Biomedical subjects

M D'Onofrio

Publications and source records attributed to M D'Onofrio.

At least 19 recordsLinked to original sources

PubMed2006

Focal liver lesions: sinusoidal phase of CEUS.

Ultrasound examination is the first imaging modality for hepatic study in neoplastic and chronic liver diseases. Focal liver lesions frequently cause diagnostic problems in terms of characterization, especially when small and hypoechoic to the rest of the parenchyma. Contrast--enhanced ultrasonography (CEUS) has shown its value in the characterization of focal liver lesions. This study assessed the value of the sinusoidal phase of CEUS with a second-generation contrast agent in the characterization of focal liver lesions to distinguish benign from malignant. Two hundred hepatic lesions with suspicious features at baseline ultrasound were prospectively studied with CEUS. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the sinusoidal phase in the characterization of benign versus malignant liver lesions were evaluated. Hypoechogenicity of the focal liver lesion, during the sinusoidal phase of CEUS, allowed the diagnosis of malignancy with a sensitivity of 85%, specificity of 88%, positive predictive value of 92%, negative predictive value of 77%, and diagnostic accuracy of 86%. The diagnostic confidence in the diagnosis of malignancy significantly increased, with receiver operating characteristic curve areas from 0.536 for baseline ultrasound to 0.902 for the sinusoidal phase of CEUS.

Adolescent↗

PubMed2006

Angiosonography in suspicious breast lesions with non-diagnostic FNAC: comparison with power Doppler US.

PURPOSE: The purpose of this study was to evaluate the accuracy of angiosonography in comparison with colour Doppler ultrasound (US) in the discrimination of suspicious breast lesions with nondiagnostic fine-needle aspiration cytology (FNAC). MATERIALS AND METHODS: Pre-operative Power Doppler US and angiosonography were prospectively performed in 20 suspicious breast lesions with non-diagnostic FNAC. A second-generation US contrast agent was utilised with a high-frequency transducer and a contrast-specific algorithm (low acoustic pressure CnTI). The enhancement characteristics of all lesions were analysed using qualitative and quantitative parameters obtained from time-intensity curves with the different imaging modalities. The final diagnosis was confirmed at pathology in all cases. Microvessel density (MVD) was assessed in the surgical specimen using CD34. RESULTS: The correct assessment of biological behaviour was achieved in all cases by angiosonography (sensitivity of 100%; specificity of 91%) and colour Doppler US (45% sensitivity; 78% specificity). MVD correlated with the biological behaviour. CONCLUSIONS: Angiosonography is more accurate than colour Doppler US in the correct assessment of biological behaviour of suspicious breast lesions.

Adult↗

PubMed2006

Doppler ultrasound and contrast-enhanced magnetic resonance angiography in assessing carotid artery stenosis.

PURPOSE: This study prospectively compares Doppler ultrasound (Doppler US) and contrast-enhanced magnetic resonance angiography (CE-MRA) with digital subtraction angiography (DSA) and endarterectomy findings to determine the accuracy in assessing carotid artery stenosis. MATERIALS AND METHODS: Thirty-two patients underwent carotid endarterectomy, 21 studied with Doppler US, CE-MRA and DSA and 11 with Doppler US and CE-MRA. In 41 carotid arteries, the degree of stenosis was analysed with Doppler US and CE-MRA and compared with DSA by using the Spearman rank correlation coefficient. Nine out of 32 endarterectomies were done using the eversion technique, and it was possible to compare Doppler US, CE-MRA and DSA with the specimen measurement. Twenty-three out of 32 endarterectomies were done using the standard technique, and the presence of ulcers was documented. RESULTS: There was a significant Doppler US/DSA (Rs=0.86; p<0.001) and CE-MRA/DSA (Rs=0.81; p<0.001) correlation for the degree of stenosis. The diagnostic accuracy of the three methods was the same (89%). Ulcers were most frequently seen at CE-MRA, with a diagnostic accuracy of 85%. CONCLUSIONS: These data suggest that endarterectomy on the basis of Doppler US and CE-MRA can be considered appropriate. CEMRA was the best noninvasive imaging modality to detect plaque ulceration.

Angiography, Digital Subtraction↗

PubMed2005

Familial basilar migraine associated with a new mutation in the ATP1A2 gene.

