migration of different subsets of mature thymocytes during human thymus lymphopoiesis.

CD8-Positive T-Lymphocytes↗
PubMed2001

Production of IL-4 and leukemia inhibitory factor by T cells of the cumulus oophorus: a favorable microenvironment for pre-implantation embryo development.

The nature and the functional activity of immunocytes present in the cumulus oophorus, a mass of cells surrounding the oocyte, were examined here for the first time. The cumuli oophorus were obtained from women who had taken part in an in vitro fertilization program and were suffering from blocked fallopian tubes. Both macrophages and CD4(+) T cells were detected in all cumuli. CD4(+) T cell clones, generated from T cells of these cumuli, showed higher potential to produce IL-4 and leukemia inhibitory factor (LIF) than CD4(+) T cell clones generated from peripheral blood or ovary specimens from the same women. More importantly, IL-4 and LIF, but not IFN-gamma mRNA was found to be constitutively expressed in vivo by cumulus oophorus cells. Progesterone is highly produced by the cumulus oophorus/oocyte complex. We recently showed that progesterone up-regulates the production of LIF by T cells and that the progesterone-induced LIF production is mediated by IL-4. Progesterone produced by cumulus granulosa cells may favor IL-4 production by T cells, which in turn can produce LIF. As the treatment with LIF enhances the in vitro growth and development of mammalian embryos, our data suggest that T cells present in the cumulus oophorus produce cytokines that may provide a microenvironment suitable for pre-implantation development of the mammalian embryo.

Adult↗
PubMed2001

Reversal of human allergen-specific CRTH2+ T(H)2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide.

BACKGROUND: The chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) is a receptor for prostaglandin D(2), which among human T cells is selectively expressed by T(H)2 and type 2 cytotoxic effectors. OBJECTIVE: Our purpose was to assess whether the cytokine production profile of T(H)2 effectors could be reversed by exploiting their selective expression of CRTH2. METHODS: CRTH2(+) T cells were purified from the blood of allergic subjects, stimulated with the specific allergen in the absence or presence of IL-12, and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-gamma after antigen or polyclonal stimulation. RESULTS: Both IL-12 and the PS-DSP30 oligodeoxynucleotide enabled CRTH2(+) allergen-stimulated T(H)2 cells to produce IFN-gamma. This change in the profile of cytokine production by T(H)2 cells from allergic subjects was related to the upregulation of IL-12 receptor beta2 chain and was associated with the loss of CRTH2. CONCLUSIONS: These data demonstrate that the cytokine production pattern of fully differentiated T(H)2 effectors can be changed to a less polarized profile, thus providing the physiologic basis for new immunotherapeutic strategies in allergic disorders.

Allergens↗
PubMed2001

Oligoclonal T cell repertoire in cerebrospinal fluid of patients with inflammatory diseases of the nervous system.

OBJECTIVE: To evaluate the T cell receptor beta chain variable region (TCRBV) gene usage ex vivo in CSF cells and peripheral blood mononuclear cells (PBMCs) collected from patients with autoimmune and inflammatory diseases of the nervous system. METHODS: A novel sensitive seminestedpolymerase chain reaction coupled with heteroduplex analysis was developed. RESULTS: Under these experimental conditions, the minimal number of cells required for the analysis of the whole T cell repertoire was established at 2.5x10(4)-sufficient to evaluate most of the samples collected during diagnostic lumbar punctures. In the 21 patients examined, restrictions in TCRBV gene family usage were not seen. However, using heteroduplex analysis, oligoclonal T cell expansions were found in the CSF of 13 patients and monoclonal expansions in five patients. The T cell abnormalities found did not correlate with intrathecal IgG production or with any clinical variable considered. CONCLUSION: T cell clonal expansions, useful for further characterisation of pathogenetic T cells, can be found during the course of nervous system inflammations, but this abnormality is probably not disease specific.

Adult↗
PubMed2001

Microchimerism and systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs. SSc is an immunologically mediated disease. A prominent immunological abnormality in SSc patients is the presence of circulating autoantibodies against a variety of nuclear proteins. Furthermore, SSc is characterized by the presence of increased numbers of activated T cells, with the prevalence of CD4+ cells, present in the periphery of skin lesions as well as in other organs in the early stages of the disease. We have recently shown the existence of a predominant activation of IL-4-producing Th2-like T cells in patients with SSc, which may account for the major alterations which occur in this disease. SSc has clinical and serological similarities to chronic graft versus host disease (cGVHD), although there are some important differences. T cells, which orchestrate the tissue damage, are present in great amounts in the inflammatory infiltrates in SSc- and cGVHD-affected tissues. More importantly, T cells from cGVHD tissues produce Th2-like cytokines, thus showing a pathogenetic similarity with SSc. SSc has been postulated as a type of cGVHD resulting from the transplacental transfer of cells between mother and fetus. Very recently, we have shown that in SSc, the microchimeric T cells react with the maternal MHC antigens and are able to produce Th2-type cytokines. Both features are characteristics of cGVHD, supporting the hypothesis that SSc is a disease similar to cGVHD.

Chimera↗
PubMed2001

Chemoattractant receptors expressed on type 2 T cells and their role in disease.

The existence of two functionally distinguished populations among T cells has been established in both mice and humans. Type 1 T helper (Th1) cells are involved in the defense against intracellular bacteria and many viruses, while type 2 Th cells (Th2) are the major actors in the response against parasites and play a central role in allergic inflammation. More recently, several data have suggested that some chemokine receptors are tightly regulated on T cells, and in accordance with this selective expression, Th1 and Th2 cells can be differentially recruited by specific chemokines to the inflammatory sites. Among Th2-associated chemokine receptors, CCR3, CCR4 and CCR8 have been described to play a central role in allergic inflammation. However, CCR3 is mainly expressed on basophils, eosinophils and mast cells, but it is poorly expressed by Th2 cells, and CCR4 is also expressed by Th subsets different from Th2 cells. So far, the chemoattractant receptors which among T cells appear to be selectively expressed by Th2 cells or their subsets are CCR8 and CRTH2. The ligand for CRTH2 is not a chemokine, but is prostaglandin (PG)D2, which is able to attract basophils, eosinophils, Th2 cells and type 2 cytotoxic (Tc2) CD8+ T lymphocytes. The selective expression of CRTH2 on Th2 and Tc2 cells may be useful to develop new therapeutic strategies against allergic diseases and against other immune disorders. Additional studies, however, are required to understand its effective importance in the induction and maintenance of Th2- or Tc2-mediated response and inflammation.

Animals↗