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Biomedical subjects

S Fontana

Publications and source records attributed to S Fontana.

At least 19 recordsLinked to original sources
PubMed2006

Diffusion dynamics during the nucleation and growth of Ge/Si nanostructures on Si(111).

We report a low energy electron microscopy study of the relation between self-organized Ge/Si(111)nanostructures and their local environment. By comparison with Monte Carlo simulations, three-dimensional islands are shown to display a substantial tendency towards self-ordering. This tendency may result from the diffusive nature of the nucleation processes. The size of individual nanostructures does not significantly correlate with the distance between neighboring islands. Thus energetic factors are thought to govern the competition among coexisting nanostructures to capture the deposited mass.

Journal Article↗
PubMed2006

Treatment of thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange (PE) therapy in the 1970s. Based on clinical studies, daily PE has become the first-choice therapy since 1991. Recent findings may explain its effectiveness, which may include, in particular, the removal of anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers and/or supply of ADAMTS13 in acquired idiopathic or congenital TTP. Based on currently available data, the favoured PE regimen is daily PE [involving replacement of 1-1.5 times the patient's plasma volume with fresh-frozen plasma (FFP)] until remission. Adverse events of treatment are mainly related to central venous catheters. The potential reduction of plasma related side-effects, such as transfusion-related acute lung injury (TRALI) or febrile transfusion reactions by use of solvent-detergent treated (S/D) plasma instead of FFP is not established by controlled clinical studies. Uncontrolled clinical observations and the hypothesis of an autoimmune process in a significant part of the patients with acquired idiopathic TTP suggest a beneficial effect of adjunctive therapy with corticosteroids. Other immunosuppressive treatments are not tested in controlled trials and should be reserved for refractory or relapsing disease. There is no convincing evidence for the use of antiplatelet agents. Supportive treatment with transfusion of red blood cells or platelets has to be evaluated on a clinical basis, but the transfusion trigger for platelets should be very restrictive. Further controlled, prospective studies should consider the different pathophysiological features of thrombotic microangiopathies, address the prognostic significance of ADAMTS13 and explore alternative exchange fluids to FFP, the role of immunosuppressive therapies and of new plasma saving approaches as recombinant ADAMTS13 and protein A immunoadsorption.

ADAM Proteins↗
PubMed2006

Validation of rt-PCR assays for molecular characterization of porcine teschoviruses and enteroviruses.

Porcine enteroviruses (PEVs) and teschoviruses (PTVs) are described as causative agents of neurological disorders, fertility disorders and dermal lesions of swine. Difficulties in the serological detection of these viruses may lead to a significant underestimation of infections with clinical symptoms. With the recent availability of genome sequence data for all the serotypes, molecular diagnosis is a possibility. The present study describes a new approach to molecular 'serotyping' of PTVs and PEV-B viruses, involving the amplification and sequencing of a genomic fragment of the VP1 coding region. A molecular characterization of Italian entero-teschovirus isolates was performed using a set of previously published and newly designed polymerase chain reaction primers. A total of 33 porcine isolates and 10 reference strains were analysed. Porcine enterovirus-B samples were first diagnosed as positive for enterovirus by amplification of the 5'-non-translated region. Samples were then typed by amplification and sequencing of a portion of the VP1 coding region. Porcine enterovirus-A and PTVs were detected by a published assay in the 5'-NC region that allows them to be differentiated according to the size of amplification product, using the same set of primers. For serotype characterization of PTV, we evaluated four different regions: the N terminus of the capsid protein VP2, the region encoding for RNA-dependent RNA polymerase, and the capsid VP1 and VP4 regions. The newly designed primers in the VP1 region was proved to be broad in range and suitable for serotype assessment and therefore constitute a useful diagnostic tool for molecular diagnosis of porcine teschovirus/enterovirus strains and for the study of molecular epidemiology and evolution of these viruses.

Animals↗
PubMed2005

Proteomic analysis of protein components in periodontal ligament fibroblasts.

BACKGROUND: Characterization of periodontal ligament (PDL) fibroblast proteome is an important tool for understanding PDL physiology and regulation and for identifying disease-related protein markers. PDL fibroblast protein expression has been studied using immunological methods, although limited to previously identified proteins for which specific antibodies are available. METHODS: We applied proteomic analysis coupled with mass spectrometry and database knowledge to human PDL fibroblasts. RESULTS: We detected 900 spots and identified 117 protein spots originating in 74 different genes. In addition to scaffold cytoskeletal proteins, e.g., actin, tubulin, and vimentin, we identified proteins implicated with cellular motility and membrane trafficking, chaparonine, stress and folding proteins, metabolic enzymes, proteins associated with detoxification and membrane activity, biodegradative metabolism, translation and transduction, extracellular proteins, and cell cycle regulation proteins. CONCLUSIONS: Most of these identified proteins are closely related to the extensive PDL fibroblasts' functions and homeostasis. Our PDL fibroblast proteome map can serve as a reference map for future clinical studies as well as basic research.

