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S Mirabella

Publications and source records attributed to S Mirabella.

11 recordsLinked to original sources
PubMed2004

Room temperature migration of boron in crystalline silicon.

We demonstrate that substitutional B in silicon can migrate even at room temperature and below, stimulated by a high interstitial flux. Once mobile B is formed, it migrates for long distances with a diffusivity >5 x 10(-13) cm(2)/s, until it assumes an immobile configuration with a migration length independent of the temperature. This phenomenon is present during secondary ion mass spectrometry (SIMS) analyses of B profiles, altering the profile during the analysis itself. These results shed new light on all the data based on SIMS analyses and reported in literature in the last decades.

Journal Article↗
PubMed2004

Sequential liver-kidney transplantation.

The indications for sequential liver and kidney transplantation have not been well defined. Two categories of patients may benefit from this procedure: patients with primary renal disease associated with hepatic disorders (glomerulonephritis, tubulointerstitial nephritis, metabolic diseases, and structural diseases) and patients who develop renal failure after liver transplantation. Chronic renal failure is a frequent long-term complication after liver transplantation. End-stage renal disease develops in 2% to 10% of cases by 10 years after transplantation. Kidney transplantation appears to be a better option than dialysis for the treatment of end-stage renal disease after liver transplantation. In contrast, survival rates, after kidney transplantation are significantly lower among liver transplant patients than primary-only kidney transplant recipients. Considering the donor shortage, kidney transplantation should be cautiously considered in liver transplantation patients. New immunosuppressive drugs and protocols are needed to reduce chronic renal failure after liver transplantation.

Humans↗
PubMed1990

Impaired humoral immune responses to mycobacterial antigen in aged murine gut-associated lymphoid tissues.

Senescence-related alterations of local gut mucosal immune responses to enteric mycobacterial antigen (Ag) were examined. Both aged (greater than 24 months old) and young adult (4-5 months old) BALB/c mice were enterically immunized with crude Mycobacterium paratuberculosis (M. paratbc) protoplasmic Ag, and in vitro Ag- and class-specific immunoglobulin (g) production by lymphocytes from gut-associated lymphoid tissues (GALT) (Peyer's patches, PP; mesenteric lymph nodes, MLN) and non-GALT (spleen, SPN) were determined against semipurified M. paratbc Ag. Ag-specific spontaneous immunoglobulin production by aged B cells from both GALT and non-GALT was enhanced only to a minor extent. Similarly, the functional activity of the Ag-specific T (Th) (CD3+, CD4+) cell in both GALT and non-GALT was not profoundly affected by senescence (qualitative preservation). However, that of the suppressor T (Ts) (CD3+, CD8+) cell was considerably diminished (qualtative defect). Thus, oral tolerance (systemic immunologic hyporesponsiveness) to M. paratbc Ag in aged mice is impaired. These age-related changes, manifested as hyperreactive humoral responses to the enteric microbial Ag, are due, at least in part, to hyporeactivity of the Ts cell, resulting in relative hyperfunction of the Ag-specific Th cell, despite the quantitative defect of the latter cell.

Aging↗
PubMed1990

In vivo immunologic intervention in age-related T cell defects in murine gut-associated lymphoid tissues by IL2.

Our recent studies indicate that the aging process impairs gut mucosal humoral immune responses to mycobacterial antigen (Ag), largely owing to defects in T cell function--in particular, that of suppressor T cells. To correct the age-associated Ag-specific T cell-mediated immune alteration recombinant IL2 (50,000 units/s.c./mouse/day) was administered for 3 weeks to the aged (greater than 24 months) mice (BALB/c), which were divided into 4 groups (Gr) [Gr. 1, fed intragastrically (i.g.) with saline; Gr. 2, immunized i.g. with Mycobacterium paratuberculosis (M. paratbc) protoplasmic Ag; Gr. 3, administered IL2 alone; Gr. 4, immunized i.g. with the Ag and given IL2]. In addition, young adult mice were also grouped and treated as the aged. First, we examined the effect of exogenous IL2 on Ag-specific immunoglobulin (Ig) production by gut-associated lymphoid tissues (GALT) (Peyer's patches, PP; mesenteric lymph nodes, MLN) and non-GALT (spleen, SPN) cells. Aged Gr. 4 (treated with both Ag and IL2) GALT and SPN unfractionated cells showed significantly reduced production of Ag-specific IgM, IgG, and IgA, as compared to aged Gr. 2 (treated with Ag alone) cells. Second, in co-culture experiments with aged T and B cells, aged GALT-derived CD8+ suppressor T (Ts)-depleted T cell subsets of Gr. 4 helped Ag-specific IgM and IgA production by GALT B cells, but to a slightly lesser extent, than those of the Gr. 2. GALT CD4+ T cells of aged Gr. 4 augmented IgM and IgA production by GALT B cells nearly to the levels of the corresponding cocultures of the Gr. 2. In contrast to aged Gr. 2 cocultures, GALT CD4+ plus CD8+ cells of aged Gr. 4 decreased IgM and IgA production to a considerable extent, and in those of SPN, IgG production was also diminished. The humoral immune responses of aged unprimed Gr. 1 (treated with saline) and Gr. 3 (treated with IL2 alone) GALT and SPN cells remained almost unchanged. Similarly, in all Gr. from young adult mice, oral tolerance was maintained regardless of IL2 administration. Third, together with the deletion experiments of the Ts cells, the results of the cross experiments, in which the young adult B and CD4+ Th cells and aged CD8+ Ts cells were cocultured, clearly support the view that the corrective mechanism of the humoral immune responses in aged GALT by exogenous IL2 is attributed to the partial recovery of the Ts cell functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1988

