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Biomedical subjects

G Rossi

Publications and source records attributed to G Rossi.

At least 163 records · Page 9Linked to original sources
PubMed2000

Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress.

Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet; in vitro iodide is cytotoxic, inhibits cell growth, and induces morphological changes in thyroid cells of some species. In this study, we investigated the effect of iodide excess in an immortalized thyroid cell line (TAD-2) in primary cultures of human thyroid cells and in cells of nonthyroid origin. Iodide displayed a dose-dependent cytotoxicity in both TAD-2 and primary thyroid cells, although at different concentrations, whereas it had no effect on cells of nonthyroid origin. Thyroid cells treated with iodide excess underwent apoptosis, as evidenced by morphological changes, plasma membrane phosphatidylserine exposure, and DNA fragmentation. Apoptosis was unaffected by protein synthesis inhibition, whereas inhibition of peroxidase enzymatic activity by propylthiouracil completely blocked iodide cytotoxicity. During KI treatment, reactive oxygen species were produced, and lipid peroxide levels increased markedly. Inhibition of endogenous p53 activity did not affect the sensitivity of TAD-2 cells to iodide, and Western blot analysis demonstrated that p53, Bcl-2, Bcl-XL, and Bax protein expression did not change when cells were treated with iodide. These data indicate that excess molecular iodide, generated by oxidation of ionic iodine by endogenous peroxidases, induces apoptosis in thyroid cells through a mechanism involving generation of free radicals. This type of apoptosis is p53 independent, does not require protein synthesis, and is not induced by modulation of Bcl-2, Bcl-XL, or Bax protein expression.

Annexin A5↗
PubMed2000

Amiodarone induces cytochrome c release and apoptosis through an iodine-independent mechanism.

Amiodarone (AMD) is one of the most effective antiarrhythmic drugs available. However, its use is often limited by side-effects, mainly hypo- or hyperthyroidism. As AMD displays direct toxic effect on different cell types, we investigated the cytotoxic effect of AMD and its main metabolite, desethylamiodarone (DEA), in thyroid (TAD-2) and nonthyroid (HeLa) cell lines. Both AMD and DEA displayed a dose-dependent toxicity in TAD-2 and HeLa cells, although DEA was more effective. Both TAD-2 and HeLa cells underwent apoptosis, as evidenced by plasma membrane phosphatidylserine exposure and DNA fragmentation. Inhibition of protein synthesis with cycloheximide and inhibition of endogenous peroxidase activity with propylthiouracil did not affect this AMD- and DEA-induced apoptosis in TAD-2 cells. Western blot analysis did not display variations in the expression of p53, Bcl-2, Bcl-XL, and Bax proteins during the treatment with AMD and DEA. Generation of reactive oxygen species, investigated by flow cytometry with dichlorofluorescein diacetate, did not show the production of free radicals during drug treatment. Furthermore, Western blot analysis of cytosolic and mitochondrial fractions prepared from AMD-treated cells demonstrated that AMD induces the release of cytochrome c into the cytosol from the mitochondria. These data indicate that AMD induces cytochrome c release from mitochondria, triggering apoptosis through an iodine-independent mechanism, and that this process is not mediated by modulation of p53, Bcl-2, Bcl-XL, or Bax protein expression and does not involve the generation of free radicals.

Amiodarone↗
PubMed2000

Serum withdrawal-induced apoptosis in thyroid cells is caused by loss of fibronectin-integrin interaction.

In some cell types, including a fetal thyroid cell line, denial of adhesion to extracellular matrix induces a type of apoptosis called anoikis. Serum withdrawal in dog and transformed rat thyroid cells also induces programmed cell death. Because serum can stimulate cells to produce some components of the extracellular matrix, it was of interest to determine the role of the matrix in the apoptosis induced by serum withdrawal in normal human thyroid cells in primary culture. The present report demonstrates that thyroid cells selectively produce and deposit insoluble fibronectin (FN) only when stimulated by serum. Adhesion in the presence of serum is dependent upon integrin-FN interaction. Serum withdrawal determines a degradation of the insoluble FN deposited and a detachment of the cells from the plates. In these conditions, cells undergo anoikis, demonstrated by DNA fragmentation and annexin V staining. Apoptosis was prevented by exogenous FN immobilized onto the plates. These results indicate that serum withdrawal induces apoptosis in human thyroid cells, determining FN degradation and loss of cell-matrix adhesion.

Annexin A5↗
PubMed2000

[Congestive heart failure in the elderly: specific aspects].

Heart failure is becoming the most prevalent cardiovascular disorder in the older population, in part as a consequence of the declining fatality rate of hypertension, myocardial infarction and ictus, resulting in progressive increment of older subjects at increased risk of developing heart failure. In this review the principal aspects of congestive heart failure in the elderly are described, underlining the necessity of distinguish the "normal" ageing process from the many noxae that cause this disease. Moreover a discussion is given about the peculiarity of the physiopathology and symptomatology of heart failure in the aged patients, with particular emphasis to the diastolic ventricular dysfunction that is very frequent in these patients, posing complex problems of diagnosis and therapy.