Adolescent↗
PubMed2004

Implementation of the JACIE standards for a haematopoietic progenitor cell transplantation programme: a cost analysis.

The purpose of the present project was to analyse the costs incurred by the implementation of JACIE standards at a University Hospital with 1000 beds, performing some 40 autologous transplants per year. The cost analysis was performed on the basis of a prospective assessment of the time spent by all staff members involved with the implementation over a 14-month period of the quality management system (QMS) required by the JACIE standards. Two physicians worked on JACIE Section A (management=82 h), one physician and two nurses for section Ba (clinical unit adults=125.75 h), two physicians and three nurses for section Bp (clinical unit paediatrics=206 h), one physician, two nurses and one technician for section C (progenitor cell collection facility=105.75 h), and one physician and two technicians for section D (progenitor cell processing facility=426 h). The total time spent on the project amounted to 945.5 h with a total salary cost of \[euro]150 000. We concluded that implementation of the JACIE standards was accomplished within a 14-month period with a financial impact of approximately \[euro]150 000. The impact on quality parameters (eg clinical and laboratory end points, side effects) on HPC transplantation will be assessed in a second report after the first year of practical implementation.

Academic Medical Centers↗
PubMed2004

Interaction between natural killer and dendritic cells: the role of CD40, CD80 and major histocompatibility complex class i molecules in cytotoxicity induction and interferon-gamma production.

This study focuses on the differential role of CD40 and CD80 costimulatory molecules and major histocompatibility complex class I (MHC-I) antigens in the regulation of the interplay between dendritic cells (DCs) and interleukin (IL)-2-activated human natural killer (NK) lymphocytes. Our data indicate that CD40 and CD80 molecules might play a preferential role in the induction of cytotoxic function but not in the interferon-gamma(IFN-gamma) production by human IL-2-activated NK effectors in the presence of autologous and allogeneic DCs. In addition, a critical role of CD94-dependent MHC-I recognition in the regulation of both IFN-gamma production and target cell lysis was shown in the functional interaction between NK and DCs.

B7-1 Antigen↗
PubMed2004

Plasma adrenomedullin concentrations in patients with renovascular or malignant hypertension.

AIM: The aim of the present study was to investigate the behaviour of plasma adrenomedullin (AM), a hypotensive peptide, in patients with malignant (MHT) and renovascular hypertension (RVH), 2 pathologic conditions in which renin-angiotensin system (RAS) is activated and to compare them with those in essential hypertensive patients (EHT) and normotensive subjects (NS). METHODS: Three groups of hypertensive patients have been studied: group 1 (4 patients with MHT), group 2 (10 patients with RVH), group 3 (24 patients with EHT) and 21 patients NS were enrolled as controls. In all patients, 10 ml vein blood samples were collected and AM was measured with specific radioimmunoassay. RESULTS: As expected, the plasma renin activity (PRA) levels in the RVH and MHT patients were significantly higher (p<0.0001) respect to NS and EHT. The mean plasma AM (+/-SD) concentrations in EHT (22.5+/-9.1 pg/ml) and RVH (46.8+/-19.4 pg/ml) were significantly (p<0.0001) higher than those in NS (13.7+/-6.1 pg/ml). The plasma AM concentrations were further elevated in MHT patients (107+/-12.3 pg/ml) and were significantly higher (p<0.0001) than those in EHT and RVH patients. In the MHT patients the elevated plasma AM levels, similarly to blood pressure and PRA values, declined after antihypertensive treatment (36.8+/-5.7 pg/ml; p<0.01). CONCLUSION: In conclusion, the findings demonstrated that the plasma AM concentrations were increased in proportion to the severity of arterial hypertension. RAS was activated in patients with MHT and RVH suggesting that activation of this system may contribute to increased in the plasma levels of AM.

Adrenomedullin↗
PubMed2002

Leptin as a novel therapeutic target for immune intervention.

The recent cloning of the leptin (obese, ob) gene has determined fundamental insight into the understanding of the regulation of food intake, basal metabolism and reproductive function. Leptin, mainly secreted by adipocytes, belongs to the helical cytokine family and its plasma concentrations correlate with fat mass and respond to changes in energy balance. Initially, leptin was considered as an anti-obesity hormone, but experimental evidence has also shown pleiotropic effects of this molecule on hematopoiesis, angiogenesis, lymphoid organ homeostasis and T lymphocyte functions. More specifically, leptin links the pro-inflammatory T helper (Th)-1 immune response to the nutritional status and the energy balance. Indeed, decreased leptin concentrations during conditions of food deprivation lead to impaired immune capabilities. This review focuses on the potential therapeutic utilities for agents that manipulate the leptin-adipocyte axis and discusses novel strategies for an immune intervention in pathologic conditions.

