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Biomedical subjects

A Ferri

Publications and source records attributed to A Ferri.

At least 37 records · Page 2Linked to original sources
PubMed2000

Limitations of the computerized laryngeal analyzer (CLA) in the assessment of the swallowing mechanism.

This study was devised to assess the repeatability of measurements obtained from the Computerized Laryngeal Analyzer (CLA), a commercial system which monitors global laryngeal activity through a piezoelectric transducer positioned at the level of the thyroid cartilage. Twenty-two healthy subjects (37+/-7 yr) were asked to repeat three consecutive times the deglutition of three types of bolus: dry (saliva only), liquid (10 ml water) and solid (1 cm(3) biscuit). The whole recording session was repeated 4+/-3 days apart. Two parameters were considered: amplitude and duration of the deglutition. Both intra- and inter-sessions repeatability were assessed by the standard error of measurement. The amplitude measurements were often found to be clipped at 100 mV, making duration the only parameter suitable for analysis. The duration was homogenous for the three types of bolus and no trend effect was found either intra- or inter-sessions. Inter-sessions repeatability was significantly lower than the intra-session one (P<0.05). As a practical implication, a change in duration >/=1 s (=65% of the observed mean value) between two separate measurements is required in order to be 95% confident that it is not due to chance alone. We conclude that the observed limitations in the measurements provided by the CLA system, in conjunction with its intrinsic characteristic of providing only an uncalibrated measurement of global laryngeal activity, seriously question the possibility of using the CLA system either as a diagnostic tool or as a substitute of the gold standard method (videofluorography).

Adult↗
PubMed2000

Short- and long-term effect of glyceryl trinitrate (GTN) ointment 0.2% and 2% on anal canal pressure in patients with chronic anal fissures.

Controversial data are available on the duration of action of glyceryl trinitrate after acute and chronic application on anal canal pressure. Our aim was to assess the effect of glyceryl trinitrate at 0.2% and 2% on anal canal pressure before and after eight weeks of treatment. Anal canal pressure was evaluated in 12 patients with chronic anal fissures with an electronic probe with three recording sites before and after the application of glyceryl trinitrate, 120 mg on the external anal verge. Six patients received glyceryl trinitrate at 0.2% and six at 2%. Glyceryl trinitrate 0.2% and 2% equally reduce basal anal canal pressure in all three recording sites (P < 0.001) with major effect on the inner site of the canal toward the rectum, for a 60-min period. Eight weeks after application, the effect of glyceryl trinitrate was unchanged. In conclusion, glyceryl trinitrate ointment at 0.2% and 2%, equally reduces anal canal pressure for 60 min and this effect is kept unchanged after eight weeks of application.

Adult↗
PubMed2000

Inhibition of phosphoinositide 3-kinase impairs pre-commitment cell cycle traverse and prevents differentiation in erythroleukaemia cells.

During the early hours after exposure to differentiation inducing agents, Friend erythroleukaemia cells undergo alterations which commit them to cessation of growth and development of the characteristics of differentiation. Our current experiments have compared the expression and activity of phosphoinositide 3-kinase (PI 3-kinase) in control cells with cells undergoing differentiation which has been induced by dimethyl sulfoxide (DMSO). When the cultures were initiated with stationary phase cells and DMSO was added at the time of seeding, PI 3-kinase activity was stimulated in both treated and control cells during the first 3 h from seeding. This event appears to be a rate limiting step in commitment since pretreatment of cells with 10 microM LY294002 or down-regulation of p85 expression prior to adding DMSO completely prevents commitment to erythropoiesis. Accordingly, PI 3-kinase inhibition during the commitment period prevents DNA-binding of the transcription factor GATA-1, essential for erythroid differentiation. However, once cells are committed to differentiate, PI 3-kinase activity and expression dramatically decreases along with the differentiation programme, to become barely detectable after 96 h. Remarkably, LY294002 treatment leads to accumulation of cell in G1 phase and prevents DMSO-dependent cyclin D3 induction. Based on these data, we suggest that PI 3-kinase is rate limiting for the completion of the first round cycle of cell division required for initiation of erythrocytic differentiation. On the other hand, the late decrease of PI 3-kinase associated with the differentiation process seems to be part of the programmed shut off of genes not needed in mature erythrocytes.