Basilar migraine (BM), familial hemiplegic migraine (FHM), and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by motor symptoms, which are absent in BM. Mutations in CACNA1A and ATP1A2 have been found in FHM. The authors detected a novel mutation in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and FHM may be allelic disorders.

Adolescent↗

PubMed2005

Search for Higgs bosons decaying into bb and produced in association with a vector boson in pp collisions at square root of s = 1.8 TeV.

We present a new search for H0V production, where H0 is a scalar Higgs boson decaying into bb with branching ratio beta, and V is a Z0 boson decaying into e+e-, mu+mu-, or nunu. This search is then combined with previous searches for H0V where V is a W+/- boson or a hadronically decaying Z0. The data sample consists of 106 +/- 4 pb(-1) of pp collisions at square root of s = 1.8 TeV accumulated by the Collider Detector at Fermilab. Observing no evidence of a signal, we set 95% Bayesian credibility level upper limits on sigma(pp --> H0V) x beta. For H0 masses of 90, 110, and 130 GeV/c2, the limits are 7.8, 7.2, and 6.6 pb, respectively.

Journal Article↗

PubMed2005

Measurement of charged-particle multiplicities in gluon and quark jets in pp collisions at square root of s = 1.8 TeV.

We report the first largely model independent measurement of charged particle multiplicities in quark and gluon jets, Nq and Ng, produced at the Fermilab Tevatron in pp collisions with a center-of-mass energy of 1.8 TeV and recorded by the Collider Detector at Fermilab. The measurements are made for jets with average energies of 41 and 53 GeV by counting charged particle tracks in cones with opening angles of theta(c) = 0.28, 0.36, and 0.47 rad around the jet axis. The corresponding jet hardness Q = Ejet theta c varies in the range from 12 to 25 GeV. At Q = 19.2 GeV, the ratio of multiplicities r = Ng/Nq is found to be 1.64+/-0.17, where statistical and systematic uncertainties are added in quadrature. The results are in agreement with resummed perturbative QCD calculations.

Journal Article↗

PubMed2004

PHCCC, a specific enhancer of type 4 metabotropic glutamate receptors, reduces proliferation and promotes differentiation of cerebellar granule cell neuroprecursors.

Exposure of immature rat cerebellar granule cell cultures to the type 4 metabotropic glutamate (mGlu4) receptor enhancer N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) reduced [3H]thymidine incorporation. Its action was sensitive to the growth conditions and was attenuated by two mGlu4 receptor antagonists. An antiproliferative action of PHCCC was also seen in cultures from wild-type, but not mGlu4, knock-out mice. At least in rat cultures, PHCCC was not neurotoxic and enhanced neuritogenesis. Although PHCCC reduced the increase in cAMP formation and phospho-AKT levels induced by forskolin, none of these transduction pathways significantly contributed to the reduction of [3H]thymidine incorporation. Interestingly, PHCCC reduced the expression of Gli-1, a transcription factor that mediates the mitogenic action of Sonic hedgehog. Finally, we treated newborn rats with PHCCC either intracerebrally (infusion of 5 nmol/2 microl in the cerebellar region once every other day) or systemically (5 mg/kg, i.p., once daily) from postnatal days 3-9. Local infusion of PHCCC induced substantial changes in the morphology of the developing cerebellum. In contrast, systemic injection of PHCCC induced only morphological abnormalities of the cerebellar lobule V, which became visible 11 d after the end of the treatment. These data suggest that mGlu4 receptors are involved in the regulation of cerebellar development.

Animals↗

PubMed2004

Inclusive search for anomalous production of high-pT like-sign lepton pairs in pp collisions at square root s = 1.8 TeV.

We report on a search for anomalous production of events with at least two charged, isolated, like-sign leptons, each with pT > 11 GeV/c using a 107 pb(-1) sample of 1.8 TeV pp collisions collected by the CDF detector. We define a signal region containing low background from standard model processes. To avoid bias, we fix the final cuts before examining the event yield in the signal region using control regions to test the Monte Carlo predictions. We observe no events in the signal region, consistent with an expectation of 0.63(+0.84)(-0.07) events. We present 95% confidence level limits on new physics processes in both a signature-based context as well as within a representative minimal supergravity (tanbeta = 3) model.

