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Biomedical subjects

G Arena

Publications and source records attributed to G Arena.

At least 19 recordsLinked to original sources
PubMed2000

Kaposi's sarcoma cells of different etiologic origins respond to HIV-Tat through the Flk-1/KDR (VEGFR-2): relevance in AIDS-KS pathology.

Kaposi's sarcoma (KS) is an hyperplastic lesion whose main histological features are typical spindle shaped cells with a mixed endothelial-mesenchymal-macrophage phenotype, an intense vascularization and an inflammatory infiltrate. The etiology of KS appears to be linked to activation of a latent HHV8 infection. Sporadic and iatrogenic KS are slow progressing lesions that can undergo spontaneous regression. In contrast, KS, which is frequently associated with HIV infection, is found in a highly aggressive form in AIDS patients. The HIV-1 Tat has been shown to activate the VEGF receptor KDR in endothelial and KS spindle cells, suggesting this HIV protein could contribute to KS pathogenesis. We used primary 'reactive' KS cell culture from sporadic and epidemic KS, and an immortal KS-line (KS-Imm) isolated in our laboratory from a iatrogenic KS lesion, to verify if Tat-induced cell signaling is able to mediate cellular responses. We demonstrate that KS cells migrated in response to Tat and that VEGF is able to compete with the Tat chemotactic activity towards these cells. A function-blocking anti-KDR antibody was able to abrogate both VEGF and Tat-induced KS chemotactic response, indicating a direct involvement of this receptor. Our data show that HIV-Tat can also activate KS cells derived from sporadic or iatrogenic lesions, suggesting that in AIDS patients Tat could cooperate with VEGF in activation of KDS on KS precursor spindle and endothelial cells, and contribute to the aggressiveness of AIDS-KS lesions.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Is calcium antagonist administration necessary after aortocoronary bypass with the radial artery?].

Calcium channel blocker therapy after total arterial revascularization is very frequent. The purpose of this study was to verify the real efficacy of calcium channel blocker therapy after coronary artery bypass graft with radial artery conduit. We have divided our patients (n = 50) into two groups: the first was discharged with calcium channel blocker therapy for 6 months; the second was discharged without calcium channel blocker therapy. Angiography and clinical evaluation showed no difference between the two groups regarding wall reactivity of radial artery conduit. However, we think that the efficacy of coronary artery bypass graft with radial artery conduit and calcium channel blocker therapy will require long-term follow-up.

Calcium Channel Blockers↗
PubMed2000

Ocular effects of fenretinide, a vitamin A analog, in a chemoprevention trial of bladder cancer.

Fenretinide is a vitamin A derivative under investigation in cancer prevention trials. Because all available pharmacologic and toxicologic data were obtained from breast cancer patients, we measured plasma drug, metabolite, and vitamin A levels and studied their relationship with visual and ocular symptoms in a cohort formed mostly by male subjects belonging to a bladder cancer prevention trial. After 1 year, the mean plasma retinol levels (+/- standard deviation [SD]) were 168.2 +/- 75.8 ng/ml in 31 subjects treated with fenretinide and 594.5 +/- 168.4 ng/ml in 36 control subjects (P < .001). Plasma retinol levels were correlated inversely to drug and metabolite concentrations, which in turn were correlated inversely to the interval from last drug intake. The decline of plasma vitamin A levels accounted for a 41.7% cumulative incidence of diminished dark adaptability in the retinoid arm as compared to 6.8% in the control arm (odds ratio = 13.8; 95% confidence interval, 2.9-66.1). Although compliance as assessed by capsule count was high, three subjects originally assigned to the treatment group who proved to be noncompliers (8.8%, or 3 of 34) had no detectable plasma drug or metabolite levels. Our data confirm the specific pharmacologic and visual effects of fenretinide also in a male population and strengthen the importance of multiple blood measurements to monitor treatment compliance in prevention trials.

