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Biomedical subjects

M Paci

Publications and source records attributed to M Paci.

At least 19 recordsLinked to original sources
PubMed2006

Thymolipoma of the anterior mediastinum: videothoracoscopic removal using a bilateral approach.

Thymolipoma, a rare benign neoplasm of the anterior mediastinum, is often asymptomatic and as a result it can become quite large before it is diagnosed. CT is the most accurate diagnostic technique to identify the adipose tissue, but it often cannot make a differential diagnosis differentiating it from other anterior mediastinal masses; transthoracic biopsy also reveals the presence of fatty tissue, but a definitive diagnosis can only be achieved by means of surgical excision, which is also curative. We describe the case of a young woman who presented with a fatty neoplasm of the anterior mediastinum. The mass was removed using single-stage bilateral sequential videothoracoscopy. The histopathological diagnosis was thymolipoma.

Adult↗
PubMed2004

Characterization of the conformational behavior of peptide Contryphan Vn: a theoretical study.

In this work we report the study of a peptide, the Contryphan Vn produced by Conus ventricosus, a vermivorous cone snail living in the temperate Mediterranean sea. This cyclic peptide of nine residues is a ring closed by a Cys-Cys (Cys: cysteine) disulfide bond containing two proline (Pro) residues and two tryptophans (Trp), one of them being a D-Trp. We present a statistical mechanical characterization of the peptide, simulated in water for about 200 ns with classical molecular dynamics (MD). In recent years there has been a growing interest in the study of the mechanics and dynamics of biological molecules, and in particular for proteins and peptides, about the relationship between collective motions and the active conformations which exert the biological function. To this aim we used the essential dynamics analysis on the MD trajectory and extracted, from the total fluctuations of the molecule, the dominant dynamical modes responsible of the principal conformational transitions. The Contryphan Vn small size allowed us to investigate in details the all-atoms dynamics and the corresponding thermodynamics in conformational space defined by the most significant intramolecular motions.

Animals↗
PubMed2003

Fungus colonisation of pulmonary rheumatoid nodule.

This report describes a 69 year old woman, suffering from active rheumatoid arthritis since the age of 60 and presenting with severe dyspnoea and cough. A computed tomography scan of the chest showed multiple bilateral pulmonary nodules, sometimes cavitated, associated with reticular opacities and pleural effusion. A videothoracoscopic excision of a cavitated nodule was performed. Seven days after surgery, a right pneumothorax developed, and the patient died of septicaemia one month later. Microscopically, the excised nodule was composed of necrotic fibrinoid material with a peripheral rim of palisaded histiocytes, extending to the pleural surface and containing several fungal hyphae morphologically consistent with aspergillus. A diagnosis of pulmonary rheumatoid nodule with fungus colonisation was made. In the lung, fungus colonisation is a rare complication of rheumatoid nodules. The most important differential diagnostic considerations are briefly discussed.

Aged↗
PubMed2003

[Primary leiomyoma of the lung, with clear-cell features and admixed alveolar spaces: description of a case presenting with pneumothorax].

OBJECTIVE: To report about a primary leiomyoma of the lung, with clear cell features and with admixed alveolar epithelium. RESULTS AND CONCLUSIONS: The patient, a 18-year-old female, non smoker, presented with a well-delimited pleuro-pulmonary mass, 6,5 cm across, located in the right upper lobe. The mass was discovered 5 years previously, following an episode of spontaneous pneumothorax; initially interpreted as an intralobar pulmonary sequestration, it was subsequently removed due to a small dimensional increase. A gynaecological examination, a thoracic CT-scan obtained 2 years after operation, and a recent abdomino-pelvic echography were negative. The patient is alive and well 7 years after surgery. Microscopically, the lesion was well delimited and it was punctuated by multiple cysts of variable dimensions, covered by bland cubic cells. The solid part of the lesion was composed by oval, clear cells, merging with fusiform elements with densely eosinophilic cytoplasm. Significant atypia, mitoses and necrosis were absent. Immunohistochemically, both oval and spindle cells were strongly positive for vimentin, smooth muscle actin, desmin and h-caldesmon, negative for cytokeratin, EMA, CD-34, CD-10, CD-117, HMB-45, TTF-1, BCL-2, GFAP, calretinin, chromogranin, estrogen and progesterone receptors. Cells covering the cystic spaces were positive for cytokeratin, TTF-1 and EMA, negative for all the other antibodies tested. Smooth muscle proliferations of the lung are briefly discussed, together with the most important problems in differential diagnosis.

Adolescent↗
PubMed2001

Preoperative localization of indeterminate pulmonary nodules before videothoracoscopic resection.

