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Biomedical subjects

M Russo

Publications and source records attributed to M Russo.

At least 19 recordsLinked to original sources

Postsynaptic enrichment of Eps8 at dendritic shaft synapses of unipolar brush cells in rat cerebellum.

Epidermal growth factor receptor pathway substrate 8 (Eps8) is a widely expressed multidomain signaling protein that coordinates two disparate GTPase-dependent mechanisms: actin reorganization via Ras/Rac pathways and receptor trafficking via Rab5. Expression of Eps8, the gene encoding the founding member of the Eps8 family of proteins, was found in cerebellum by virtual Northern analysis and in situ hybridization. Because the cerebellum has a well-known cellular architecture and is a favored model to study synaptic plasticity and actin dynamics, we sought to analyze Eps8 localization in rat cerebellar neurons and synapses by light and electron microscopy. Specificity of Eps8-antibody was demonstrated by immunoblots and in brain sections. In cerebellum, unipolar brush cells (UBCs) were densely Eps8 immunopositive and granule cells were moderately immunostained. In both types of neuron immunoreaction product was localized to the somatodendritic and axonal compartments. Postsynaptic immunostained foci were demonstrated in the glomeruli in correspondence of the synapses formed by mossy fiber terminals with granule cell and UBC dendrites. These foci appeared especially evident in the UBC brush, which contains an extraordinary postsynaptic apparatus of actin microfilaments facing synaptic junctions of the long and segmented varieties. Eps8 immunoreactivity was conspicuously absent in Purkinje cells and their actin-rich dendritic spines, in all types of inhibitory interneurons of the cerebellum, cerebellar nuclei neurons, and astrocytes. In conclusion, Eps8 protein in cerebellum is expressed exclusively by excitatory cortical interneurons and is intracellularly compartmentalized in a cell-class specific manner. This is the first demonstration of the presence of a member of the Eps8 protein family in UBCs and its enrichment at postsynaptic sites.

Adaptor Proteins, Signal Transducing↗

Rabbit allergens: a significant risk for allergic sensitization in subjects without occupational exposure.

BACKGROUND: Although rabbits are becoming popular as pets, data about the characteristics of allergic sensitization to rabbit allergens in patients without professional exposure are scarce. AIMS OF THE STUDY: To determine the characteristics of allergic sensitization to pet rabbits, and the role of direct and indirect exposure to rabbits and rabbit allergens in non-professionally exposed patients. METHODS: From among 1124 consecutive outpatients, we selected all subjects with an immediate skin reaction to rabbit dander. A clinical history including a careful evaluation of the modality of rabbit exposure, the results of skin-prick tests (SPTs) and total/specific IgE antibodies were recorded. The prevalence of rabbit ownership in the Naples area was also calculated. RESULTS: Among 753 SPT-positive patients, 20 (2.65%) were sensitized to rabbit dander (5 patients were mono-sensitized). Fifteen patients reported direct rabbit contact (7 were rabbit owners and 8 had occasional contact outside the home); 3 patients had indirect exposure through contact with rabbit owners and 2 patients denied any direct or indirect exposure. Rabbit mono-sensitized owners of pet rabbits had persistent (moderate-severe) symptoms. The prevalence of rabbit ownership is 1.56%. CONCLUSIONS: In susceptible not professionally exposed individuals, direct rabbit contact and, in some cases, indirect or no apparent exposure, may induce allergic sensitization to rabbit allergens. A progressive increase in rabbit sensitization (also by indirect exposure) may be expected as a consequence of the increase in rabbit ownership.

Adolescent↗

Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma.

BACKGROUND: The down regulation of protein p27(kip1) (p27) in most cases of thyroid cancer has relevant diagnostic and prognostic implications. However, the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma expresses more p27 than benign oxyphilic lesions do. AIM: To evaluate the mechanism underlying this difference in expression of p27. METHODS: Because high levels of cyclin D3 lead to p27 accumulation in cell lines and clinical samples of thyroid cancer, the immunocytochemical pattern of cyclin D3 in oxyphilic (n = 47) and non-oxyphilic (n = 70) thyroid neoplasms was investigated. RESULTS: In the whole study sample, there was a significant correlation between p27 and cyclin D3 expression (Spearman's r: 0.64; p<0.001). The expression of cyclin D3 and p27 was significantly higher in the oxyphilic variant of follicular carcinomas than in non-oxyphilic carcinomas (p<0.001). In the former, cyclin D3 overexpression and p27 accumulation were observed in a median of 75% and 55% of cells, respectively. In co-immunoprecipitation experiments, the level of p27-bound cyclin D3 was much higher in oxyphilic neoplasias than in normal thyroids and other thyroid tumours. CONCLUSION: These results show that increased p27 expression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma results from cyclin D3 overexpression.