Adrenergic beta-Antagonists↗
PubMed2000

Adequate timing of fetal ultrasound to guide metabolic therapy in mild gestational diabetes mellitus. Results from a randomized study.

BACKGROUND: Ultrasound assessment of abdominal circumference early in the third trimester had been proposed to introduce insulin therapy in order to prevent fetal overgrowth in women with mild gestational diabetes mellitus. The purpose of this study was to investigate adequate weeks gestation timing for testing this parameter. METHODS: One hundred and forty-one women were included in a randomized trial. Seventy-three women were evaluated at both 28 and 32 weeks gestation whereas 68 women were investigated only at 32 weeks gestation. In both groups, insulin therapy was promptly started when abdominal circumference exceeded the 75th percentile. Macrosomic rates were compared using the Fisher's exact test. RESULTS: Twenty-nine women whose fetal abdominal circumference exceeded the 75th percentile were considered eligible for insulin therapy. In this group, we observed a statistically significant increase in the percentage of macrosomic infants born from women whose ultrasound abdominal circumference assessment was performed only at 32 weeks gestation when compared to women evaluated at both 28 and 32 weeks gestation (71.43% vs 33.33%, p<0.05). CONCLUSIONS: Our results support the need for fetal ultrasound at 28 weeks gestation to direct metabolic therapy since insulin administration introduced after 32 weeks gestation has a poor effect on fetal growth.

Abdomen↗
PubMed1999

Sporadic Creutzfeldt-Jakob disease: co-occurrence of different types of PrP(Sc) in the same brain.

Phenotypic heterogeneity of sporadic Creutzfeldt-Jakob disease (CJD) has been linked to biochemically distinct types of the protease-resistant form of the prion protein (type 1 and type 2 PrP(Sc)). We investigated 14 cases of sporadic CJD and found that both type 1 and type 2 PrP(Sc) coexisted in 5 subjects. The distinct PrP(Sc) isoforms were associated with different patterns of PrP deposition and severity of spongiform changes, suggesting that the PrP(Sc) type plays a central role in determining the neuropathologic profile of CJD.

Aged↗
PubMed1999

The International Prognostic Index can be used as a guide to treatment decisions regarding patients with human immunodeficiency virus-related systemic non-Hodgkin lymphoma.

BACKGROUND: The International Prognostic Index (IPI) effectively separates aggressive lymphomas into four groups with significantly different responses to therapy and survival. The authors have applied the IPI to evaluate a series of patients with human immunodeficiency virus (HIV) related lymphoma, a disease for which treatment strategies are still controversial and prognostic indicators are therefore particularly important. METHODS: Sixty-nine consecutive evaluable patients with HIV-related systemic non-Hodgkin lymphoma (NHL) diagnosed at a single Institution during a 10-year period were analyzed. Primary cerebral lymphoma was not considered. Forty-nine patients (71%) received aggressive combination chemotherapy (CT), 45 of whom were treated with the same program: cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, and methotrexate with lecuovorin and prednisone (ProMACE-CytaBOM). Univariate and multivariate methods were used for statistical analysis. End points were response to treatment in patients receiving aggressive CT and survival of treated patients and all patients. RESULTS: According to age-adjusted IPI, 5 patients (7%) belonged to the low risk group, 12 (17%) to the low-intermediate risk group, 16 (23%) to the high-intermediate risk group, and 36 (52%) to the high risk group. Among the four groups with increasing IPI scores, the mean CD4 cell count at NHL diagnosis was 313, 230, 151, and 72/microL, respectively (P = 0.0085). The complete response (CR) rates were 100%, 88%, 50%, and 32% (P = 0. 0001) and the median survival of all patients was >60, 17, 10.9, and 6.8 months (P = 0.0002) for patients with low, low-intermediate, high-intermediate, and high risk IPI scores, respectively. In multivariate analysis, among patients receiving aggressive CT, high risk IPI (P = 0.013) and systemic symptoms (P = 0.014) were the only parameters related to CR, and high risk IPI (P = 0.016) and achievement of CR (P < 0.001) were the only parameters related to survival. When all patients were considered, high risk IPI had significant prognostic value for overall survival (P = 0.01), as did age (P = 0.019) and achievement of CR (P < 0.001). CONCLUSIONS: IPI was a reliable prognostic indicator in an unselected series of patients with HIV-related systemic NHL. The outcomes of patients without high risk IPI treated with aggressive CT were similar to those expected for HIV negative patients with lymphoma. However more than half of patients with HIV-related NHL had IPI high risk disease, and their outcomes were poor even after aggressive CT. The degree of immunodeficiency was related to increasing IPI score, suggesting that immunodeficiency may be an important factor contributing to the aggressive clinical presentation of lymphoma.