BACKGROUND: The management of a solitary pulmonary nodule is the subject of debate and minimally invasive diagnostic approaches have low sensitivity for small peripheral nodules. We discuss the role of video-assisted thoracoscopic surgery (VATS) in the management of solitary pulmonary nodules (SPNs) < or = 1 cm performed with a preoperative computed tomography-guided wire localization. METHODS: Thirty-five selected patients underwent VATS resection for SPN, with localization by guide wire before surgery. RESULTS: Seven patients, after VATS exploration, underwent thoracotomy because of pleuropulmonary adhesions, depth or dimensions. Histological diagnosis was obtained in all procedures; there was no postoperative morbidity or morbidity. CONCLUSION: Preoperative computed tomography hook-wire localization is a suitable strategy for peripheral nodules < or = 1 cm in diameter.

Humans↗
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

Unfolding and inactivation of monomeric superoxide dismutase from E. coli by SDS.

The inactivation and the unfolding of the naturally monomeric Cu, Zn, superoxide dismutase from E. coli upon addition of sodium dodecylsulphate have been studied. In contrast to the bovine enzyme, CD, EPR, NMR spectroscopy and pulsed low resolution NMR measurements found an unfolding transition followed by inactivation of the enzyme. During this transition the active site becomes accessible to the bulk water. The unfolding is reversible and both, the tridimensional structure of the protein and the active site, can be restored upon dialysis. In addition, unfolding occurs without loss of metals in the solution.

Animals↗
PubMed2001

A synthetic peptide corresponding to the 550-585 region of alpha-dystroglycan binds beta-dystroglycan as revealed by NMR spectroscopy.

We have probed the binding of a synthetic peptide corresponding to the region 550-585 of the alpha subunit of dystroglycan with a recombinant protein fragment corresponding to the N-terminal extracellular region of beta-dystroglycan (654-750), using NMR in solution. In a 30:1 molar ratio, the peptide binds to the recombinant protein fragment in the fast/intermediate exchange regime. By monitoring the peptide intra-residue HN-Halpha peak volumes of the 2D TOCSY NMR spectra, both in the absence and in the presence of the recombinant fragment, we determined the differential binding affinities of each amino acid. We found that the residues in the region 550-565 (SWVQFNSNSQLMYGLP) are more influenced by the presence of the protein, whereas the C-terminal portion is marginally involved. These NMR results have been confirmed by solid-phase binding assays.

Amino Acid Motifs↗
PubMed2001

Transxiphoid bilateral palpation in video-assisted thoracoscopic lung metastasectomy.

OBJECTIVE: To evaluate indications, limits, and merits of transxiphoid bilateral palpation during video-assisted thoracoscopy (VAT) lung metastasectomy. DESIGN: Survey retrospective study with a minimum follow-up of 1 year. SETTING: University hospital. PATIENTS: From December 1995 to September 1999, 29 of 45 patients operated on for pulmonary metastasectomy were approached through a transxiphoid VAT. Primary sites were colon-rectum (n = 13), kidney (n = 4), limb osteosarcoma (n = 3), uterus (n = 2), larynx (n = 2), breast (n = 1), skin melanoma (n = 1), prostate gland (n = 1), back fibrosarcoma (n = 1), and ovary (n = 1). Bilateral palpation was performed in 23 patients, although only 10 had radiological evidence of bilateral disease. RESULTS: No perioperative or 30-days postoperative mortality was recorded. Acute and chronic pain was similar to that of other VATs and significantly less than sternotomy. Mean +/- SD chest-drain time and hospital stay were 2.8 +/- 1.19 days and 4.3 +/- 1.78 days, respectively. Sixty-nine lesions, 60 of them metastatic, were resected by laser (n = 29) or stapler (n = 40). Bilateral exploration permitted the discovery of 15 radiologically undetected lesions, 11 of which were found to be malignant. Contralateral metastases were found in 5 patients predicted to have unilateral disease. Mean +/- SD follow-up was 22.89 +/- 10.87 months (range, 9-60 months). Six patients developed new pulmonary metastases after a mean interval of 13.6 months; 3 of these patients relapsed in the unexplored hemithorax after 6, 9, and 12 months, respectively. CONCLUSIONS: The use of the transxiphoid VAT approach was safe, applicable in many instances, and effective in detecting occult metastases by manual bilateral palpation. The advantages of a VAT procedure can be coupled with those provided by a radical operation.

Adult↗
PubMed2001

Combined effects of an oxidative enzyme and dissolved humic substances on (13)C-labelled 2,4-D herbicide as revealed by high-resolution (13)C NMR spectroscopy.

