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Biomedical subjects

M Falconi

Publications and source records attributed to M Falconi.

At least 37 records · Page 2Linked to original sources
PubMed2003

Effect of interferon on human thymus microenvironment.

Interferon, a thymic immunostimulator, was used with the aim of assessing the importance of adrenergic nerve fibers (ANF) and/or AChE-positive nerve fibers (AChENF) in the regulation of some immunological functions in humans. Thymic normal control fragments and/or thymic fragments of immunostimulated patients were removed during surgical biopsies. Thymic slices were stained with eosin-orange (for the recognition of microanatomical details of the microenvironment) and with Bodian's method for staining of nerve fibers. Histofluorescence microscopy was employed for staining ANF. AChENFs were detected by means of the direct-coloring thiocholine method. All images were submitted to quantitative morphometrical analysis and statistical comparisons of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates of the same patients. Treatment with interferon induces substantial changes in the thymic microenvironment, on ANF, on AChENFs and on the total amount of proteins and noradrenaline in thymic tissue homogenates. In conclusion immunostimulation with interferon induces substantial changes in the whole thymus and in its microenvironment, involving both sympathetic and parasympathetic nerve fibers.

Adrenergic Agents↗
PubMed2003

High recurrence rate after atypical resection for pancreatic metastases from renal cell carcinoma.

BACKGROUND: Pancreatic metastases from renal cell carcinoma are rare but highly resectable. The aim of this study was to review a series of patients with this condition. METHODS: The study involved 22 consecutive patients with histologically proven pancreatic metastases from renal cell cancer. RESULTS: Seventeen of the 22 patients had surgery. No patient died but eight of the 17 patients had a postoperative complication. Median follow-up was 33 (range 1-96) months. The 24- and 60-month survival probabilities were 0.84 and 0.53 respectively. Five patients who did not undergo surgery had 24- and 60-month survival probabilities of 0.53 and 0.26 respectively. The difference between the two groups was significant (P = 0.040). CONCLUSION: Despite the slow development of these secondaries and their well encapsulated morphology, the high rate of recurrence after limited resection suggests that radical resection should be recommended.

Adult↗
PubMed2003

Carcinoma of pancreatic body and tail: are there improvements in diagnosis and treatment modalities over the past decade?

BACKGROUND AND AIM OF STUDY: The aim of the present study is to assess whether or not there has been improvement in the therapeutic strategy for body-tail pancreatic carcinoma over the past decade. PATIENTS AND METHODS: A total of 215 patients suffering from cytologically and histologically documented ductal carcinoma in the pancreatic body-tail, observed from 1990 to 1999, were analysed. Changes in tumour stage at diagnosis, in the percentage of patients treated surgically, in resectability rates and in the use of anticancer therapies over the years were sought. Survival curves were evaluated in relation to the treatments adopted. RESULTS: Over the 10-year period, no significant differences were observed with respect to the stage at diagnosis, resectability or type of surgery adopted. There was a significant increase in the percentage of unoperated patients (p < 0.0001) and, as expected, in the percentages of patients submitted to chemo- and/or radiotherapy (p < 0.0001). With the sole exception of tumour stage in the case of patients undergoing radiotherapy, a comparison between groups revealed no element of patient selection bias other than time. The survival of patients undergoing chemotherapy is significantly better, also at multivariate analysis, than that of patients not undergoing such therapy (13 vs. 5.8 months; p < 0.0001). CONCLUSIONS: There has been no change over the years in the direction of earlier diagnosis and the prognosis remains distinctly poor. More extensive use of anticancer therapies, however, has led to a significant increase in median survival. Radical resection, when possible, assures the longest survival.

Carcinoma, Ductal, Breast↗
PubMed2003

Prokaryotic Cu,Zn superoxide dismutases.

