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E Bucci

Publications and source records attributed to E Bucci.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles.

We determined whether addition of hemoglobin to the plasma would inhibit endothelial-dependent dilation in brain where tight endothelial junctions limit hemoglobin extravasation. Pial arteriolar diameter was measured by intravital microscopy through closed cranial windows in anesthetized cats either without transfusion (hematocrit = 32%) or after exchange transfusion with an albumin or sebacyl-cross-linked human hemoglobin solution (hematocrit = 18%). Dilation of small, medium, and large arterioles to acetylcholine and ADP was not significantly altered by hemoglobin transfusion. The dilatory responses were inhibited by the nitric oxide synthase inhibitor NG-nitro-L-arginine, although significant dilation to 30 microM acetylcholine persisted in small arterioles in the control and albumin-transfused group but not in the hemoglobin-transfused group. The dilatory response to the nitric oxide donor 3-morpholinosydnonimine was unaffected by albumin or hemoglobin transfusion, but the response to nitroprusside was reduced by one-third after hemoglobin transfusion. When cross-linked hemoglobin was superfused through the cranial window, the acetylcholine response became inhibited at a hemoglobin concentration of 0.1 microM and was completely blocked at 10 microM. Because this concentration is substantially less than the 500 microM hemoglobin concentration in plasma after transfusion when there was no inhibition of the acetylcholine response, hemoglobin permeation of the blood-brain barrier was considered negligible. We conclude that exchange of red cell-based hemoglobin with plasma-based hemoglobin does not produce a more effective sink for endothelial-derived nitric oxide evoked by agonist receptor-mediated activation. Furthermore, decreased hematocrit does not affect agonist-evoked endothelial-dependent dilation.

Acetylcholine↗
PubMed1997

Primary cardiac lymphoma in immunocompetent patients: diagnostic and therapeutic management.

BACKGROUND: Primary cardiac lymphoma (PCL) is extremely rare in immunocompetent patients. Different definition criteria have been employed in published series. Prognosis is poor due to diagnostic delay and relevance of the site of disease. METHODS: Two cases observed at the study institution are reported, with a review of 48 cases published in the literature from 1980 to 1996. Only patients with lymphoma confined to the heart and/or pericardium and those with a single and asymptomatic extracardiac site were considered for analysis. RESULTS: Eight patients had minimal extracardiac disease. The most common presentation was unresponsive heart failure. Electrocardiography findings were not specific. PCL usually arose in the right chambers as a mass, with or without pericardial effusion (> 80%). Chest X-rays, transthoracic echocardiography, and computed tomography scans are standard in diagnostic workup, but transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) showed a sensitivity > 90%. Cytology of pericardial effusion was diagnostic in 67% of cases. Thoracotomy was diagnostic in all cases, whereas less invasive procedures had high false-negative rates. Gross resection has no role. Early anthracycline-containing chemotherapy appears to improve survival, whereas the role of radiotherapy has not yet been defined. CONCLUSIONS: The diagnosis of PCL should be considered in patients with a cardiac mass and/or unexplained refractory pericardial effusion. Adequate diagnostic workup, including TEE and MRI, allows confirmation of the early suspicion of PCL. In the absence of a diagnostic cytology, an open biopsy may be indicated to avoid treatment delay. There is no evidence that PCL should be treated differently from other bulky aggressive lymphomas arising at other anatomic sites.

Adolescent↗
PubMed1997

Time-resolved fluorescence of hemoglobin species.

We used time-resolved fluorescence in the pico- to nanosecond time range to monitor the presence of tetramers, dimers and monomers in carbonmonoxyhemoglobin (COHb) solutions and to investigate how their distributions change under different experimental conditions. Comparison of fluorescence lifetime computed from the atomic coordinates of COHb (Vasquez et al., 1996) with those experimentally measured allowed identification of molecular species present in the hemoglobin solution. It was possible to observe modification of the distribution of tetramers, dimers, monomers and species with disordered hemes produced by different experimental conditions. Protein concentration affected the detectable lifetimes, indicating increasing amounts of dimers and monomers at low protein concentrations, while the amount of inverted hemes was not modified. Titration with up to 1 M NaCl modified only the extent of dissociation of hemoglobin into dimers, without affecting heme inversion and monomer formation. Hyperbaric pressure increased the amounts of dimers and monomers. This is the first time that monomeric subunits of hemoglobin have been detected at neutral pH in the normal system.

Carboxyhemoglobin↗
PubMed1997

Effect of central metal substitution on linear dichroism of porphyrins: evidence of out-of-plane transition moments.

