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Biomedical subjects

F Piazza

Publications and source records attributed to F Piazza.

At least 19 recordsLinked to original sources
PubMed2005

Slow energy relaxation of macromolecules and nanoclusters in solution.

Many systems in the realm of nanophysics from both the living and the inorganic world display slow relaxation kinetics of energy fluctuations. In this Letter we propose a general explanation for such a phenomenon, based on the effects of interactions with the solvent. Within a simple harmonic model of the system fluctuations, we demonstrate that the inhomogeneity of coupling to the solvent of the bulk and surface atoms suffices to generate a complex spectrum of decay rates. We show for myoglobin and for a metal nanocluster that the result is a complex, nonexponential relaxation dynamics.

Kinetics↗
PubMed2005

Anti-cooperativity in diffusion-controlled reactions with pairs of anisotropic domains: a model for the antigen-antibody encounter.

The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anti-cooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anti-cooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discussed.

Animals↗
PubMed2005

Dynamics of antibodies from cryo-electron tomography.

The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in molecular biology. In cryo-electron tomography experiments one takes several snapshots of a given biological macromolecule. In principle, a large enough collection of snapshots may then be used to calculate its equilibrium configuration in terms of the experimentally accessible degrees of freedom, and hence estimate its potential energy. Consequently, one could analyze the biological functions of biomolecules by directly accessing their dynamics. In this work, we analyze the results of cryo-electron tomography experiments on monoclonal murine IgG2a antibodies. With the aid of a novel software for image processing, we measure the equilibrium distribution of the angles which describe the configuration of the molecule. This helps us shed some critical light on recent results from X-ray crystallography. We then build a model of the antibody dynamics, which enables us to use the measured angular distribution in order to derive an explicit expression of the IgG potential energy. Finally, as a preliminary application of our results, we investigate the dynamical effects in the rate of formation of the antigen-antibody encounter complex. In particular, we suggest that the dynamics of antibodies operates in the direction of decreasing anticooperativity of the two antigen binding arms.

Animals↗
PubMed2004

Freezing immunoglobulins to see them move.

The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in different fields of molecular biology. In cryo-electron tomography experiments one may take several snapshots of a given biological macromolecule. In principle, a large enough collection of snapshots of the molecule may then be used to calculate its equilibrium configuration in terms of the experimentally accessible degrees of freedom and, hence, to estimate its potential energy. This information would be crucial in order to analyze the biological functions of biomolecules by directly accessing the relevant dynamical indicators. In this article, we analyze the results of cryo-electron tomography experiments performed on monoclonal murine IgG2a antibodies. We measure the equilibrium distribution of the molecule in terms of the relevant angular coordinates and build a mechanical model of the antibody dynamics. This approach enables us to derive an explicit expression of the IgG potential energy. Furthermore, we discuss the configuration space at equilibrium in relation to results from other techniques, and we set our discussion in the context of the current debate regarding conformation and flexibility of antibodies.

Cryoelectron Microscopy↗
PubMed2004

[Neurological and psychological evolution of adolescents with vertical transmission HIV infection].

AIM: Personal experience in a sample group of children with AIDS vertically transmitted followed from birth to adolescence (out of 56 cases with documented HIV infection, 9 who have reached the age of 13 have been studied) is presented. METHODS: The evaluation protocol includes: hematochemical, serological and virological tests to monitor the infectious status, as well as annual EEG, CT/MRI scan to detect anatomical alteration of CNS, neurological examination, intelligence test (WISC-R), interview and projective test (Blacky Pictures) to investigate emotional situation. RESULTS: As to the status of the disease, according to the CDC classification, 2 patients are asymptomatic, 2 paucisymptomatic, 2 with moderate symptoms, 2 severely symptomatic; 1 patient died due to progressive encephalopathy. Of the 2 severely symptomatic cases, 1 presents cortical atrophy and the other basal nuclei calcifications. No one of them has clinical signs of encephalopathy. All patients receive anti-retroviral medications. From tests and interviews emotional problem-emerge, future is seen as menacing and insidious, and defensive mechanisms are fragile and inconstant; denial can lead to a refusal of the pharmacological therapy; families themselves often refuse medical staff the consent to communicate the diagnosis fearing that this could induce unbearable anguish. CONCLUSIONS: It seems important that patients are informed, considering their capacity to make front to the communication, even if one must bear in mind that understanding and accepting the diagnosis may be a long and painful process requiring a long time.

Adolescent↗
PubMed2003

Hearing results in stapes surgery using two different prosthesis.

