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A Bonetti

Publications and source records attributed to A Bonetti.

At least 19 recordsLinked to original sources
PubMed2007

Ultrastructural characterization of calcification onset and progression in subdermally implanted aortic valves. Histochemical and spectrometric data.

Detailed characterization of the subdermal model is a significant tool for better understanding of calcification mechanisms occurring in heart valves. In previous ultrastructural investigation on six-week-implantated aortic valve leaflets, modified pre-embedding glutaraldehyde-cuprolinic-blue reactions (GA-CB) enabled sample decalcification with concurrent retention/staining of lipid-containing polyanionic material, which lined cells and cell-derived matrix-vesicle-like bodies (phthalocyanin-positive layers: PPLs) co-localizing with the earliest apatite nucleation sites. Additional post-embedding silver staining (GA-CB-S) revealed PPLs to contain calcium-binding sites. This investigation concerns valve leaflets subjected to shorter implantation times to shed light on the modifications associated with PPLs generation and calcification onset/progression. Spectrometric estimations revealed time-dependent calcium increase, for unreacted samples, and copper modifications indicating an increase in acidic, non-glycanic material, for GA-CB-reacted samples. Two-day-implant thin sections showed emission and subsequent reabsorption of lamellipodium-like protrusions by cells, originating ECM-containing vacuoles, and/or degeneration stages characterized by the appearance of GA-CB-S-reactive, organule-derived dense bodies and progressive dissolution of all cell membranes. In one-week-implants, the first PPL-lined cells were found to co-exist with cells where GA-CB-S-reactive material accumulated, or exudated towards their edges, or outcropped at the ECM milieu, so acquiring PPL features. PPL-derived material was observed increasingly to affect the ECM on thin sections of one-week- to six-week-implants. These results show an endogenous source for PPLs and reveal that a peculiar cascade of cell degenerative steps is associated with valve mineralization in the subdermal model, providing new useful parameters for more reliable comparison of this experimental calcification process versus the physiological and pathological processes.

Animals↗
PubMed2006

LRRK2 G2019S mutation and Parkinson's disease: a clinical, neuropsychological and neuropsychiatric study in a large Italian sample.

We analysed the Leucine-Rich Repeat Kinase 2 (LRRK2) gene for the G2019S mutation in 1245 consecutive, unrelated patients with primary degenerative parkinsonism, and collected information on medical history, motor, cognitive and neuropsychiatric functions to characterize the clinical phenotype associated to the G2019S mutation. The mutation was detected in heterozygous state in 19 probands (1.7%), and in five additional affected relatives. Clinical features in carriers were those of typical, idiopathic Parkinson's disease. However, behavioural abnormalities were frequent (87%), suggesting a more widespread limbic involvement in G2019S carriers.

Adult↗
PubMed2006

Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson's disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus.

BACKGROUND: The clinical condition of advanced Parkinson's disease (PD) patients is often complicated by motor fluctuations and dyskinesias which are difficult to control with available oral medications. OBJECTIVE: To compare clinical and neuropsychological 12 month outcome following subcutaneous apomorphine infusion (APO) and chronic deep brain stimulation of the subthalamic nucleus (STN-DBS) in advanced PD patients. METHODS: Patients with advanced PD and medically untreatable fluctuations underwent either APO (13 patients) or STN-DBS (12 patients). All patients were clinically (UPDRS-III, AIMS, 12 h on-off daily) and neuropsychologically (MMSE, Hamilton-17 depression, NPI) evaluated at baseline and at 12 months. APO was discontinued at night. RESULTS: At 12 months APO treatment (74.78+/-24.42 mg/day) resulted in significant reduction in off time (-51%) and no change in AIMS. Levodopa equivalent medication doses were reduced from 665.98+/-215 mg/day at baseline to 470+/-229 mg/day. MMSE, NPI, and Hamilton depression scores were unchanged. At 12 months STN-DBS resulted in significant clinical improvement in terms of reduction in daily off time (-76%) and AIMS (-81%) as well as levodopa equivalent medication doses (980+/-835 to 374+/-284 mg/day). Four out of 12 patients had stopped oral medications. MMSE was unchanged (from 28.6+/-0.3 to 28.4+/-0.6). Hamilton depression was also unchanged, but NPI showed significant worsening (from 6.58+/-9.8 to 18.16+/-10.2; p<0.02). Category fluency also declined. CONCLUSIONS: Both APO and STN-DBS resulted in significant clinical improvement in complicated PD. STN-DBS resulted in greater reduction in dopaminergic medications and provided 24 h motor benefit. However, STN-DBS, unlike APO, appears to be associated with significant worsening on NPI resulting from long term behavioral problems in some patients.