Journal Article↗

PubMed2004

Pure post-stroke cerebellar cognitive affective syndrome: a case report.

Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The 'cerebellar cognitive affective syndrome' is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event-related potentials showed abnormal P300. These data suggest a pure "cerebellar cognitive affective syndrome"and strengthen the hypothesis of cerebellar cognitive function modulation.

Aged↗

PubMed2001

Isolation and characterization of two peroxidases from Cucumis sativus.

Two heme peroxidases of 35.2 and 36.5 kDa have been isolated from cucumber (Cucumis sativus) peelings and characterized through electronic and 1H NMR spectra in the pH range 3.5-10.5. Their spectroscopic and catalytic properties, which are closely similar, are characteristic of highly homologous isoenzymes. Both proteins, as isolated, exist as a mixture of two ferric forms containing a high-spin and a low-spin heme in an approximately 2:1 molar ratio. The latter form likely contains a hydroxide ion axially coordinated to the heme iron and is proposed to be the result of partial irreversible protein inactivation due to the purification procedure. Both proteins in the reduced form are fully high-spin. The high-spin ferric form is sensitive to two acid-base equilibria with apparent pKa values of approximately 5 and 8.5, which have been assigned to the distal histidine and the arginine adjacent to it, respectively. These equilibria also affect the catalytic activity and the interaction with inorganic anions such as azide and fluoride. The reactivity of both proteins is closely similar to that of other plant peroxidases, primarily horseradish peroxidase; however, they also show spectroscopic properties similar to those of cytosolic ascorbate peroxidase. Therefore, overall, these two species show molecular, spectroscopic and catalytic features which are rather peculiar among plant peroxidases.

Azides↗

PubMed2001

Involvement of astrocytes in purine-mediated reparative processes in the brain.

Astrocytes are involved in multiple brain functions in physiological conditions, participating in neuronal development, synaptic activity and homeostatic control of the extracellular environment. They also actively participate in the processes triggered by brain injuries, aimed at limiting and repairing brain damages. Purines may play a significant role in the pathophysiology of numerous acute and chronic disorders of the central nervous system (CNS). Astrocytes are the main source of cerebral purines. They release either adenine-based purines, e.g. adenosine and adenosine triphosphate, or guanine-based purines, e.g. guanosine and guanosine triphosphate, in physiological conditions and release even more of these purines in pathological conditions. Astrocytes express several receptor subtypes of P1 and P2 types for adenine-based purines. Receptors for guanine-based purines are being characterised. Specific ecto-enzymes such as nucleotidases, adenosine deaminase and, likely, purine nucleoside phosphorylase, metabolise both adenine- and guanine-based purines after release from astrocytes. This regulates the effects of nucleotides and nucleosides by reducing their interaction with specific membrane binding sites. Adenine-based nucleotides stimulate astrocyte proliferation by a P2-mediated increase in intracellular [Ca2+] and isoprenylated proteins. Adenosine also, via A2 receptors, may stimulate astrocyte proliferation, but mostly, via A1 and/or A3 receptors, inhibits astrocyte proliferation, thus controlling the excessive reactive astrogliosis triggered by P2 receptors. The activation of A1 receptors also stimulates astrocytes to produce trophic factors, such as nerve growth factor, S100beta protein and transforming growth factor beta, which contribute to protect neurons against injuries. Guanosine stimulates the output of adenine-based purines from astrocytes and in addition it directly triggers these cells to proliferate and to produce large amount of neuroprotective factors. These data indicate that adenine- and guanine-based purines released in large amounts from injured or dying cells of CNS may act as signals to initiate brain repair mechanisms widely involving astrocytes.

Adenine↗

PubMed2001

HCV and GBV-c/HGV infection in HIV positive patients in southern Italy.