Androstadienes↗
PubMed2000

Role of antimicrobial susceptibility testing on efficacy of triple therapy in Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori treatment failure may be due to resistance to macrolides and 5-nitroimidazoles. AIM: To test whether a preliminary in vitro susceptibility test of H. pylori to tinidazole and clarithromycin and a consequent specific regimen could improve the eradication rate. METHODS: A total of 109 consecutive H. pylori-positive patients with dyspeptic symptoms were included. At endoscopy, biopsy from the antrum was obtained for H. pylori culture and antimicrobial susceptibility testing. Fifty-six patients were treated with omeprazole, tinidazole and clarithromycin for 10 days (group OTC) and 53 patients received therapy on the basis of the susceptibility test (group SUSC). Treatment success was evaluated by the 13C-urea breath test 1 month after the end of therapy. RESULTS: Eight patients dropped out. Overall primary resistance to clarithromycin, tinidazole and both antibiotics was 13%, 33% and 4%, respectively. In group OTC, H. pylori was eradicated in 81% and 75% of patients by per protocol and intention-to-treat analysis, respectively. Per protocol and intention-to-treat eradication rates for group SUSC were 98% and 91% (P < 0.05 vs. group OTC). CONCLUSIONS: These data show that in H. pylori infection, antibiotic therapy based on the results of culture and susceptibility testing gives, in comparison to standard therapy, a significant improvement in eradication rate.

Adult↗
PubMed2000

IAP family proteins delay motoneuron cell death in vivo.

Neuronal apoptosis inhibitory protein (NAIP), and human inhibitors of apoptosis 1 and 2 (HIAP1 and HIAP2) are three members of the mammalian family of antiapoptosis proteins called 'inhibitors of apoptosis' (IAP). These molecules can prevent apoptosis in vitro and the over-expression of NAIP can decrease ischemic damage in the hippocampus. The goal of our experiments was to determine whether administration of NAIP, HIAP1 and HAIP2 could rescue motoneurons following axotomy of a peripheral nerve. In young rats, an adenoviral gene transfer technique was used to deliver and express these proteins in motoneurons; a fluorescent tracer was simultaneously added as a means for quantitatively assessing the rescue of fluorescently labelled motoneurons in serial sections of the lumbar spinal cord. Control experiments using adenoviral vectors (adv) expressing the lacZ gene showed that 14% of the sciatic motoneuron pool could be transfected indicating the existence of a subpopulation of spinal motoneurons susceptible to this class of viral vectors. The administration of an adv-NAIP, adv-HIAP1 and adv-HIAP2 rescued 30-40% of motoneurons at one week after sciatic axotomy. The efficiency of these proteins was similar to that of two neurotrophic factors, ciliary neurotrophic factor and brain-derived neurotrophic factor, administrated by the same viral technique. The effect of the IAP proteins on motoneuron survival decreased with time but was still present after 4 weeks postaxotomy; the duration of the response was dependent upon the viral titre. These experiments demonstrate that IAP family proteins can prevent motoneuron cell death in vivo and may offer a new therapeutic approach for motoneuron diseases.

Adenoviridae↗
PubMed2000

Calcineurin activity is regulated both by redox compounds and by mutant familial amyotrophic lateral sclerosis-superoxide dismutase.

Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular responses to calcium-mobilizing signals, and a role for this enzyme in neuropathology has been postulated. We have investigated the possibility that redox modulation of CN activity is relevant to neuropathological conditions where an imbalance in reactive oxygen species has been described. We have monitored CN activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that CN activity is promoted by treatment with ascorbate or dithiothreitol and impaired by oxidative stress. Evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild-type antioxidant Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from oxidative inactivation. On the contrary, overexpression of mutant SOD1s associated with familial amyotrophic lateral sclerosis (FALS) impairs CN activity both in transfected human neuroblastoma cell lines and in the motor cortex of brain from FALS-transgenic mice. These data suggest that CN might be a target in the pathogenesis of SOD1-linked FALS.

Animals↗
PubMed2000

Molecular analysis in Brazilian cystic fibrosis patients reveals five novel mutations.

