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G Nicolini

Publications and source records attributed to G Nicolini.

At least 55 records · Page 3Linked to original sources
PubMed1997

Increased serum levels of circulating intercellular adhesion molecule 1 predict the risk of graft rejection after bone marrow transplantation for thalassemia.

Beta thalassemia is a hereditary anemia curable by bone marrow transplantation (BMT). Class 3 patients have a much worse outcome with a high incidence of rejection after BMT. Adhesion molecules, including the intercellular adhesion molecule 1 are thought to play an essential role in the rejection process. To investigate whether increased levels of soluble intercellular adhesion molecule 1 (sICAM-1) may be predictive of graft rejection, the pretransplant serum concentration of sICAM-1 of 27 beta thalassemic patients who rejected the graft was compared to that of 68 beta thalassemic patients who achieved a sustained engraftment. Fifty serum samples, obtained from marrow donors, matched for age and sex, served as controls. Beta thalassemic patients had significantly higher sICAM-1 concentrations as compared to controls (P = 0.0001). Significantly increased levels of sICAM-1 were found in the patients who subsequently rejected the graft (mean (95% CI) = 490 ng/ml (440; 540)) as compared to those with sustained engraftment (400 ng/ml (384; 415)), (P = 0.004). The mean level of sICAM-1 in patients with early rejection was significantly higher than that in patients with late rejection (P = 0.04). This may indicate a transfusion-mediated role of sICAM-1: some beta thalassemic patients with high sICAM-1 levels, induced by the transfusion support, may remain immunologically active, despite the conditioning regimen, therefore such patients are likely to have an early graft rejection. Our findings indicate that sICAM-1 could be a useful indicator of immune activation in polytransfused patients with beta thalassemia who have a high risk of rejection. Determination of sICAM-1 has potential clinical implications in predicting which patients may reject after BMT.

Adolescent↗
PubMed1996

Post-transcriptional control regulates transforming growth factor alpha in the human carcinoma KB cell line.

Expression of epidermal growth factor receptor (EGF-R) antisense RNA results in a drastic reduction of EGF-R levels in the human carcinoma KB cell line and induces a reversion of their transformed phenotype (Moroni, M. C., Willingham, M. C., and Beguinot, L. (1992) J. Biol. Chem. 267, 2714-2722). We used parental and EGF-R antisense KB clones as a genetic system to study, in the same cell line, the role of transforming growth factor alpha (TGF-alpha) in the establishment and maintenance of the transformed phenotype. KB cells produce TGF-alpha mRNA, and their conditioned medium is able to sustain growth of antisense cells, mimicking the effect of exogenous EGF or TGF-alpha. In antisense cells there is a marked reduction of TGF-alpha mRNA steady-state levels. In addition, the decrease in TGF-alpha parallels the levels of residual EGF-R in the various antisense clones, indicating a direct correlation between receptors and growth factor levels. The addition of exogenous TGF-alpha (10 ng/ml) to antisense clones induces TGF-alpha levels. The half-life of TGF-alpha mRNA is 40-60 min in antisense cells and more than 8 h in parental KB cells, as determined by actinomycin D decay curves. This result indicates a predominant regulation of TGF-alpha mRNA at the post-transcriptional level. Nuclear run-on experiments show that there is only a marginal effect at the transcriptional level. We conclude that the autocrine loop responsible for the transformed phenotype of the human carcinoma KB cell line is dependent on both elevated levels of EGF-R and the presence of TGF-alpha. In addition, TGF-alpha is able to induce its own mRNA via a signal due to activation of the EGF-R acting predominantly at the post-transcriptional level.

Animals↗
PubMed1996

Classification tree methods for analysis of mesoscale distribution of Ixodes ricinus (Acari:Ixodidae) in Trentino, Italian Alps.

Cases of Lyme disease and tick-borne encephalitis were recognized recently in the Province of Trento, Italian Alps. Assessment of areas of potential risk for these tick-borne diseases is carried out by a model based on classification and regression trees (CART), using both discrete and continuous variables. Data on Ixodes ricinus (L.) occurrence resulted from extensive sampling carried out by standard methods in 99 sites over an area of approximately 2,700 km2 in the Province of Trento. A series of environmental parameters were recorded from each site and population densities of roe deer, Capreolus capreolus (L.), were considered. The CART model discriminates 2 variables that appear to have the greatest effect on the mesoscale occurrence of ticks: altitude and geological substratum, with a drastic decrease of tick frequency above an altitude of approximately 1,100 m and on volcanic substrata. The model is effective in identifying the mesoscale areas at greater potential risk, with a relatively low sampling effort.

Animals↗
PubMed1995

Cytotoxic T-lymphocyte clones from different patients display limited T-cell-receptor variable-region gene usage in HLA-A2-restricted recognition of the melanoma antigen Melan-A/MART-1.