Absorption anisotropy and emission anisotropy measurements in poly(vinyl) alcohol (PVA) films of different porphyrin derivatives are reported. Wavelength dependent absorption anisotropy in oriented PVA films, and wavelength dependent excitation spectrum of emission anisotropy of fluorescent porphyrin derivatives in isotropic PVA films indicate the presence of multiple transition moments with different well-defined orientation. Comparison of linear dichroism and orientation behavior in stretched PVA films of deuteroporphyrin III (C2V symmetry) and its iron derivative reveals significant out-of-plane transition moment components. A considerable participation of out-of-plane polarized absorption components is also observed for metal derivatives of non-symmetrical protoporphyrin IX. It appears that central metal substitutions in porphyrin rings do not produce 'circular' degeneration of electronic transition moments. Instead, the presence of metal induces absorption components orthogonal to the porphyrin plane.

Anisotropy↗
PubMed1997

Morphometric study of nucleolar organiser regions (AgNOR) in HPV-associated precancerous lesions and microinvasive carcinoma of the oral cavity.

A morphometric study of silver-stained nucleolar organiser regions (NOR) was performed on histological sections from routinely paraffin-embedded blocks of 26 oral biopsy specimens (21 cases of leukoplakia consisting of 13 low, 4 moderate, 4 severe degree of dysplasia, and 5 cases of microinvasive carcinomas). In situ hybridisation (ISH) for HPV-DNA was performed on serial sections of the same samples. The following parameters were studied: V NOR (single AgNOR volume per nucleus), TV NOR (total AgNOR volume per nucleus), and R.I. (AgNOR's roundness index). The results highlight that not all the morphometric features of AgNORs allow the discrimination between lesions with dysplasia of low, moderate and severe degree and microinvasive carcinoma. TV NOR appeared useful, while the other morphometric parameters appeared statistically not significant i differentiating between the different lesions. These findings suggest that high values of TV NOR in oral dysplasia could represent a risk marker, identifying a subgroup of lesions with a worse prognosis, constituting then a possible indication for rigorous clinical management and/or for complex treatment of these HPV-associated preneoplastic lesions.

Adult↗
PubMed1997

Oral pemphigus: clinical significance of esophageal involvement: report of eight cases.

The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

Adrenal Cortex Hormones↗
PubMed1997

Immunocytochemical detection of autoantibody deposits in Tzanck smears from patients with oral pemphigus.

Eighteen patients, ten affected by pemphigus vulgaris and four affected by herpes simplex of the oral mucosa, together with four healthy patients as controls, were investigated by cytologic examination of Papanicolaou stained smears obtained by scraping the oral mucosa. In all cases additional smears were immunostained with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies against human heavy IgG chains and lambda light chains. The results have shown that, for a cytological diagnosis of pemphigus, this technique can be used as an easy substitute for the immunofluorescence test and does not require any specialized training or equipment. The findings are clearly detectable by light microscopy and allow, together with the immunostaining, an adequate visualization of cell morphology.

Adult↗
PubMed1997

Introduction of negative charges to a crosslinked hemoglobin: lack of effect on plasma half time.

Intramolecularly crosslinked hemoglobins do not dissociate into alpha 1 beta 1 dimers. As a result, they escape glomerular filtration and have plasma half times of 4 hours. This value is shorter than for albumin (5.2 hours) with similar molecular weight but higher negative charge. The present study was done to determine if increased negative charge on a hemoglobin covalently crosslinked with bis (3,5-dibromosalicyl) sebacate would lengthen its plasma half time. Negative charge was introduced by acylation with succinic anhydride. The product had a higher negative charge; however, plasma half time was not increased. A larger fraction of the succinylated material was excreted in the urine suggesting molecular instability.

Animals↗
PubMed1996

Positive and negative cooperativities at subsequent steps of oxygenation regulate the allosteric behavior of multistate sebacylhemoglobin.