Adult↗
PubMed1999

Incessant nonreentrant atrioventricular nodal tachycardia due to multiple nodal pathways treated by radiofrequency ablation of the slow pathways.

In patients with dual AV nodal physiology, simultaneous anterograde fast and slow pathway conduction resulting in an unusual form of nonreentrant AV nodal tachycardia has been observed. We describe the case of a young patient with an incessant form of complex supraventricular tachycardia who underwent electrophysiologic evaluation, which showed simultaneous conduction via multiple AV nodal pathways that caused a unique form of incessant nonreentrant AV nodal tachycardia. Radiofrequency ablation of the spatially closed intermediate and slow pathways effectively treated the tachycardia. The electrophysiologic determinants of simultaneous conduction through the multiple nodal pathways and the apparently different behavior of the fast pathway before and after ablation are discussed.

Adolescent↗
PubMed1997

[Reintervention in mitral valve prostheses. Analysis of risk factors].

From 1980 to 1996, 111 patients (83 females, 28 males, mean age 51.47 +/- 15.73 years, range 1-76) underwent mitral valve replacement. Seventy-five patients underwent replacement of a biological valve and 36 of a mechanical valve. Three patients underwent a third operation. Seventy prostheses were replaced because of a structural dysfunction. Other causes of valve failure were: 24 thrombosis (23 mechanical and 1 biological), 10 endocarditis (7 mechanical, 3 biological) and 4 leakages (3 mechanical and 1 biological). One patient who had recurrent anticoagulant-related haemorrhage underwent reoperation to replace his mechanical valve with a biological prosthesis. Two patients had their valve replaced because of mismatch between size of the valve and body surface area. Thirteen operations were performed on emergency and 29 on urgency. There were 22 in-hospital deaths with a hospital mortality of 19.82%. Fourteen deaths (63.63%) occurred in patients operated on emergency or urgency. All deceased patients were in NYHA functional class III or IV. Our data suggest that risk of reoperation on mitral prosthesis is highly influenced by the preoperative functional class. In spite of the fact that replacement of biological valves should be more elective than that of mechanical valves, we did not find any difference between the two groups of patients.

Adolescent↗
PubMed1996

Alternative splicing of the estrogen receptor primary transcript normally occurs in estrogen receptor positive tissues and cell lines.

Several laboratories have described estrogen receptor mRNA variants created by skipping internal exons. Some of the putative proteins encoded for by these variants have been functionally characterized by transfection analyses. The variant lacking exon 5 would lead, if translated, to a truncated receptor which shows dominant positive transactivation activity in the absence of hormone. It has been postulated that the variant could account for anti-estrogen resistant tumor growth and for expression of the progesterone receptor in estrogen negative tumors. In order to understand the possible role this and other variants may have in the tumorigenesis of mammary tissue we have carried out a thorough analysis of variants expressed in a tumor cell line (MCF-7), in a tumor sample and in a sample of normal breast tissue derived from mammary reduction surgery. We performed rt-PCR analyses followed by hybridization with exon specific oligonucleotide probes. By these means we have detected nine different variants co-expressed in MCF-7 cells and at least the major variants were equally expressed in normal and neoplastic breast tissue. The same is true for the variant lacking exon 5 which, however, resulted to be a variant of low expression in the three samples analyzed. Variant formation appeared to be restricted to the estrogen receptor messenger since several other members of the superfamily of nuclear receptors did not show variant formation. We also have analyzed the effect of the most abundantly expressed variant, the exon 4 lacking variant, on normal estrogen receptor function, on the growth and on the response to estradiol and to tamoxifen of MCF-7 cells. Although over-expressed at high levels this variant has, if any, only marginal effects on the expression of endogenous estrogen regulated genes and on growth and response to the hormone and its antagonist. Although the lack of function of this variant cannot be extrapolated to other variants, their involvement in tumor formation appears rather unlikely since they are also expressed in normal tissue and the single variant is expressed in addition to many others, some of which might have opposing effects. Variant formation is, however, specific for the estrogen receptor and apparently regulated with tissue specificity as our expression analysis in normal mouse tissues shows. Therefore the variants probably have a physiological significance yet to be discovered.