AIM OF THE STUDY: Evaluation of hearing results after implantation of a fluoroplastic-platinum piston (FP) and of a titanium piston (T) with a shaft diameter of respectively 0.6 mm and 0.4 mm, in cases of otosclerosis requiring stapedotomy. MATERIAL AND METHODS: Pre-operative and post-operative hearing results obtained after primary stapedotomy by implantation of 30 FP and 30 T performed by the same expert author (C.Z.) were reviewed. In each patient we evaluated pre- and post-operative auditory thresholds, as recommended. RESULTS: All patients of both groups showed a significant air-bone gap (ABG) improvement for all frequencies after surgery ( P < 0. 001). Post-operative ABG comparison between the two groups showed a better ABG for lower frequencies in the FP group and for higher frequencies in the T group, but the difference was not significant. No post-operative complications, including sensorineural hearing loss, were found. Bone conduction improvement was better in the FP group than in the T one and this difference was statistically significant at 1000 and 2000 Hz. There was no statistically significant difference in the post-operative outcomes between the two prosthesis. Better results of FP for lower frequencies suggest that an increase in diameter of the prosthesis results in a greater improvement in the hearing threshold at low frequencies, while a decrease of diameter results in a greater improvement in the hearing threshold at high frequencies, as indicated by previous international studies. CONCLUSION: Our data shows that titanium piston is a as good as fluoroplastic piston in stapes surgery for otosclerosis.

Adult↗
PubMed2002

Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4.

Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs. These findings demonstrate an important mechanism of immune regulation.

Antigen-Presenting Cells↗
PubMed2002

Improved liver tests and greater biliary enrichment with high dose ursodeoxycholic acid in early stage primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid is currently used for the treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not return to normal at this dose. Studies reported here were designed to test whether a higher dose of ursodeoxycholic acid than is currently used would induce still greater biliary enrichment of ursodeoxycholic acid and whether such enrichment would lead to still further improvement in liver tests in patients with early primary biliary cirrhosis. METHODS: A total of 20 patients with histologically proven primary biliary cirrhosis were enrolled. Patients had early stage primary biliary cirrhosis as serum bilirubin levels were normal and the Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of periods was randomized. Each treatment period lasted 3 months followed by a further 3 months during which a standard dose of ursodeoxycholic acid was given. At the end of each treatment period, liver tests were evaluated, and biliary bile acid pattern of duodenal bile was determined using high pressure liquid chromatography. RESULTS: Biliary bile acid became enriched in ursodeoxycholic acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase [p < 0.0001), aspartate aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver tests showed a stronger correlation with biliary concentrations of ursodeoxycholic acid than with the administered dose. CONCLUSIONS: In early primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more effective than doses currently recommended.

Alkaline Phosphatase↗
PubMed2001

The theory of APL.

Acute promyelocytic leukemia (APL) is associated with reciprocal and balanced chromosomal translocations always involving the Retinoic Acid Receptor alpha (RARalpha) gene on chromosome 17 and variable partner genes (X genes) on distinct chromosomes. RARalpha fuses to the PML gene in the vast majority of APL cases, and in a few cases to the PLZF, NPM, NuMA and STAT5b genes. As a consequence, X-RARalpha and RARalpha-X fusion genes are generated encoding aberrant fusion proteins that can interfere with X and/or RARalpha function. Here we will review the relevant conclusions and the open questions that stem from a decade of in vivo analysis of APL pathogenesis in the mouse in transgenic and knock-out models.

Animals↗
PubMed2001

Analytical performance of luminescent immunoassays of different format for serum daidzein analysis.

Two sensitive competitive-type solid-phase immunoassays for serum daidzein analysis have been developed and optimized. The first is a chemiluminescent enzyme immunoassay that uses black polystyrene microtiter wells in which daidzein-specific antibodies raised in rabbits are immobilized and a daidzein derivative is coupled to horseradish peroxidase (HRP) as a label. The HRP activity of the antibody-bound tracer is measured with an enhanced chemiluminescent system (luminol/H2O2/enhancer). The second immunoassay is based on the use of bovine serum albumin-daidzein derivative immobilized on microtiter plates and a secondary anti-rabbit IgG-Fc fragment conjugated with 4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA). Formation of the complex Eu3+-BCPDA enables time-resolved fluorescence-mode detection of the amount of antibody bound to the immobilized antigen. Both methods fulfilled all the requirements of accuracy and precision. The detection limit was the same for each method, 10 pg/well; this is better than that of other immunoassays. The specificity of the two methods was different, because of their competitive-type mechanisms. The performance of the chemiluminescence method is better, because the cross-reactivity of the main interfering compound (genistein) was 5%, compared with 25% for the time-resolved fluoroimmunoassay.

4-Butyrolactone↗
PubMed2001

Closed tympanoplasty in cholesteatoma surgery: long-term (10 years) hearing results using cartilage ossiculoplasty.