The Cu,ZnSODs (Cu,Zn superoxide dismutases) comprise a class of ubiquitous metalloenzymes that catalyse the dismutation of the superoxide radical anion into oxygen and hydrogen peroxide. The dismutation reaction involves two successive encounters of the superoxide anion with a catalytic copper centre hosted by the enzyme at the dead end of a narrow protein channel. Cu,ZnSOD is found in all eukaryotic species as a homodimeric enzyme of approx. 2x16 kDa. Cu,ZnSODs are also widely distributed in the prokaryotic phyla, and are found in the periplasmic space of bacterial pathogens, where they are likely to play a defensive role against extracellular oxidative stress, particularly with respect to phagocytic processes. The crystallographic structures of prokaryotic Cu,ZnSODs have shown that the core structural organization of the enzyme is based on a flattened antiparallel beta-barrel, composed of eight strands arranged in a Greek-key topological order, which usually forms a dimeric structure through the interaction of residues provided by beta-strands 4f and 5e with the 2,3 and 7,8 loops. The interface residues are arranged to form a closed ring, which surrounds a central cavity filled by water molecules that are arranged differently depending on the species. The interface variability of residues and solvent structure observed in bacterial enzymes permits fine tuning of the subunit association that results in the presence of monomeric and dimeric species, and confers a particular protein flexibility that gives rise to long-range communications between different region of the enzyme.

Catalysis↗
PubMed2003

A preliminary analysis of the morphology of lateral canals after root canal filling using a tooth-clearing technique.

AIM: This study used a modified tooth-clearing technique to allow observation of accessory canals following filling with a warm gutta-percha technique and one of two endodontic cements. METHODOLOGY: Ten extracted human maxillary molars with three roots were selected and divided into two equal groups of five teeth. Each group had 15 canals. Root canal preparation was performed with a modified double flared technique; irrigation with 5% NaOCl and lubrication with RC-Prep were used. The canals were then filled with gutta-percha and cement utilizing a warm vertical condensation technique in the apical third followed by thermo-mechanical compaction in the middle and coronal thirds. Pulp Canal Sealer or AH-Plus were used in the experimental groups. The teeth were demineralized with a modified buffered acid solution, cleared in methylsalicylate and examined under a stereomicroscope. Accessory canals were evaluated in the apical, middle and coronal thirds of each root canal and categorized as narrow or wide, following observation on four surfaces. The depth of penetration of gutta-percha and cement into lateral canals was scored using a 5-point system. RESULTS: Complete transparency of the roots was achieved. Accessory canals were detected in all specimens. In coronal ramifications, gutta-percha filled the empty spaces (coronal thirds, grades 3 and 4: 70.9% in AH-Plus group and 68.8% in Pulp Canal Sealer group). In the apical accessory canals, gutta-percha entered less frequently (apical thirds, grades 3 and 4: 17.9% in the AH-Plus group and 3.2% in the Pulp Canal Sealer group); cement without gutta-percha (grades 1 and 2) was present in 55.5% in the AH-Plus group and 38.7% of the Pulp Canal Sealer group. Analysis showed that AH-Plus cement resulted in significantly greater filling of the apical accessory canals compared to Pulp Canal Sealer. CONCLUSIONS: The modified tooth-clearing technique allowed observation of fine morphological details in all specimens. Effective gutta-percha filling was evident in most of the wide coronal lateral canals whilst the apical narrow ramifications were often incompletely filled by cement. Overall AH-Plus demonstrated better diffusion into lateral accessory canals compared to Pulp Canal Sealer.

Citrates↗
PubMed2003

Staging of digestive endocrine tumours using helical computed tomography and somatostatin receptor scintigraphy.

BACKGROUND: In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor scintigraphy (SRS) is considered the 'gold standard' imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. PATIENTS AND METHODS: Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. RESULTS: SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. CONCLUSIONS: Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.

Adolescent↗
PubMed2003

Outcome of open necrosectomy in acute pancreatitis.

Twenty percent of all acute pancreatitis patients present with necrotizing pancreatitis. Infected necrosis is responsible for 80% of deaths in the course of the disease though, thanks to antibiotic prophylaxis, the infection rate is decreasing. When infection occurs, the prognosis is poor, and the need for debridement and drainage of the necrosis is mandatory. The aim of this study was to review the most recent literature in order to present an update of open surgical management of infected necrosis.

Debridement↗
PubMed2002

Flexibility in monomeric Cu,Zn superoxide dismutase detected by limited proteolysis and molecular dynamics simulation.