We have performed molecular genetic analyses on 160 Brazilian patients diagnosed with cystic fibrosis (CF). Screening of mutations in 320 CF chromosomes was performed through single strand conformation polymorphism (SSCP) and heteroduplex analyses assay followed by DNA sequencing of the 27 exons and exon/intron boundaries of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of CFTR variants of T-tract length of intron 8 (IVS8 Tn) was also investigated. This analysis enabled the detection of 232/320 CF mutations (72.2%) and complete genotyping of 61% of the patients. The deltaF508 mutation was found in 48.4% of the alleles. Another fifteen mutations (previously reported) were detected: G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 621+1G-->T, V232D, 1717-1G-->A, 2347 delG, R851L, 2789+5G-->A, and W1089X. Five novel mutations were identified, V201M (exon 6a), Y275X (exon 6b), 2686 insT (exon 14a), 3171 delC (exon 17a), and 3617 delGA (exon 19). These results contribute to the molecular characterization of CF in the Brazilian population. In addition, the identification of the novel mutation Y275X allowed prenatal diagnosis in a high-risk fetus.

Alleles↗
PubMed2000

Gastric emptying of a solid-liquid meal measured with 13C octanoic acid breath test and real-time ultrasonography: a comparative study.

OBJECTIVES: The 13C octanoic acid breath test (OBT) has been proposed as a reliable noninvasive test to measure gastric emptying. OBT has been compared with scintigraphy; however, there are no data comparing it with gastric emptying measured with real-time ultrasonography (RUS) The aim of the study was to correlate gastric emptying of a solid-liquid meal, with OBT and RUS simultaneously evaluated in a group of normal volunteers. METHODS: A total of 14 normal subjects ingested a standard test meal (one scrambled egg with two slices of white bread, 10 g of butter, and 300 ml of tap water). The egg yolk was mixed with 0.1 ml of 13C octanoic acid. Breath samples for 13CO2 analysis were collected in breath bags and were analyzed by means of isotope-selective nondispersive infrared spectrometry (IRIS). RUS was simultaneously performed by calculating the antral area following a previous validated method. Breath samples and antral area were taken at baseline and every 15 min after the meal during the first 2 h and every 30 min for another 2 h. Lag time (Tlag) and gastric half emptying time (T(1/2)) were calculated for OBT and RUS. Data were analyzed by the Student's t test for paired data, correlation coefficient, and regression line. RESULTS: The results show a statistically significant longer Tlag and T(1/2) for OBT in comparison with RUS (p < 0.001). A significant correlation and positive regression line was computed between OBT and RUS for Tlag and for T(1/2). CONCLUSIONS: Our results show that OBT overestimates gastric emptying parameters of a solid-liquid meal in comparison with RUS. However, both techniques give data in good correlation. Because OBT is less operator-dependent than RUS, it may be useful in comparative gastric emptying studies.

Adult↗
PubMed2000

Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome.

Microglial nodules associated with opportunistic and HIV-related lesions are frequently found in the brains of AIDS patients. However, in many cases, the causative agent is only presumptively suspected. We reviewed 199 brains of AIDS patients with micronodular lesions to clarify their etiology by immunohistochemistry (to Toxoplasma gondii, cytomegalovirus, herpes simplex virus I/II, varicella zoster virus and HIV-p24 core protein), PCR (for herpetic viruses and Mycobacterium tuberculosis) and electron microscopy. Productive HIV infection was observed in 110 cases (55.1%): 30 cases with Toxoplasma gondii encephalitis, 30 with cytomegalovirus encephalitis, eight with multiple cerebral diseases, while in the remaining 42 cases HIV was the only pathogenetic agent. Multinucleated giant cells (hallmark of HIV infection) were found in the MGNs of 85/110 cases with HIV-related lesions; the remaining 25 cases had only p24 positive cells but no multinucleated giant cells. In these latter cases the micronodular lesions had been initially attributed to the main opportunistic agent found in the brain, or defined as subacute encephalitis. Individual microglial nodules positive for an opportunistic pathogen were generally negative for HIV antigens. In 13 cases no opportunistic agent or HIV productive infection was found. In these cases, PCR and electron microscopy examination for HIV and other viral infections were negative. Our data suggest that HIV-immunohistochemistry should be used for the etiological diagnosis of micronodular lesions in AIDS brains, even in the presence of other pathogens. After extensive search, the etiology of the microglial nodules remains unknown in only a small percentage of cases.

