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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 55 records · Page 3Linked to original sources
PubMed2001

Collapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115 neuroblastoma cells and is regulated by Rho kinase.

The formation and directional guidance of neurites involves dynamic regulation of Rho family GTPases. Rac and Cdc42 promote neurite outgrowth, whereas Rho activation causes neurite retraction. Here we describe a role for collapsin response mediator protein (Crmp-2), a neuronal protein implicated in axonal outgrowth and a component of the semaphorin 3A pathway, in switching GTPase signaling when expressed in combination with either dominant active Rac or Rho. In neuroblastoma N1E-115 cells, co-expression of Crmp-2 with dominant active RhoA V14 induced Rac morphology, cell spreading and ruffling (and the formation of neurites). Conversely, co-expression of Crmp-2 with dominant active Rac1 V12 inhibited Rac morphology, and in cells already expressing Rac1 V12, Crmp-2 caused localized peripheral collapse, involving Rho (and Cdc42) activation. Rho kinase was a pivotal regulator of Crmp-2; Crmp-2 phosphorylation was required for Crmp-2/Rac1 V12 inhibition, but not Crmp-2/RhoA V14 induction, of Rac morphology. Thus Crmp-2, regulated by Rho kinase, promotes outgrowth and collapse in response to active Rho and Rac, respectively, reversing their usual morphological effects and providing a mechanism for dynamic modulation of growth cone guidance.

3T3 Cells↗
PubMed2001

Quasipure Bose-Einstein condensate immersed in a Fermi sea.

We report the observation of coexisting Bose-Einstein condensate (BEC) and Fermi gas in a magnetic trap. With a very small fraction of thermal atoms, the 7Li condensate is quasipure and in thermal contact with a 6Li Fermi gas. The lowest common temperature is 0.28 microK approximately 0.2(1)T(C) = 0.2(1)T(F) where T(C) is the BEC critical temperature and T(F) the Fermi temperature. The 7Li condensate has a one-dimensional character.

Journal Article↗
PubMed2001

alpha2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells.

Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha2-chimaerin mRNA expression resembles that of cyclin-dependent kinase regulator p35 (CDK5/p35) which participates in neuronal differentiation and with which chimaerin interacts. To determine whether alpha2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. When plated on poly-lysine, transient alpha2-chimaerin but not alpha1-chimaerin transfectants formed neurites. Permanent alpha2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha2-chimaerin mutated in the SH2 domain (N94H) generated an alpha1-chimaerin-like phenotype, protein partitioned in the particulate fraction, and in NGF-stimulated pheochromocytoma cell line 12 (PC12) cells, neurite formation was inhibited. These results indicate a role for alpha2-chimaerin in morphological differentiation for which its SH2 domain is vital.

Aging↗
PubMed2001

Acute and mid-term results of phosphorylcholine-coated stents in primary coronary stenting for acute myocardial infarction.

The aim of this pilot study was to evaluate the safety and efficacy of the BiodivYsio phosphorylcholine-coated stent in the primary treatment of acute myocardial infarction. The BiodivYsio stent (Biocompatible) is a balloon-expandable stent, laser etched from a 316 L stainless steel tube. This device is coated with phosphorylcholine, a synthetic, hemocompatible phospholipid polymer that has been shown in experimental studies to reduce platelet and protein adhesion to the surface of the metal. One hundred consecutive patients within 24 hr of symptoms of onset of acute MI, treated with primary PTCA, were enrolled. After PTCA, stenting was attempted in all eligible lesions (reference diameter > or = 2.5 mm; no bend lesion > 45 degrees ). Poststenting regimens contained ticlopidine (500 mg/day) and aspirin (325 mg/day) and 6-12 hr of heparin infusion. Procedural success (TIMI > or = II and residual stenosis < 30%) was obtained in 70/74 cases (95%). TIMI grade III was restored in 90% of cases. In the patient group with procedural success (70 cases), 70 BiodivYsio stents were placed. After stenting, diameter stenosis decreased from 96% +/- 11% to 22% +/- 12% (P < 0.01) and minimal luminal diameter increased from 0.13 +/- 0.29 to 2.47 +/- 0.43 (P < 0.01). Nominal stent diameter was between 3.0 and 4.0 mm (mean, 3.5 +/- 0.4 mm). Stent length was between 11 and 28 mm (mean, 17 +/- 4.5 mm). Clinical follow-up was obtained in all patients; angiographic follow-up was performed in 65/70 (93%). No acute or subacute thrombosis was reported. Two in-hospital major adverse cardiac events (MACE) were reported due to a nontreated left main disease that required coronary artery bypass graft (CABG) surgery. At follow-up, MACE were found in 9 of 68 patients (13%), target lesion revascularization (TLR) in 6%, and CABG in the remaining 6%. Primary stenting with phosphorylcholine-coated stent leads to excellent short- and mid-term clinical outcomes and is associated with a restenosis rate of 12%.