Animals↗
PubMed2001

Development and validation of a high-performance liquid chromatography-tandem mass spectrometry assay for the determination of sanfetrinem in human plasma.

A rapid, selective and accurate high-performance liquid chromatography-tandem mass spectrometry assay for the quantification of sanfetrinem in human plasma has been developed and validated. The performance of manual and automated sample preparation was assessed; 50 microl of plasma sample was deproteinized with acetonitrile, followed by dilution with water and injection onto the LC system. Chromatographic separation was achieved on a Phenomenex Luna C18(2), 50x2.0 (5 microm) column with a mobile phase consisting of water-acetonitrile with 0.1% formic acid followed by detection with a Perkin-Elmer API3000 mass spectrometer in multiple reaction monitoring mode. The lower limit of quantification was improved by five times compared to the UV method previously reported. A range of concentration from 10 ng/ml to 5 microg/ml was covered. The method was applied to the quantification of sanfetrinem in human plasma samples from healthy volunteers participating in a clinical study.

Anti-Bacterial Agents↗
PubMed2001

Requirement for leptin in the induction and progression of autoimmune encephalomyelitis.

Recent evidence indicates that leptin modifies T cell immunity, and may provide a key link between nutritional deficiency and immune dysfunction. To study the influence of leptin on autoimmunity, susceptibility to experimental autoimmune encephalomyelitis induced by immunization with a myelin-derived peptide was examined in leptin-deficient, C57BL/6J-ob/ob mice, with or without leptin replacement, and in wild-type controls. Leptin replacement converted disease resistance to susceptibility in the C57BL/6J-ob/ob mice; this was accompanied by a switch from a Th2 to Th1 pattern of cytokine release and consequent reversal of Ig subclass production. Our findings suggest that leptin is required for the induction and maintenance of an effective proinflammatory immune response in the CNS.

Adoptive Transfer↗
PubMed2001

Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males.

SJL (H-2s) female mice are more susceptible than males to experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin-derived peptides. The reasons for this sexual dimorphism are unclear, but may include such factors as sex-related differences in immune responsiveness, hormonal effects and sex-linked genetic factors. Recent evidence indicates that leptin modifies T cell immunity promoting T helper (Th) 1 pro-inflammatory immune responses. Circulating leptin levels show a marked sexual dimorphism, being higher in females than in males. In the present study, we investigated whether leptin treatment altered the course of relapsing-remitting EAE, induced by the proteolipid protein peptide (PLP(139-151)), in SJL susceptible females and EAE-resistant males. Administration of leptin to female SJL mice before or after disease onset significantly worsened the disease, with a concomitant increase in the PLP(139-151)-specific delayed-type hypersensitivity (DTH) reactivity and in vitro IFN-gamma secretion. Leptin treatment at priming with antigen or before disease onset rendered male SJL mice susceptible to EAE, with the appearance of PLP(139-151)-specific DTH reactivity and a switch from a Th2 to Th1 pattern of cytokine release. Our findings indicate that leptin administration to susceptible females resulted in a more severe disease, and that reduced leptin levels in male SJL mice may contribute to the gender-related differences in the induction phase of EAE.

Amino Acid Sequence↗
PubMed2001

Circadian rhythm of hunger sensation in obese patients: effects of a short-term, moderately hypocaloric diet with a substitutive meal.

This investigation deals with the circadian rhythm (CR) of hunger sensation (HS) in obese patients before and after a four-week, moderately hypocaloric diet with a substitutive meal. The study was performed on 25 non-diabetic obese patients (5 males and 20 females, mean age: 39.7 +/- 7, mean BMI: 27.9 1.4 Kg/m2), whose obesity was not associated with impaired glucose tolerance (IGT), binge eating, nor endocrine diseases. Their daily HS profile (orexigram) was analysed chronobiometrically. The moderately hypocaloric diet with a substitutive meal reduced the daily HS by about 10% by the fourth week. This reduction was apparently due to a tonic and amplitude modulation of the HS CR and was not accompanied by its disruption. No conclusions, however, could be drawn with regard to its orectic and clinical effects beyond four weeks.

Adult↗
PubMed2001

Zymographic analysis of circulating and tissue forms of colon carcinoma gelatinase A (MMP-2) and B (MMP-9) separated by mono- and two-dimensional electrophoresis.