Adenocarcinoma, Follicular↗

Ultrasonographic characteristics of early pregnancy failure in bitches.

Resorption of conceptuses was identified in 6 of 20 bitches examined daily from 15 to 35 d after the estimated pre-ovulatory LH surge. One or more conceptuses were resorbed in each bitch but there was continuation of the remaining pregnancy to term. This paper details the ultrasonographic embryological features of normal and resorbing conceptuses. Impending resorption may be predicted by detecting a delay in the time of development of a specific embryological feature or measuring a slow growth rate. Interestingly, there were greater number of conceptuses initially identified in bitches that subsequently resorbed than in those which did not.

Animals↗

Evaluation of acute perihematomal regional apparent diffusion coefficient abnormalities by diffusion-weighted imaging.

In this study, we investigated 40 patients (18 male, 22 female; mean age = 64.5 +/- 11.0; GCS = 9 to 14) with acute supratentorial spontaneous intracerebral hemorrhage (SICH) at admission by using a 1-tesla magnetic resonance imaging (MRI) unit equipped for single-shot echo-planar spin-echo isotropic diffusion-weighted imaging (DWI) sequences. All DWI studies were obtained within 48 hours after symptom onset. Regional apparent diffusion coefficient (rADC) values were measured in 3 different regions of interest (ROIs) drawn freehand on the T2-weighted images at b 0 s/mm2 on every section in which hematoma was visible: 1) the perihematomal hyperintense area; 2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim; 3) an area mirroring the region including the clot and perihematomal hyperintense area placed in the contralateral hemisphere. rADC mean values were higher in perihematomal hyperintense and in contralateral than in normal appearing areas (p < 0.001), with increased rADC mean levels in all regions examined. Our findings show that rADC values indicative of vasogenic edema were present in the perihematomal area and in normal appearing brain tissue located both ipsilateral and contralateral to the hematoma, with lower levels in non-injured areas located in the T2 hyperintense rim around the clot.

Cerebral Hemorrhage↗

Management of atrial fibrillation--what are the possibilities of early detection with home monitoring?

A large number of patients implanted with dual-chamber pacemakers exhibit symptoms of recurrent or new atrial fibrillation. Scheduling follow-up visits for every 6-12 months in this setting may be disadvantageous on three grounds. First, delayed information about the onset of atrial fibrillation does not allow an immediate reaction with pharmacological or dedicated pacing therapy. Second, the efficacy of the chosen therapy cannot be evaluated until the next scheduled follow-up. Third, real-time awareness of a significant atrial fibrillation burden is critical to use appropriate anticoagulation therapy for the prevention of thromboembolic events. The new Home Monitoring technology (Biotronik, Berlin) offers real-time transmission of diagnostic data stored in the pacemaker memory to the physician. This may represent a useful tool for the detection and treatment of patients with atrial fibrillation. Daily documentation of atrial rhythm via Home Monitoring allows a quick reaction to the onset of atrial fibrillation and real-time control of the therapeutic efficacy. The ongoing, international, randomized Home-PAT clinical trial aims at defining and quantifying the importance of Home Monitoring for the diagnosis and treatment of atrial fibrillation in patients with dual-chamber pacemakers.

Anti-Arrhythmia Agents↗

Role of B-type natriuretic peptide in cardiovascular state monitoring in a hemodialysis patient with primary amyloidosis.

BACKGROUND: Cardiac involvement occurs in up to 50% of patients with primary or A amyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic peptide (BNP) has been proposed as a guide for treatment of heart failure patients and as an index of myocardial dysfunction in patients with ALA. Data about BNP dosage for cardiovascular monitoring of patients with ALA on renal replacement therapy are lacking. CASE: A 64 year old Caucasian man was admitted because of nephrotic syndrome in July 2003. Renal diagnosis was ALA. Melphalan and prednisolone were given but renal function worsened and in April 2004 standard bicarbonate hemodialysis was started. In March 2004 thalidomide was added to his therapy. During the follow-up ejection fraction was stable and was 65% on the contrary E/A ratio gradually increased and overtook 1. BNP plasma levels were increased and the values recorded during the follow-up were: 2505 pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005. In September 2005 BNP was 3380 pg/mL. The patient was still alive after a follow-up longer than two years. CONCLUSION: In ALA patients a powerful prognostic role of BNP has been reported whose expression is increased in ventricular myocytes of patients with cardiac involvement. BNP level monitoring does not appear to be superior to standard echocardiography in evaluating cardiovascular status of uremic patients with ALA.