Limited proteolysis by trypsin of monomeric Cu,Zn superoxide dismutase from Escherichia coli induces a specific cleavage of the polypeptide chain at the level of Lys60 located in the S-S subloop of loop 6,5 where, when compared to the eukaryotic enzyme, a seven-residues insertion, completely exposed to the solvent, is observed. This result suggests that this subloop is disordered and flexible, thus enabling binding and adaptation to the active site of the proteolytic enzyme. Indeed, molecular dynamics simulation indicates that the S-S subloop undergoes high fluctuations and that its high flexibility coupled to an high solvent accessibility can explain the specific bond selection of the protease. As a matter of fact, of the possible 14 solvent accessible proteolytic sites only the Lys60 flexible site is cleaved. High flexibility and solvent exposure are confirmed by the short water residence time for the residues corresponding to the cleavage site evaluated by molecular dynamics simulation. These experiments demonstrate that molecular dynamics simulation and limited proteolysis are complementary and unambiguous tools to identify flexible sites in proteins.

Amino Acid Sequence↗
PubMed2002

Dentin proteoglycans: an immunocytochemical FEISEM study.

Dentin proteoglycans are fundamental constituents of the dentin matrix and are distributed ubiquitously both in dentin and cement. They have several important functional properties; in particular, they have a fundamental role in the maintenance and the correct stabilization of collagen fibers. The use of phosphoric acid on dentin, as proposed in most common dental adhesive systems to establish a reliable bond, may affect the molecular structure of proteoglycans. The aim of this study was to evaluate, after the application of EDTA or phosphoric acid on dentin, the dentin proteoglycans with an immunocytochemical approach with high resolution SEM. For this purpose, dentin disks obtained from recently extracted human molars were etched with a 35% water solution of phosphoric acid for 15 s, 30 s, and 60 s. Control specimens were conditioned with EDTA. Specimens were immunolabeled with a monoclonal antibody antichondroitin sulfate and visualized with a gold-conjugated secondary antibody. Conditioning dentin with EDTA resulted in a distinct labeling of the proteoglycans, as visualized on branching fibrillar structures in the order of 10-20 nm. The use of 35% phosphoric acid on dentin revealed a coagulation of proteoglycans after etching for 15 s while a very low labeling signal was detectable after 30 s. No labeling was obtained after etching dentin with phosphoric acid for 60 s. These results suggest that the use of 35% phosphoric acid on dentin is able to produce significant structural modifications of the dentin proteoglycans even after short application times. Additionally, when applied on the dentin surface for more than 30 s, phosphoric acid produces a dramatic decrease in proteoglycans' antigenicity, probably due to structural modifications of the three-dimensional conformation of these molecules.

Dentin↗
PubMed2002

Review of the clinical, histological, and molecular aspects of pancreatic endocrine neoplasms.

Pancreatic endocrine neoplasms (PENs) are rare tumors, and little is known about their genetic and chromosomal alterations. Elucidation of the molecular events involved in PEN carcinogenesis has been hindered by the fact that PENs have been considered a single disease entity. The emergence of novel molecular characterization strategies has, however, made it apparent that these lesions exhibit diverse molecular fingerprints, which will facilitate the precise delineation of PEN prognosis, histopathology, and carcinogenesis.

Carcinoma, Islet Cell↗
PubMed2002

Evaluation of lanreotide effects on human exocrine pancreatic secretion after a single dose: preliminary study.

BACKGROUND: Total parenteral nutrition and somatostatin or analogues represent a consolidated therapeutic approach for external fistulas, a frequent complication of major pancreatic surgery. AIMS: To establish the effects of the somatostatin analogue lanreotide on exocrine pancreatic secretion. METHODS: Eight patients, undergoing pancreaticoduodenectomy for malignancy, were enrolled in the trial. The volume and composition of pancreatic secretion were evaluated after one single subcutaneous injection of lanreotide 0.5 mg or placebo in a randomised, double-blind cross-over trial. RESULTS: In the seven patients completing the study, the 24-h output volume was 208.6+/-41.3 and 253.9+/-72.4 ml after lanreotide and placebo, respectively. During the first 6 hours values were 48.1+/-14.7 and 77.6+/-21.4 ml (p=0. 02). No significant difference between treatments was detected in the qualitative composition of 24-h pancreatic secretion, although bicarbonate secretion remained lower after the active drug at all the observation intervals. Peak lanreotide levels were detected 15-30 min after drug injection. Clinical and laboratory tolerability was good. CONCLUSIONS: Lanreotide induced a statistically significant reduction in the output volume with respect to placebo in the first 6 hours after administration, but not thereafter. The present results encourage a new study to be undertaken in a larger sample and with a multiple dosing scheme of treatment.