Aged↗
PubMed2004

A two-stage study on multiple sclerosis susceptibility and chromosome 2q33.

We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.

Antigens, CD↗
PubMed2003

Adherence of Lactobacillus plantarum P 17630 in soft-gel capsule formulation versus Döderlein's bacillus in tablet formulation to vaginal epithelial cells.

BACKGROUND: To evaluate in vitro the adherence capability of two bacteria to vaginal epithelial cells (VEC) by comparing product A containing L. plantarum P 17630, in soft-gel capsule formulation* and product B containing Döderlein's bacillus, now classified as L. gasseri, in vaginal tablet formulation, marketed for many years in Italy. METHODS: The comparative study of two commercially available preparations followed an open, controlled trial. Collection of VEC samples was done in an ambulatory setting; the adherence tests were carried out at the Institute of Microbiology of the Università Cattolica del Sacro Cuore, Piacenza. The study was made on intact VEC, washed and drawn from 20 patients affected by bacterial vaginitis and/or vaginosis. One capsule or tablet, suspended in physiological solution, was mixed with a suspension of VEC. Adherence of lactobacilli to the VEC was counted by light microscopy and by CFU cultured on the plates. The type of adhesion was evaluated as well. RESULTS: The mean number of lactobacilli adhering to individual VEC was higher for product A containing L. plantarum P 17630. On the plate cultures, 10(6)-10(8) CFU/sample were found for product A, compared with 10(2)-10(4) CFU/sample for product B. L. plantarum P-17630 adhere prevalently to single cells, whereas L. gasseri adhere by forming small chains. CONCLUSIONS: Product A has a better capability of adherence to VEC than does product B. Even the type of adhesion of L. plantarum P 17630 enabled it to remain better attached to the VEC. The results suggest that in vivo product A may be more likely to provide better colonization, thus affording better protection of the vaginal milieu.

Bacterial Adhesion↗
PubMed2001

Use of the ratio of time to progression following first- and second-line therapy to document the activity of the combination of oxaliplatin with 5-fluorouracil in the treatment of colorectal carcinoma.

BACKGROUND: It has been proposed that the activity of a second-line treatment regimen can be documented by showing that the time to progression (TTP) following second-line therapy is longer than the TTP following first-line therapy in the same patients. PATIENTS AND METHODS: The ratio of TTP during first and second-line therapy, identified as the growth modulation index (GMI), was determined in 34 patients with advanced colorectal cancer. First-line chemotherapy consisted of one of several schedules of leucovorin (LV)-modulated 5-fluorouracil (5-FU) or raltitrexed. Second-line therapy consisted of the combination of LV-modulated 5-FU and oxaliplatin (1-OHP). Patients were switched to second-line therapy upon evidence of progressive disease following first-line therapy. RESULTS: Median TTP following first-line therapy was 13 weeks (95% confidence interval (CI): 7.6-18.7), while median TTP following second-line therapy was 31 weeks (95% CI: 21.3-41.0). Sixteen patients (47%; 95% CI: 35%-59%), showed a GMI > or = 1.33, while the remaining 18 patients (53%; 95% CI: 40%-66%) had a GMI < 1.33. Log-rank analysis of the Kaplan-Meier curves of TTP following first- versus second-line therapy demonstrated a statistically significant difference in favour of second-line therapy (P = 0.0081). CONCLUSIONS: This study demonstrates the utility of the GMI as a tool for assessing the activity of novel second-line therapeutic programs.

Adult↗
PubMed2000

The beta-amyloid precursor protein functions as a cytosolic anchoring site that prevents Fe65 nuclear translocation.