Amyloidosis↗

Stimulation, inhibition and death of macrophages infected with Trichophyton rubrum.

Trichophyton rubrum is the most common pathogen causing dermatophytosis, accounting for approximately 80% of the reported cases of onychomycosis. Since 90% of the chronic dermatophyte infections are caused by T. rubrum, it is likely that this pathogen must have evolved mechanisms that evade or suppress cell-mediated immunity. Several reports have highlighted the participation of phagocytes in the immune defense against fungi; however, few studies have addressed the role of these cells in dermatophytosis. In this study, we investigated the interactions of resident and peritoneal macrophages with T. rubrum. We show here that the interaction of T. rubrum conidia with resident macrophages results in the production of TNF-alpha and IL-10 but not IL-12 and nitric oxide. Infected macrophages down-regulated the expression of co-stimulatory molecules (CD80 and CD54). We also show that phagocytosis of T. rubrum conidia is inhibited by the addition of fungal exoantigens or mannan. Cytotoxicity assays indicated that after 8 h of conidia ingestion macrophage viability decreased drastically. Electron microscopy revealed that the ingested conidia grow and differentiate into hyphae inside macrophages leading to rupture of the macrophage membrane.

Animals↗

Infection with Anaplasma phagocytophilum in a seronegative patient in Sicily, Italy: case report.

BACKGROUND: Anaplasma phagocytophilum causes human granulocytic anaplasmosis (HGA) in humans, which has been recognized as an emerging tick-borne disease in the United States and Europe. Although about 65 cases of HGA have been reported in Europe, some of them do not fulfill the criteria for confirmed HGA. Confirmation of HGA requires A. phagocytophilum isolation from blood, and/or identification of morulae in granulocytes and/or positive PCR results with subsequent sequencing of the amplicons to demonstrate specific rickettsial DNA. Seroconversion or at least fourfold increase in antibody titers to A. phagocytophilum has been used as criteria for confirmed HGA also. CASE PRESENTATION: Infection with A. phagocytophilum was confirmed by PCR in a patient in Sicily, Italy, who had negative serology for A. phagocytophilum. A fragment of A. phagocytophilum 16S rDNA was amplified by two independent laboratories and sequenced from two separate patient's blood samples. The 16S rDNA sequence was identical in both samples and identical to the sequence of the A. phagocytophilum strain USG3 originally obtained from a dog. CONCLUSION: Infection with A. phagocytophilum was confirmed in a patient without a detectable antibody response against the pathogen. The results reported herein documented the first case of confirmed HGA in Sicily, Italy. These results suggested the possibility of human infections with A. phagocytophilum strains that result in clinical symptoms and laboratory findings confirmatory of HGA but without detectable antibodies against the pathogen.

Anaplasma phagocytophilum↗

Assessment of acute spontaneous intracerebral hematoma by CT perfusion imaging.

A single-section deconvolution-derived computerized tomographic perfusion imaging was performed in 45 patients (22 male and 23 female; mean age=69.89+/-10.07 years) with acute supratentorial spontaneous intracerebral hemorrhage. Mean rCBF and rCBV were lower in the hemorrhagic core than in the perihematomal low density area (p<0.001), and in the perihematomal low density area than in normal appearing brain parenchyma (p<0.001). Mean rMTT values were higher in perihematomal low density area than in normal appearing area (p<0.01) and in both hemorrhagic and perihematomal area than in controlateral ROI (p<0.001). There were no differences in rMTT mean values between hemorrhagic core and perihematomal area, as well as between normal appearing and controlateral areas. We found a concentric distribution of all CT perfusion parameters characterized by an improvement from the core to the periphery, with low perihematomal rCBF and rCBV values suggesting edema formation.

Acute Disease↗

The degree of serological sensitization to cat allergen in patients with or without cat at home.

BACKGROUND: The relationship between exposure to cat/dog in domestic environments and development of allergic sensitization to pet allergens is still controversial. OBJECTIVE: To test the role of indirect exposure to cat, we aimed to evaluate the amounts of cat specific IgE in sensitized subjects with or without cat at home. METHODS: Three hundred six adult patients with a previous diagnosis of allergic sensitization to cat allergens (by skin prick test) were enrolled for this study. Among 306 men and women sensitized to cat (and other allergens), 150 owned a cat for at least 10 years ( direct exposure) and 156 had never owned this animal (indirect exposure). An internal questionnaire specifically designed for the study was completed by the same allergists during the screening consultation: the results of skin prick tests, personal and clinical data, periods of symptoms and characteristics of cat ownership were carefully recorded. Specific IgE to cat extract was determined by the Pharmacia CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) and Immulite 2000 (Diagnostic Products Corporation, Los Angeles, USA) RESULTS: Although specific IgE to cat allergen were significantly higher in patients with cat at home (F = 42.77; p < 0.001), high amounts of these antibodies were found also in sera of subjects indirectly exposed to cats. DISCUSSION: The results of our study demonstrate that the degree of serological sensitization to cat allergens may be relevant also in subjects without any direct contact with cats (indirect exposure).