Gelatinase A (MMP-2) and gelatinase B (MMP-9) play a key role in the proteolytic cascade leading to ECM degradation during invasion and metastasis. The enzyme activity is regulated both at the intra- and extra-cellular level. Extracellular regulation is achieved mainly through the balance between proenzyme activation and inhibition, which appears to be altered in cancer patients. One of the mechanisms of MMP inhibition is the binding of the enzymes to appropriate tissue inhibitors (TIMP). In the recent literature, it has been suggested that MMP-2 and/or MMP-9 are indeed over-produced in many carcinomas, while the identity of the various enzymatic forms (latent, activated and enzyme/inhibitor complexes) remains to be elucidated. In this study we have analyzed the circulating forms of MMP-9 and MMP-2 in serum samples of patients with colon carcinoma, as well as the enzymatic activities present in tissue extracts from surgical fragments (primary tumor and its paired healthy tissue). Proteins were separated by means of mono-dimensional or bidimensional electrophoresis, and the enzymes detected by gelatin zymography and immunological assays. The results of densitometric analyses demonstrate that proMMP-9, but not proMMP-2, is significantly higher in the oncologic sera vs. the normal sera. In addition, several oligomeric circulating and tissue forms of MMP-9 are preferentially found in the oncologic samples, both in mono- and second-dimension zymograms. The activated forms of MMP-2 and MMP-9 are uniquely present in the primary tumor extracts, thus confirming the involvement of the tissue microenvironment in gelatinase activation and function.

Adult↗
PubMed2001

Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor-cleaving protease.

Complete deficiency of von Willebrand factor-cleaving protease (VWF-cp) has recently been identified as a pathogenetically important factor for thrombotic thrombocytopenic purpura (TTP). Microangiopathic haemolytic anaemia (MAHA) with thrombocytopenia in patients with metastasizing neoplasms is clinically similar to TTP, however, the pathogenesis of the condition is unclear. Partial deficiency of VWF-cp in metastasizing malignancy has recently been reported in patients without MAHA. Our study shows normal or subnormal VWF-cp activity in four patients with metastasizing neoplasia-associated MAHA but, in contrast to classical TTP, no complete deficiency of VWF-cp despite the full clinical picture of MAHA.

ADAM Proteins↗
PubMed2001

The fine specificity of human T cell lines towards myelin basic protein peptides in southern Italian multiple sclerosis patients.

We studied the relationship between the HLA specificities associated with multiple sclerosis (MS) susceptibility in southern Italy and the reactivity of the human myelin basic protein (hMBP) immunogenic peptides 84-98 and 143-168, using short-term T-cell lines established from 9 MS patients and from 8 healthy individuals. In our population, DR15 was significantly associated with MS (34.9% in MS versus 13.7% in healthy controls, P < 0.05). This result is in agreement with the association found in northern Europe, but not with data obtained in a population from the island of Sardinia (Italy). In MS patients the frequency of reactive T-cell lines (TCL), tested for fine specificity against the immunodominant hMBP peptides 84-98 and 143-168, was increased for the hMBP 143-168 peptide (P < 0.05) but not for the 84-98 peptide. Although this reactivity was higher in DR15+ MS patients than in DR 15- MS patients, it seemed not to be associated with DR15 specificity in the MS population. Furthermore, there were no significant differences in frequency of reactive TCL to hMBP peptide 84-98 in DR15-positive or DR15-negative MS patients. Consequently, it appears that peptide 84-98, considered as a relevant autoantigen, is not implicated in the pathogenesis of MS in our population from southern Italy.

Autoantigens↗
PubMed2001

Is melatonin circadian rhythm a physiological feature associated with healthy longevity? A study of long-living subjects and their progeny.

The study investigates the circadian rhythm (CR) of urinary 6-sulphatoxy-melatonin (aMT6s) in long-living (longevous) subjects and their progeny. The aim is to detect whether or not the melatonin CR is a physiological feature associated with healthy longevity. The aMT6s CR was investigated in 10 longevous subjects, 8 of their children and 9 of their grandchildren, all in good health. Control data were obtained respectively from 13 adult subjects and 9 young subjects, in good health, but characterized by a negative family history for longevity. All the subjects were born and living in the same city. The study was performed in the summer of 1996. The aMT6s CR was found to persist in longevous subjects, being characterized by a lower mesor and amplitude. The aMT6s CR was found not to show properties consistently different in children and grandchildren as compared respectively to their adult and young controls. Because of its preservation in longevous subjects, it can be argued that the melatonin CR is a physiological feature associated with healthy longevity. Because of the comparability of aMT6s CR in children and grandchildren, with respect to their controls without a positive family history of longevity, it can be argued that the melatonin CR is not a marker that can be used for an earlier identification of the candidates for longevity.

Adult↗