Aged↗
PubMed2001

Revascularization of severe hibernating myocardium in the beating heart: early hemodynamic and metabolic features.

BACKGROUND: We investigated the effects of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) in selected patients with severe hibernating myocardium. METHODS: Twelve patients (EF = 25% +/- 0.7%) with reversible ventricular dysfunction (from 2.0 +/- 0.06 to 1.6 +/- 0.05 left ventricular score index by echodobutamine, p < 0.01) in the territory of the left anterior descending artery (LAD) have been studied. Revascularization was achieved by anastomosing the left internal mammary artery to the LAD. The ischemic time of LAD was 9.0 +/- 0.4 minutes. RESULTS: Left ventricular function increased 6 hours and 48 hours after revascularization (left ventricular stroke work index from 32 +/- 1.8 to 42 +/- 1.5 and 40 +/- 0.6 gxm/m2, respectively: p = 0.0001). During the surgical procedure, the heart did not release lactate or creatine phosphokinase. There were no perioperative deaths or severe complications. CONCLUSIONS: Early hemodynamic and metabolic features of CABG without CPB in patients with hibernating myocardium suggest that this procedure is safe and results in a significant improvement of cardiac function without affecting myocardial metabolism.

Adult↗
PubMed2001

A placebo-controlled, double-blind study of mesoglycan in the treatment of chronic venous ulcers.

OBJECTIVES: to assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the healing of venous ulcers. Design randomised, placebo-controlled, double-blind, multicentre trial. METHODS: non-diabetic outpatients with chronic venous insufficiency confirmed by duplex ultrasound, normal ankle/arm pressure index and presence of a leg ulcer were eligible. Patients were randomised to mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally, or matching placebo, as an adjunct to compression therapy and topical wound care. Treatment and observation were continued until complete ulcer healing or for 24+/-1 weeks. Time to ulcer healing and healing rates were estimated with the Kaplan-Meier method. RESULTS: One hundred and eighty-three patients were randomised and included in the analysis (92 mesoglycan, 91 placebo). Median ulcer area upon inclusion was 3.6 cm(2)in the mesoglycan group and 3.9 cm(2)in the placebo group. The estimated time to heal 75% of the patients was 90 days on mesoglycan versus 136 days on placebo, while the cumulative rate of healing by the end of observation was 97% versus 82%, respectively. The difference in favour of mesoglycan was statistically significant (p < 0.05, centre-stratified Cox's model). The relative risk of ulcer healing with mesoglycan was 1.48. The rate of adverse events was 7/92 on mesoglycan and 6/91 on placebo. CONCLUSIONS: treatment with mesoglycan in addition to established venous ulcer therapy resulted in a significantly faster and more frequent ulcer healing, and did not raise any safety concerns.

Chronic Disease↗
PubMed2001

Etoposide induces the dispersal of DNA ligase I from replication factories.

In eukaryotic cells DNA replication occurs in specific nuclear compartments, called replication factories, that undergo complex rearrangements during S-phase. The molecular mechanisms underlying the dynamics of replication factories are still poorly defined. Here we show that etoposide, an anticancer drug that induces double-strand breaks, triggers the redistribution of DNA ligase I and proliferating cell nuclear antigen from replicative patterns and the ensuing dephosphorylation of DNA ligase I. Moreover, etoposide triggers the formation of RPA foci, distinct from replication factories. The effect of etoposide on DNA ligase I localization is prevented by aphidicolin, an inhibitor of DNA replication, and by staurosporine, a protein kinase inhibitor and checkpoints' abrogator. We suggest that dispersal of DNA ligase I is triggered by an intra-S-phase checkpoint activated when replicative forks meet topoisomerase II-DNA--cleavable complexes. However, etoposide treatment of ataxia telangiectasia cells demonstrated that ataxia-telangiectasia-mutated activity is not required for the disassembly of replication factories and the formation of replication protein A foci.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Hypothesis and development of a minimally invasive approach for percutaneous transmyocardial revascularization with holmium laser.