Air Pollution, Indoor↗

[Ocular toxoplasmosis: our experience].

Ocular toxoplasmosis can be a progressive and recurring disease that can threaten visual function. Retinochoroiditis develops gradually weeks to years after subclinical congenital toxoplasmosis; this is the preponderant form, which is frequently bilateral; with healing, white or dark-pigmented scars may result. Toxoplasmosis acquired in older children and adults rarely progresses to retinochoroiditis; it is generally unilateral. We report the results of a clinical study concerning 16 patients with ocular toxoplasmosis observed for the first time in the period from 1992 to 2004 and followed up until today. The patients came to the Department of Infectious Diseases of the Second University of Naples. We studied 16 patients, 10 of whom were females; 11 cases presented ocular signs of congenital toxoplasmosis, while in 5 cases ocular impairment was related to an acquired toxoplasmosis. Only one case of congenital toxoplasma chorioretinitis was symptomatic at birth: it was complicated by microphthalmia and strabismus, calcifications in the brain and epilepsy; 10 congenital cases were asymptomatic at birth and were recognized after several years because of a reactivation of infection. In 5 patients congenital chorioretinitis was bilateral, with presence of scars in the contralateral eye. The 5 cases of acquired toxoplasma retinitis were ascertained by anamnestic, serologic and ophthalmologic examinations; in 4 of them the lesion was typical and unilateral; the 5th case was a 6-year-old boy with acquired toxoplasma bilateral neuroretinitis. 13/16 cases of ocular toxoplasmosis were treated with the combination of pyrimethamine, sulfadiazine; they were followed up and re-treated if necessary. The therapy was curative in each case. Our experience confirms that late-onset retinal lesions and relapse can occur many years after birth but that the overall ocular prognosis is satisfactory when congenital damage is recognized early and treated appropriately. Prevention of congenital and acquired toxoplasmosis is very important in controlling ocular toxoplasmosis.

Adolescent↗

Evaluation of the nocebo effect during oral challenge in patients with adverse drug reactions.

The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance. The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure. We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions. Six hundred patients, seen in three different centres (Genoa, Naples and Verona) with a history of reactions to drugs, underwent a blind oral challenge with the administration of an indifferent substance and active drugs. The administration of an inert substance provoked untoward reactions in 54 patients (27%) in Verona, 60 (30%) in Naples and 48 (24%) in Genoa. The overall occurrence of nocebo effect was 27%. The majority of reactions were subjective symptoms (itching, malaise, headache etc), perceived as troublesome by all subjects. The occurrence was significantly higher in women than in men. Our data, collected in a large population, confirm that the nocebo effect occurs frequently in clinical practice. In managing adverse drug reactions through oral challenge the nocebo effect is mandatory to recognize false positive responses.

Adolescent↗

A method for multiple sequential analyses of macrophage functions using a small single cell sample.

Microbial pathogens such as bacillus Calmette-Guérin (BCG) induce the activation of macrophages. Activated macrophages can be characterized by the increased production of reactive oxygen and nitrogen metabolites, generated via NADPH oxidase and inducible nitric oxide synthase, respectively, and by the increased expression of major histocompatibility complex class II molecules (MHC II). Multiple microassays have been developed to measure these parameters. Usually each assay requires 2-5 x 10(5) cells per well. In some experimental conditions the number of cells is the limiting factor for the phenotypic characterization of macrophages. Here we describe a method whereby this limitation can be circumvented. Using a single 96-well microassay and a very small number of peritoneal cells obtained from C3H/HePas mice, containing as little as <=2 x 10(5) macrophages per well, we determined sequentially the oxidative burst (H2O2), nitric oxide production and MHC II (IAk) expression of BCG-activated macrophages. More specifically, with 100 micro l of cell suspension it was possible to quantify H2O2 release and nitric oxide production after 1 and 48 h, respectively, and IAk expression after 48 h of cell culture. In addition, this microassay is easy to perform, highly reproducible and more economical.

Animals↗

Absence of peripheral blood mononuclear cells priming in hemodialysis patients.

As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC) priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP) and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 +/- 141 vs 697 +/- 130 U/10(6) cells). Lipopolysaccharide (5 microg/ml) did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-a production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli.

Adult↗