AIDS-Related Opportunistic Infections↗
PubMed1999

Aberrant copper chemistry as a major mediator of oxidative stress in a human cellular model of amyotrophic lateral sclerosis.

We have investigated the response to oxidative stress in a model system obtained by stable transfection of the human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type human Cu,Zn superoxide dismutase or a mutant of this enzyme (H46R) associated with familial amyotrophic lateral sclerosis. We report that expression of mutant H46R Cu,Zn superoxide dismutase induces a selective increase in paraquat sensitivity that is reverted by addition of D-penicillamine. Furthermore, expression of this mutant enzyme affects the activity of the endogenous wild-type enzyme both in basal conditions and in copper overloading experiments. Our data indicate that aberrant metal chemistry of this mutant enzyme is the actual mediator of oxidative stress and that concurrent impairment of the activity of wild-type endogenous enzyme compromises the cell's ability to respond to oxidative stress.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells.

Although interleukin 1 (IL-1) functions have been extensively characterized, the mechanisms by which IL-1 signals are transduced from the plasma membrane to the nucleus are less known. Recent evidence indicates that phosphatidylinositol 3-kinase (PI3-kinase) could be activated by a direct association with the activated IL-1 receptor. In this study we analyzed the effects of IL-1 on the intracellular distribution of PI3-kinase in wild-type Saos-2 human osteosarcoma cells, and in cell clones overexpressing type I IL-1 receptor (IL-1RI). PI3-kinase intracellular distribution displays two distinct patterns. In quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus; following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. Both immunoblotting and immunofluorescence data indicate that IL-1 causes a rapid and transient translocation of PI3-kinase from the cytoplasm to the nucleus. This phenomenon is prevented by PI3-kinase inhibitors, suggesting that the maintenance of PI3-kinase activity is essential for IL-1-induced translocation. Indeed, in cell clones stably transfected with Y479F receptor mutant, in which the binding of the enzyme to the activated receptor is blocked, IL-1-induced PI3-kinase translocation to the nucleus is completely prevented. These data suggest that PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation.

Base Sequence↗
PubMed1998

Phosphatidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor I.

Interleukin 1 (IL-1) delivers a stimulatory signal which increases the expression of a set of genes by modulating the transcription factor NF-kappaB. The IL-1 receptors are transmembrane glycoproteins which lack a catalytic domain. The C-terminal portion of the type I IL-1 receptor (IL-IRI) is essential for IL-1 signalling and for IL-1 dependent activation of NF-kappaB. This portion contains a putative phosphatidylinositol 3-kinase (PI 3-kinase) binding domain (Tyr-E-X-Met), which is highly conserved between the human, mouse and chicken sequences, as well as the related cytoplasmic domain of the Drosophila receptor Toll. This observation prompted us to investigate the role of PI 3-kinase in IL-1 signalling. Here we report evidence that PI 3-kinase is recruited by the activated IL-IRI, causing rapid and transient activation of PI 3-kinase. We also show that the receptor is tyrosine phosphorylated in response to IL-1. Expression of a receptor mutant lacking the putative binding site for p85 demonstrates that Tyr479 in the receptor cytoplasmic domain is essential for PI 3-kinase activation by IL-1. Our results indicate that PI 3-kinase is likely to be an important mediator of some IL-1 effects, providing docking sites for additional signalling molecules.

Binding Sites↗
PubMed1998

Voltage-activated sodium currents in a cell line expressing a Cu,Zn superoxide dismutase typical of familial ALS.

The whole-cell configuration of the patch-clamp recording was used to study the voltage-dependent Na+ currents in a model system for the familial form of amyotrophic lateral sclerosis (ALS) associated with mutations in Cu,Zn superoxide dismutase. Here we report that the amplitude of voltage-gated Na+ currents is significantly reduced in cell lines expressing mutant Cu,Zn superoxide dismutase G93A when compared with the parental, untransfected cell line and to a cell line expressing the wild-type enzyme. This effect is associated with a shift toward positive values of the steady-state inactivation curve of the Na+ currents. These results indicate that expression of a Cu,Zn superoxide dismutase typical of patients affect with familial ALS influence the functionality of the voltage-dependent Na+ channels; this effect may contribute to the pathogenesis of the disease.