Aged↗
PubMed2002

Temperature change within gutta-percha induced by the System-B Heat Source.

AIM: This study evaluated the temperature change within gutta-percha during the vertical compaction technique performed with a System-B Heat Source. METHODOLOGY: Extracted human teeth were prepared and divided in two equal groups depending on the apex diameter (group 1: 0.20-0.25 mm and group 2: 0.30-0.35 mm). Teeth were root treated with a combination of step-back and coronal flaring instrumentation using Gates Glidden burs and hand stainless steel K- and H-files. Two thermocouples were connected to the outer surface of the root: the first one was placed 2 mm apically from cement-enamel junction (CEJ) (point C); and the second one 1.5 mm from the apex (point A). The instrumented canals were filled with size F gutta-percha cones. All teeth were then immersed in a thermostatic bath at a constant temperature of 37 degrees C and warm vertical compaction was performed using a System-B Heat Source. delta T values were recorded by means of a digital thermometer connected to the thermocouples. RESULTS: Increments of temperature (delta T) recorded in point A revealed a mean value of 0.5 +/- 0.5 degree C for group 1 and 0.9 +/- 1.1 degrees C for group 2; delta T values recorded at point C gave a mean value of 4.1 +/- 1.7 degrees C for group 1 and 3.9 +/- 1.81 degrees C in group 2. No statistical difference was found between the groups, whilst a difference was present between the measurements at points A and C (P < 0.01). CONCLUSIONS: The use of the System-B Heat Source on root canals maintained at a constant body temperature by a thermostatic bath revealed that the increase of temperature of the gutta-percha at the apical third of the canal was negligible and that the compaction of the mass of the gutta-percha close to the apex was performed at body temperature. Minor changes in temperature of the outer surface of the root canals occurred, suggesting no danger for the periradicular tissues.

Analysis of Variance↗
PubMed2001

Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.

BACKGROUND: The role of adjuvant treatment in pancreatic cancer remains uncertain. The European Study Group for Pancreatic Cancer (ESPAC) assessed the roles of chemoradiotherapy and chemotherapy in a randomised study. METHODS: After resection, patients were randomly assigned to adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after 2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months). Clinicians could randomise patients into a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or into one of the main treatment comparisons (chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy). The primary endpoint was death, and all analyses were by intention to treat. Findings 541 eligible patients with pancreatic ductal adenocarcinoma were randomised: 285 in the two-by-two factorial design (70 chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); a further 68 patients were randomly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median follow-up of the 227 (42%) patients still alive was 10 months (range 0-62). Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without; hazard ratio 1.18 [95% CI 0.90-1.55], p=0.24). There was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66 [0.52-0.83], p=0.0005). Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Spectroscopic and molecular dynamics simulation studies of the interaction of insulin with glucose.

The interaction between monomeric insulin and monosaccharides has been investigated through circular dichroism, fluorescence spectroscopy and two dimensional nuclear magnetic resonance. CD spectra indicate that D-glucose interacts with monomeric insulin whereas D-galactose, D-mannose and 2-deoxy-D-glucose have a lower effect. Fluorescence emission was quenched at sugar concentrations of 5-10 mM. Titration with the different sugars produces a quenching of the tyrosine spectrum from which a binding free energy value for the insulin-sugar complexes has been evaluated. Transfer nuclear Overhauser enhancement NMR experiments indicate the existence of dipolar interactions at short interatomic distances between C-1 proton of D-glucose in the beta form and the monomeric insulin. Further, NMR total correlation spectra experiments revealed that the hormone is in the monomeric form and that upon addition of glucose no aggregation occurs. The interaction does not involve relevant changes in the secondary structure of insulin suggesting that the interaction occur at the side chain level. Molecular dynamics simulations and modeling studies, based on the dynamic fluctuations of potential binding moiety sidechains, argued from results of NMR spectroscopy, provide additional informations to locate the putative binding sites of D-glucose to insulin.