In this study we addressed the question of the intracellular localization of Fe65, an adaptor protein interacting with the beta-amyloid precursor protein (APP) and with the transcription factor CP2/LSF/LBP1. By using tagged Fe65 expression vectors, we observed that a significant fraction of Fe65 is localized in the nucleus of transfected COS7 cells. Furthermore, the isolation of nuclei from untransfected PC12 cells allowed us to observe that a part of the endogenous Fe65 is present in the nuclear extract. The analysis of Fe65 mutant constructs demonstrated that the region of the protein required for its nuclear translocation includes the WW domain, and that, on the other hand, a small fragment of 100 residues, including this WW domain, contains enough structural information to target a reporter protein (green fluorescent protein (GFP)-GFP) to the nucleus. To evaluate whether the Fe65-APP interaction could affect Fe65 intracellular trafficking, COS7 cells were cotransfected with APP(695) or APP(751) and with GFP-Fe65 expression vectors. These experiments demonstrated that Fe65 is no longer translocated to the nucleus when the cells overexpress APP, whereas the nuclear targeting of GFP-Fe65 mutants, unable to interact with APP, is unaffected by the coexpression of APP, thus suggesting that the interaction with APP anchors Fe65 in the cytosol.

Active Transport, Cell Nucleus↗
PubMed2000

Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.

PURPOSE: In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point. PATIENTS AND METHODS: Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m(2)/d) followed by a 5FU bolus (400 mg/m(2)/d) and 22-hour infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1. RESULTS: Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival (median, 9.0 v 6.2 months; P =.0003) and better response rate (50.7% v 22.3%; P =.0001) when compared with the control arm. The improvement in overall survival did not reach significance (median, 16.2 v 14.7 months; P =. 12). LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia (41. 7% v 5.3% of patients), grade 3/4 diarrhea (11.9% v 5.3%), and grade 3 neurosensory toxicity (18.2% v 0%), but this did not result in impairment of quality of life (QoL). Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment (P =.004). CONCLUSION: The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of QoL.

Adenocarcinoma↗
PubMed2000

Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: A randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology Group.

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m(2) over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m(2) over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m(2) every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Adult↗
PubMed2000

Effect of ubidecarenone oral treatment on aerobic power in middle-aged trained subjects.

BACKGROUND: Coenzyme Q10 (CoQ10) plays an important role in oxidative mithocondrial phosphorylation and prevents lipid peroxidation in biological membranes. During sustained physical exercise, reactive oxygen species (ROS) production increase through several mechanism; one of them is the purine nucleotide cycle activation by shifting xanthine-dehydrogenase to xanthine-oxidase during AMP breakdown. The aim of this study was to evaluate the effect of CoQ10 treatment on aerobic power. METHODS EXPERIMENTAL DESIGN: according to a single blind study design, 28 health male cyclists were randomized into two groups (CoQ10 or placebo) and remained on treatments for eight weeks; there were 5 drop-outs and only 23 subjects were completely evaluated. Before and at the end of the eight weeks, cyclists underwent cardiopulmonary exercise testing. MEASURES: a software system performed the necessary calculations to obtain the following parameters: oxygen uptake, CO2 production, minute ventilation, oxygen ventilatory equivalent, carbon dioxide ventilatory equivalent, oxygen pulse. Finally oxygen peak and anaerobic threshold were determined. Moreover blood inosine, hypoxanthine, xanthine, lactate and CoQ10 levels were measured before and immediately after each test. RESULTS: The results of this study showed that at the end of the eight weeks there was no difference between the two groups concerning physiological and metabolic parameters, but muscular exhaustion was reached at higher workloads in the CoQ10 group. CONCLUSIONS: In our experience ubidecarenone oral treatment does not improve aerobic power. The little improvement of tolerance to higher workloads may be due to the antioxidant activity of CoQ10.

Adult↗
PubMed1999

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients.

Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis.

Aged↗
PubMed1998

Ovarian cancer cisplatin-resistant cell lines: multiple changes including collateral sensitivity to Taxol.