Adenocarcinoma↗
PubMed1996

Is local myocardial contractility related to endocardial acceleration signals detected by a transvenous pacing lead?

The availability of sensors monitoring cardiac function parameters may offer many interesting new applications in cardiac pacing. A microaccelerometer sensor (BEST, Biomechanical Endocardial Sorin Transducer) located at the tip of a pacing lead (PL) has been developed by Sorin Biomedica. The signal detected by the accelerometer, peak endocardial acceleration (PEA), was shown to reflect cardiac contractility and to be related to the dP/dt signal. Whether the PEA detected by the BEST sensor in different cardiac locations is the expression of local acceleration forces or reflects the whole heart contractility has not yet been demonstrated in humans. Endocardial acceleration and PEA were evaluated in five patients (4 males, 1 female, mean age 68 years) who underwent cardiac catheterization. Sinus rhythm was present in four patients and chronic atrial fibrillation was present in one. The BEST PL was introduced through the left subclavian vein and PEA signals were recorded: (1) at the apex of the right ventricle (RV), (2) within the coronary sinus (CS), (3) at the right atrial appendage (RAA), and (4) floating in the right atrium. The PEA signals were recorded simultaneously with surface ECG, intracardiac electrograms, and RV pressure. At each recording site, PEA signals with significant amplitude were always recorded during the preejection period, during the isovolumic contraction phase, independently of the recording site and cardiac rhythm. The PEA amplitude was higher in the RV (mean value 1.32 g) and it decreased in the RAA and CS (0.75 and 0.45 g, respectively). The same behavior of PEA was observed during sinus rhythm or atrial fibrillation. The amplitude and the timing of the PEA signals detected by the BEST accelerometer were independent of the recording site and atrial rhythm; they appeared to be strictly related to the global ventricular contractility. These results suggest that the BEST could be used either as an effective sensor in closed loop pacing systems, or primarily as a diagnostic hemodynamic sensor.

Acceleration↗
PubMed1996

[Osteoma of the tongue].

An osteoma of the tongue of a 50-year-old woman is reported. The nosology of this rare lesion is briefly described.

Female↗
PubMed1995

Induction of kinetochore-containing micronuclei by exogenous O6-methylguanine requires conversion of the methylated base to a nucleotide.

It has been reported that exogenous alkylated purines, such as O6-methylguanine (O6meG), induce aneuploidy in mammalian cells. It is shown here that the aneugenic effect of O6meG, evidenced by its ability to induce micronuclei in rodent cells, is dependent on its conversion to O6-methyl-guanosine-5'-monophosphate (O6me-5'-GMP) by hypoxanthine-guanine phosphoribosyl transferase (HPRT). This conclusion, in contrast with previous in vitro data showing that O6meG does not seem to be a substrate for HPRT, was based on the following observations: 1) O6meG did not induce micronuclei in HPRT-deficient Chinese hamster cells, but did induce micronuclei in HPRT-proficient cells, and in mouse cells partially or totally deficient in adenine phosphoribosyl transferase; 2) O6meG was not metabolized in HPRT-deficient cells, while in wild-type cells a number of metabolites were detected by high performance liquid chromatography (HPLC) analysis of cold acid extracts, one of them coeluting with O6me-5'-GMP used as a marker; 3) when de novo synthesis of purine nucleotides was inhibited by aminopterin, O6meG sustained the growth of HPRT-proficient, but not of HPRT-deficient, cells; and 4) when HPRT-deficient cells were treated with liposomes charged with O6me-5'-GMP, induction of micronuclei was shown. The finding that methylated guanine exerts its aneugenic action through methylated nucleotide(s) provides an important, though indirect, support to the hypothesis that alkylating agents may induce aneuploidy via nucleotide pool alkylation.