The aim of this retrospective study was to evaluate the long-term hearing results of using costal cartilage prostheses in ossicular chain reconstruction procedures in subjects operated on for a middle ear cholesteatoma with an intact canal wall tympanoplasty. Thirty-six patients (four with bilateral disease) followed up for 10 years who underwent an ossiculoplasty with a cartilage prostheses between January 1987 and December 1989 constituted the population studied. All the subjects underwent a staged intact canal wall tympanoplasty with mastoidectomy. Ossiculoplasty with total or partial chondroprosthesis was performed during the second stage. The long-term outcome was evaluated in terms of hearing according to the guidelines of the Committee on Hearing and Equilibrium (1995), and in terms of complications (anatomical and functional). In 18 patients a partial cartilage ossicular replacement prosthesis (PORP) was used, while in 22 a total cartilage ossicular replacement prosthesis (TORP) was used. In the PORP group the mean preoperative air-bone gap (ABG) was 22.4 dB hearing level (HL); before the second stage the ABG was 37.9 dB HL, at 2 years it was 12.1 dB HL, at 5 years 15.3 dB HL and at 10 years 15.8 dB HL. In the TORP group the mean preoperative ABG was 31.6 dB HL; before the second stage the ABG was 41.1 dB HL, at 2 years it was 14.4 dB HL, at 5 years 17 dB HL and at 10 years 18.5 dB HL. In both groups the number of cases with a postoperative ABG of < 20 dB HL remained stable (P > 0.05) over time. The failure rate was 17.5%, but only in 5% of cases was a functional revision needed. No cases of extrusion of the prostheses were encountered. The use of a chondroprosthesis is associated with functional results similar to those obtained by other authors. The efficacy of the prostheses remains stable over time and is associated with a very low rate of complications and failures. In this series no extrusion occurred and in no case did an infectious disease develop after cartilage transplantation.

Adolescent↗
PubMed2001

A rapid and sensitive method for methyl tert-butyl ether analysis in water samples by use of solid phase microextraction and gas chromatography-mass spectrometry.

This work describes a rapid and sensitive solid-phase microextraction (SPME) method for the isolation and analysis of methyl tert-butyl ether in water samples. Methyl tert-butyl ether was extracted from aqueous solutions using SPME fibre coated with Divinylbenzene/Carboxen/polydimethylsiloxane (30 microm film thickness) and analysed by GC-MS with a Hewlett Packard 6890/5973 system equipped with a capillary column coated with Vocol (30 m x 0.25 mm, 1.5 microm film thickness). Extraction parameters and chromatographic separation conditions were optimised. The developed method showed good analytical performance in terms of precision (RSD between 2% and 8%) and accuracy (mean recovery from 96% to 104%) with a detection limit of 14 ppt. Finally the method was applied to surface, tap and commercial mineral water samples, as well as snow samples collected along a busy road of Bologna town area. The median concentration of methyl tert-butyl ether in all these samples (0.05-0.4 ppb) was well below the maximum aqueous contamination levels in water adopted in the United States (13 ppb).

Carcinogens↗
PubMed2001

Distinct mRNA microarray profiles of tolerogenic dendritic cells.

Dendritic cells are crucial to the activation as well as suppression of the immune response. Previous reports have illustrated that APC interacting with antigen-specific T suppressor cells become tolerogenic, inducing T helper anergy. To characterize the molecular changes occurring in tolerogenic APC, the mRNA profile of KG-1 dendritic cells exposed to allospecific T helper and T suppressor cells were analyzed. This study now provides evidence that immature dendritic cells stimulated by T suppressor cells differentiate into mature dendritic cells with a distinct phenotype. The identification of Ts induced pathways of dendritic cell differentiation is critical to the development of new therapeutic strategies.

Antigens, Differentiation↗
PubMed2001

Facial nerve paralysis in temporal bone fractures: outcomes after late decompression surgery.

The aim of this paper was to address some of the unanswered questions regarding management of facial nerve paralysis in temporal bone fractures (TBF), such as the outcomes after late facial nerve decompression surgery. The study design was a retrospective review of a consecutive clinical series. Thirteen patients who underwent late decompression surgery for facial nerve paralysis due to TBF involving the perigeniculate ganglion region were analyzed. Patients were operated on 27-90 days after trauma. A transmastoid extralabyrinthine approach was used in all cases. Facial nerve-sheath slitting was performed routinely. Normal or subnormal facial nerve function (HB 1 or HB 2) was achieved in 7/9 cases (78%) evaluated at > or = 1 year after surgery. Good functional results were also obtained in two patients operated on 3 months after trauma. Bases on the outcomes observed in the present series, in patients unable to be operated on early, presenting 1 to 3 months with >95% denervation on EnoG, facial nerve decompression may have a beneficial effect.

Decompression, Surgical↗
PubMed2001

[Long-term audition results in patients with chronic endolymphatic hydrops after selective vestibular neurotomy and endolymphatic sac surgery].