Regulation of mucosal IgA production in vitro by autoreactive immunoregulatory T cells from murine Peyer's patches.

In this study, we investigated whether Peyer's patch-derived T-cell subsets participate in vitro in self major histocompatibility (MHC) class II antigen (Ag)-mediated immunoregulatory circuits for gut-mucosal IgA isotype selection in the presence of Peyer's patch (PP)-derived syngeneic surface immunoglobulin M (sIgM)-bearing B cells. When fresh (in vitro unstimulated) sIgM-bearing B cells were cocultured with fresh, PP-derived L3T4+ Vicia villosa-nonadherent (VV-) T cells (T helper (Th) cells), the production of all class-specific immunoglobulins (Ig), but, in particular, IgA, was enhanced two- to sixfold. This augmented Ig production was, however, reduced by nearly 50% when fresh PP-derived Lyt2+ VV-T cells (suppressor T cells) were added. Furthermore, addition of PP-derived L3T4+ VV+ and Lyt 2+ VV+ T cells abrogated, by nearly 100%, the suppression induced by the Lyt 2+ VV-T cells (contrasuppression). When lipopolysaccharide (LPS)-stimulated, PP-derived sIgM-bearing B cells were cocultured with the Th cells, the production of each class-specific Ig was similarly enhanced, but Ig levels exceeded those obtained with cultures of the unstimulated B cells (P less than 0.001). Anti-I-A or anti-I-E monoclonal antibody (mAb) inhibited the induction of each immunoregulatory T-cell effector activity (P less than 0.001), and anti-I-A/E inhibited it synergistically. Thus, unstimulated fresh PP-derived T cells appear to be activated and then to exert T-cell effector functions in the sequential development of helper, suppressor, and contrasuppressor immunoregulatory networks in the presence of PP-derived sIgM B cells and, particularly, LPS-preactivated sIgM B cells. Based on the blocking effect of anti-I-A and/or anti-I-E mAb on the induction of each T-cell-mediated immunoregulatory function in class-specific Ig production, it appears that the autoreactive (self MHC class II Ag-reactive) activation of PP T cells evoked by Ia Ag on PP sIgM B cells largely controls mucosal IgA production by the latter cells. Furthermore, this immunoregulation by autoreactive effector T cells, especially the L3T4+ VV- helper T cell, may play a significant role in vivo in gut-mucosal IgA isotype production.

Animals↗
PubMedDate not supplied

Use of hepatitis C virus-positive grafts in liver transplantation: a single-centre experience.

AIM: Our goal was to evaluate the outcome of HCV(+) recipients after liver transplantation (LT) using HCV(+) donors and the interaction between donor and recipient viral strain. METHODS: We performed a retrospective analysis of 21 LT performed between 1998 and 2004 using livers from HCV(+) donors in HCV(+) recipients. Two hundred thirty-seven patients with HCV cirrhosis who underwent LT with livers from HCV(-) donors were the control group. Ishak score (IS) was evaluated for all HCV(+) grafts. The considered variables included donor age, hepatic enzymes, intensive care unit stay, HCV genotype, ischemia time, recipient age, UNOS status, Child score, HCV genotype (before and 6 months after LT) and IS (after LT). We analyzed patient, graft, and disease-free survival. RESULTS: HCV(+) donors were significantly older than HCV(-) donors. The cumulative 5-year patient and graft survivals and disease free intervals were not different between groups. IS grading was more than 2/18 in two cases; the only graft with a staging score over 2/6 was retransplanted for early nonfunction. In two cases, different HCV genotypes were matched and donor strain took over the recipient strain. In one patient, donor genotyping 2a-2c took over recipient genotyping 1b and 9 months after LT recurrent hepatitis was documented, but antiviral therapy cleared HCV. CONCLUSIONS: Livers from HCV(+) donors can safely be used in HCV(+) recipients. Hepatic biopsy must always be performed; livers with bridging fibrosis should not be used. The takeover of one strain by another may change the prognosis of the patient if the predominant strain is more sensitive to antiviral therapy.

Disease-Free Survival↗
PubMedDate not supplied

Mycophenolate mofetil monotherapy in liver transplantation.