BACKGROUND: Percutaneous transluminal myocardial revascularization (PTMR) is a new procedure to improve perfusion of the ventricular wall for patients with intractable angina and untreatable by surgery or conventional catheter-based intervention. Actually PTMR requires femoral approach to utilize 8F-9F system device. We now report the feasibility study of PTMR using a laser delivered through a novel Eclipse system and new 6F and 7F guiding catheters that allow to perform PTMR even in patients with peripheral vascular disease and particularly suitable for alternative small vascular access. METHODS: Percutaneous vascular access for PTMR treatment was obtained via the femoral or radial artery. A 6F or 7F mono-directional catheter carrying flexible fiber optics was used with a Holmium laser (Eclipse system) and was placed across the aortic valve into the left ventricular cavity to create channels of 5 mm in depth from the endocardial surface into the myocardial tissue. From June 1999 to September 2000, 39 patients (28 males, 11 females, mean age 72 +/- 8 years, range 58-86 years) underwent PTMR with the Eclipse system. Preoperative mean Canadian Cardiovascular Society (CCS) angina class was 3.5 +/- 0.5 and previous myocardial procedures had been performed in 39 patients (18 coronary artery bypass graft and 31 coronary angioplasty). RESULTS: The procedure was well tolerated and a procedural success was obtained in all patients (100%). We performed a mean of 19 +/- 7 channels in a mean fluoroscopy time of 21 +/- 9 min. We report only one procedural complication: one embolic stroke (2.4%). No hospital major adverse cardiac events were observed. The average length of hospital stay was 3.1 days. The mean CCS angina class at entry was 3.5 and it declined from 3.5 +/- 0.5 to 1.25 +/- 0.8 at discharge. At the follow-up of 8.2 +/- 3.9 months the mean CCS was 1.5 +/- 0.7. CONCLUSIONS: This experience confirmed the safety and technical feasibility of PTMR with this mini-invasive approach with a reduction in operative and fluoroscopy time. The PTMR with the 6F or 7F guiding catheter is feasible in high risk patients even when the femoral approach is contraindicated. Immediate and short-term results confirm that a clinical improvement is obtained in most patients.

Aged↗
PubMed2001

IABP assistance: a test bench for the analysis of its effects on ventricular energetics and hemodynamics.

IABP assistance is frequently used to support heart recovery, improving coronary circulation and re-establishing the balance between oxygen availability and consumption. Hemodynamic and energetic parameters (endocardial viability ratio, ventricular energetics) are used to evaluate its effectiveness which depends on internal (timing, balloon volume and position) and external factors (circulatory conditions). Considering short, medium and long-term effects of IABP, the first depends on its mechanical action, the latter on the changes induced in circulatory parameters. The analysis of the first is important because conditions for the onset of a virtuous cycle able to support ventricular recovery are created. Simulation systems could be helpful in this analysis for the implicit reliability and reproducibility of the experiments, provided that they are able to reproduce both hemodynamic phenomena and energetic relationships. The aim of this paper is to present a system originally developed to test mechanical heart assist devices and modified for IABP testing. Data reported here are obtained from in vitro experiments. A partial verification, obtained from the literature is presented.

Coronary Circulation↗
PubMed2001

[Combined neoplasia of the lung: description of a case of adenocarcinoma mixed with typical carcinoid].

OBJECTIVE: To report about a lung tumor that was a combination of typical carcinoid and adenocarcinoma. RESULTS AND CONCLUSIONS: The patient, a 71-year-old male, presented with a 2.5-cm pulmonary nodule that, microscopically, was a combination of an adenocarcinoma (tubular with clear cell features and bronchioloalveolar) and a typical carcinoid. Immunohistochemically, both components were positive for cytokeratin, but only the carcinoid component was positive for chromogranin and synaptophysin. In the range of neuroendocrine tumors of the lung, a combination with other histological types of carcinoma (squamous, adeno, large cell and pleomorphic) can be found with both small cell carcinoma and large cell neuroendocrine carcinoma, but is very rare with typical and atypical carcinoids.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Mono and bi-ventricular assistance: their effect on ventricular energetics.

When mono- and bi-ventricular mechanical assistance is used for heart recovery, its control strategy and circulatory variables affect ventricular energetics (external work-EW, oxygen consumption-VO2, cardiac mechanical efficiency-CME). This study is based on the data obtained in vitro and presents an analysis of the effects of the mono- and bi-ventricular mechanical assistance on ventricular energetics. The assistance was conducted on the principle of counterpulsation with atrio-arterial connection. It includes the following stages: 1) the characterisation of the isolated ventricle model in terms of EW, VO2 and CME as a function of the filling pressure and peripheral resistance, 2) modelling of left ventricular and pulmonary dysfunction, followed by left ventricular and bi-ventricular assistance. Experimental data enable us to draw the following conclusions: * in general, the greatest hemodynamic improvement does not correspond to the highest energetic improvement, * LVAD assistance deteriorates left ventricular CME while its effect on right ventricular energetics depends on the value of right ventricular elastance (Emax). Right ventricular CME is deteriorated by BVAD assistance irrespective of right Emax, * the energetics optimisation in bi-ventricular assistance is closely related to the right Emax, which could probably be a deciding factor in the choice of the assistance mode.