The purpose of the present study was to evaluate the long-term auditory results in the ears of patients suffering from unilateral Ménière's disease (Md) who had undergone retrolabyrinthine vestibular neurotomy (RVN) associated with endolymphatic sac (ES) surgery. Retrospective evaluation was performed on 45 patients with unilateral Md who had undergone RVN between 1982-1997. All patients had previously been treated with medical therapy for at least 6 months without showing any response. The forms of ES surgery performed were as follows: simple ES decompression (ESD) in 15 patients, chronic endolymphatic mastoid shunt (EMS) using a sylastic sheet in 15 ears and ES exclusion (ESE) of the proximal section in the remaining 15 patients. Evaluation of the results was performed using the parameters indicated by the "Committee on Hearing and Equilibrium"--AAO-HNS 1995. Comparison of the average post-operative and preoperative PTAs revealed a worsening of 9.2 dB (sd: +/- 17.1) in the ESE group. This variation was statistically significant (p < 0.05). When the individual patients were evaluated, the PTA remained unchanged in 10 cases (67%) in the ESD group, in 13 (87%) in the EMS group and in 10 (67%) in the ESE group. In no case did hearing improve. Statistical analysis did not reveal any significant difference between the three groups of patients. Tinnitus, present prior to surgery in all patients, disappeared or improved in 6 patients (40%) in the ESD group, in 6 (40%) of the EMS group and in 5 (33%) of the ESE group. The differences between groups were not significant. The sensation of plugged ears, present prior to surgery in 11 patients in the ESD and EMS groups and in 13 patients in the ESE group disappeared or improved respectively in 9 (82%), 10 (91) and 11 (85%) of the patients. The 10 remaining patients who did not have the sensation of plugged ears prior to surgery did not refer its appearance after surgery. Again for this symptom the difference between groups was not significant. The results of this research would appear to indicate that in patients with Md, evolution of the hearing symptoms observed after RVN can be improved by applying an EMS. This finding must be validated in a larger sampling.

Adult↗
PubMed2001

[Acoustic neuroma: clinical-functional finding, results and surgical complication].

The present work provides clinical-functional findings, results and surgical complications observed in a consecutive series of 100 subjects with acoustic neuroma (AN). Analysis of the data has made it possible to draw some important conclusions. Compromised hearing is found in 90% of the ears affected by AN. Indeed the percentage of normal hearing in such cases does not exceed 5%. There is, however, no clear correlation between degree of hearing and tumor size. The symptoms of AN do not always present unilateral or asymmetrical hearing loss, unilateral tinnitus and/or dizziness. At times AN presents atypical symptoms and can even be asymptomatic. Sudden onset of unilateral hearing loss, acute vertigo, persistent monolateral tinnitus and even isolated symptoms of the V or VI cranial nerve should lead one to suspect AN. Only by applying the diagnosis of suspected AN in a large number of cases is it possible to lower the time gap between the onset of symptoms and the definitive diagnosis of AN, increasing the number of cases diagnosed while the AN is still small. Auditory brainstem responses (ABR) are still the means of choice for screening and following up subjects where AN is suspected. Reduced ABR sensitivity reported in the literature for intracanal ANs must induce further testing with magnetic resonance imaging with gadolinium in all subjects where an AN is suspected, even when the ABR is normal. Recording of transient evoked otoacoustic emissions in the presence and in the absence of contralateral white noise has proved to be a simple, inexpensive, non-invasive test for the diagnosis of suspected retrocochlear pathologies. A deficit in vestibular function is most frequently encountered when the AN is already quite large and an alteration in the smooth pursuit test is only found when the AN involves the brainstem. These data have led us to conclude that vestibular reflex studies do not play any role in early diagnosis of AN. Surgical exeresis is the treatment of choice in those cases where "watch and scan" (only hearing ear in the absence of neurological complications; AN < 0.5 cm in the ponto-cerebellar angle, particularly in elderly patients) is not indicated. The enlarged translabyrinthine approach is indicated in all cases of AN, no matter what the tumor size and extent of pre-operative hearing. Promptly and correctly treating intra and postoperative complications, most frequently encountered in patients with AN > 2 cm, reduces the mortality and morbidity to a minimum. Modern otological microsurgery and monitoring techniques make it possible to preserve the VIIth facial nerve in more than 90% of the ears, consequently preserving or nearly preserving normal VIIth nerve function 1 year after surgery in at least three out of four patients. No matter what approach is used, hearing can be preserved measurably in approximately 50% of the ears undergoing surgery and to a socially useful or nearly useful level in a significantly lower proportion of patients. In this regard the most satisfactory results are obtained when preoperative hearing is normal and the AN is < 2 cm.

Adolescent↗