Phenoxyalkanoic acids are a widely used class of herbicides. This work employed high-resolution (13)C NMR to study the structural changes induced by humic substances and horseradish perodixase on 2,4-dichorophenoxyacetic acid (2,4-D) (13)C-labelled in the side chain. NMR spectra showed that humic substances chemically catalyze abiotic splitting of [(13)C]2,4-D into 2,4-dichlorophenol and [(13)C]acetic acid at pH 7 but not at pH 4.7. Peroxidase did not catalyze the oxidative degradation of [(13)C]2,4-D at any pH tested and inhibited the effect of humic substances. Catalytic degradation by humic substances was attributed to free-radical reactions enhanced by the stereochemical contribution of large conformational structures formed by heterogeneous humic molecules at neutral pHs. Inhibition of 2,4-D degradation when humic substances were combined with peroxidase was explained by modification of both chemical and conformational humic structure due to peroxidase-promoted oxidative cross-coupling among humic molecules. Our findings show for the first time that the abiotic degradation of 2,4-D is catalyzed by dissolved humic substances at neutral pH. 70-76.

Journal Article↗
PubMed2001

Irreversible inhibition of pig kidney copper-containing amine oxidase by sodium and lithium ions.

Copper amine oxidase was found to be inhibited in a complex way by small alkali metal ions. Classic enzyme kinetic studies showed that Li+ and Na+ were weak noncompetitive inhibitors, whereas the larger alkali metals K+, Rb+ and Cs+ were not inhibitors. However, freezing in the presence of Na+ or Li+ surprisingly resulted in complete and irreversible inactivation. In the case of Li+, it was possible to show that one ion per subunit was retained permanently in the inactivated enzyme, suggesting a structural rearrangement. The mechanism of inhibition was studied using a wide range of spectroscopic and analytic techniques. Only minor changes in the protein structure could be detected, except for a significant change in the geometry of the copper site. The unique topaquinone cofactor was apparently functional and able to proceed through the reductive half of the catalytic cycle, but the enzyme no longer reacted with oxygen. The effect of Na+ and Li+ was source-specific for pig kidney and bovine kidney amine oxidases, while the enzymes from bovine serum or plants were not inactivated, consistent with a mechanism dependent on small structural differences. A model for irreversible inactivation is proposed in which the cofactor is co-ordinated directly to copper, in analogy with the inactivation reported for Escherichia coli amine oxidase under crystal growth conditions.

Aldehydes↗
PubMed2001

Surgical management of solitary pulmonary nodules. An unexpected lucky case.

The case of a 63-year-old woman with a solitary pulmonary nodule (SPN) is reported. Surgical wedge resection revealed an hamartoma. Digital examination of the lung parenchyma showed an unexpected (not previously visualized by thoracic imaging) second nodule that intraoperative frozen examination revealed an adenocarcinoma. The operation was completed with a right upper lobectomy and complete lymphoadenectomy. The authors recommend an early open surgical procedure for any SPNs with risk factors for developing lung cancer.

Adenocarcinoma↗
PubMed2001

[Bronchiolitis obliterans-organizing pneumonia (BOOP) containing asbestos bodies: clinico-pathological study of a case].

We describe a case of bronchiolitis obliterans-organizing pneumonia (BOOP) with asbestos bodies. A 65-year-old man, treated in the past for gastric lymphoma and with an history of asbestos exposure, presented with fever and two nodular opacities in the lower lobe of the left lung. Histologic examination revealed a BOOP pattern; in the inflammatory tissue some asbestos bodies were present. Patients exposed to asbestos may rarely present with localized inflammatory pulmonary lesions. In these cases, the possible etiopathogenetic role of asbestos needs further studies.

Aged↗
PubMed2000

Investigation of the active site of Escherichia coli Cu,Zn superoxide dismutase reveals the absence of the copper-coordinated water molecule. is the water molecule really necessary for the enzymatic mechanism?

The active site of the Cu,Zn superoxide dismutase from Escherichia coli in the oxidized Cu(II) state has been studied by nuclear magnetic relaxation dispersion (NMRD), optical and nuclear magnetic resonance spectroscopy. The orientation of some metal ligands is different with respect to all the other Cu,Zn superoxide dismutases. Moreover, NMRD measurements demonstrate the lack of a copper-coordinated water molecule. In spite of these differences the enzymatic activity is still high. Azide also binds copper with normal affinity and induces modifications in the active site comparable to those previously observed in the eukaryotic enzymes. Our results suggest that, in this enzyme, the copper-coordinated water molecule appears not necessary for the enzymatic reaction. A role for the copper-coordinated water molecule is discussed in the light of recent crystallographic studies.