Cross-linked human hemoglobin (HbA) is obtained by reaction with bis(3,5-dibromosalicyl) sebacate. Peptide maps and crystallographic analyses confirm the presence of the 10 carbon atom long sebacyl residue cross-linking the two beta82 lysines of the beta-cleft (DecHb). The Adair's constants, obtained from the oxygen binding isotherms, show that at the first step of oxygenation normal hemoglobin and DecHb have a very similar oxygen affinity. In DecHb negative binding cooperativity is present at the second step of oxygenation, which has an affinity 27 times lower than at the first step. Positive cooperativity is present at the third binding step, whose affinity is 380 times that of the second step. The fourth binding step shows a weak negative cooperativity with an affinity one-half that of the third step. Crystals of deoxy-DecHb diffracted to 1.9 angstroms resolution. The resulting atomic coordinates are very similar to those of Fermi et al. [(1984) J. Mol.Biol. 175, 159-174] and Fronticelli et al. [(1994) J. Biol Chem. 269, 23965-23969] for deoxy-HbA. The electron density map of deoxy-DecHb indicates the presence of the 10 carbon bridge between the beta82 lysines. Molecular modeling confirms that insertion of the linker into the T structure requires only slight displacement of the two beta82 lysines. Instead, insertion of the linker into the R and R2 structures [Shaanan (1983) J. Mol. Biol. 171, 31-59; Silva et al. (1992) J. Biol. Chem. 267, 17248-17256] is hindered by serious sterical restrictions. The linker primarily affects the partially and fully liganded states of hemoglobin. The data suggest in DecHb concerted conformational changes at each step of oxygenation.

Allosteric Regulation↗
PubMed1996

Stabilization of the tetrameric structure of human and bovine hemoglobins by pseudocrosslinking with muconic acid.

In previous studies mono-3,5-dibromosalicyl-fumarate was used to introduce an intramolecular crosslink (pseudo-crosslink) in the beta cleft between hemoglobin beta subunits. Sedimentation velocity analysis indicated that the product had a mean molecular weight indicating a tetramer with low dissociability. The product had a P50 higher than that of native hemoglobin and a plasma retention time in the rat of about 3 h, i.e., four times longer than untreated hemoglobin. However, the product contained a fraction which was rapidly eliminated in the urine and which had a short plasma half-time of about 20 min, indicating the presence of a dissociable fraction. We have attempted to further enhance the tetrameric stability of hemoglobin and prevent urine elimination by positioning a longer chain carboxylic acid than fumaric acid into the beta cleft. We reason that a longer molecule would allow for greater stabilizing interactions across the beta cleft. In the present study human and bovine hemoglobins were reacted with mono-3-5-dibromosalicyl muconate. Muconic acid is two carbons longer than fumaric acid. The products were acylated at the beta 82 (human) and beta 81 (bovine) lysines of the beta-cleft and had a low degree of dissociability. For reasons not presently understood, urine excretion was high and plasma half-time was not increased above that of untreated hemoglobin. In conclusion, it appears that only covalently crosslinked hemoglobins which are completely nondissociable tetramers escape filtration; tetramers with any degree of dissociability into dimers are filterable.

Amino Acid Sequence↗
PubMed1996

Production and characteristics of an infusible oxygen-carrying fluid based on hemoglobin intramolecularly cross-linked with sebacic acid.

Research on red cell substitutes requires the availability of oxygen-carrying fluids for physiologic experiments. This article describes the procedure for in-house production of such a fluid. It contains a hemoglobin-based oxygen carrier obtained by reacting human hemoglobin with bis-(3,5-dibromosalicyl) sebacate. This reagent produces intramolecular cross-links between the beta 82 lysines and between the alpha 99 lysines, respectively. The oxygen half-saturation pressure (P50) of the fluid is near 34 mm Hg at 37 degrees C, with a Hill's parameter of n = 2.2. The half-time of intravascular retention is near 3.0 hours in the rat and 6.5 hours in the cat. Spectrophotometric analyses of arterial and venous plasma from an infused rat reveal an efficient oxygen delivery to the tissues by the oxygen carrier. Therefore, this new cross-linked human hemoglobin can be produced in quantities sufficient for in vivo evaluation and with an oxygen affinity and cooperativity adequate for oxygen unloading in plasma.

Amino Acid Sequence↗
PubMed1996

Isolated left ventricular filling abnormalities may predict interleukin-2-induced cardiovascular toxicity.

Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration of high-dose IL-2 is limited by important cardiovascular side effects such as hypotension, fluid retention, arrhythmias, and myocardial ischemia, which often cause dose reduction and/or treatment withdrawal. The occurrence of these toxic events is not predicted by routine pretreatment examinations. The aim of the present study was to test the reliability of serial echocardiography in predicting subsequent cardiac adverse effects in patients undergoing IL-2 administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27-71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two-dimensional and Doppler echocardiography before and immediately after 28 continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for 4 days. Left ventricular systolic function and the diastolic transmitral flow pattern were assessed before and after IL-2 administration. Significant changes of two indexes of left ventricular filling were noted: a decrease of the ratio of maximal flow velocity in early diastole to that in late diastole (E/A) (basal: 1.12 +/- 0.46, mean +/- SD; posttreatment: 0.83 +/- 0.27; p < 0.01) and an increase of the percentage of the atrial contribution to left ventricular filling (basal: 37.75 +/- 11.58%; posttreatment: 49.43 +/- 16.48%; p < 0.01). Eight major cardiovascular events causing IL-2 infusion withdrawal were observed (two ischemic electrocardiographic modifications, three grade III-IV hypotension, one atrial fibrillation, one pericardial effusion, one acute heart failure). These major cardiovascular events were observed more often when an abnormal basal E/A ratio < 1.0 (p < 0.05) was found. We conclude that Doppler transmitral flow pattern analysis before and subsequent to IL-2 infusion is a useful and easily available procedure for the monitoring of cardiac modifications during CIVI IL-2 administration. It might also predict a major cardiovascular event during IL-2 administration. Patients with basal E/A ratio < 1.0 should be more carefully monitored during treatment and/or should be treated with lower IL-2 doses to avoid cardiovascular toxicity.

Adult↗
PubMed1996

Regional blood flow alterations after bovine fumaryl beta beta-crosslinked hemoglobin transfusion and nitric oxide synthase inhibition.

OBJECTIVES: a) To determine whether isovolemic exchange transfusion with cell-free, bovine fumaryl beta beta-crosslinked hemoglobin results in a different pattern of regional blood flow distribution than transfusion with a poor oxygen-carrying, colloidal solution. b) Because of potential nitric oxide scavenging by plasma-based hemoglobin, to determine whether blood flow differences are reduced after nitric oxide synthase inhibition. DESIGN: A prospective, randomized design with repeated blood flow measurements within groups. SETTING: Experimental physiology laboratory in a university medical center. SUBJECTS: Pentobarbital-anesthetized female cats. INTERVENTIONS: Three groups of eight cats were studied: a) a control group with no transfusion (hematocrit of 32%); b) an anemia group in which exchange transfusion with an albumin-containing solution reduced hematocrit to 18% over a 40- to 50-min period; and c) a group in which cell-free hemoglobin was exchanged transfused to reduce hematocrit to 18%, without a proportional reduction in oxygen-carrying capacity. Bovine hemoglobin was covalently crosslinked intramolecularly between the 81-lysine residues on the beta-subunits to stabilize the tetramer. Regional blood flow was measured by the radiolabeled microsphere technique before transfusion and at 10, 100, and 180 mins from the start of transfusion. At 190 mins, N omega-nitro-L-arginine methyl ester (L-NAME; 10mg/kg) was infused to inhibit nitric oxide synthase and blood flow was measured 30 mins later. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure was unchanged in the control and albumin-transfused groups. However, mean arterial pressure increased rapidly in the hemoglobin-transfused group. With hemoglobin transfusion, there were marked reductions in blood flow to the intestines, kidneys and adrenal glands. Administration of L-NAME after hemoglobin transfusion failed to increase arterial pressure or cause further reductions in intestinal, renal, or adrenal blood flow. Administration of L-NAME to the control and albumin-transfused groups increased arterial pressure and reduced intestinal, renal, and adrenal blood flows to values attained with hemoglobin transfusion. In contrast, in skeletal muscle and left ventricle, blood flow rates increased in the albumin-transfused group and were greater than those values found in the control group and hemoglobin-transfused group. The greater flow in the albumin-transfused group persisted after L-NAME administration. There was no difference in renal sodium, potassium, or osmolar excretion, or in urine flow between groups. CONCLUSIONS: Transfusion with cell-free, bovine crosslinked hemoglobin in cats can selective reductions in blood flow in the intestines, kidneys, and adrenal glands without evidence of renal dysfunction by a mechanism consistent with nitric oxide scavenging. In skeletal and cardiac muscle, the increase in blood flow persisted after nitric oxide inhibition in the albumin group relative to the hemoglobin-transfused group at equivalent hematocrit values. This finding is consistent with compensatory vasoconstriction with hemoglobin transfusion due to improved oxygenation by this oxygen carrier.

Animals↗
PubMed1996

Cerebral O2 transport with hematocrit reduced by cross-linked hemoglobin transfusion.

