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Biomedical subjects

G Paroni

Publications and source records attributed to G Paroni.

12 recordsLinked to original sources
PubMed2001

The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis.

Gas2 is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. Here we provide evidence that overexpression of Gas2 efficiently increases cell susceptibility to apoptosis following UV irradiation, etoposide and methyl methanesulfonate treatments, and that these effects are dependent on increased p53 stability and transcription activity. To investigate possible pathways linking Gas2 to p53, a yeast two-hybrid screen swas performed, indicating m-calpain as a strong Gas2- interacting protein. Moreover, we demonstrate that Gas2 physically interacts with m-calpain in vivo and that recombinant Gas2 inhibits calpain-dependent processing of p53. Importantly, the Gas2 dominant-negative form (Gas2171-314) that binds calpain but is unable to inhibit its activity abrogates Gas2's ability to stabilize p53, to enhance p53 transcriptional activity and to induce p53-dependent apoptosis. Finally, we show that Gas2 is able to regulate the levels of p53 independently of Mdm2 status, suggesting that, like calpastatin, it may enhance p53 stability by inhibiting calpain activity.

Animals↗
PubMed2001

Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3.

Mammalian caspases are a family of cysteine proteases that plays a critical role in apoptosis. We have analyzed caspase-2 processing in human cell lines containing defined mutations in caspase-3 and caspase-9. Here we demonstrate that caspase-2 processing, during cell death induced by UV irradiation, depends both on caspase-9 and caspase-3 activity, while, during TNF-alpha-dependent apoptosis, capase-2 processing is independent of caspase-9 but still requires caspase-3. In vitro procaspase-2 is the preferred caspase cleaved by caspase-3, while caspase-7 cleaves procaspase-2 with reduced efficiency. We have also demonstrated that caspase-2-mediated apoptosis requires caspase-9 and that cells co-expressing caspase-2 and a dominant negative form of caspase-9 are impaired in activating a normal apoptotic response and release cytochrome c into the cytoplasm. Our findings suggest a role played by caspase-2 as a regulator of the mitochondrial integrity and open questions on the mechanisms responsible for its activation during cell death.

Amino Acid Substitution↗
PubMed1999

Reduction of mdr1 gene amplification in human multidrug-resistant LoVo DX cell line is promoted by triple helix-forming oligonucleotides.

We have demonstrated previously that the GT triplex-forming oligodeoxyribonucleotide (TFO) d(TGTGTTTTTGTTTTGTTGGTTTTGTTT), named TFO ID, targeted to a polypyrimidine-polypurine coding sequence located within human multidrug-resistance mdrl gene, specifically and significantly reduced mdrl mRNA levels in the drug-resistant T-leukemic CEM-VLB100 cell line. In this article, we demonstrate that TFO 1D is effective at inhibiting not only transcription but also replication of mdrl genes, leading to a loss of amplified gene copies in the drug-resistant colon adenocarcinoma LoVo DX cell line. In contrast, TFO ID does not alter replication of the constitutive mdrl gene copy in the corresponding parental sensitive LoVo 109 cell line. A specific reduction in mdrl gene amplification levels was also obtained with the pyrimidine TFO d(CTTTTTCTTTTCTTCCTTTTCTTT), named TFO 24TC, directed against the same polypyrimidine-polypurine sequence of the mdrl gene. We suggest that triple helix-forming oligonucleotides might affect the replication of unstable chromosomal elements as amplicons in actively replicating cells by causing a local impairment of DNA polymerase activity. This study lends support to the notion that TFO may be used to reduce gene amplification aiming to control neoplastic progression in cancer cells bearing amplified oncogenes.

Base Sequence↗
PubMed1996

[Surgical treatment of post-mastectomy lymphedema of the upper limb].

The authors analyze their experience of surgical treatment of post-mastectomy lympho-edemas of the upper arm. They have performed 14 operations, each upon patients with praecox or later oedema, following Cariati's classification, and with median age of 56.5 years. Seven patients were present at the follow-up in 6 has been performed microsurgical lympho-venous anastomosis, in 1 a fasciotomy of the forearm and in 1 patient some silastic tubes were positioned in her subcutaneous tissue. An improvement of the subjective symptoms has been recorded in 57.14% of the patients, while the objective ones have improved in 50% of the patients. The authors think that the microsurgical treatment of the lymphedema post-mastectomy of the upper arm is the first choice nowadays.

Adult↗
PubMed1992

False aneurysm of the anterior tibial artery in lower leg fractures treated with the Ilizarov external fixator. Case report.

A case of open segmental fracture of the right lower leg treated with an Ilizarov external fixator in emergency surgery is presented. Approximately two months after operation, swelling in the anterior compartment of the tibia and repeated episodes of bleeding from one of the Kirschner wire holes led the authors to perform an angiography, which revealed the presence of a false aneurysm of the anterior tibial artery. The intraoperative finding of a double lesion in the anterior tibial artery confirmed the iatrogenous nature of the injury.