Binding Sites↗
PubMed2001

High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications.

A high resolution allelotype for nonfunctional pancreatic endocrine tumors (NF-PETs) has been generated by microsatellite analysis of DNA from 16 frozen cases, each probed with 394 markers. Two subgroups of NF-PETs were found. Seven cases showed frequent, large allelic deletions [loss of heterozygosity (LOH)] with an average fractional allelic loss (FAL) of 0.55, whereas nine cases showed a small number of random losses with a FAL of 0.15. Designated high or low FAL, respectively, these genetic phenotypes showed correlation with the ploidy status: high-FAL tumors were aneuploid, low-FAL were diploid. Chromosomes 6q and 11q showed LOH in >60% of cases. About 50% of cases had losses on 11p, 20q, and 21. Selected LOH analysis on an additional 16 paraffin-embedded NF-PETs confirmed the high frequency of 6q and 11q LOH. The allelotype of NF-PET is markedly different from that of either ductal or acinar tumors of the pancreas as well as from that of functional-PETs. Moreover, whereas deletions involving chromosome 11 also are a feature of functional-PETs, the involvement of chromosome 6q is characteristic of NF-PETs. Survival analysis showed that none of the single chromosomal alterations was associated with outcome, whereas ploidy status is an independent factor adding prognostic information to that furnished by the proliferative index measured by Ki-67 immunohistochemistry.

Adenoma, Islet Cell↗
PubMed2001

Role of disease-causing genes in sporadic pancreatic endocrine tumors: MEN1 and VHL.

Pancreatic endocrine tumors (PETs) occur in association with multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau (VHL) syndromes caused by germline alterations in MEN1 and VHL, respectively. It is thus expected that these genes will also be altered in a proportion of sporadic PETs. Indeed, MEN1 is altered in about 25% of nonfamilial PETs, although no mutations have been found in VHL. For all clinical subtypes, the frequency of allelic loss on chromosome arm 11q mirrors observed mutational frequencies, with the exception of nonfunctional tumors (NF-PETs), in which mutations have been reported in only 8% of cases. As allelic loss on 11q is the most frequent event found in these neoplasms, this low frequency is somewhat puzzling, particularly in light of the fact that most MEN1-associated PETs are nonfunctioning. To clarify the role of these genes in sporadic PETs, we analyzed 31 sporadic NF-PETs, nine insulinomas, and one VIPoma for alterations in MEN1 and VHL. As somatic mutations were observed in eight (26%) of the NF tumors and in one insulinoma, it would therefore appear unlikely that an additional tumor suppressor gene related to sporadic PET pathogenesis is located on 11q. One insulinoma also had a somatic mutation in VHL, and thus this gene may also be altered in these neoplasms, albeit in a small proportion of cases.

Genes, Tumor Suppressor↗
PubMed2001

Properties of purified cytosolic isoenzyme I of Cu,Zn-superoxide dismutase from Nicotiana plumbaginifolia leaves.

The isoenzyme I of cytosolic Cu,Zn-superoxide dismutase (SOD) from Nicotiana plumbaginifolia (tobacco) leaves has been purified to apparent homogeneity. The relative molecular mass of the native isoenzyme, determined by gel filtration chromatography, is about 33.2 kDa. SDS-polyacrylamide gel electrophoresis shows that the enzyme is composed of two equal subunits of 16.6 kDa The isolectric point, assayed by isoelectric focusing, in the pH range of 3.5-6.5, is 4.3. The enzyme stability was tested at different temperatures, pH, and concentration of inhibitors (KCN and H(2)O(2)). The catalytic constant (k(cat)) was 1.17 +/- 0.14 x 10(9) M(-1) s(-1) at pH 9.9 and 0.1 M ionic strength. The activation energy of the thermal denaturation process is 263 kJ mol(-1). The electrostatic surface potential of the modeled tobacco Cu,Zn-SOD I was calculated showing that the functional spatial network of charges on the protein surface has been maintained, independently of the amino acid substitution around the active sites.

Amino Acid Sequence↗