AIM: Calcineurin inhibitors (CI) are associated with significant morbidity in transplant recipients. The aim of this study was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in liver transplantation (LT). METHODS: We analysed 32 patients (24 males, 8 female, of mean age 55.7 years) who underwent LT between 1994 and 2003. In 29 patients immunosuppressive therapy was cyclosporine; in three patients it was tacrolimus. Eleven patients were submitted for LT due to hepatitis B cirrhosis; eight for hepatitis C cirrhosis, six for alcoholic cirrhosis, and seven for other diseases. In these patients, MMF was added gradually, simultaneously reducing the dosage of CI up to complete withdrawal. We considered the efficacy (decrease in serum creatinine) and the incidence of complications (acute and chronic rejection, leukopenia, diarrhea). RESULTS: Patients were converted to MMF after a median of 50 months after LT. MMF monotherapy was started after a median of 9 months in association with CI. Indications for switch to MMF monotherapy were adverse effects of CI (renal disfunction in 30 patients) and de novo tumoral evidence after LT in two patients. Median dosage of MMF was 750 mg twice daily (500-1500 mg). There was a statistically significant decrease in serum creatinine levels (2.02-1.7 mg/dL; P = .0001). Side effects were: leukopenia in five of 32 patients (15.6%), diarrhea in four of 32 patients (12.5%), and one acute rejection. CONCLUSION: MMF monotherapy improved renal function and was not associated with a significant risk of allograft rejection. Side effects were mild with dose regimens up to 750 mg twice daily.

Adult↗
PubMedDate not supplied

New-onset diabetes after liver transplantation.

AIM: The impact of new-onset diabetes (NOD) posttransplantation has been underestimated in the past. The aim of this study was to evaluate the incidence of diabetes after liver transplantation. METHODS: We retrospectively analyzed the incidence of NOD in 899 patients transplanted in our center. According to International Consensus 2003 Guidelines, criteria for diagnosis of diabetes were: fasting plasma glucose > or =126 mg/dL, symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dL, and 2-hour plasma glucose levels > or =200 mg/dL during an oral glucose tolerance test. We considered only patients with follow-up over 10 months. We evaluated the risk factors correlated with NOD (age, hepatitis C virus [HCV] positivity, tacrolimus vs cyclosporine, steatosic graft), and the outcomes of diabetic patient and their grafts. RESULTS: The incidence of NOD was 10.8% (90/830 patients). Sixty nine patients were diabetic before transplantation. Recipient age >45 years (14.7% vs 6.8%, P = .002, OR = 2.4) and HCV positivity (15.5% vs 7.8%, P = .001, OR = 2.2) significantly correlated with NOD. Multivariate analysis confirmed these variables to be independently associated with diabetic risk. Tacrolimus was associated with an increased risk of NOD (16.2% in HCV-negative patients, 25% in HCV-positive patients), but this difference was not statistically significant. Steatotic grafts (>10%) were associated with an increased risk of NOD (28.6% vs 10%, P = .001, OR = 3.6). The outcome of patients and grafts in the group of diabetic patients was not significantly different from all other patients. CONCLUSIONS: The incidence of NOD was more relevant in patients older than 45 years and/or HCV-positive. A steatotic graft was an important risk factor, and the match with high-risk patients should be avoided.

Age Factors↗
PubMedDate not supplied

Autoreactive T cell hybridoma-derived B cell stimulatory factor(s) governing IgA isotype immunoglobulin production by murine Peyer's patch B cells.

In the present study we investigated whether autoreactive T cells derived from murine Peyer's patches (PP) have the capacity to regulate mucosal B cell differentiation to IgA-producing plasma cells in vitro. We also examined whether B cell development is mediated by lymphokines from immunoregulatory T cells - that is, B cell stimulatory factors (BSF) and cofactors (coBSF) - which include B cell growth factor (BCGF), putative alpha B cell immunoglobulin (Ig) heavy chain switch factor (BSWF alpha), and B cell differentiation factor (BCDF), as well as interleukin-2 (IL-2). To this purpose we developed in vitro a variety of BSF (especially putative BSWF alpha)-producing autoreactive (self-class II molecules responsive) T cell hybridoma cell clones from murine PP, and studied the functional activity of the BSF, especially a putative alpha Ig heavy chain switch (mu----alpha) factors(s). These T hybridome cell lines possessed the surface phenotypes of Thy 1.2, CD4+, CD5+ and CD8- and produced a variety of BSF, including two kinds of BCGF (IL-5, and a BCGF that did not require additional costimulators to induce proliferation of preactivated B cells), putative BSWF alpha/gamma, BCDF, and/or IL-2. The results strongly support the view that the autologous T cell plays an important role not only in B cell proliferation and terminal maturation, but also in alpha heavy chain switching in PP. This T-B cell interation is mediated at least in part through BSF lymphokines elaborated by the autoreactive T cell, probably activated in situ in the lymphoid tissue microenvironment.

Animals↗