Elasticity↗
PubMed2001

[Acute myocardial infarction during labor: report of a case and review of the literature].

Acute myocardial infarction in pregnancy is a rare condition with substantial risk of maternal and fetal death. There is very little information about the use in this setting of percutaneous coronary interventional therapy. Together with literature review on this topic, we present the case of a 33-year-old 39-week pregnant woman who sustained during labor an acute transmural anterior myocardial infarction. Immediately after successful cesarean section, she was treated by primary percutaneous coronary angioplasty and direct stenting of the left anterior descending coronary artery with maternal and fetal excellent outcome.

Adult↗
PubMed2001

A hybrid (numerical-physical) model of the left ventricle.

Hydraulic models of the circulation are used to test mechanical devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive. The solution proposed here is to merge the characteristics and the flexibility of numerical models with the functions of physical models. The result is a hybrid model with numerical and physical sections connected by an electro-hydraulic interface - which is to some extent the main problem since the numerical model can be easily changed or modified. The concept of hybrid model is applied to the representation of ventricular function by a variable elastance numerical model. This prototype is an open loop circuit and the physical section is built out of a reservoir (atrium) and a modified windkessel (arterial tree). The corresponding equations are solved numerically using the variables (atrial and arterial pressures) coming from the physical circuit. Ventricular output flow is the computed variable and is sent to a servo amplifier connected to a DC motor-gear pump system. The gear pump, behaving roughly as a flow source, is the interface to the physical circuit. Results obtained under different hemodynamic conditions demonstrate the behaviour of the ventricular model on the pressure-volume plane and the time course of output flow and arterial pressure.

Heart Ventricles↗
PubMed2001

Treatment of intermittent claudication with mesoglycan--a placebo-controlled, double-blind study.

OBJECTIVE: To assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the walking capacity of patients with stage II peripheral arterial disease. METHODS: Non-diabetic outpatients with intermittent claudication, duplex ultrasound evidence of peripheral atherosclerosis, ankle/arm index <0.80, systolic ankle pressure >50 mmHg, and absolute walking distance (AWD) between 100 and 300 m (standardised treadmill test) were eligible. After a 5-week run-in on single-blind placebo, patients were randomised to double-blind treatment with mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally for 20 weeks, or matching placebo. All patients received low-dose aspirin and lifestyle instructions. Clinical response was defined as an AWD increase at Week 23 >50% over baseline. Health-related quality of life and ischaemic events were assessed as secondary efficacy variables. RESULTS: 242 patients were randomised and 237 were assessed for clinical response. Patients achieving clinical response were 59/118 with mesoglycan (50.0%) and 31/119 with placebo (26.1%; p <0.001). Geometric mean AWD increased from 192 to 298 m with mesoglycan, and from 192 to 238 m with placebo (p <0.001). Pain-free walking distance showed a non-significant increase with mesoglycan (p = 0.057). Changes in quality of life scores were in favour of mesoglycan. The rate of ischaemic events was 1/120 on mesoglycan and 6/122 on placebo (p = 0.053). The rate of non-ischaemic adverse events leading to treatment discontinuation was 7/120 and 4/122, respectively. CONCLUSION: Treatment with mesoglycan improves the walking capacity of patients with intermittent claudication, and might confer additional antithrombotic protection over that of aspirin.

Aged↗
PubMed2000

Toward epidermal stem cell-mediated ex vivo gene therapy of junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a group of severe, inherited skin diseases caused by mutations in the genes encoding laminin 5 or other components of the hemidesmosome. Since human epidermis is a self-renewing tissue, gene therapy of JEB requires the stable integration of the transgene into the genome of the epidermal stem cell. Human epidermal stem cells can indeed be cultivated and stably transduced with replication-defective retroviral vectors, allowing full phenotypic correction of the adhesion properties of JEB keratinocytes. Epidermal stem cells generate cohesive sheets of stratified epithelium suitable for the permanent coverage of massive skin defects, and genetically modified epidermal sheets maintain long-term expression of the transgene after transplantation on immunodeficient animals. Moreover, we have developed a clinical procedure that allows transplantation of cultured epidermal sheets on large body areas under local anesthesia and without cicatricial outcomes. Thus, (1) the possibility of cultivating lining epithelia, (2) the availability of noninvasive surgical procedures that allow the grafting of large skin areas, and (3) the demonstration of sustained transgene expression in vitro and in vivo by epidermal stem cells, prompt us to propose the implementation of a phase I/II clinical trial aimed at the ex vivo gene therapy of selected JEB patients. The aim of the trial is to validate the ex vivo procedure in a clinical setting, to prove its overall safety, and to analyze critical issues such as long-term survival of the genetically modified implant, immune response against the transgene product, and persistence of transgene expression at therapeutic levels.

Cells, Cultured↗