Adenine↗
PubMed1995

The induction of aneuploidy by alkylated purines: effects on early and late cell cycle events.

It has been shown that alkylated bases induce aneuploidy in mammalian cells in culture. The mechanism of action is not clear, however, data with 6-dimethyl amino purine (6DMAP) suggest that this analogue might act by affecting the cytoskeleton and protein kinases involved in cell cycle regulation (cdc2/p34). The aim of this work was to study the effect of O6methylguanine (O6meG), O6ethylguanine (O6etG) and 6DMAP on DNA synthesis induced by growth factors in two cell lines, 3T3 and CHEF/18 fibroblasts, which respond in opposite ways to substances affecting the cytoskeleton, colchicine and cholera toxin: DNA synthesis initiation is stimulated in 3T3 cells and inhibited in CHEF/18 cells by such compounds. Our results indicate that O6meG and O6etG behave like cholera toxin, in as much as they inhibit DNA synthesis induced by epidermal growth factor plus insulin in CHEF/18 cells, and stimulate it in 3T3 cells. 6DMAP behaves differently and inhibits DNA synthesis in both cell lines. The inhibition (or stimulation) was greater when alkylated bases were added before S phase started, suggesting that these compounds might affect early events of the cell cycle. In CHEF/18 cells the three alkylated bases were able to induce aberrant metaphases and ana-telophases with different efficiency (70-100%). The effect was not dependent on the G1-S block and it was reversible even after cell commitment to DNA synthesis.

3T3 Cells↗
PubMed1994

Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters.

The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.

Administration, Oral↗
PubMed1993

Cytotoxic and cytostatic activity of copper(II) complexes. Importance of the speciation for the correct interpretation of the in vitro biological results.

The cytotoxicity of some copper(II) compounds against the mouse cancer cell line B16, murine L929, human KB cells, and fibroblasts was investigated. All the copper(II) systems tested were shown to have pronounced toxicity against transformed cells and a cytostatic effect against untransformed cells, i.e., human fibroblasts. A careful speciation of the actual in vitro conditions reveals that copper(II) is essentially present as mixed complexes formed with the amino acids of the culture medium, [Cu(glutamine)(histidine)] being the main species. It was found that the cytotoxic activity is related to the amount of copper(II) contained in the tested compounds.

Acetates↗
PubMed1992

Multicenter clinical evaluation of a new SSIR pacemaker.

A multicenter clinical evaluation of Sorin Swing 100, a new SSIR pacemaker with a gravimetric sensor, was performed by seven different centers enrolling a total of 89 patients, 56 men and 33 women, mean age 73.1 years, for pacemaker implantation (73 patients) or pacemaker replacement (16 patients). Pacing mode was VVIR in 73 patients and AAIR in 16. The behavior of pacing rate was evaluated 3 months after the implant by performing a 24-hour Holter monitor, an exercise stress test, and tests for the assessment of mechanical external interference (MEI). A physiological behavior of the paced rate was always observed during Holter monitoring. In 52 completely paced patients mean diurnal, nocturnal, and maximal heart rate were, respectively, 74.9 +/- 5.7 ppm, 58.1 +/- 5.8 ppm, and 113.4 +/- 12.7 ppm; a paced rate exceeding 100 ppm was reached on the average 5.6 times/Holter monitor. In all but two patients the sleep rate (55 ppm) was reached during the night or long resting time. During exercise stress test a direct correlation between the increase in pacing rate and the increase in workload was observed; the mean maximal heart rate reached in 49 completely paced patients was, respectively, 102.8 +/- 9 ppm in 17 patients who accomplished stage 1, 116.2 +/- 13.6 ppm in 28 patients who accomplished stage 2, and 133 +/- 6.7 ppm in 10 patients who accomplished stage 3 of the Bruce protocol. MEI testing never increased the pacing rate over the noise rate (10 ppm over the basic rate). In only seven patients the results obtained suggested to change the nominal set up of the pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