To determine whether T-cell-receptor (TCR) usage by T cells recognizing a defined human tumor antigen in the context of the same HLA molecule is conserved, we analyzed the TCR diversity of autologous HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones derived from five patients with metastatic melanoma and specific for the common melanoma antigen Melan-A/MART-1. These clones were first identified among HLA-A2-restricted anti-melanoma CTL clones by their ability to specifically release tumor necrosis factor in response to HLA-A2.1+ COS-7 cells expressing this tumor antigen. A PCR with variable (V)-region gene subfamily-specific primers was performed on cDNA from each clone followed by DNA sequencing. TCRAV2S1 was the predominant alpha-chain V region, being transcribed in 6 out of 9 Melan-A/MART-1-specific CTL clones obtained from the five patients. beta-chain V-region usage was also restricted, with either TCRBV14 or TCRBV7 expressed by all but one clone. In addition, a conserved TCRAV2S1/TCRBV14 combination was expressed in four CTL clones from three patients. None of these V-region genes was found in a group of four HLA-A2-restricted CTL clones recognizing different antigens (e.g., tyrosinase) on the autologous tumor. TCR joining regions were heterogeneous, although conserved structural features were observed in the complementarity-determining region 3 sequences. These results indicate that a selective repertoire of TCR genes is used in anti-melanoma responses when the response is narrowed to major histocompatibility complex-restricted antigen-specific interactions.

Amino Acid Sequence↗
PubMed1993

T cell receptor (TCR) structure of autologous melanoma-reactive cytotoxic T lymphocyte (CTL) clones: tumor-infiltrating lymphocytes overexpress in vivo the TCR beta chain sequence used by an HLA-A2-restricted and melanocyte-lineage-specific CTL clone.

HLA-A2+ melanomas express common melanoma-associated antigens (Ags) recognized in vitro by autologous cytotoxic T lymphocytes (CTL). However, it is not known whether tumor Ags can drive in vivo a selective accumulation/expansion of Ag-specific, tumor-infiltrating T lymphocytes (TIL). Therefore, to evaluate this possibility, 39 CTL clones isolated from several independent mixed lymphocyte tumor cultures (MLTC) of TIL and peripheral blood lymphocytes (PBL) of an HLA-A2+ melanoma patient and selected for T cell receptor (TCR)-dependent, HLA-restricted tumor lysis, were used for analysis of TCR alpha and beta chain structure by the cDNA polymerase chain reaction (PCR) technique with variable gene-specific primers followed by sequencing. Despite absence of oligoclonality in fresh TIL and PBL, as well as in T cells of day 28 MLTC (day of cloning), sequence analysis of TCR alpha and beta chains of TIL clones revealed a dominance of a major category of melanoma-specific, HLA-A2-restricted T cells expressing a V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1 TCR. The same TCR was also found in 2 out of 14 PBL clones. The other PBL clones employed a V alpha 2.1 gene segment associated with either V beta 13.2, 14, or w22. Clones A81 (V alpha 2.1/J alpha IGRJ alpha 04/C alpha and V beta 14/D beta 1/J beta 1.2/C beta 1) and A21 (V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1), representative of the two most frequent TCR of PBL and TIL, respectively, expressed different lytic patterns, but both were HLA-A2 restricted and lysed only HLA-A2+ melanomas and normal melanocytes, thus indicating recognition of two distinct HLA-A2-associated and tissue-related Ags. Finally, by the inverse PCR technique, the specific TCR beta chain (V beta 2.1/D beta 1/J beta 1.1/C beta 1) expressed by the dominant TIL clone was found to represent 19 and 18.4% of all V beta 2 sequences expressed in the fresh tumor sample and in the purified TIL, respectively, but < 0.19% of V beta 2+ sequences expressed in PBL. These results are consistent with the hypothesis that a clonal expansion/accumulation of a melanocyte-lineage-specific and HLA-A2-restricted T cell clone occurred in vivo at the site of tumor growth.

Amino Acid Sequence↗
PubMed1992

Expansion of major histocompatibility complex-restricted antimelanoma cytotoxic T-cell lymphocyte clones with identical T-cell receptor from tumor-infiltrating lymphocytes.

Tumor-infiltrating lymphocytes (TILs) were isolated from a subcutaneous metastasis of melanoma and cytotoxic T-cell lymphocyte (CTL) lines were obtained by sensitizing in vitro four separate aliquots of TILs with autologous tumor cells and recombinant interleukin-2. All CTL lines were predominantly WT31+, CD3+, and CD8+ and displayed a preferential cytotoxic activity against the autologous tumor. T-cell receptor (TCR) composition was analyzed by using the polymerase chain reaction with 5' variable region (V alpha or V beta)-specific primers and 3' constant (C alpha or C beta) primers. The entire repertoire of the V alpha and V beta gene families tested was present in fresh TILs and in the CTL lines, although, in the latter, consistent quantitative variations in transcripts of several V alpha and V beta occurred. CTL clones that exhibited CD3-dependent and major histocompatibility complex-restricted killing of the autologous melanoma were isolated from the four TIL cultures. TCR analysis indicated that, independently from the culture of origin, only two combinations of V alpha and V beta gene families were present in the majority of these CTL clones. These V alpha and V beta gene families were not found in a panel of CTL clones that did not lyse the autologous tumor. This study indicates that recognition of melanoma antigens can strongly select for certain types of TCR-bearing T-lymphocytes.