Aged↗
PubMed1990

Measuring left ventricular dimensions by conductance catheter in the rabbit.

A miniaturized (3.5 F), six-electrode conductance catheter was tested in 18 anaesthetized adult rabbits (weight 3.8-4.6 kg, ethylurethane 2.5 g kg-1). In eight animals, the reference stroke volume (ref-SV) was obtained by an electromagnetic flow probe, while reference end-diastolic volume (ref-LVEDV) was computed by dividing ref-SV by undamped thermal dilution ejection fraction (ref-EF) estimates. Comparisons with conductance indexes (z-SV, z-LVEDV and z-EF) were made at baseline, subsequent levels of graded haemorrhage and reinfusion state. In 10 animals intraventricular segmental conductance was compared with echocardiographic left ventricular cross-section (5 MHz short-focus probe), in the basal state and during acute left ventricular volume changes generated by inferior vena cava balloon occlusion. In each experiment, parallel conductance due to the tissues surrounding the left ventricle (Gp) was determined by infusing a 5M NaCl solution bolus into the right ventricle. Linear regression analysis showed fairly good correlations between z-SV, z-LVEDV and z-EF and reference indexes (r = 0.84, r = 0.83, and r = 0.72, respectively; P less than 0.001 in all cases). A linear regression analysis from 17 interventions (inferior vena cava balloon occlusion) showed a good correlation between left ventricular echocardiographic cross-sectional area and conductance, and higher correlation coefficients, r ranging from 0.870 to 0.986 were obtained from continuously sampled conductance and echographic measurements. Parallel conductance Gp was correlated (r = 0.807, P less than 0.01) with the intercept of the regression line of echographic vs conductance data. The determination of Gp thus improved the accuracy of the left ventricular dimension estimate. These results add further evidence for the possibility of continuous monitoring of left ventricular dimension by means of a conductance catheter, and demonstrate the feasibility of such studies on small experimental animals.

Animals↗
PubMed1988

Quantitative lymphoscintigraphy.

A radioisotopic method was used to evaluate the state and dynamics of the lymphatic system in 92 patients affected by chronic oedema of the limbs and in 12 control subjects. After interstitial injections of 99mTc-sulphur microcolloid, scans were obtained using a LFOV camera linked to a data processor. The quantitative indices of clearance and lymph node uptake obtained showed good correlation with lymphoedema etiology, controls and ostensibly healthy limbs of patients affected by monolateral disease. In conclusion, quantitative lymphoscintigraphy appears to be a feasible indicator of early changes in the lymph pathophysiology and supports the hypothesis that lymphoedema generally arises from a predisposing congenital pathology.

Adolescent↗
PubMed1987

[Lymphoscintigraphy in the study of lymphedema of the arms].

The aim of this work has been the study of the mechanism of lymph formation and drainage in the upper limb in patients with monolateral lymphoedema (15 limbs, L) in comparison with the apparently healthy limb (S) as well as with a control group (8 limbs, C). After interstitial injection of 99mTc sulphur micro-colloid, scans were obtained employing a LFOV camera linked to a data processor. Results were expressed as percentage of the id removed from the injection site 1 and 6 hr pi, mean T6%/h it is (T6-T1)/5 and percentage lymph nodes uptake at the same times. Mean T6%/h is significantly different between C and L, but not between L and S, while lymph node uptake at 6 hr shows a significant difference even between C and S. Quantitative lymphoscintigraphy appears to be a feasible indicator of early changes in the lymph pathophysiology and supports the hypothesis that lymphoedema generally arises from a predisposing congenital pathology.

Arm↗
PubMedDate not supplied

Effect of oligomer length and base substitutions on the cytotoxic activity and specific nuclear protein recognition of GTn oligonucleotides in the human leukemic CCRF-CEM cell line.

We have identified phosphodiester oligonucleotides composed of G and T bases, named GTn, which are able to inhibit the cellular growth of human cancer cell lines by recognising specific nuclear proteins. We demonstrated that GTn oligonucleotides require a length of at least 20 nucleotides in order to exert a significant cytotoxic effect and to retain the specific protein binding ability. In addition, we found that GTn cytotoxicity was lost when A or C bases were introduced at either 3' and 5' end or within the GTn sequences.

Biopolymers↗
PubMedDate not supplied

[The carotid chemodectoma. Presentation of 4 clinical cases and review of the literature].

After a brief introduction about carotid body tumor's etiopathogenesis and clinical presentation, four clinical cases observed between January 1996 and December 1998 are described. Three of them have been classified as I and the last as III type according to Shamblin's classification. The diagnostic trial and surgical option needed by each patient are presented. The surgical treatment and the possibility of alternative or complementary techniques such as endovascular embolization and/or irradiation are discussed. The conclusion is drawn that surgical option for carotid body tumor is the best choice. Embolization, some hours before surgical treatment, can be a very useful procedure in order to reduce intraoperative risks and bleeding. Nevertheless surgery of carotid body tumor must be performed by surgical teams experienced in supra-aortic vessel treatment.

Adult↗