Binding Sites↗
PubMed2000

The ATT strand of AAT.ATT trinucleotide repeats adopts stable hairpin structures induced by minor groove binding ligands.

AAT.ATT is the most abundant and also the most frequently polymorphic class of trinucleotide repeats in the human genome. To characterize its structural properties and conformational changes induced by minor groove ligands, (AAT)(6) and (ATT)(6) oligomers as well as their complexes with DAPI were investigated by electrophoretic mobility and UV thermal stability as well as fluorescence and NMR spectroscopy. The results show that individual (AAT)(6) and (ATT)(6) strands exist principally as monomeric non-hydrogen-bonded structures. Their individual interaction with DAPI induces the formation of base-paired structures with different thermal stabilities by quite spectroscopically distinct binding mechanisms. In the presence of DAPI, (ATT)(6) forms a monomeric hairpin structure stabilized by two ligands located in the minor groove with a strong apparent binding constant of 3.4 x 10(6) M(-)(1). The DAPI-induced (ATT)(6) hairpin is characterized by well-stacked A.T Watson-Crick and T.T wobble base pairs, a high electrophoretic mobility, and a melting temperature of 41 degrees C. Interaction of DAPI with the complementary (AAT)(6) strand favors less stable base-paired structures, and the results are consistent with electrostatic and hydrogen-bond interactions of the ligand with the phosphodiester backbone of (AAT)(6) by minor involvement of DNA bases.

Base Pairing↗
PubMed2000

Ordered structure acquisition by the N- and C-terminal domains of the small proline-rich 3 protein.

The cell envelope (CE) is a vital structure for barrier function in terminally differentiated dead stratified squamous epithelia. It is assembled by transglutaminase (TGase) cross-linking of several proteins, including hSPR3 in certain specialized epithelia normally subjected to mechanical trauma. Biochemical studies show that hSPR3 serves as a complete substrate for TGase1, TGase2, and TGase3. Multiple adjacent glutamines and lysines of only head-and-tail domain sequences are used by each enzyme for cross-linking. Structural data suggest that the hSPR3 central repeats, as well as hSPR1 and hSPR 2, are highly flexible and mobile; thus, the TGases might not be able to recognize the residues localized on the repeats as adequate substrate. To investigate this hypothesis further and to complete the structural investigation of hSPR3, we performed circular dichroism (CD) studies on peptides corresponding to the N- and C-terminal domain. CD spectra have also been carried out in the presence of different concentrations of the structure-promoting agent cosolvent trifluoroethanol (TFE), which mimics a partial hydrophobic environment found in vivo in or next to the membrane. In fact, this agent increases the dielectric constant of water proportionally, depending on its concentration, and confers structuring properties to the solution, to peptides and proteins that have a structuring propensity. The results indicate that in both the N-terminal and C-terminal, peptides acquire a more ordered structure as a function of the TFE concentration in water. This ability of both N- and C-terminal domain to acquire a more stable ordered conformation might be relevant for SPR3 to act as substrate of TGases. Indeed, only the N- and C-terminus is cross-linked by TGase1 and 3.

Amino Acid Sequence↗
PubMed2000

Transxiphoid video-assisted pulmonary metastasectomy: relevance of helical computed tomography occult lesions.

BACKGROUND: The new transxiphoid video-assisted approach allows manual palpation of both lungs, thus permitting better evaluation of helical computed tomography (CT) in detection of pulmonary metastases. METHODS: From December 1995 to May 1999, 22 patients underwent a transxiphoid video-assisted pulmonary metastasectomy. Manual palpation of both lungs was possible in 18 patients, whereas only 13 had radiologic evidence of unilateral disease. Primaries were colon-rectum (n = 8), kidney (n = 3), uterus (n = 2), larynx (n = 2), limb osteosarcoma (n = 2), and one each of breast, skin melanoma, prostate, fibrosarcoma, and ovary. RESULTS: No perioperative death occurred. Fifty-eight lesions, 49 metastatic, were resected, whereas only 46 had been predicted by helical CT scan. Twelve occult lesions were discovered, eight of which were malignant. Overall sensitivity for proved metastases was 83.7% (41 of 49) and 75.8% (22 of 29) for those less than or equal to 5 mm. Mean follow-up was 15.27 months. Only 2 patients had pulmonary relapse at 6 and 12 months. CONCLUSIONS: Despite helical CT, occult metastases may still be identified in almost one-third of the patients. The transxiphoid approach allows routine bilateral palpation and safe resection, and overcomes this critical limitation of video-assisted metastasectomy.

Disease-Free Survival↗