4-Aminopyridine↗
PubMed1997

Expression of a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells.

We have set up a model system for familial amyotrophic lateral sclerosis (FALS) by transfecting human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type human Cu,Zn superoxide dismutase (Cu,ZnSOD) or a mutant of this enzyme (G93A) associated with FALS. We have tested mitochondrial function and determined cytosolic Ca2+ concentration in control cells (untransfected) and in cells expressing either wild-type Cu,ZnSOD or G93A. We report that G93A induces a significant loss of mitochondrial membrane potential, an increased sensitivity toward valinomycin and a parallel increase in cytosolic Ca2+ concentration. The above phenomena are not related to total Cu,ZnSOD content and activity in the cell.

Amyotrophic Lateral Sclerosis↗
PubMed1997

[The estimation of the absorbed dose with wedge fields].

In the dose calculation at an arbitrary point in a water-equivalent homogeneous medium irradiated by an X-ray megavoltage wedged beam (w), several treatment planning systems (TPS) based on the Bently-Milan data processing procedure use algorithms which do not distinguish between wedged OF(s)w and open OF(s)o output factor or between field size dependent WF(s) and not WF wedge factor. This is equivalent to neglecting the difference between open (o) and wedged (w) fields both in relation to back-scattered radiation from secondary collimators to the beam monitor chamber and to scattered radiation generated by the water-phantom at the depth of measurement. The output factor can be expressed by: OF(s) = Sc(s)* Sp(s) where Sc(s) is the collimator scatter factor and Sp(s) is the phantom scatter factor. The approximation between wedged OF(s)w and open OF(s)o is thus equivalent to ignoring the fact that the insertion of the wedge in an open field modifies the back-scattered radiation from secondary collimators to the beam monitor chamber and the scattered radiation in the phantom. The lack of wedge factor's field size dependence WF(s) or the equivalent lack of wedged field output factor OF(s)w in the beam data installed in TPS is in appreciable source of systematic error in the calculation of the absorbed dose. This systematic uncertainty can be evaluated by measuring the wedge factor's field size dependence. In our study of WF(s) for 25-MV X-rays generated by our Linac "Saturne-43" (by GE), the relative wedge factor variation with respect to the reference value WF(so) ranges from (-.7%) for the smallest wedged field size (5 x 5) cm2 to (+2.6%) for the largest wedged field size (20 x 20) cm2. It is clear that the same relative variation reproduces itself identically as a systematic uncertainty in the calculation of the absorbed dose.

Absorption↗
PubMed1995

Production of reactive oxygen-derived species by redox reactions between Fe(II)cytochrome c and oxygen. A kinetic study.

In aerated water solutions Fe(II)Cytochrome c is slowly oxidized to Fe(III)Cytochrome c by molecular oxygen, from which superoxide anion radicals are produced (kobs = 2.7 x 10(-4) min-1 at 37 degrees C and pH = 7.3). The biological importance of this reaction has been evidenced by kinetic investigations in the presence of scavengers. In the presence of Superoxide dismutase the oxidation rate is strongly enhanced (kobs = 3 x 10(-3) min-1 at 37 degrees C). Catalase and mannitol reduce the rate constant values by 50% and 25% respectively either in the presence or in the absence of Superoxide dismutase: differences between rate constants correspond to the differences in stoichiometric redox ratios indicating that hydrogen peroxide and hydroxyl radicals are formed subsequently to the production of superoxide anion radicals.

Animals↗
PubMed1994

Phospholipids metabolism in platelets stimulated with collagen.

Collagen addition to platelets suspended in Calcium-free medium induces slow shape change followed by fast aggregates formation. Time courses of membrane phospholipids metabolism and arachidonic acid oxidative metabolism indicate that phospholipase C is the immediate target of the stimulus, and subsequently phospholipase A-2 is activated by synergistic action of released calcium and protein kinase C.

Arachidonic Acid↗