Flaviviridae-hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV)--and human immunodeficiency virus (HIV) frequently show similar modes of transmission. HCV and GBV-C/HGV infection was assessed in 134 consecutive patients with evidence of HIV infection, living in Campania, Italy. Data obtained from this cohort were compared with those obtained from 252 age- and sex-matched HCV infected patients without evidence of HIV infection (HCV control group). Following enzymatic immunoassays, samples were tested for the presence of HCV-RNA by RT-PCR. The HCV-RNA positive sera were genotyped by LiPA procedure. The prevalence of HCV infection in HIV patients was 19.40% and the largest group of HIV-HCV co-infected patients (84.62%) was represented by intravenous drug users (IVDU). The distribution of HCV genotypes in HIV-HCV patients was different, compared to that observed in HCV control group. HCV genotypes la (50%) and 3a (23.08%) were more frequently detected in HIV HCV patients, compared to HCV control group (5.16 and 5.56% for la and 3a, respectively). Conversely, HCV genotypes lb (55.70%) and 2a/2c (30.26%) were more represented in HCV control group, compared to HIV-HCV patients (15.38 and 0% for lb and 2a/2c, respectively). GBV-C/HGV seroprevalence was 41.04% in HIV patients and 6.54% in healthy control individuals. Differently from HCV, GBV-C/HGV infection did not correlate to a preferential risk behaviour in the HIV cohort. Comparative analysis of HCV and GBV-C/HGV infection indicates that the use of injecting drugs might play a key role in the epidemiology of HCV and, in particular, of la and 3a HCV genotypes, in HIV patients.

Adult↗

PubMed2001

Neuroprotection mediated by glial group-II metabotropic glutamate receptors requires the activation of the MAP kinase and the phosphatidylinositol-3-kinase pathways.

The mGlu2/3 receptor agonists 4-carboxy-3-hydroxyphenylglycine (4C3HPG) and LY379268 attenuated NMDA toxicity in primary cultures containing both neurons and astrocytes. Neuroprotection was abrogated by PD98059 and LY294002, which inhibit the mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI-3-K) pathways, respectively. Cultured astrocytes lost the ability to produce transforming growth factor-beta1 (TGF-beta1) in response to mGlu2/3 receptor agonists when co-incubated with PD98059 or LY294002. As a result, the glial medium was no longer protective against NMDA toxicity. Activation of the MAPK and PI-3-K pathways in cultured astrocytes treated with 4C3HPG or LY379268 was directly demonstrated by an increase in the phosphorylated forms of ERK-1/2 and Akt. Similarly to that observed in the culture, intracerebral or systemic injections of mGlu2/3 receptor agonists enhanced TGF-beta1 formation in the rat or mouse caudate nucleus, and this effect was reduced by PD98059. PD98059 also reduced the ability of LY379268 to protect striatal neurons against NMDA toxicity. These results suggest that activation of glial mGlu2/3 receptors induces neuroprotection through the activation of the MAPK and PI-3-K pathways leading to the induction of TGF-beta.

Amino Acids↗

PubMed2001

Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs.

Metabotropic glutamate (mGlu) receptors have been considered as potential targets for neuroprotective drugs, but the lack of specific drugs has limited the development of neuroprotective strategies in experimental models of acute or chronic central nervous system (CNS) disorders. The advent of potent and centrally available subtype-selective ligands has overcome this limitation, leading to an extensive investigation of the role of mGlu receptor subtypes in neurodegeneration during the last 2 years. Examples of these drugs are the noncompetitive mGlu1 receptor antagonists, CPCCOEt and BAY-36-7620; the noncompetitive mGlu5 receptor antagonists, 2-methyl-6-(phenylethynyl)pyridine, SIB-1893, and SIB-1757; and the potent mGlu2/3 receptor agonists, LY354740 and LY379268. Pharmacologic blockade of mGlu1 or mGlu5 receptors or pharmacologic activation of mGlu2/3 or mGlu4/7/8 receptors produces neuroprotection in a variety of in vitro or in vivo models. MGlu1 receptor antagonists are promising drugs for the treatment of brain ischemia or for the prophylaxis of neuronal damage induced by synaptic hyperactivity. MGlu5 receptor antagonists may limit neuronal damage induced by a hyperactivity of N-methyl-d-aspartate (NMDA) receptors, because mGlu5 and NMDA receptors are physically and functionally connected in neuronal membranes. A series of observations suggest a potential application of mGlu5 receptor antagonists in chronic neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer disease. MGlu2/3 receptor agonists inhibit glutamate release, but also promote the synthesis and release of neurotrophic factors in astrocytes. These drugs may therefore have a broad application as neuroprotective agents in a variety of CNS disorders. Finally, mGlu4/7/8 receptor agonists potently inhibit glutamate release and have a potential application in seizure disorders. The advantage of all these drugs with respect to NMDA or AMPA receptor agonists derives from the evidence that mGlu receptors do not "mediate," but rather "modulate" excitatory synaptic transmission. Therefore, it can be expected that mGlu receptor ligands are devoid of the undesirable effects resulting from the inhibition of excitatory synaptic transmission, such as sedation or an impairment of learning and memory.