Adult↗
PubMed1999

Apoptosis induced by denied adhesion to extracellular matrix (anoikis) in thyroid epithelial cells is p53 dependent but fails to correlate with modulation of p53 expression.

In normal epithelial cells, impaired cell-matrix contact leads to induction of programmed cell death, a process that has been termed 'anoikis'. We investigated the role of p53 and other apoptotic proteins in anoikis in thyroid epithelial cells. Western blot analysis demonstrated that neither p53 nor Bcl-2, Bcl-XL and Bax protein expression changed during anoikis. However, loss of endogenous p53 activity in cells transfected with a dominant-negative mutated p53 inhibited anoikis demonstrating the involvement of p53-dependent processes. The phosphatase inhibitor sodium orthovanadate opposed anoikis when added to the cells within 6 h, suggesting a role for phosphorylated proteins.

Apoptosis↗
PubMed1999

Cleavage of urokinase receptor regulates its interaction with integrins in thyroid cells.

The urokinase-type plasminogen activator uPA-R can regulate integrin functions by associating with several types of beta-subunit. We have recently shown that normal thyroid TAD-2 cells express both a native and a cleaved form of uPA-R which lacks the binding domain for uPA. We found this cleaved form to be present in reduced amounts in papillary and follicular thyroid carcinoma cells and completely absent in cells derived from an anaplastic thyroid carcinoma (ARO). We now report that in normal thyroid cells the intact form of uPA-R strongly associates with beta-1 integrins, whereas its cleaved form does not. uPA-R expressed by ARO cells shows a stronger resistance to the cleavage mediated by uPA, plasmin and chymotrypsin than does uPA-R expressed by normal thyroid cells. This resistance to cleavage correlates with the higher level of glycosylation of uPA-R of ARO cells as compared to that of cleavable uPA-R of normal thyroid cells. These results suggest that uPA-R cleavage, which occurs in several cell types, represents a mechanism regulating the interactions of uPA-R with integrins and, possibly, the subsequent integrin-mediated cell adhesion. Moreover we hypothesize that glycosylation regulates uPA-R cleavage and, indirectly, its interaction with integrins.

Amidohydrolases↗
PubMed1999

Therapy of molecular relapse in acute promyelocytic leukemia.

Fourteen patients with PML/RARalpha-positive acute promyelocytic leukemia (APL) were given salvage therapy at the time of first molecular relapse. All patients had achieved first molecular remission after the AIDA protocol (all-trans retinoic acid [ATRA] + idarubicin) and were being prospectively monitored by reverse transcriptase-polymerase chain reaction (RT-PCR). Molecular relapse was defined as reappearance of RT-PCR-positivity for the PML/RARalpha fusion (sensitivity 10(-4)) in 2 successive marrow samples collected during postconsolidation monitoring. The median duration of first molecular remission was 7.5 months (range, 2 to 25). Salvage therapy consisted of oral ATRA for 30 days followed by 4 daily courses of chemotherapy (CHT) with cytarabine 1 g/m(2)/d and mitoxantrone 6 mg/m(2)/d. Second molecular remission was obtained in 12 of 14 patients (86%). Seven of these 12 attained molecular remission after ATRA alone. Of the 2 patients who persisted PCR(+) after CHT, 1 died in remission and 1 progressed to hematologic relapse. Of 12 patients PCR(-), 8 received consolidation with autologous bone marrow transplantation (ABMT), and 4 received ATRA-containing maintenance. Ten patients in this group are in sustained second molecular remission at a median time of 9.5+ months (range, 4 to 22+) and 2 underwent hematologic relapse 6 and 13 months, respectively, after transient second molecular remission. The 2-year Kaplan and Meier survival estimate from time of relapse was 92% (95% confidence interval [CI]: 61% to 98%) in this series, and 44% (95% CI: 35% to 52%) in a previous series of 37 patients who received the same treatment at the time of hematologic recurrence (P <.05, by log-rank test). This study suggests that early administration of salvage therapy is advantageous in APL and represents the first experience on therapy of molecular relapse in acute leukemia.

Adult↗
PubMed1999

An approximate CUSUM procedure for surveillance of health events.

The CUSUM method is frequently used by epidemiologists for detecting a shift in the incidence of rare health events. An exact solution for a Poisson process has been proposed by other works, but potential applications have been limited by the fact that the size, the structure of the at-risk population and the baseline rate may not be constant during the period of surveillance. Furthermore, for practical use tables of critical values are available only for some expected values and in any case less then 9. This paper proposes an approximate CUSUM procedure, based on the normal approximation to a Poisson process, which may be an efficient solution of the problems previously pointed out. Analyses of simulated and actual data sets illustrate the usefulness of the proposed procedure. An application to mortality data for respiratory diseases in a north Tuscany area, characterized by the presence of chemical plants, is showed. No shift in the mortality rate during the 1980-1989 period was detected compared with the 1970-1979 period, in contrast with the result obtained with the standard CUSUM method for a Poisson variate.

Air Pollutants↗