The purpose of this study was to dissociate effects of reduced viscosity from those of low arterial O2 content (CaO2) on cerebral blood flow (CBF) during anemia. Three groups (n = 8) of pentobarbital sodium-anesthetized cats were studied: 1) a time-control group with a hematocrit of 32 +/- 1% (SE), 2) an anemia group that underwent an isovolumic exchange transfusion with albumin in a salt solution to decrease hematocrit to 18 +/- 1%, and 3) a group transfused with cell-free, tetramerically stabilized hemoglobin to decrease hematocrit equivalently to that in the albumin-transfused group. CaO2 (in ml/dl) in the hemoglobin-transfused group (11.8 +/- 0.3) and the control group (15.0 +/- 0.6) was greater than that in the albumin group (8.7 +/- 0.3). CBF (in ml.min-1.100 g-1) in the hemoglobin group (45 +/- 3) and control group (36 +/- 4) was less than that in the albumin group (60 +/- 3). Consequently, cerebral O2 transport (CaO2 x CBF) was similar in the hemoglobin, control, and albumin groups (5.3 +/- 0.3, 5.3 +/- 0.4, and 5.2 +/- 0.2 ml.min-1.100 g-1, respectively). After infusion of N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide (NO) synthase, CBF in the hemoglobin group remained lower than that in the albumin group, suggesting that NO scavenging by hemoglobin did not solely account for the lower CBF. In contrast, the neurohypophysis (posterior pituitary) exhibited substantial decreases in blood flow that were not augmented by L-NAME administration after hemoglobin transfusion and that were similar in magnitude to L-NAME alone. Thus NO scavenging by cell-free hemoglobin may be more prominent in high-flow, protein-permeable regions enriched with NO synthase. These results support the hypothesis that O2 transport to cerebrum is well regulated when CaO2 is manipulated independently of hematocrit and viscosity.

Animals↗
PubMed1995

Heme-protein interactions in horse heart myoglobin at neutral pH and exposed to acid investigated by time-resolved fluorescence in the pico- to nanosecond time range.

We measured the steady state and time-resolved emission intensity decay of horse heart myoglobin at various pH values from neutral to pH 4.42. The steady state intensity was reversibly increased with the decreasing pH, almost doubling at pH 4.5. Frequency domain data for emission decay were analyzed separately for each pH and simultaneously by global analyses. The results indicated the presence of four lifetime components, conserved throughout the pH titrations at 40, 116, 1363, and 4822 ps, respectively. The titration affected only their fractional intensities. Assignments of the lifetimes were based on the Förster theory of radiationless dipole-dipole interaction and the atomic coordinates of the system. We assigned the two shorter lifetimes to Trp-14 and Trp-7, respectively, in the presence of normal hemes. The 1363-ps lifetime was assigned to Trp-7 with inverted hemes (i.e. rotated 180 degrees around the alpha-gamma-meso axis of the porphyrin ring). The 4822-ns lifetime was assigned to reversibly heme-dissociated myoglobin. Lorentzian lifetime distributions were narrow for the lifetimes at 40, 116, and 4822 ps, indicating a homogeneous protein structure. Instead the lifetime at 1363 ns had a broad, pH-independent distribution consistent with small angle wobblings of inverted hemes inside the heme pocket. These analyses revealed the presence of three species originating from heme-protein interactions: the native form of crystalline myoglobin, the conformation with disorder hemes, and the reversibly dissociated heme-free myoglobin. There was increased heme inversion and heme dissociability at lower pH, consistent with the titration of the proximal and distal histidines inside the heme pocket.

Animals↗
PubMed1995

Serum levels of soluble cell adhesion molecules (ICAM-1, VCAM-1, E-selectin) and of cytokine TNF-alpha increase during interleukin-2 therapy.

Circulating levels of soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin were measured in 20 advanced cancer patients at different times during recombinant interleukin-2 immunotherapy. The concentration of all three molecules progressively increased as did the levels of circulating tumor necrosis factor-alpha (TNF-alpha), which is known to induce endothelial cell activation. A fair direct relationship (but not statistically significant) between the raised concentration of soluble cell adhesion molecules and TNF-alpha was observed. We suggest that elevated levels of soluble adhesion molecules and TNF-alpha in the blood of IL-2-treated patients may arise from a systemic inflammatory reaction producing endothelial cell activation.

Adult↗
PubMed1995

Early diagnosis of multiple hamartoma and neoplasia syndrome (Cowden disease). The role of the dentist.

A typical case of Cowden disease is presented. This is rare mucocutaneous disease, genetically determined, with multiple organ system involvement in which a malignancy, particularly of breast and thyroid gland, may develop. The disease can be diagnosed in its early stages by gingival and cutaneous manifestations. We emphasize that the dentist may be the first health care professional who recognizes the syndrome, which is a crucial step to prevent and cure the predictable malignancy.

Adult↗