BACKGROUND: Alteration in apoptosis pathways (in particular mutations of p53 gene) may result in resistance of ovarian carcinoma to cisplatin. However, cisplatin resistance is likely to be multifactorial. An understanding of the molecular alterations associated with the development of resistance may be of considerable relevance in an attempt to optimize the therapeutic approach. STUDY DESIGN: Two cisplatin-resistant sublines (IGROV-1/Pt0.5 and IGROV-1/Pt1), both characterized by mutant p53 (Cancer Res 1996; 56: 556-62), but with different degree of resistance were studied in terms of pattern of cross-resistance, susceptibility to drug-induced apoptosis, expression of gluthathione-dependent system, cellular pharmacokinetics, drug-induced DNA damage. The resistance index (ratio between the IC50 of resistant and sensitive cells) after a 96-hour drug exposure was 10 for IGROV-1/Pt0.5 and 14 for IGROV-1/Pt1 cells. RESULTS: Resistant cells were cross-resistant to DNA-damaging agents and, interestingly, they had a collateral sensitivity to Taxol. The cellular response to Taxol paralleled the drug ability to induce apoptosis. The intracellular glutathione level was significantly increased in IGROV-1/Pt cells compared to the sensitive counterpart. In contrast, glutathione S-transferase level was consistently reduced in both sublines. gamma-Glutamyl transpeptidase activity, which was lower in resistant than in sensitive cells, was not directly correlated with glutathione level, thus suggesting a complex regulation of cellular glutathione content. In the resistant cells with the highest glutathione content, a reduced level of cisplatin-induced cross-link was found. Analysis of DNA platination revealed a slight decrease of DNA-bound platinum only in IGROV-1/Pt1 cells. Again, this reduction is consistent with a protective role for glutathione. The expression of metallothionein IIa was increased in both resistant variants. CONCLUSIONS: Multiple changes are involved in acquired resistance of ovarian carcinoma cells including reduced susceptibility to apoptosis as consequence of inactivation of p53 and expression of defence mechanisms. The relative contribution is related to the degree of drug resistance. In particular, the glutathione-dependent system could have a role only in the development of a high degree of resistance. Finally, the finding that Taxol was very effective in inducing apoptosis in resistant sublines with p53 mutation supports the expression of an intact p53-independent pathway of apoptosis and suggests the pharmacological interest of Taxol in the treatment of p53-mutated tumors.

Adenocarcinoma↗
PubMed1998

Free circulating magnesium and renal magnesium handling during acute metabolic acidosis in humans.

Ion-selective electrodes have been designed for determining the ionized concentration of magnesium in blood, the biologically active form of this ion. The effect of acute acidosis induced by ammonium loading on circulating and urinary magnesium was investigated in 11 volunteers. No changes in plasma total and ionized magnesium were noted following administration of ammonium chloride. On the contrary, administration of ammonium chloride increased the plasma free magnesium fraction and the urinary magnesium excretion. The study demonstrates that the hypermagnesiuria induced by acute acidosis is not caused by ionized hypermagnesemia and supports the theory that acidosis decreases the circulating magnesium fraction that is bound to proteins.

Acidosis↗
PubMed1998

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.

Adult↗
PubMed1997

Ki-67 immunostaining in 322 primary breast cancers: associations with clinical and pathological variables and prognosis.

Cell-proliferation markers are very important in the clinical management of cancer patients, and the identification of Ki-67 (a monoclonal antibody that recognizes proliferating cells) can make it easier to define the level of proliferative activity. This study investigated the associations between the Ki-67 levels measured by means of immunohistochemistry, and other clinical and pathological variables and prognosis in 322 breast-cancer patients. A significant association was found (p < 0.001) between Ki-67 values and tumor size, nodal status, estrogen and progesterone receptor status; multivariate analysis showed that Ki-67 levels were associated with disease-free and overall survival, thus confirming that it is an independent prognostic variable. Various statistical approaches were used in an attempt to establish the best cut-off point for dividing patients into groups at high or low risk of relapse but, in this series, we could find no evidence leading to a single "best" cut-off point. We conclude that the quantitative level of Ki-67 could be used as a prognostic factor in breast-cancer patients.

Breast Neoplasms↗
PubMed1997

Bone marrow micrometastases in 109 breast cancer patients: correlations with clinical and pathological features and prognosis.

BACKGROUND: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. PATIENTS AND METHODS: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2-4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15-62): 22 patients relapsed and 7 died. RESULTS: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33-6.86) and 0.93 for DFS (95% CI: 0.35-2.45). CONCLUSIONS: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.

Antibodies, Monoclonal↗