Base Sequence↗
PubMed1991

Bone marrow transplantation in thalassemia.

Since 1983, 350 patients aged 1 to 19 years with beta-homozygous thalassemia were given infusions of HLA-identical marrow after high doses of busulphan and cyclophosphamide. Survival and event-free survival leveled off about 1 year after bone marrow transplantation at 82% and 75%, respectively. In 172 consecutive patients who were treated with our current regimen since June 1985, a multivariate analysis demonstrated that portal fibrosis, hepatomegaly, and a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly, portal fibrosis, and inadequate chelation therapy. Class 1 had none of the factors and class 3 had all three factors; class 2 had different associations of two out of the three factors. For class 1 patients, the 3-year probabilities of survival and event-free survival were 97% and 94%, respectively. For class 2 patients, the probabilities were 86% and 83%, and for class 3 patients, 58% and 52%. Bone marrow transplantation from HLA-identical donors is followed by a high probability of event-free survival in thalassemic patients, particularly if they belong to class 1.

Adolescent↗
PubMed1988

Low molecular weight heparin prevention of post-operative deep vein thrombosis in vascular surgery.

Ninety-two patients undergoing vascular surgery took part in a controlled clinical trial to study the effectiveness of a new low molecular weight (LMW) heparin for prevention of post-operative deep vein thrombosis. Forty-six patients were treated daily, for 7 days after operation, with a single subcutaneous injection of 15,000 Anti X-activated Factor Units of the new LMW heparin; the remaining 46 patients were treated, for the same period, with 2 daily subcutaneous injections of 5,000 International Units of calcium heparin. Deep vein thrombosis detection was by the radioactive fibrinogen uptake test, performed each day during therapy in all patients. A very low incidence of sub-clinical deep vein thrombosis was observed; in 3 (6.5%) patients in the LMW heparin group and in 4 (8.6%) patients of the calcium heparin group. The results of laboratory investigation showed that the antithrombotic activity (inhibition of Factor Xa) of the LMW preparation was significantly greater than that of calcium heparin, while activated partial thromboplastin time was greater in the calcium heparin group. The new preparation also showed better local tolerance, with less pain on subcutaneous injections.

Aged↗
PubMed1986

HLA compatibility for patients with thalassemia: implications for bone marrow transplantation.

In order to evaluate the possibility of a patient with thalassemia finding an HLA-identical sibling donor, we performed an analysis of HLA antigens in families of thalassemic patients. The pattern distribution was not significantly different from the expected ratio 25:50:25. When the siblings were subdivided according to the age of the patients (under or over 5 years), the above pattern remained unmodified for both the age groups. The average size of the 129 thalassemic families was 2.4. Thus, taking into account that thalassemic patients have an average of 1.4 siblings and that the HLA genotype distribution is expected as such, HLA-matched siblings are available for 33% of the patients. Because an additional 8.5% of the patients were found HLA-phenotypically identical to one parent, the chance for a patient with thalassemia to find a suitable donor for bone marrow transplantation would be increased to 41.5%. Our preliminary data cannot be extrapolated to the overall Italian thalassemic population; however, it can be inferred that for a patient with thalassemia, the chance of finding a suitable donor for bone marrow transplantation is not reduced.

Bone Marrow Transplantation↗
PubMed1985

Bone marrow donors other than HLA genotypically identical siblings for patients with thalassemia.

This report describes the successful bone marrow transplantation of three children with thalassemia who received bone marrow, one from an HLA identical but mixed lymphocyte culture-reactive sibling, the other two from an HLA phenotypically identical parent. Evidence of engraftment was detected early (19-21 days) in all three children and only grade II acute GvHD was observed in one patient. Our report indicates that thalassemic patients can be cured by bone marrow transplantation from selected donors other than HLA genotypically identical siblings.

Bone Marrow↗
PubMedDate not supplied

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Review article: non-invasive methods for the diagnosis of Helicobacter pylori infection.

Non-invasive tests for the diagnosis of Helicobacter pylori infection are widely used in clinical practice and the management of patients with gastrointestinal disease. The serology and 13C-urea breath test are widely available, whereas salivary and faecal assay are still being developed. The non-invasive tests represent notable savings for the patient both in terms of money and discomfort. Whilst serology is the most widespread test its use is not advised in post-treatment follow-up. The 13C-urea breath test is a simple, safe and highly accurate method ideal to evaluate, in the short-term follow-up, Helicobacter pylori eradication after treatment.

Breath Tests↗