Animals↗

PubMed2001

Therapeutic embolization of idiopathic renal arteriovenous fistula using the "stop-flow" technique.

PURPOSE: To present a case of massive idiopathic arteriovenous fistula (AVF) successfully treated with an endovascular procedure. CASE REPORT: A 42-year-old woman with microscopic hematuria was found to have a massive idiopathic renal AVF. Percutaneous embolization was undertaken using a dual approach to deliver an occluding balloon through the draining vein and an arterial access to selectively catheterize the aneurysmal afferent artery. With the balloon inflated to interrupt flow ("stop-flow" technique), acrylic glue was delivered precisely to occlude the lesion. Duplex scans at 12 months have documented continued complete occlusion of the anomalous communication. CONCLUSIONS: The dual arterial and venous approach with the "stop-flow" technique makes it possible to successfully treat idiopathic AVFs that have constant high-flow connections.

Adult↗

PubMed2000

mtDNA A3243G MELAS mutation is not associated with multigenerational female migraine.

The authors searched for mitochondrial DNA (mtDNA) A3243G mutation in peripheral blood leukocytes from female migraine patients with pure matrilinear history of migraine along two or three generations. The current study was designed to exclude any male transmission of the disease. The mutation was absent in all patients. We conclude that mtDNA A3243G mutation does not contribute to the pathogenesis of pure matrilinear multigenerational migraine with or without aura.

Adult↗

PubMed2000

Redox thermodynamics of low-potential iron-sulfur proteins.

The enthalpy and entropy changes associated with protein reduction (deltaHdegrees,(rc), deltaSdegrees,(rc)) were determined for a number of low-potential iron-sulfur proteins through variable temperature direct electrochemical experiments. These data add to previous estimates making available, overall, the reduction thermodynamics for twenty species from various sources containing all the different types of metal centers. These parameters are discussed with reference to structural data and calculated electrostatic metal-environment interaction energies, and redox properties of model complexes. This work, which is the first systematic investigation on the reduction thermodynamics of Fe-S proteins, contributes to the comprehension of the determinants of the differences in reduction potential among different protein families within a novel perspective. Moreover, comparison with analogous data obtained previously for electron transport (ET) metalloproteins with positive reduction potentials, i.e., cytochromes c, blue copper proteins, and HiPIPs, helps our understanding of the factors controlling the reduction potential in ET species containing different metal cofactors. The main results of this work can be summarized as follows.

Desulfovibrio↗

PubMed2000

Expression of neurotrophin receptors in normal and malignant B lymphocytes.

In order to define a cellular model suitable for studying, in vitro, the molecular properties and functions of neurotrophin receptors in human lymphocytes, TrkA, TrkB, TrkC and p75(NTR) expression was investigated in a panel of EBV immortalized lymphoblastoid (LCL) and Burkitt lymphoma-derived cell lines (BLs) compared to primary B lymphocytes by RT-PCR and flow cytometric analysis. Our data show that trkA and trkB are transcribed in most B cell lines of normal and malignant origin. For several of them, we also gained first evidence of trkC expression in B cells. All cell lines and primary B cells lack p75(NTR) expression. These data suggest that neurotrophin receptors expression in the B cell lines correlates to some extent with the phenotypic maturation stage and endogenous viral activity levels. Our data suggest that TrkA and TrkB, once activated, provide a partial rescue from apoptosis, whereas TrkC stimulates the progression through the cell cycle without affecting cell survival. Finally, the identification of a number of cell lines showing single expression of one of the Trk receptors has disclosed the availability of a cellular tool for further studies on their function, and mechanisms of signal transduction in the B cell moiety in the absence of p75(NTR).

Animals↗